bluuebunny/crossref_metadata_2025 huggingface dataset:
Lactose intolerance: Magnitude and Associated factors among malnourished under-five Children in Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia
Authors: Gebremariam Birhane , Edao Abebe , Bacha Tigist , Wolde Mistire
Published: September 2020

Background

Lactose intolerance (LI) is a pathological condition characterized by the inability to digest sugar, lactose, due to the absence or insufficient activity of the lactase enzyme (β-galactosidase). Currently, laboratory diagnostic procedures for LI are poorly practiced in Ethiopia, and so LI treatment is based on an empirical diagnosis. Thus, theobjectiveof the study was to determine the magnitude and associated factors of lactose intolerance among malnourished under-five children in Yekatit 12 Hospital Medical College, Addis Ababa, Ethiopia from March 2018 – July 2018.

Methods

A cross-sectional study was conducted among malnourished under-five children admitted in the pediatric unit, Yekatit 12 Hospital Medical College, Ethiopia. By using a convenient sampling technique structured questionnaire was administered to gather information on the socio-demographic characteristics of study participants and associated risk factors of LI. Moreover, a fresh stool sample was collected from the study participants to measure stool pH, reducing substances, and microscopy examination for intestinal parasites. Data entery and analysis was done using the Statistical Package for Social Sciences (SPSS 21) software.

Results

The study included 169 malnourished under-five children. Among those 90 (53.3%) were male with a median age of 12 months. The magnitude of LI was 18.3%. Among the study participants, the highest numbers of LI cases were in the age group of less than 12 months; 17(10.1%) followed by 13-24 months; 13(7.7%). Factors that show significant association with LI on bi-variate logistic analysis were family history of lactose intolerance (P=0.043) and diarrhea (P=0.001). In addition; the problem after taking milk (P=0.007), type of therapeutic milk formula (P=0.001), and frequency of stool/24hr (P=0.023) were found to be independent predictors factors of lactose intolerance in the study population.

Conclusion

The magnitude of LI was high in the study setting. Thus, more attention should be given on the proper laboratory diagnosis of LI, for better management of cases at the Yekatit 12 hospital. In addition, similar large scale studies at the molecular level are required to strengthen the present findings of LI in Ethiopia.
Expression of a gene for an MLX56 defense protein derived from mulberry latex confers strong resistance against a broad range of insect pests on transgenic tomato lines
Authors: Murata Mika , Konno Kotaro , Wasano Naoya , Mochizuki Atsushi , Mitsuhara Ichiro
Published: September 2020

Insect pests cause serious damage in crop production, and various attempts have been made to produce insect-resistance crops, including the expression of genes for proteins with anti-herbivory activity, such as BT toxins. However, the number of available genes with sufficient anti-herbivory activity is limited. MLX56 is an anti-herbivory protein isolated from the latex of mulberry plants, and has been shown to have a strong growth-suppressing activity against the larvae of a variety of lepidopteran species. As a model of herbivore-resistant plants, we produced transgenic tomato lines expressing the gene for MLX56. The transgenic tomato lines showed strong anti-herbivory activities against the larvae of the common cutworm,Spodoptera litura. Surprisingly, the transgenic tomato lines also exhibited strong activity against the attack of the western flower thrips,Frankliniera occidentalis. Further, growth of the hadda beetle,Henosepilachna vigintioctopunctatafed on leaves of transgenic tomato was significantly retarded. The levels of damage caused by both western flower thrips and hadda beetles were negligible in the high-MLX56-expressing tomato line. These results indicate that introduction of the gene for MