Leaf disc-mediated oral delivery of small molecules in the absence of surfactant to the two-spotted spider mite, Tetranychus urticae

Abstract

The two-spotted spider mite (TSSM), Tetranychus urticae, is a chelicerate herbivore with a wide host range and strong ability to develop pesticide resistance. Experimental TSSM populations are easy to maintain, and the recent publication of the complete TSSM genome sequence and development of RNA interference-based reverse genetics protocols make this species an ideal chelicerate model for the study of pesticide resistance and plant–herbivore interactions. In such studies, treated leaf discs are often used for oral delivery of test compounds. When preparing these leaf discs, the organosilicone surfactant Silwet L-77 is used to promote wetting of the leaf surface and distribution of the test compound across the entire leaf surface. Here, we examined the toxicity of Silwet L-77 and found it to be toxic to TSSMs. We then developed a novel means of preparing leaf discs in which a polypropylene sheet rather than Silwet L-77 was used to ensure distribution of a tracer dye across the entire leaf surface. These leaf discs were then successfully used to deliver the tracer dye into the midgut of TSSMs. No significant differences were observed in the survival, fecundity, or feeding activity of TSSMs fed on leaf discs treated with water via our novel method compared with those fed on untreated leaf discs. Thus, our novel method of preparing leaf discs eliminates concerns regarding the bioactivity of surfactants in TSSMs, and we anticipate that it will be useful for improving oral delivery-based bioassays that use TSSMs.

http://bit.ly/2Fd9YdO

Hydrology-driven environmental variability determines abiotic characteristics and Oribatida diversity patterns in a Sphagnum peatland system

Abstract

We investigated oribatid mite communities in a Sphagnum-dominated boreal peatland system characterised by a mosaic of oligotrophic and meso-eutrophic areas. We aimed to determine the relative importance of environmental factors (pH, Sphagnum nutrient content, water table level, diversity of vascular plants and bryophytes in the surrounding plant community) and spatial variation in influencing abundance, diversity and community composition of aquatic and terrestrial oribatid mites. Among environmental variables, water table level (micro-topography), pH, and K in Sphagnum tissues were the main predictors of Oribatida community structure. Aquatic species were associated with pools; two terrestrial species—Hoplophthiracarus illinoisensis and Nothrus pratensis—were associated with oligotrophic hummocks; the rest of terrestrial species were associated with dryer mesotrophic and eutrophic habitats. Low water table depth (hummocks), high local plant diversity, and high P in Sphagnum tissues were predictors of high abundance of terrestrial Oribatida. Species richness of terrestrial Oribatida was linked with low water table and high plant diversity. For aquatic Oribatida abundance, water table depth was the single most important predictor variable. Plot trophic class (its status on the peatland poor-rich gradient assigned based on plant indicator species) was also a significant predictor of terrestrial Oribatida abundance, richness, and community structure. Spatial structuring was important for terrestrial Oribatida community composition, weak (P < 0.10) for terrestrial Oribatida abundance and richness, and not significant for aquatic Oribatida.

http://bit.ly/2Fczmko

Facile fabrication of Pt – Ni alloy nanoparticles supported on reduced graphene oxide as excellent electrocatalysts for hydrogen evolution reaction in alkaline environment

Abstract

Development of high-performance electrocatalysts in basic electrolyte is of significance for the decrease in unnecessary energy consumption for production of hydrogen. Herein, we have demonstrated one-step chemical reduction strategy to fabricate platinum–nickel alloy nanoparticle–supported reduced graphene oxide (rGO) as excellent electrocatalysts for hydrogen evolution reaction (HER) in basic condition. Graphene-supported alloy nanocatalysts are achieved by simply controlling the molar ratios of bimetallic precursors. We confirm that nickel species on the surface of as-synthesized nanocatalysts tend to be oxidized as nickel hydroxide during the fabrication. Our nanocatalysts synthesized at the equivalent molar ratios of platinum and nickel salts exhibit much higher electrocatalytic activity for HER than the commercial Pt/C and graphene-supported Pt counterparts in same conditions. The performance improvement is not only attributed to nickel hydroxide layer on our nanocatalysts facilitating the decomposition of water in basic media but also ascribed to the partial replacement of Pt atoms by Ni ones decreasing the Pt–H bond energy and improving desorption of hydrogen atoms on Pt–Ni alloy nanocatalysts. Furthermore, our nanocatalysts present excellent HER catalytic stability. Our results will provide a facile and effective strategy on the development of the excellent Pt-containing composite nanocatalysts for applications in electrocatalysis.

Graphical Abstract

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http://bit.ly/2Rc9POH

Capillaureum caryovora gen. sp. nov. ( Cryphonectriaceae ) pathogenic to pequi ( Caryocar brasiliense ) in Brazil

Abstract

Caryocar brasiliense Camb. (Ca. brasiliense) is a typical tree of the Brazilian Cerrado commonly known as pequi. The pequi fruits have a high potential for use in cosmetic and food industries. Due to its economic importance, during the fruiting period, numerous families living in the Cerrado biome benefit from direct fruit harvesting, which is often their only income source. There are no commercial plantations, and the only source of the pequi fruits is the natural Brazilian Cerrado. During a disease survey, an unknown fungus was observed on stem cankers of dying trees. The fungus has similar characteristics to the well-known family of canker pathogens, the Cryphonectriaceae. Thus, the aims of this study were to isolate and identify the fungus from those canker symptoms and assess its pathogenicity. Identification of the fungus was based on morphological characteristics as well as DNA sequence data. DNA from the internal transcribed spacer (ITS) regions, two fragments of the b-tubulin gene (BT1 and BT2), and large subunit of rDNA (LSU) was sequenced and compared with published sequences for 20 genera in the Cryphonectriaceae family. Pathogenicity tests were conducted on Ca. brasiliense seedlings. Morphological characterizations revealed that the fungus isolated from Ca. brasiliense differed from those typically found in the Cryphonectriaceae, especially for the presence of ostiolar septate single or branched hyphae. Phylogenetic analyses showed that this novel fungus from Ca. brasiliense grouped separately from other genera in the Cryphonectriaceae. Pathogenicity tests on Ca. brasiliense showed that the fungus is able to cause stem cankers. Taking all findings together, we propose that the pathogenic fungus isolated from Ca. brasiliense is a novel genus and a novel species in the Cryphonectriaceae, and thus, we named it as Capillaureum caryovora.

http://bit.ly/2CRZAGM

Randomized clinical trial of class II restoration in permanent teeth comparing ART with composite resin after 12 months

Abstract

Objective

This study evaluated the effectiveness of class II restorations, in permanent teeth, through the ART technique in comparison to composite resin.

Materials and methods

Participants (154), aged 8 to 19 years, with good general health, with class II cavities in permanent teeth, and without pulp involvement and tooth pain were included in this parallel and randomized clinical trial. The Ethics Committee approval number was CAAE: 24012913.0.1001.5417. Seventy-seven restorations were made with each restorative material (Equia Fil-GC Corporation and Z350-3M). Evaluations occurred at 6 and 12 months by the criteria of ART and the USPHS modified. Data were analyzed by Mann-Whitney, chi-square, Fisher's exact, chi-square tests with linear trend and logistic regression by enter method (p < 0.050). The Kaplan-Meier test evaluated the survival rates of the restorations. The log-rank test compared the survival curves.

Results

Regardless of the evaluation criteria used, the success rates of ART restorations were 98.7% (6 months) and 95.8% (12 months) and for composite resins were 100% (6 months) and 98.7% (12 months), with no statistical difference of restoration groups (p > 0.050). Survival rates for restorations, regardless of the evaluation criteria used, are the same as the success rates, with the exception of ART restorations at 12 months of follow-up (94.8%).

Conclusion

No differences in the success rates of class II restorations of ART compared to resin composite, in permanent teeth, were observed after 12 months.

Clinic significant

HVGIC can safely be used to restore proximal cavities in permanent teeth up to 12 months.

http://bit.ly/2LUUrAk

Letter to the Editor replying to Armen Nersesyan about the article published in Clinical Oral Investigations tilted “Smoking increases the frequency of micronuclei in the oral mucosa of adults relative to non-smokers—a systematic review and meta-analysis”

http://bit.ly/2sagPgd

Effects of Glucose Concentration on Ethanol Fermentation of White-Rot Fungus Phanerochaete sordida YK-624 Under Aerobic Conditions

Abstract

White-rot fungi are microorganisms capable of ethanol fermentation; however, the specific conditions activating ethanol fermentation are unclear in contrast to fermentation by yeasts. In this study, we investigated the conditions favoring ethanol fermentation by the white-rot fungus Phanerochaete sordida YK-624, which is able to produce ethanol from woody material. In aerobic stationary cultivation with various concentrations of glucose (0.8–33 g/l), the fungus produced ethanol in media containing an initial glucose concentration of 2.8 g/l or higher. The amount of glucose consumption, mycelial weight, and ethanol production on the second day of culture increased in a concentration-dependent manner at low glucose concentrations; however, these were saturated at high concentrations. Biomass yields (growth/glucose consumption) were decreased until the initial glucose concentration increased to 6.0 g/l, after which the biomass yields showed constant values at higher concentrations (12–33 g/l). On the other hand, ethanol yields increased with decreasing biomass yields. In short shaking cultivation using mycelial suspension, trace amounts of instantaneous aerobic ethanol production were observed with 1.1 and 2.1 g/l glucose, but the relative gene expression levels of key enzymes at the pyruvate branch point showed no significant differences between ethanol production and non-production conditions. From these experimental results, it appears that the white-rot fungus P. sordida YK-624 produces ethanol due to overflow in sugar metabolism under aerobic conditions, although P. sordida YK-624 prioritizes glucose utilization for respiratory growth.

http://bit.ly/2F6GWwe

Anaerobic Degradation of Chloroanilines by Geobacter sp. KT5

Abstract

A chloroaniline-degrading bacterial strain isolated from polluted sediment in the Mekong River was identified as Geobacter sp. KT5. The obtained isolate was found to utilize a wide range of trichloroanilines (TCAs), dichloroanilines (DCAs), monochloroanilines (MACs), and aniline as sources of carbon and energy. It also used Fe(III) as a terminal electron acceptor under anaerobic conditions. Among the chlorinated anilines, KT5 utilized 2,3,4-trichloroaniline (234TCA) with the highest rate (2.48 ± 0.32 µM day⁻¹). On determining the degradation pathway for chloroanilines (CAs) in Geobacter sp. KT5, it showed that the removal of ortho and para halogen was dominant. Firstly, KT5 ortho-dechlorinated some TCAs to DCAs, and then reductively transformed them into MACs and aniline prior to complete degradation with the iron reduction stoichiometry and release of nitrogen and chlorine. The KT5 augmentation in sediment slurry enhanced the degradation of CAs and aniline; however, the anaerobic degradation rates in slurry were significantly lower compared to those in liquid media.

http://bit.ly/2SBGMkA

Application of MALDI Biotyper System for Rapid Identification of Bacteria Isolated from a Fresh Produce Market

Abstract

MALDI-TOF MS has revolutionized the identification of microorganisms and has become an indispensable part of routine diagnostics in the clinical microbiological laboratory. However, application of this technique in microbial surveillance outside of clinical settings is limited. In this study, we have evaluated the performance of a Bruker MALDI Biotyper System for the identification of bacteria isolated from the hand palms of fresh produce handlers and their surrounding environments in a wholesale fresh produce market in Doha, Qatar. The accuracy was verified against the results obtained by bacterial 16S rRNA gene sequencing. A total of 105 isolates were tested, of which 67 (64%) isolates were identified by MALDI-TOF MS and 101 isolates (96%) were identified by 16S rRNA gene sequencing, either at the genus level or species level. However, MALDI-TOF MS identified more isolates (41%) at the species level than 16S rRNA gene sequencing (28%). MALDI-TOF MS was particularly useful in the species level identification of Enterobacteriaceae. MALDI-TOF MS successfully identified most known human pathogens in a rapid and cost-effective manner but failed to identify a significant number of isolates that were of environmental origin, suggesting room for further expansion of the reference database.

http://bit.ly/2F4wncT

Paracoccidioides spp. in Soil from the Pampa Biome in Southern Brazil

Abstract

High rates of paracoccidioidomycosis disease and infection have been recently reported in southern Brazil. However, the knowledgment about the ecoepidemiology of Paracoccidioides spp. in the region is limited, therefore, this study aimed to evaluate the presence of Paracoccidioides spp. DNA in soil samples from a rural area in Southern Rio Grande do Sul, Brazil. Thirty pools of soil samples from Bagé, RS (31º19′53"S 54º06′25"W) were submitted to physicochemical analysis, and to fungal DNA extraction by Norgen Biotek® Kit (Thorold, Canada), followed by Nested PCR technique with ITS4 and ITS5 as external primers, and PBITS-E and PBITS-T as internal primers. DNA amplification products of about 424 bp compatible with Paracoccidioides spp. were detected in eight (26.7%) of the 30 pools of samples, being three were sequenced and identified as P. brasiliensis. Positive soils were characterized by high levels of humidity, organic matter, basic saturation, and pH. This study shows for the first time the presence of Paracoccidioides spp. DNA at soils from the Brazilian Pampa Biome, proving that people living in those areas are exposed to the main agent of paracoccidioidomycosis.

http://bit.ly/2SwkaSh

SOS Response Inhibitory Properties by Potential Probiotic Formulations of Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933 Obtained by Solid-State Fermentation

Abstract

The ability of fermentates of two potential probiotic strains, Bacillus amyloliquefaciens B-1895 and Bacillus subtilis KATMIRA1933, to lower the SOS response in bacteria was evaluated using Escherichia coli-based Lux biosensors (pRecA-lux) and the tested bacilli fermentates obtained through solid-state fermentation. The SOS response was stimulated by the addition of ciprofloxacine. Preparations of both Bacillus fermentates demonstrated SOS-inhibitory activity (up to 54.21%). The strain КATMIRA1933 was characterized by higher SOS-inhibitory activity. The active components of the fermentates were stable against heating, proteinase, and RNase action.

http://bit.ly/2F3K5gW

Flavobacterium sharifuzzamanii sp. nov., Isolated from the Sediments of the East China Sea

Abstract

A novel bacterial strain A7.6^T was isolated from the sediments collected near the Zhairuo Island located in the East China Sea and characterized using a polyphasic approach. Cells were Gram-stain-negative, rod-shaped, non-spore forming, non-flagellated but motile by gliding. The strain was aerobic, positive for oxidase and catalase activities. The strain can grow at 4–35 °C, pH 5.5–9.0, and 0–3% (w/v) NaCl concentration. The major polar lipid was phosphatidylethanolamine, the predominant fatty acids (> 10%) were iso-C_15:0 and summed feature 3 (C_16:1 ω7c and/or C_16:1 ω6c). The genomic G+C content was 33.6 mol% and the major respiratory quinone was menaquinone 6. Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain A7.6^T belonged to the genus Flavobacterium and was closely related to Flavobacterium tistrianum GB 56.1^T (98.4% similarity), F. nitrogenifigens NXU-44^T (98.4%), F. ginsenosidimutans THG 01^T (98.0%) and F. anhuiense D3^T (97.7%). Average nucleotide identities and digital DNA–DNA hybridizations values for genomes ranged from 75.9 to 91.4% and 21.4 to 43.9% between strain A7.6^T and its closest phylogenetic neighbors. The polyphasic characterization indicated that strain A7.6^T represented a novel species of the genus Flavobacterium, for which the name Flavobacterium sharifuzzamanii is proposed. The type strain is A7.6^T (= KCTC 62405^T = MCCC 1K03485^T). The NCBI GenBank accession number for the 16S rRNA gene of A7.6^T is MH396692, and for the genome sequence is QJGZ00000000. The digital protologue database (DPD) Taxon Number is TA00643.

http://bit.ly/2As14Wo

In Vitro Comparative Analysis of Probiotic and Functional Attributes of Indigenous Isolates of Bifidobacteria

Abstract

In the present study, probiotic, safety and functional characteristics of eight indigenous bifidobacterial isolates were compared to identify suitable strains for functional food application. Among the isolates, six strains of Bifidobacterium longum and one each of Bifidobacterium breve and Bifidobacterium bifidum were identified by 16S rRNA, xfp and hsp60 gene sequencing. Diversity among these strains was established by RAPD and Rep-PCR. Genes associated with sortase-dependent pili (SDP) (credited for role in adhesion) and serpin (immunomodulation) which can serve as potential marker genes for rapid identification of probiotic Bifidobacterium, was also evaluated. All the isolates exhibited potential probiotic, functional (antimicrobial activity, antioxidant activity, phytase activity, milk fermentation ability) and safety attributes. However, among them, B. breve NCIM5671 exhibited, better tolerance to low pH, amylase activity and exopolysaccharide producing ability. B. bifidum NCIM5697 and B. longum NCIM5672 demonstrated higher adherence ability to Caco-2 cells. NCIM5697 also displayed exopolysaccharide producing ability while NCIM5672 showed strong antibacterial activity against pathogens tested. Further, with respect to presence of adhesion marker genes, disparity was observed among B. longum strains. B. longum NCIM5684 and B. longum NCIM5686 displayed presence of subunits of SDP reported to be present in B. breve. In addition, B. longum NCIM5686 also lacked SDP present in all other B. longum isolates. B. breve NCIM5671, B. longum NCIM5672 and B. bifidum NCIM5697 with appreciable traits qualifies as potential probiotic cultures. Further, the variations observed in molecular and functional characteristics of isolates signify genetic diversity among the cultures.

http://bit.ly/2Aq4GIF

Salmonella Typhimurium is Attracted to Egg Yolk and Repelled by Albumen

Abstract

Salmonella Typhimurium is the causative agent of non-typhoidal, foodborne salmonellosis. Contamination of hen eggs by the bacterium is a common source of S. Typhimurium infection. S. Typhimurium is peritrichous, and flagellum-dependent motility and chemotaxis are believed to facilitate egg contamination despite the presence of many antimicrobial egg components. We performed motility and chemotaxis assays to demonstrate that S. Typhimurium cells are attracted to egg yolks and are repelled by albumen. The bacterial flagellar motor shows bidirectional rotation, and counterclockwise-biased rotation allows cells to swim smoothly. A rotation assay for a single flagellum showed that, in comparison with thin albumen, the thick albumen more strongly affected the directional bias of the flagellar rotation, resulting in a remarkable suppression of the migration distance. Nevertheless, the S. Typhimurium cells retained positive chemotaxis toward the yolk in the presence of the albumens, suggesting that motility facilitates the growth of S. Typhimurium and survival in eggs.

http://bit.ly/2SBGMRC

Cell Wall Hydrolytic Enzymes Enhance Antimicrobial Drug Activity Against Mycobacterium

Abstract

Cell wall hydrolases are enzymes that cleave bacterial cell walls by hydrolyzing specific bonds within peptidoglycan and other portions of the envelope. Two major sources of hydrolases in nature are from hosts and microbes. This study specifically investigated whether cell wall hydrolytic enzymes could be employed as exogenous reagents to augment the efficacy of antimicrobial agents against mycobacteria. Mycobacterium smegmatis cultures were treated with ten conventional antibiotics and six anti-tuberculosis drugs—alone or in combination with cell wall hydrolases. Culture turbidity, colony-forming units (CFUs), vital staining, and oxygen consumption were all monitored. The majority of antimicrobial agents tested alone only had minimal inhibitory effects on bacterial growth. However, the combination of cell wall hydrolases and most of the antimicrobial agents tested, revealed a synergistic effect that resulted in significant enhancement of bactericidal activity. Vital staining showed increased cellular damage when M. smegmatis and Mycobacterium bovis bacillus Calmette–Guérin (M. bovis BCG) were treated with both drug and lysozyme. Respiration analysis revealed stress responses when cells were treated with lysozyme and drugs individually, and an acute increase in oxygen consumption when treated with both drug and lysozyme. Similar trends were also observed for the other three enzymes (hydrolase-30, RipA-His₆ and RpfE-His₆) evaluated. These findings demonstrated that cell wall hydrolytic enzymes, as a group of biological agents, have the capability to improve the potency of many current antimicrobial drugs and render ineffective antibiotics effective in killing mycobacteria. This combinatorial approach may represent an important strategy to eliminate drug-resistant bacteria.

http://bit.ly/2Syjufp

Enhancement the Cellulase Activity Induced by Endophytic Bacteria Using Calcium Nanoparticles

Abstract

The huge applications of cellulosic and lignocellulosic materials in the various fields of life lead to accumulation of its wastes that became one of the major sources of environmental pollution. In this study, a Gram-positive cellulose-decomposing endophytic bacterium (Chi-04) was isolated from medicinal plant Chiliadenus montanus which inhabitant Saint Catherine (Sinai) region in Egypt. The bacterial strain was identified based on the sequence analysis of 16S rRNA genes as Lysinibacillus xylanilyticus. This isolate was capable of degrading 58% of cellulosic filter paper (100 g/l) within 15 days of incubation. The soluble and reduced sugars were spectrophotometrically determined as cellulose decomposition metabolites. The bacterial isolate exhibited an obvious activity toward cellulase enzyme production. The maximum cellulase activity (0.18 U/min) was detected after 12 days of incubation while the maximum release of soluble sugars (11.85 mg/ml) was detected after 15 days of incubation. CaCl₂ nanoparticles (100 nm) were chemically prepared to enhance the activity of the enzyme. The optimum concentration of CaCl₂ nanoparticles that showed the highest activity of cellulase (0.3 mg/ml reduced sugar) was 0.6%. The bacterial isolates showed potential convert of cellulose into reducing sugars which could be used in several applications.

Graphical Abstract

http://bit.ly/2Ao92jq

Magnetic material diversity in Brazilian ants: displacement behaviour and environmental adaptability

Abstract

How geomagnetic field information is collected and processed by insects for orientation and navigation remains elusive. In social insects, magnetic particles are well accepted as magnetic sensors. Ants have the ability to home and hunt, and some migratory and nomadic species can migrate or move over long distances for which magnetoreception is an important mechanism. It was shown previously that ferromagnetic resonance (FMR) spectral parameters of one migratory and one nomadic ant could be distinguished from Brazilian Solenopsis ant species and that these parameters correlate to the local geomagnetic field. The present work focuses on genera engaged in long-distance group raids and emigration collected mainly in the Amazon rainforest. A diversity of specimens of the genus was individually measured by FMR. Cluster analysis of the occurrence of the FMR Low Field component, associated with large or aggregated nanoparticles, and their spectral angular dependence resulted in a phylogenetic dendrogram of the genera of ants, principally from the North Brazilian region. The magnetic material characteristics of ants of the Invertebrate Collection from the Museum Paraense Emilio Goeldi were tested looking for their relation to ant genera and the local geomagnetic field. The observed spectral differences of the magnetic particles suggest that they are related to their capacity for adaptation to their environment and/or to displacement behaviour.

http://bit.ly/2QlGDzx

Concentration-dependent effects of mercury and lead on Aβ42: possible implications for Alzheimer’s disease

Abstract

Mercury (Hg) and lead (Pb) are known to be toxic non-radioactive elements, with well-described neurotoxicology. Much evidence supports the implication of metals as potential risk cofactors in Alzheimer's disease (AD). Although the action mechanism of the two metals remains unclear, Hg and Pb toxicity in AD could depend on their ability to favour misfolding and aggregation of amyloid beta proteins (Aβs) that seem to have toxic properties, particularly in their aggregated state. In our study, we evaluated the effect of Hg and Pb both on the Aβ42 ion channel incorporated in a planar lipid membrane made up of phosphatidylcholine containing 30% cholesterol and on the secondary structure of Aβ42 in an aqueous environment. The effects of Hg and Pb on the Aβ42 peptide were observed for its channel incorporated into a membrane as well as for the peptide in solution. A decreasing Aβ42 channel frequency and the formation of large and amorphous aggregates in solution that are prone to precipitate were both dependent on metal concentration. These experimental data suggest that Hg and Pb interact directly with Aβs, strengthening the hypothesis that the two metals may be a risk factor in AD.

http://bit.ly/2F1MPeP

Identification and expression pattern of a new digestive invertebrate-type lysozyme from the earthworm

Abstract

Background

The invertebrate type (i-type) lysozyme not showing a clear homology with the known types of lysozyme was first demonstrated from a marine bivalve, conch and earthworm by N-terminal sequence. An i-type lysozyme isolated from the earthworm found to be up-regulated upon bacterial challenge, suggesting this lysozyme to function as an inducible immune factor. However, information on the i-type lysozyme related with digestive function is very limited in the earthworm.

Objective

The objective of this study is to investigate the molecular characteristics and function of the new i-type lysozyme from the earthworm.

Methods

To identify a new i-type lysozyme, multiple amino acid sequence alignment and phylogenetic analyses were employed. Its mRNA expression pattern was observed by fluorescent in situ hybridization (FISH).

Results

A new i-type lysozyme (Ea-iLys) from an earthworm, Eisenia andrei with the open reading frame of 678 bp (226 amino acid residues) appeared to comprise conserved 14 cysteine residues for disulfide bridges and amino acid residues for the enzyme activities of lysozyme and isopeptidase, of which mRNA expression is mainly localized in the lining of midgut epithelium. No significant expression signal was detected in immune competent sites such as chloragogue tissue, typhlosole region, body coelom and muscle layers.

Conclusion

Our results suggest that this enzyme primarily acts as a digestive enzyme rather than an innate immune factor.

http://bit.ly/2F90gtI

Different divergence events for three pairs of PEBPs in Gossypium as implied by evolutionary analysis

Abstract

Introduction

The phosphatidylethanolamine-binding protein (PEBP) gene family plays a crucial role in seed germination, reproductive transformation, and other important developmental processes in plants, but its distribution in Gossypium genomes or species, evolutionary properties, and the fates of multiple duplicated genes remain unclear.

Objectives

The primary objectives of this study were to elucidate the distribution and characteristics of PEBP genes in Gossypium, as well as the evolutionary pattern of duplication and deletion, and functional differentiation of PEBPs in plants.

Methods

Using the PEBP protein sequences in Arabidopsis thaliana as queries, blast alignment was carried out for the identification of PEBP genes in four sequenced cotton species. Using the primers designed according to the PEBP genome sequences, PEBP genes were cloned from 15 representative genomes of Gossypium genus, and the gene structure, CDS sequence, protein sequence and properties were predicted and phylogenetic analysis was performed. Taking PEBP proteins of grape as reference, grouping of orthologous gene, analysis of phylogeny and divergence of PEBPs in nine species were conducted to reconstruct the evolutionary pattern of PEBP genes in plants.

Results

We identified and cloned 160 PEBPs from 15 cotton species, and the phylogenetic analysis showed that the genes could be classified into the following three subfamilies: MFT-like, FT-like and TFL1-like. There were eight single orthologous group (OG) members in each diploid and 16 double OG members in each tetraploid. An analysis of the expression and selective pressure indicated that expression divergence and strong purification selection within the same OG presented in the PEBP gene family.

Conclusion

An evolutionary pattern of duplication and deletion of the PEBP family in the evolutionary history of Gossypium was suggested, and three pairs of genes resulted from different whole-genome duplication events.

http://bit.ly/2Fd1gfs

Native low density lipoprotein increases the production of both nitric oxide and reactive oxygen species in the human umbilical vein endothelial cells

Abstract

Background

Nitric oxide synthases (NOSs) are a unique family of enzymes that catalyze the production of nitric oxide (NO) from l-arginine. Atherogenic action of oxidized low-density lipoproteins (oxLDL) may be mediated partly by the formation of NO in endothelial cells.

Objective

The objective of this study was to identify sources of reactive oxygen species (ROS) causing native LDL (nLDL)-induced senescence of cultured human umbilical vein endothelial cells (HUVECs).

Methods

HUVECs were treated with nLDL and NO production was assessed using Griess reagent as substrate and spectrophotometry in the absence or presence of specific inhibitors of endothelial NOS (eNOS) and inducible NOS (iNOS). In addition, expression levels of eNOS and iNOS were measured with ELISA and western blotting, and ROS was evaluated using 2′,7′-dichlorofluorescin diacetate (DCF-DA) and a fluorescence microplate reader.

Results

NO formation in nLDL-treated HUVECs was significantly increased. Long-term treatment with nLDL up-regulated both eNOS and iNOS proteins. Such increase of NO production in HUVECs induced by nLDL was significantly suppressed by treatment with iNOS-selective inhibitor 1400 W, but not by the eNOS-selective inhibitor L-NIO. Native LDL treatment uncoupled Hsp90, the regulatory binding protein of eNOS, from the enzyme in HUVECs. Native LDL also significantly increased ROS production in HUVECs.

Conclusion

These findings suggest that oxidative stress originated from induction of iNOS and eNOS could be a causative factor for nLDL-induced senescence of HUVECs.

http://bit.ly/2F90cds

Expression analysis of miR-221-3p and its target genes in horses

Abstract

Background

A microRNA (miRNA) is a small non-coding RNA (ncRNA) approximately 20 nucleotides long and it affects gene expression through mRNA cleavage or translational repression. Horses (Equus caballus) have been domesticated and bred to enhance their speed for racing. It has been studied extensively with genetic diversity, origins and evolution.

Objectives

We examined expression patterns of miR-221-3p and its target gene CDKN1C in various horse tissues.

Methods

We used bioinformatic tools to examine target gene, seed region and evolutionary conservation of miR-221-3p. The expression patterns of miR-221-3p and its target gene CDKN1C were analyzed by quantitative polymerase chain reaction (qPCR).

Results

Among eight tissues of horse, miR-221-3p was highly expressed in cerebellum and spleen. On the other hand, only medulla was highly expressed in CDKN1C gene.

Conclusion

Our study provides expression data of miR-221-3p and CDKN1C gene in horse and suggests the fundamental information for future studies in relation to functional importance.

http://bit.ly/2FbWnmT

Roles of paxillin phosphorylation in IL-3 withdrawal-induced Ba/F3 cell apoptosis

Abstract

Background

Ba/F3, a mouse pro-B cell line, is dependent on IL-3 for its survival and proliferation. IL-3 withdrawal causes cells to round, stop in G1 phase, then undergo apoptosis. Additionally, IL-3 is known to induce tyrosine phosphorylation of paxillin, a scaffold and signaling protein. We previously determined that overexpression of paxillin prohibited Ba/F3 cell apoptosis induced by IL-3 withdrawal.

Objective

Address whether phosphorylation is essential for the anti-apoptotic effect of overexpressed paxillin.

Methods

Mutations were introduced into paxillin cDNA at five phosphorylation sites—Y31F, Y40F, Y118F, Y181F, S273A, or S273D. After overexpression of paxillin mutants in Ba/F3 cells, the apoptotic proportions of cell populations were measured by an annexin V conjugation assay while cells were undergoing IL-3 withdrawal.

Results

The anti-apoptotic effect of paxillin overexpression was abolished by site-directed mutagenesis replacing Y31, Y40, Y118, and Y181 with phenylalanine, and S273 with aspartic acid. In contrast, the mutation replacing S273 with alanine had no effect on the anti-apoptotic effect.

Conclusion

The above results suggest that paxillin-mediated phosphorylation at Y31, Y40, Y118, and Y181 is essential for the anti-apoptotic effect of paxillin overexpression in Ba/F3 cells and contributes to the cell survival signaling pathway triggered by IL-3. Conversely, phosphorylation at S273 is involved in the negative regulation of the anti-apoptotic action of overexpressed paxillin.

http://bit.ly/2Fd114S

Effect of PPR on the pore formation behavior and pore performances of β - i PP microporous membrane used for Lithium-ion battery separator

Abstract

In this article, six different PPR content samples were prepared to study the effect of PPR on the pore formation behavior and pore performances of β nucleated isotactic polypropylene microporous membranes used for lithium-ion battery separator. Different scanning calorimetry (DSC) and the wide angle X-ray diffraction (WXRD) results indicate that the PPR slightly inhibits the formation of β-crystal and significantly reduces the melting point of the sample. Furthermore, the morphological evolution of samples with different PPR contents during biaxial stretching is characterized by tensile testing and SEM. As the PPR content increases, the mechanical performance of the sample increases, but the deformation uniformity of the sample decreases. Especially, the deformation of samples with high PPR content is more inhomogeneous and denser regions are generated during the stretching process, which not only broadens the pore size distribution of the sample but also reduces the connectivity between the micropores. Interestingly, samples with low PPR content (less than 30%) and high PPR content (higher than 30%) have different effects on sample porosity and pore connectivity at elevated temperatures. In other words, the microporous membranes of different PPR components have completely different pore shutdown mechanisms at high temperatures.

http://bit.ly/2Reh0Gn

Clampless aortic punch system for making a large-diameter access route without side-biting clamp: a preliminary study

Abstract

Although thoracic endovascular aneurysm repair (TEVAR) has been getting popularity as a less-invasive procedure, the treatment of thoracic aortic aneurysm with atherosclerotic aortic disease is still challenging. In hybrid TEVAR through the median sternotomy approach, side-biting clamp of the ascending aorta is often necessary for making an access route; however, it could cause embolic complication and aortic dissection. This study aimed to present the results of our preliminary study on the clampless aortic punch system (APS). The swine aorta was used as experimental specimen (diameter 16–20 mm). A 10-mm collagen-impregnated knitted Dacron graft was anastomosed to the aorta, and the APS was inserted into it. After piercing the aorta with the inner fish hook of the APS, the aortic wall was scooped out by an outer round cutter. Three different-angled cutters (0°, 15°, and 30°) were tested three times. The diameter of the punched-out lesion ranged from 6 to 9 mm (median 8 mm). Macroscopically, no major vessel injuries were seen 15° series, whereas minor or major vessel injuries were seen 30° and 0° series, respectively. Histological findings of 15° series confirmed the sharp edge of the stump and abrupt interruption of the elastic fiber without destruction of the normal three-layer structure of the aortic wall. This study suggests that our clampless APS could reduce the risk of stroke and aortic injury in hybrid TEVAR, and an animal study confirming its utility is now under consideration.

http://bit.ly/2TtMO6I

Global assessment of the effectiveness of adaptation in coastal areas based on RCP/SSP scenarios

Abstract

The objective of this study is to assess the global impact of sea level rise and to evaluate the effectiveness of adaptation. Global areas of inundation due to sea level rise are identified. The affected populations and the economic damage caused by inundation due to future climate change are estimated for a number of scenarios involving Representative Concentration Pathways (RCP) and Shared Socioeconomic Pathways (SSP). The effects of adaptation in coastal areas, specifically the effects of elevating dikes, are evaluated. According to study results, dikes 1 m in height may reduce the total inundated area by approximately 40% below the no-adaptation baseline under the same RCP. The cost of adaptation was estimated using an original cost database to establish the cost of protection in future socioeconomic scenarios. It was found that the incremental adaptation cost was less than the economic damage in almost all cases of RCP/SSP, providing an incentive to take action to respond to climate change.

http://bit.ly/2CSiXQ2

Evaluating a professional patient navigation intervention in a supportive care setting

Abstract

Purpose

Unmet supportive care needs are common among cancer patients. This study evaluates a patient navigation intervention (i.e., specially trained oncology nurse who monitors, advises, and (if needed) refers patients to supportive cancer care) in terms of need, satisfaction, advice uptake, and consumption of supportive cancer care.

Methods

Using a cross-sectional design, the intervention was evaluated among healthcare professionals, patients who participated, and patients who did not participate in the intervention. All patients were newly diagnosed with breast cancer or melanoma. Data was collected through medical records and online surveys.

Results

In total, 1091 patients were offered patient navigation. Most of these patients (755) were willing to consult the patient navigator (PN). Approximately 90% of patients who completed both the intervention and the questionnaire (N = 120, response rate 54%) perceived the PN as valuable, accessible, and reliable. Approximately 80% of respondents who needed advice regarding nutrition (n = 67), fatigue (n = 98), emotions (n = 106), and work (n = 79) were adequately informed by the PN. Of the 120 respondents, 59 used some form of supportive cancer care. Most of the responding healthcare professionals (N = 70, response rate 45%) perceived the intervention as a valuable addition to current cancer care (n = 51) and mentioned that the PN should be available to all patients (n = 54).

Conclusions

The intervention was perceived as valuable by both patients and healthcare professionals. The results may, however, been biased by the large number of patients who were omitted from participation due to logistical reasons.

http://bit.ly/2SJwa3b

Leukoaraiosis is associated with poor outcomes after successful recanalization for large vessel occlusion stroke

Abstract

Background

Leukoaraiosis (LA) is related to the dysfunction of the microcirculation and results in the impairment of the perfusion state. We investigated the association of LA and poor outcomes after successful recanalization by thrombectomy.

Methods

We retrospectively analyzed 97 patients with anterior large-artery occlusion who underwent thrombectomy and had successful recanalization (modified Treatment in Cerebral Ischemia Scale score 2b or 3). All patients underwent magnetic resonance imaging (MRI). LA was evaluated using fluid-attenuated inversion recovery MRI and graded using the Fazekas scale. Poor functional outcome at day 90 and symptomatic intracerebral hemorrhage (sICH) were compared between patients with absent to mild LA and moderate to severe LA. Logistic regression analyses were performed to determine the association of LA severity and outcomes.

Results

Moderate and severe LA occurred in 28.9% and 26.8% patients respectively. A higher proportion of poor outcomes were observed in patients with moderate to severe LA compared to patients with absent to mild LA (77.8% vs. 39.5%, p < 0.001). Logistic regression analyses showed patients with moderate to severe LA had 3.77 times (95%CI 1.21–11.76, p = 0.022) higher risk of having poor outcomes compared to patients with absent to mild LA.

Conclusions

LA severity may be associated with poor outcomes after successful recanalization for ischemic stroke with anterior large vessel occlusion.

http://bit.ly/2CSIrNf

Interaction of EZH2 and P65 is involved in the arsenic trioxide-induced anti-angiogenesis in human triple-negative breast cancer cells

Abstract

Breast cancer (BC) is the most common female malignancy in the world. Triple-negative breast cancer (TNBC) is a subtype of BC characterized by the lack of estrogen receptors, progesterone receptors, and human epidermal growth factor receptor-2 (HER-2), resulting in the limited therapeutic options. Due to the aggressive behaviors at early stage, TNBC exhibits poorer outcomes compared to other BC subtypes. Hematogenous metastasis, which spreads cancerous cells to lungs and/or bones, plays a pivotal role in the progression of TNBC. Therefore, it is of great importance to study the anti-angiogenesis regulation mechanism for finding new treatment options for TNBC. Arsenic trioxide (ATO) exhibits anti-cancer effect on solid tumors, including TNBC. However, the roles and the molecular mechanism of ATO in the anti-angiogenesis of TNBC remain less well documented. Our data showed that ATO restrained the expression and secretion of vascular endothelial growth factor (VEGF) and impaired the angiogenic ability in TNBC cells. In addition, ATO suppressed the angiogenic ability in TNBC by inhibiting the interaction of the enhancer of zeste homolog 2 (EZH2) with p65, downregulating the nuclear factor-κB (NF-κB) activity, hence contributing to the regulation of IL-6/Stat3 signaling pathway. All of our findings would help to better understand the mechanism of ATO anti-angiogenesis in TNBC, thus highlighting the therapeutic potential of ATO in TNBC by targeting angiogenesis.

http://bit.ly/2C0Owp9

Prevalence of Tuberculosis Disease Among Adult US-Bound Refugees with Chronic Kidney Disease

Abstract

The association between chronic kidney disease (CKD) and tuberculosis disease (TB) has been recognized for decades. Recently CKD prevalence is increasing in low- to middle-income countries with high TB burden. Using data from the required overseas medical exam and the recommended US follow-up exam for 444,356 US-bound refugees aged ≥ 18 during 2009–2017, we ran Poisson regression to assess the prevalence of TB among refugees with and without CKD, controlling for sex, age, diabetes, tobacco use, body mass index ( kg/m²), prior residence in camp or non-camp setting, and region of birth country. Of the 1117 (0.3%) with CKD, 21 (1.9%) had TB disease; of the 443,239 who did not have CKD, 3380 (0.8%) had TB. In adjusted analyses, TB was significantly higher among those with than without CKD (prevalence ratio 1.93, 95% CI: 1.26, 2.98, p < 0.01). Healthcare providers attending to refugees need to be aware of this association.

http://bit.ly/2CTdXKZ

Prophylactic sivelestat for esophagectomy and in-hospital mortality: a propensity score-matched analysis of claims database

Abstract

Purpose

Transthoracic esophagectomy is an invasive surgery, and the excessive surgical stress produces inflammatory cytokines, which provoke acute respiratory distress syndrome (ARDS). Sivelestat sodium hydrate—a selective neutrophil elastase inhibitor—is used to treat or prevent ARDS in patients undergoing esophagectomy, although clear evidence is lacking. We investigated the benefits and risk of prophylactic sivelestat.

Methods

This retrospective study used an administrative claims database in Japan. Adult patients who underwent transthoracic esophagectomy from 2010 to 2016 were identified and divided into a prophylactic sivelestat use group and a non-prophylactic use group that included both non-users and therapeutic users. The primary outcome was all-cause in-hospital mortality, and a secondary outcome included the proportion of ARDS. We used 1:1 propensity score matching. For sensitivity analyses, we conducted a 1:2 propensity score matching analysis and several analyses with various patient inclusion criteria.

Results

Of the 3391 patients with esophagectomy, 621 received prophylactic sivelestat. On unadjusted analysis, the sivelestat group had a higher proportion of in-hospital mortality (5.3% vs. 2.9%) compared with the control group. We created a matched cohort of 615 pairs, whose baseline characteristics were well balanced. On adjusted analysis using propensity score matching, prophylactic sivelestat administration was not associated with decreased in-hospital mortality [adjusted odds ratio (aOR) 1.65; 95% confidence interval (CI) 0.95–2.88], ARDS rate (aOR 1.25; 95% CI 0.49–3.17). The findings were also consistent with other sensitivity analyses.

Conclusion

Because mortality and postoperative complications were similar, our findings do not support prophylactic sivelestat administration for patients undergoing esophagectomy.

http://bit.ly/2RBV1by

Effects of Cornus mas Fruit Hydro-Methanolic Extract on Liver Antioxidants and Histopathologic Changes Induced by Cisplatin in Rats

Abstract

Cornelian cherry (Cornus mas) is a valuable source of phenolic antioxidants. The present study was aimed to investigate whether Cornus mas fruit hydro-methanolic extract (CMFE) can modulate the cisplatin-induced changes in liver antioxidant enzymes and histological structure. Forty Wistar rats were divided into a control group, cisplatin (Cis) group, CMFE group, CMFE 300 + Cis group, and the CMFE 700 + Cis group. After the intervention, blood and tissue samples were taken for biochemical and histopathological analysis. Cis caused reduction in the activity of liver antioxidant enzymes including SOD, GPx, TAC, and CAT and increased that of MDA. Moreover, exposure to Cis caused a reduction in serum level of AST, ALT, and ALP and a rise in serum level of GGT. Oral administration of CMFE for 16 days in the two different dosages at 300 and 700 mg/kg improved the Cis-induced changes of liver enzymes activity and serum enzymes level. Evaluating the histological structure of liver tissue, it was found that treatment by CMFE could ameliorate the Cis-induced changes to near normal histology. The results showed antioxidant and phenol contents in Cornus mas fruit could improve Cis-induced oxidative stress and liver histologic changes in rats.

http://bit.ly/2TuY7vg

Unusual magnetic relaxation behavior of hydrophilic colloids based on gadolinium(III) octabutoxyphthalocyaninate

Abstract

The work introduces the original and efficient approach toward hydrophilization of Gd(III) complex with hydrophobic octa-2,3,9,10,16,17,23,24-n-butoxyphthalocyanine (1H₂). It consists in the solvent-mediated self-assembly of the preliminary synthesized octa-2,3,9,10,16,17,23,24-n-butoxyphthalocyaninatogadolinium(III) acetate 1GdOAc into the colloid species followed by their hydrophilization through the polyelectrolyte deposition. Small-angle X-ray scattering, TEM, and DLS measurements of the aqueous colloids reveal the disk-like colloid species formation with the greatest size value about 40 nm. Deposition of polystyrene sulfonate layer onto the surface of nanocolloids does not prevent their partial aggregation in aqueous solutions. The phthalocyaninate ligand is the reason for specific electrochemical behavior of the colloids, which is affected by the nanoparticulate form of the complex. The magnetic behavior of the complex reveals it as pure paramagnetic, while magnetic relaxation behavior of the colloids points to some specificity. The r₂/r₁ ratio measured at 0.47 T is higher (2.6) than the ratios commonly reported for Gd(III) complexes, coming to 36.8 at 11.75 T. Thus, the synthesized colloids are more efficient as T₂- than T₁-contrasting agents at magnetic field strengths above 1.4 T.

Graphical abstract

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http://bit.ly/2VwiHxj

Genotoxic effects in oral mucosal cells caused by the use of orthodontic fixed appliances in patients after short and long periods of treatment

Abstract

Objective

This study aimed to evaluate the genotoxic effects in the oral epithelial cells of patients undergoing fixed orthodontic treatment and to compare these to a control group without treatment. The null hypothesis to be tested is that corrective orthodontic treatment at different periods does not cause genotoxic effects in patients.

Material and methods

An observational cross-sectional study including 74 patients enrolled in corrective orthodontic treatment and 21 control patients, between 11 and 35 years of age, of both genders, participated in the research. Patients undergoing treatment were divided into four treatment groups differentiated by treatment periods: G1, n = 21 (1 month to 12 months); G2, n = 21 (13 to 24 months); G3, n = 23 (25 to 48 months); and G4, n = 9 (over 48 months). Cells were collected by scraping the internal side of the cheek and subsequently placed in tubes containing 0.9% sodium chloride solution. The sample underwent evaluation for genotoxic effects by means of the micronucleus test (MNT). Bivariate analyses were performed using parametric tests (t test or ANOVA) and nonparametric tests (Chi-square test, Kruskal-Wallis test, Dunn post-test). The adopted level of significance was 5%.

Results

Statistically significant differences for any of the genotoxic abnormalities (binucleated, trinucleated, karyolysis, piknosis, nuclear buds) were not found except for karyolysis, which was higher in the control group than in G4 (p < 0.05).

Conclusions

This study did not demonstrate evidence of genotoxic effects even after long periods of corrective orthodontic treatment.

Clinical relevance

This study explores genotoxic effects in fixed orthodontic patients.

http://bit.ly/2FcgLnK

The impact of cerclage cabling on unstable intertrochanteric and subtrochanteric femoral fractures: a retrospective review of 465 patients

Abstract

Purpose

To assess the potential impact of using cerclage cables or wires when undertaking fixation of unstable intertrochanteric and subtrochanteric fractures.

Methods

Patients were identified from a validated hospital database which included patients from all trauma units within Northern Ireland from 2008 to 2015. The primary outcome measure was return to theatre for any reason. Secondary outcome measures included quality of reduction, tip–apex distance, length of stay, mortality at 3 and 12 months and functional outcomes assessed by Barthel Index and mobility.

Results

465 patients were included (157 in the cerclage/wire group and 308 without). Mean age of 79.6 years, with 330 females and 135 males. There was no statistical difference between the groups in relation to baseline demographics and risk factors for complications. 24 patients required further surgery, 13 (8.3%) in the cerclage group and 11 (3.6%) in those without (p < 0.03). Cabling of intertrochanteric fractures resulted in further surgery in 9.1% versus 3.4% without. Quality of reduction was improved in the cerclage group (p < 0.01), however improvements were less noticeable in intertrochanteric fractures (32.3% classified as good) compared to subtrochanteric fractures (52.4% good). Length of stay was longer in the cerclage group (p < 0.01). No differences were noted in mortality, Barthel score or mobility at 3 and 12 months.

Conclusions

Cerclage cables/wires can augment fixation in subtrochanteric fractures with potential benefits including improving quality of reduction. Evidence for their use in intertrochanteric fractures is much more contentious and we would advise they only be used where a definite improvement in reduction can be obtained with the minimum number possible.

http://bit.ly/2TvHwaD

A new model of early, integrated palliative care: palliative rehabilitation for newly diagnosed patients with non-resectable cancer

Abstract

Purpose

The aim of this paper is to describe a model of palliative rehabilitation for newly diagnosed advanced cancer patients and present data on how it was utilised during a randomised controlled trial (RCT).

Methods

We designed a highly flexible, multidisciplinary model of palliative rehabilitation consisting of a "basic offer" and tailored elements. The model was evaluated in the setting on an RCT investigating the effect of systematic referral to a palliative rehabilitation clinic concurrently with standard oncology treatment or standard treatment alone. The basic offer of palliative rehabilitation was two consultations and a 12-week possibility of contacting a palliative rehabilitation team, if needed. In addition, patients and family caregivers could be offered participation in a 12-week patient/caregiver school combined with individually tailored physical exercise in groups, individual consultations, or both. Contacts with the palliative rehabilitation team and participant evaluation were registered prospectively.

Results

Between December 2014 and December 2017, 132 adults with newly diagnosed advanced cancer were seen in the palliative rehabilitation outpatient clinic. Twenty percent of the participants received the basic offer only (n = 26), 45% additionally participated in the group program (n = 59), and 35% received supplementary individual consultations without participating in the group program (n = 47). The intervention was primarily led by nurses, and the main themes of the individual consultations were coping, pain, and nutrition. When asked if they would recommend the intervention to others in the same situation, 93% of the respondents agreed, 7% partly agreed, and no one disagreed.

Conclusion

The new model of palliative rehabilitation presented here had a flexibility to meet the needs of the participants and led to a very high degree of patient satisfaction. It could serve as an inspiration to other cancer centres wanting to integrate palliative care into standard oncology services.

http://bit.ly/2CT0e6V

Quantifying placebo responses in clinical evaluation of neuropsychiatric symptoms in Alzheimer’s disease

Abstract

Purpose

This study aimed to establish a non-linear mixed effects model to quantitatively analyze the placebo responses of neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD).

Methods

A comprehensive literature search was conducted in public databases. Placebo-controlled randomized AD clinical trials using the neuropsychiatric inventory (NPI) score as the primary or secondary outcome were included. Non-linear mixed effects model was used to describe the time course of the placebo responses of NPS in AD clinical trials. Potential affecting factors were tested as covariates.

Results

A total of 32 clinical studies (involving 3942 subjects) were included in model-based analysis. We found that the maximal placebo responses of NPS were reached at week 4 approximately, after which rebound effects appeared. The baseline NPI score had a significant impact on the placebo responses. Higher baseline NPI score tended to cause greater reductions in NPI score at week 8 and a smaller degree of rebound. For AD patients whose normalized baseline NPI score was 10 points and 30 points, the reduction in normalized NPI score at week 8 was estimated to be 0.83 and 7.43 points, respectively; and the rebound rate after week 8 was estimated to be 0.1 points/week and 0.08 points/week, respectively.

Conclusions

The duration of 4 weeks is sufficient to determine the drug efficacy for assessing NPS in AD clinical trials. The baseline NPI score was a key factor associated with placebo responses of NPS, which should be considered when designing future clinical trials and conducting comparisons across trials.

http://bit.ly/2Fa22d6

Light emitting self-healable hydrogel with bio-degradability prepared form pectin and Tetraphenylethylene bearing polymer

Abstract

Self-healable hydrogel have wide applications in bioscience. In this research, self-healable hydrogel were prepared from TPE-[P(DMA-stat-DAA)]₂ and acylhydrazide functionalized pectin. The TPE containing polymer endowed the hydrogel with light emission property while the pectin make the hydrogel biodegradable. Results showed that the pectin acylhydrazide can be prepared conveniently from pectin through hydrazinolysis. Light emissive hydrogels formed and self-healed without additional stimulus. More importantly, the hydrogel become light emitting with PL intensity higher than the polymer solution. The reason for this result is because the TPE units aggregated in the hydrophobic pectin ring and triggered AIE property. With biodegradable pectin, the hydrogel could be degraded naturally without worrying about the toxicity of the hydrogel in future bio-applications.

http://bit.ly/2CRmApe

Neurolaw in Australia: The Use of Neuroscience in Australian Criminal Proceedings

Abstract

Recent research has detailed the use of neuroscience in several jurisdictions, but Australia remains a notable omission. To fill this substantial void we performed a systematic review of neuroscience in Australian criminal cases. The first section of this article reports the results of our review by detailing the purposes for which neuroscience is admitted into Australian criminal courts. We found that neuroscience is being admitted pre-trial (as evidence of fitness to stand trial), at trial (to support the defence of insanity and substantial impairment of the mind), and during sentencing. In the second section, we evaluate these applications. We generally found that courts admit neuroscience cautiously, and to supplement more well-established forms of evidence. Still, we found some instances in which the court seemed to misunderstand the neuroscience. These cases ranged from interpreting neuroscience as "objective" evidence to admitting neuroscience when the same non-neuroscientific psychiatric evidence would be inadmissible for being common sense. Furthermore, in some cases, neuroscientific evidence presents a double-edged sword; it may serve to either aggravate or mitigate a sentence. Thus, the decision about whether or not to tender this evidence is risky.

http://bit.ly/2FbNtpy

Accuracy of tactile assessment in order to detect proximal cavitation of caries lesions in vitro

Abstract

Objectives

Discriminating non-cavitated from cavitated proximal lesions without tooth separation is only limitedly possible using visual-radiographic assessment alone. We evaluated how additional tactile assessment might increase the accuracy of this discrimination in vitro.

Methods

Surface integrity of 46 primary molars with proximal lesions extending radiographically into outer third of dentin (ICDAS-codes: 2 n = 34, 3 n = 8 and 5 n = 4) were mounted in groups of two in manikin heads and independently assessed by three examiners using visual-radiographic and additional tactile assessment using a cow-horn-ended explorer with or without gingival displacement. After examination, lesion surfaces were evaluated for possible damage using scanning-electronic microscopy. Analysis of variance (ANOVA) was performed for evaluating if tactile assessment and gingival displacement significantly affected accuracy.

Results

Tactile assessment significantly increased sensitivity of detecting cavities (p < 0.001, ANOVA), but decreased specificity (p < 0.05). Sensitivities/specificities varied between 33 (8)%/96 (1)% and 86 (6)%/84 (5)%. Gingival displacement had no significant impact on accuracy (p > 0.05). Scanning-electron microscopy revealed no cavitation.

Conclusions

In vitro, tactile assessment of proximal surfaces was useful and safe.

Clinical relevance

Analysis of the cavitation level by using a cow-horn-ended probe might be leading to useful information in addition to bitewing assessment under clinical circumstances.

http://bit.ly/2TuWVYN

How far do calcium release measurements properly reflect its multiple roles in dental tissue mineralization?

http://bit.ly/2CPx3kT

Impact of seizure-related injuries on quality of life

Abstract

Objective

Our aim is to assess the types and frequency of seizure-related injuries and to determine their effects on Quality of Life (QoL).

Methods

Fifty-seven patients with epilepsy were included to our study. The demographic and clinical data of all the participants were recorded. All patients completed the Quality of Life in Epilepsy Inventory 89 (QOLIE-89). Injury types were classified as burns, head trauma, dental traumas, fractures, body injuries, penetrating traumas, road injuries, and drowning.

Results

Forty-two patients had seizure-related physical injury history whereas 15 of them declared no history of injury. Lower education levels and more frequent seizures were associated with higher seizure-related injury rates (p < 0.05). The most common types of seizure-related injuries were head trauma (22%) and fractures (17%). Fifty-seven (64%)of the injuries took place at home. There was no difference in QOLIE-89 scores between patients with or without seizure-related injury. Multiple injuries, admission to emergency, older than 20 years of the first seizure-related injury, and shorter than 10 years after last seizure-related injury are negatively effective on the QoL scores.

Conclusion

Patients with epilepsy are likely to have seizure-related injuries which may be severe but do not affect the patients' QoL. Seizure-related injuries most commonly occur at home and therefore simple precautions (supervised bathing, using microwave ovens instead of classical stoves, avoiding electric irons and electric heaters, and sleeping close to the floor to avoid falling) taken to reduce the incidence of seizure-related injuries will help reduce hospitalizations and will also be cost-effective.

http://bit.ly/2TwXstw

Improved HEVC $$\lambda $$ λ -domain rate control algorithm for HDR video

Abstract

Widespread high dynamic range (HDR) video distribution via transmission and broadcast is imminent in the near future. However, the rate control (RC) algorithms in video coding standards, like high-efficiency video coding (HEVC), are optimized and designed for low dynamic range (LDR) content—making them inefficient in the rate-distortion (RD) sense, when applied to HDR video compression and distribution. In this paper, we propose a non-normative change to the HM16.2 HEVC \(\lambda \) -domain RC algorithm to achieve high-fidelity HDR video distribution. A new \(\lambda \) -QP relation is modeled for HDR content after assessing the suitable RD model. The results indicate that the proposed RC algorithm outperforms the default RC algorithm in HEVC, achieving on average performance gains of 1.40 dB, 0.685 units, and 0.0155 units in terms of PU-PSNR, HDR-VDP-2.2 Q factor, and HDR-VQM, respectively. Further, proposed method has bit estimation accuracy similar to the default HEVC RC algorithm. Also, the subjective evaluations corroborate the significance of the performance gained in the objective metrics.

http://bit.ly/2QljkWJ

Assessing aberrant muscle activity patterns via the analysis of surface EMG data collected during a functional evaluation

Abstract

Background

Surface electromyographic (EMG) recordings collected during the performance of functional evaluations allow clinicians to assess aberrant patterns of muscle activity associated with musculoskeletal disorders. This assessment is typically achieved via visual inspection of the surface EMG data. This approach is time-consuming and leads to accurate results only when the assessment is carried out by an EMG expert.

Methods

A set of algorithms was developed to automatically evaluate aberrant patterns of muscle activity. EMG recordings collected during the performance of functional evaluations in 62 subjects (22 to 61 years old) were used to develop and characterize the algorithms. Clinical scores were generated via visual inspection by an EMG expert using an ordinal scale capturing the severity of aberrant patterns of muscle activity. The algorithms were used in a case study (i.e. the evaluation of a subject with persistent back pain following instrumented lumbar fusion who underwent lumbar hardware removal) to assess the clinical suitability of the proposed technique.

Results

The EMG-based algorithms produced accurate estimates of the clinical scores. Results were primarily obtained using a linear regression approach. However, when the results were not satisfactory, a regression implementation of a Random Forest was utilized, and the results compared with those obtained using a linear regression approach. The root-mean-square error of the clinical score estimates produced by the algorithms was a small fraction of the ordinal scale used to rate the severity of the aberrant patterns of muscle activity. Regression coefficients and associated 95% confidence intervals showed that the EMG-based estimates fit well the clinical scores generated by the EMG expert. When applied to the clinical case study, the algorithms appeared to capture the characteristics of the muscle activity patterns associated with persistent back pain following instrumented lumbar fusion.

Conclusions

The proposed approach relies on EMG-based measures to generate accurate estimates of the severity of aberrant patterns of muscle activity. The results obtained in the case study suggest that the proposed technique is suitable to derive clinically-relevant information from EMG data collected during functional evaluations.

http://bit.ly/2RvlKGY

Kyphoscoliosis with Klippel-Trenaunay syndrome: a case report and literature review

Abstract

Background

Klippel-Trenaunay syndrome (KTS) is a rare congenital syndrome characterized by the triad of venous varicosities, capillary malformations and limb hypertrophy. However, KTS may rarely occur in combination with kyphoscoliosis.

Case presentation

We presented an 18-year-old female with KTS and kyphoscoliosis. Hypertrophy of bone and soft tissue affected her left face, trunk and lower limb. Moreover, the patient is associated with subacute thyroiditis, vitamin D deficiency and iron deficiency anemia, high level of D-dimer, swollen tonsil, kyphoscoliosis and Chiari-I-malformation without syringomyelia. A posterior correction and spinal fusion from T10 to L5 levels were performed for this patient. The lumbar curve was corrected from 105° to 60° and the kyphosis improved from 58° to 26°. The distance of trunk shift decreased from 10 cm to 1.4 cm. There were no thrombotic events occurred. At the 8th month follow-up, there was no significantly change of the curve in the coronal and sagittal radiographs. During the 31-month follow-up, the patient did not experience any discomfort. And her general appearance did not have any change until the last follow-up. However, she refused to take radiograph for worrying about radiation.

Conclusions

KTS is a rare disease with classic clinical triad. However, it can also have other different features, including kyphoscoliosis, elevated D-Dimer, vitamin D deficiency and iron-deficiency anemia. These issues should be taken into consideration when planning treatment for kyphoscoliosis in KTS patients.

http://bit.ly/2GXcJ5r

Low compartment pressure and myoglobin levels in tibial fractures with suspected acute compartment syndrome

Abstract

Background

The intense ischemic pain of acute compartment syndrome can be difficult to discriminate from the pain related to an associated fracture. Lacking objective measures, the decision to perform fasciotomy is often only based on clinical findings and performed at a low threshold. Biomarkers of muscle cell damage might help to identify and monitor patients at risk. In patients with fractures, however, markers of muscle cell damage could be elevated because of other reasons associated with the trauma, which would make interpretation difficult. In a review of all patients who underwent emergency fasciotomy in our health care district we aimed to investigate the decision-making process and specifically the use of biomarkers in patients with and without fractures.

Methods

In the southeast health care region of Sweden 79 patients (60 men) with fractures (median age 26 years) and 42 patients (34 men) without associated fractures (median age 44 years) were treated with emergency fasciotomy of the lower leg between 2007 and 2016. Differences in clinical findings, p-myoglobin and p-creatine phosphokinase as well as pressure measurements were investigated.

Results

P-myoglobin was analyzed preoperatively in 20% of all cases and p-creatine phosphokinase in 8%. Preoperative levels of p-myoglobin were lower in patients with fractures (median 1065 μg/L, range 200–3700 μg/L) compared with those without fractures (median 7450 μg/L, range 29–31,000 μg/L), p < 0.05. Preoperative intracompartmental pressure was lower in the fracture group (median 45 mmHg, range 25–90 mmHg) compared with those without fractures (median 83 mmHg, range 18–130 mmHg), p < 0.05.

Conclusions

Biomarkers are seldom used in the context of acute fasciotomy of the lower leg. Contrary to our expectations, preoperative levels of p-myoglobin and intracompartmental pressures were lower in fracture patients. These findings support differences in the underlying pathomechanism between the groups and indicate that biomarkers of muscle cell necrosis might play a more important role in the diagnosis of acute compartment syndrome than previously thought.

http://bit.ly/2RsjC2H

Knee osteoarthritis patients with more subchondral cysts have altered tibial subchondral bone mineral density

Abstract

Background

Subchondral bone cysts are a widely observed, but poorly understood, feature in patients with knee osteoarthritis (OA). Clinical quantitative computed tomography (QCT) has the potential to characterize cysts in vivo but it is unclear which specific cyst parameters (e.g., number, size) are associated with clinical signs of OA, such as disease severity or pain. The objective of this study was to use QCT-based image-processing techniques to characterize subchondral tibial cysts in patients with knee OA and to explore relationships between proximal tibial subchondral cyst parameters and subchondral bone density as well as clinical characteristics of OA (alignment, joint space narrowing (JSN), OA severity, pain) in patients with knee OA.

Methods

The preoperative knee of 42 knee arthroplasty patients was scanned using QCT. Patient characteristics were obtained, including OA severity, knee pain, JSN, and alignment. We used 3D image processing techniques to obtain cyst parameters including: cyst number, cyst number per proximal tibial volume, cyst volume per proximal tibial volume, as well as maximum and average cyst volume across the proximal tibia, as well as regional bone mineral density (BMD) excluding cysts. We used Spearman's correlation coefficients to explore associations between patient characteristics and cyst parameters.

Results

At both the medial and lateral compartments of the proximal tibia, greater cyst number and volume were associated with higher BMD. At the lateral region, cyst number and volume were also associated with lateral OA severity, lateral JSN, alignment and sex. Pain was not associated with any cyst parameters at any region.

Conclusion

Cyst number and volume were associated with BMD at both the medial and lateral compartments. Lateral cyst number and volume were also associated with joint alignment, OA severity, JSN and sex. This is the first study to use clinical QCT to explore subchondral tibial cysts in patients with knee OA and provides further evidence of the relationships between subchondral cysts and clinical OA characteristics.

http://bit.ly/2GUPXLt

Indwelling catheter can increase postoperative urinary tract infection and may not be required in total joint arthroplasty: a meta-analysis of randomized controlled trial

Abstract

Background

The purpose of this study was to investigate whether patients undergoing total joint arthroplasty (TJA) require catheterization.

Methods

PubMed, EMBASE, Web of Science, Cochrane Library and China National Knowledge Infrastructure were systematically searched. All randomized controlled trials (RCTs) receiving either a urinary catheterization or no urinary catheterization were included. Meta-analysis results were assessed by RevMan 5.3 software.

Results

Seven independent RCTs were included, with a total sample size of 1533 patients, including 750 patients in the indwelling catheter group and 783 patients in the none-indwelling catheter group. Our pooled data analysis indicated that patients in the indwelling catheter group had a higher risk of urinary tract infection than patients in the none-indwelling catheter group (RR, 3.21; P = 0.0003). However, the meta-analysis indicated that there was no significant difference between the two groups in terms of urinary retention (RR, 0.67; P = 0.13), duration of the surgery (MD, − 0.37; P = 0.55), and length of hospital stay (MD, 0.15; P = 0.38).

Conclusion

Based on the current evidence, this meta-analysis showed that urinary catheterization during TJA can increase the postoperative urinary tract infection, and it may not routinely be required for the patients undergoing TJA.

Level of evidence

Level I, therapeutic study.

http://bit.ly/2RwhDu1

Within-person pain variability and physical activity in older adults with osteoarthritis from six European countries

Abstract

Background

This study examines the association of both pain severity and within-person pain variability with physical activity (PA) in older adults with osteoarthritis (OA).

Methods

Data from the European Project on OSteoArthritis were used. At baseline, clinical classification criteria of the American College of Rheumatology were used to diagnose OA in older adults (65–85 years). At baseline and 12–18 months follow-up, frequency and duration of participation in the activities walking, cycling, gardening, light and heavy household tasks, and sports activities were assessed with the Longitudinal Aging Study Amsterdam Physical Activity Questionnaire. Physical activity was calculated in kcal/day, based on frequency, duration, body weight and the metabolic equivalent of each activity performed. At baseline and 12–18 months follow-up, pain severity was assessed using the pain subscales of the Western Ontario and McMaster Universities OA Index and the Australian/Canadian Hand OA Index. Within-person pain variability was assessed using two-week pain calendars that were completed at baseline, 6 months follow-up and 12–18 months follow-up.

Results

Of all 669 participants, 70.0% were women. Sex-stratified multiple linear regression analyses showed that greater pain severity at baseline was cross-sectionally associated with less PA in women (Ratio = 0.95, 95% CI = 0.90–0.99), but not in men (Ratio = 0.99, 95% CI = 0.85–1.15). The longitudinal analyses showed a statistically significant inverse association between pain severity at baseline and PA at follow-up in women (Ratio = 0.94, 95% CI = 0.89–0.99), but not in men (Ratio = 1.00, 95% CI = 0.87–1.11). Greater pain variability over 12–18 months was associated with more PA at follow-up in men (Ratio = 1.18, 95% CI = 1.01–1.38), but not in women (Ratio = 0.94, 95% CI = 0.86–1.03).

Conclusions

Greater pain severity and less pain variability are associated with less PA in older adults with OA. These associations are different for men and women. The observed sex differences in the various associations should be studied in more detail and need replication in future research.

http://bit.ly/2GTSlSF

“Minimal clinically important difference” estimates of 6 commonly-used performance tests in patients with chronic musculoskeletal pain completing a work-related multidisciplinary rehabilitation program

Abstract

Background

Functional tests are widely used to measure performance in patients with chronic musculoskeletal pain. Our objective was to determine the Minimal Clinically Important Differences (MCID) for the 6-min walk test (6MWT), the Steep Ramp Test (SRT), the 1-min stair climbing test (1MSCT), the sit-to-stand test (STS), the Jamar dynamometer test (JAM) and the lumbar Progressive Isoinertial Lifting Evaluation (PILE) in chronic musculoskeletal pain patients.

Methods

A single-center prospective observational study was conducted in a rehabilitation center. Patients with upper-limb, lower-limb or neck/back lesions were included over a period of 21 months. We used the anchor-based method as a reference method, supplemented by the distribution-based and opinion-based approaches, to determine the MCIDs.

Results

838 chronic musculoskeletal pain patients were included. The estimation method and thelesion location had a significant influence on the results. MCIDs were estimated at +75m and +60m for the 6MWT (lower-limb and neck/back lesions, respectively), +18 steps for the 1MSCT (lower-limb and neck/back lesions) and +6kg for the JAM (upper limb lesions). The anchor-based method could not provide valid estimations for the three other scales, but distribution and opinion-based methods provided rough values of MCIDs for the SRT (+39w to +61w), the STS (-5 sec to -7 sec) and the PILE (+4kg to +7kg).

Conclusion

The above MCID estimations for the 6MWT, 1MSCT and JAM can be used in chronic musculoskeletal pain patients participating in vocational multidisciplinary rehabilitation programs or in therapeutic trials. The use of specific anchors might give better estimations of MCIDs for the three other scales in future research.

http://bit.ly/2RvlKqs

Effects of preparation mode and doping on the genesis and properties of Ni/Ce 1-x M x O y nanocrystallites (M = Gd, La, Mg) for catalytic applications

Abstract

To create the catalytically active ceria-based nanocrystallites with the superior anti-sintering and anti-coking behavior, the peculiarity of genesis and properties of Ni/Ce_1-xM_xO_y nanocrystallites (M = Gd, La, Mg; x = 0–0.5; 1.5 ≤ y ≤ 2.0) were studied by thermal analysis, N₂ adsorption, X-ray diffraction, transmission, and scanning electron microscopy. The control of nanocrystallite characteristics was achieved by tuning of metal-support interaction through the application of different synthesis method (polymerizable complex method, sol–gel template method), doping, and conditions of thermal treatment (300-800 °C, oxidizing and reducing atmospheres). From undoped CeO₂, the mesoporous nanosized Ce_1-xM_xO_y solid solutions are distinguished by higher surface area (95 vs. 155 m²/g), smaller crystallite size (15 vs. 5 nm), and advanced thermal stability. The supported Ce_1-xM_xO_y material Ni species of different dispersion and reducibility were prepared through regulation of composition and crystallite sizes of Ce_xM_1-xO_y.The Ni dispersion increases upon a decrease of support crystallite sizes, with an increase of mole fraction of M and in the following row of doping cations: Gd ˂ Mg ˂ La. The presence of La or Mg in the nanocrystallite composition promotes the stability against sintering while small particle size provides the anti-coking resistance. The developed Ni/Ce_1-xM_xO_y nanocrystallites were remarkable for their performance in autothermal conversion of ethanol and stability against carbonaceous deposits.

http://bit.ly/2SF6xjF

Application of a RE-AIM Evaluation Framework to Test Integration of a Mindfulness Based Parenting Intervention into a Drug Treatment Program

Abstract

Background The RE-AIM framework was applied to the Mindfulness Based Parenting (MBP) intervention to evaluate the feasibility and effectiveness of this innovative trauma informed model in a drug treatment program. The MBP intervention is aimed at mitigating the stress experienced by women in treatment for substance use disorders, and thereby improving parenting and dyadic attachment between mother and child. Methods This was a single arm pre-test post-test design using repeated measure data collected between 2013 and 2016. The design also includes comprehensive process and impact evaluation data. Participants were 120 parenting women enrolled in an opioid treatment program between 2013 and 2016 in Philadelphia, PA. The MBP intervention included weekly 2-h MBP group sessions over 12 weeks, including three dyadic sessions with their child. The main outcomes of this study include the five facets of RE-AIM: Reach, Effectiveness, Adoption, Implementation, and Maintenance. Results The MBP intervention was associated with improvements in parenting across participants. Data showed implementation and sustainability are contingent upon a strong multidisciplinary team and clinical staff support and "buy-in". Iterative adaptations of interventions used in the general population may be necessary when working with a traumatized population burdened by low literacy levels, trauma history and co-occurring disorders. Conclusions MBP is a feasible and effective intervention for improving parenting and dyadic attachment between women with opioid use disorder and their children, and may be useful for other programs that serve parenting women with substance use disorders.

http://bit.ly/2C6HwH4

Educational Attainment and Pregnancy Outcomes: A Danish Register-Based Study of the Influence of Childhood Social Disadvantage on Later Socioeconomic Disparities in Induced Abortion, Spontaneous Abortion, Stillbirth and Preterm Delivery

Abstract

Objectives Socioeconomic disparities in pregnancy outcomes have been found across times and places, but there is a lack of studies investigating the underlying causes. The present study investigated the influence of child protective services in the pregnant woman's family of origin as a proxy of childhood social disadvantage. Methods The study population comprised all registered pregnancies in Denmark during the period from 2000 to 2009 that resulted in an induced abortion, spontaneous abortion, stillbirth or live birth (N = 786,054). Linear regression was used to analyze the associations between educational attainment and pregnancy outcomes in models with and without adjustment for age, parental educational attainment and child protective services in the family of origin. Further, it was tested whether child protective services in the pregnant woman's family of origin modified the associations between educational attainment and pregnancy outcomes. Results Women with low educational attainment had a higher risk of induced abortion, stillbirth and preterm delivery and a lower risk of spontaneous abortion. These associations were to some extent explained by child protective services in the family of origin. Further, child protective services in the pregnant woman's family of origin modified the association between educational attainment and risk of preterm delivery. Thus, women with high educational attainment were not found to differ in risk of preterm delivery according to child protective services in the family of origin Conclusions for Practice Information on childhood social disadvantage may enrich our understanding of the socioeconomic disparities in pregnancy outcomes

http://bit.ly/2RcG2Wk

Exploring the Risks of Repeated Pregnancy Among Adolescents and Young Women in the Philippines

Abstract

Objective Knowledge of the factors which influence repeat pregnancy can inform much needed evidence-based prevention programs. This study aims to identify correlates of repeat pregnancy in the Philippines. Methods We used data from five Philippine Demographic and Health Surveys (1993–2013). A total of 4757 women 15–24 years old who had experienced ≥ 1 pregnancy were included. Individual and partner-related factors were fitted into a series of logistic regression stepwise models with deformalized survey weights. Stratified analyses using two age groups (15–19, 20–24) were also conducted. Interaction terms were included to test for statistical differences between the groups. Results Lower wealth quintiles [odds ratio (OR) 1.71, 95% confidence interval (CI) 1.17–2.49] and partner characteristics such as age of ≥ 30 years (OR = 1.99, CI = 1.41–2.82), multiple partners (OR = 4.19, CI = 1.57–11.19) and live-in status (OR = 1.38, CI = 1.02–1.87) were found to be highly correlated with repeat pregnancy in fully adjusted analysis. Receiving prenatal care from traditional healers (OR = 1.93, CI = 1.02–3.63) during the first pregnancy and giving birth for the first time before 18 years of age (OR = 1.12, CI = 1.04–1.20) showed increased risks among 15–19 years old compared to 20–24 years old in stratified analysis. Conclusions for practice In general, partner characteristics were associated with repeat pregnancy among young women suggesting male involvement, especially older partners, in family planning. High risks for repeat pregnancy were observed among adolescent women who reported younger age at first birth and received prenatal care from a traditional healer which entail promotion of trained prenatal care. Further analysis is needed to validate these findings in other developing countries.

http://bit.ly/2BZWQoT

Biodistribution, pharmacokinetics and radioimmunotherapy of 188 Re-cetuximab in NCI-H292 human lung tumor-bearing nude mice

Summary

Background Cetuximab is a fully humanized IgG1 subclass monoclonal that binds specifically to the human epidermal growth factor receptor (EGFR). Although EGFR is expressed in normal cells, the overexpression of EGFR is detected in many human cancers, such as colon, rectum and lung tumors. In this study, cetuximab with a combination of radiotherapy nuclear ¹⁸⁸Re achieved better therapeutic effect on lung cancer. Methods¹⁸⁸Re-cetuximab administered by the i.v. route in human NCI-H292 lung tumor-bearing mice was investigated. NanoSPECT/CT images were taken to evaluate the distribution and tumor targeting of ¹⁸⁸Re-cetuximab in mice. The anti-tumor effect of ¹⁸⁸Re-cetuximab was assessed by the tumor growth inhibition, survival ratio. Results For nanoSPECT/CT imaging, a significant uptake in tumor was observed at 24 and 48 h following the injection of ¹⁸⁸Re-cetuximab. The anti-tumor effect of ¹⁸⁸Re-cetuximab was assessed by tumor growth inhibition and the survival ratio. The tumor-bearing mice treated with ¹⁸⁸Re-cetuximab showed a better mean tumor growth inhibition rate (MGI = 0.049) and longer median survival time and lifespan (62.50 d; 70.07%) than those treated with ¹⁸⁸Re-perrhenate and cetuximab only by single injection. A synergistic effect of tumor growth inhibition was observed with the combination index exceeding one for ¹⁸⁸Re-cetuximab (CI = 6.135 and 9.276). Conclusion The tumor targeting and localization of 188Re-cetuximab were confirmed in this study. Synergistic therapeutic efficacy was demonstrated for the radioimmunotherapy of ¹⁸⁸Re-cetuximab. The results of this study reveal the potential advantage and benefit obtained from ¹⁸⁸Re-cetuximab for diagnosis and therapy of oncology applications in the future.

http://bit.ly/2RxZCM3

Sensitization of colorectal cancer to irinotecan therapy by PARP inhibitor rucaparib

Summary

Intended to explore synthetic lethality and develop better combinatorial regimens, we screened colorectal cancer (CRC) cells using poly ADP-ribose (PAR) polymerase (PARP) inhibitors and cytotoxic agents. We studied four PARP inhibitors and three DNA-damaging agents, and their combinations using sulforhodamine B assay. Rucaparib demonstrated the greatest synergy with irinotecan, followed by olaparib and PJ34. Rucaparib and irinotecan was further subjected to detailed examination to determine combination index (CI) and underlying mechanism of action. Effectiveness and sequence dependence of this combination were assessed in microsatellite stable (MSS) and unstable (MSI) CRC and HCT116 isogenic cell lines. The degree of cell cycle arrest and apoptosis was determined by FACS. In vivo studies were performed to confirm efficacy of this combination. PAR levels in MSI and PARP expression in MSI and MSS cell lines were diminished upon combinatorial treatment. HCT116 isogenic cells revealed the importance of p21, p53 and PTEN in exerting synergy. In MSI cells, administration of rucaparib prior to irinotecan enhanced cytotoxicity compared to other strategies explored. FACS revealed S-phase arrest and increased late-stage apoptosis in MSS, and G2-M arrest and total and early-stage apoptosis in MSI cells. In in vivo murine xenograft models, a significant reduction in tumor volume and expression of Ki67, pancytokeratin and RPS6KB1, and increase in expression of caspase 3 were observed with the combination. In conclusion, among the various combinations studied, rucaparib plus irinotecan was the most synergistic one. Alterations in cell cycle arrest and apoptosis were dependent on MSI status in CRC cells.

http://bit.ly/2GRVrXc

Significant differences on submission lag following regulation reform for registration of novel therapeutic drugs in Taiwan

Summary

Drug lag, which delays patients' access to medicinal products, is typically associated with pharmaceutical regulations. To shorten drug lag, health authorities may establish new policies to liberalize the regulations, a step that is important in countries, such as Taiwan, with consumer demand for imported novel therapeutic agents. Taiwan's government enacted Articles 38–1 and 38–2 of Regulations for Registration of Medicinal Products to relax the regulatory barriers for new drug submission, thus conditionally exempting the requirement for the Certificate of Pharmaceutical Product (CPP). This study examined whether the enacted regulations reduce submission lag by analyzing the time gap of submission between Taiwan and the United States during 2014–2017. The results indicated that the enacted regulations substantially affected submission lag. Submission lag was significantly shorter for applications not requiring a CPP than those requiring one CPP, which in turn was significantly shorter than those requiring two CPPs. This conclusion can be applied to biological, chemical, non-orphan, and oncology drugs and also applications filed by subsidiary companies, but not orphan drugs and applications filed by contract agents. Among applications requiring one CPP, oncology drugs showed the shortest submission lag. Certain factors, such as clinical studies recruiting over-threshold Taiwanese participants and those performed before the submission of new drug application in the United States, may shorten submission lag. In summary, this study justifies the policy of the exemption from CPP requirements, which supports the hypothesis that relaxing regulatory barriers can reduce submission lag in Taiwan.

http://bit.ly/2Rwcpyp

Human antigen R and drug resistance in tumors

Summary

The human embryonic lethal abnormal visual protein, HuR, belongs to the Hu family of RNA-binding proteins. Over the past two decades, HuR has been extensively associated with multiple biological characteristics of tumors, including tumor development and progression, angiogenesis, invasion, migration and prognosis, since this protein regulates the stability of cancer-associated target mRNAs due to its posttranscriptional regulatory mechanisms. A recent investigation of the multiple functions of HuR has provided emerging evidence of its role in drug resistance in various tumors. Herein, we demonstrate the roles of HuR proteins in the development of drug resistance, examine their involvement in various mechanisms, including apoptosis, the ABC transporter family, the cell cycle and the DNA damage response, and provide insight into ongoing studies for developing therapeutic strategies aimed at targeting this molecule in tumor cells.

http://bit.ly/2GVyq5H

Prediagnostic markers of idiopathic Parkinson’s disease: Gait, visuospatial ability and executive function

Publication date: February 2019

Source: Gait & Posture, Volume 68

Author(s): Nathalie Chastan, Woei-Nan Bair, Susan M. Resnick, Stephanie A. Studenski, Leslie M. Decker

Abstract

Background

Idiopathic Parkinson’s disease (IPD) has a long preclinical phase.

Research question

This study assesses data on prediagnostic markers of IPD from a longitudinal, natural history study of aging.

Methods

Participants were selected from the database of the Baltimore Longitudinal Study of Aging, and included 10 prediagnosed IPD cases (eight men and two women) and 30 age and sex matched healthy controls. Patients with prediagnosed IPD had already had an assessment for IPD 2.6 ± 1.3 years (range 1.0–5.3 years) before the actual diagnosis, including: gait speed (six-meter corridor walk), spatio-temporal gait parameters using Vicon motion capture, balance, upper-limb motor skills, neuropsychological profile, and non-motor symptoms.

Results

Prediagnosed IPD cases compared to controls had slower gait speed (Δ=-0.13 m.s⁻¹, p = 0.03) due to shorter step length (Δ=−5 cm, p = 0.004), worse visuospatial ability (card rotation test, Δ=-42, p = 0.0001) and worse executive function (category fluency test, Δ=-2.6, p = 0.04).

Significance

Our findings identify dimensions that merit further study as prediagnostic markers of Idiopathic Parkinson’s disease to identify patients who might benefit from future neuroprotective therapy in order to delay, or prevent, clinical manifestations.

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Subtle alterations in whole body mechanics during gait following anterior cruciate ligament reconstruction

Publication date: February 2019

Source: Gait & Posture, Volume 68

Author(s): Paige E. Lin, Susan M. Sigward

Abstract

Background

Clinically, normalization of gait following anterior cruciate ligament reconstruction (ACLr) is defined as the absence of observable deviations. However, biomechanical studies report altered knee mechanics during loading response (LR); a time of double limb support and weight transfer between limbs. It is conceivable that subtle adjustments in whole body mechanics, including center of mass (COM) velocity and ground reaction force (GRF) peaks and timing, are present.

Research question

The purpose was to compare limb and whole body mechanics during LR of gait in the surgical and non-surgical limbs post-ACLr.

Methods

Anterior and vertical COM velocity at initial contact; knee flexion range of motion, peak knee extensor moment, peak vertical and posterior GRF, minimum vertical COM position and maximum anterior and vertical COM velocity during LR were identified for twenty individuals 112 ± 17 days post-ACLr without observable gait deficits. To assess differences in timing of COM variables, coupling angles (vector coding) were calculated for multidirectional coordination of vertical and anteroposterior COM velocities and GRFs and categorized as in-phase, anti-phase, vertical phase, or anteroposterior phase coordination. Paired t-tests compared peaks between limbs; non-parametric Wilcoxon signed-rank tests compared coordination pattern frequency.

Results

Less knee range of motion (5.6 °), 30% smaller knee extensor moment, 11% smaller posterior GRF, and slower anterior COM velocity at initial contact (2%) and peak during LR (1.3%; all p < 0.05) were observed in the surgical compared to the non-surgical limb. For COM velocity coordination, lesser anti-phase (7.38%) and greater in-phase coordination (2.88%) were observed in the surgical limb. For GRF coordination, less in-phase coordination (1.94%) was observed in the surgical limb.

Significance

Differences in coordination patterns, suggest that individuals post-ACLr make subtle adjustments in timing of whole body mechanics; particularly in COM velocity during gait. These adjustments are consistent with reduced sagittal plane loading in the surgical knee.

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Slow and faster post-stroke walkers have a different trunk progression and braking impulse during gait

Publication date: February 2019

Source: Gait & Posture, Volume 68

Author(s): Noémie C. Duclos, Cyril Duclos, Sylvie Nadeau

Abstract

Background

Braking forces absorbed by the leading paretic limb are greater than expected with regard to gait speed and not correlated with propulsive forces generated by the non-paretic limb in individuals with severe hemiparesis. Altered foot placement due to poor sensorimotor capacities may explain excessive braking forces.

Research question

The main objective of this study was to determine whether paretic foot placement was related to paretic braking forces in post-stroke individuals with various self-selected walking speeds and motor deficits.

Methods

In this cross-sectional study, 34 chronic hemiparetic post-stroke individuals, divided into slow (< 0.7 m/s, n = 17) and faster (n = 17) subgroups, walked at their self-selected speed. Kinematic and kinetic parameters were measured. Braking impulses, peak braking forces, step characteristics and clinical status were compared between groups and limbs, and their correlations were tested using Pearson (or Spearman) correlation tests.

Results

On the paretic side, braking impulses and step length were similar between groups despite the slower walking speed in the slow group. Paretic peak braking forces and step length were correlated in both groups (r = 0.5). Paretic braking forces were correlated with walking speed, foot placement ahead of the pelvis, trunk progression (TP) from non-paretic initial contact to paretic initial contact, and better motor function of the paretic limb for the faster walkers (0.6 < r < 0.7), but not for the slow walkers. Among the slow walkers, reduced TP ahead of the paretic foot was correlated with a higher paretic impulse (r =  -0.6).

Significance

Better motor function likely helped the faster walkers to decelerate their center of mass appropriately relative to their walking speed. In the slow hemiparetic walkers, TP ahead of the paretic foot was perturbed. Clinicians should therefore consider vasti and plantar flexor muscle tone and activity that likely restrict TP ahead of the paretic foot and increase braking forces.

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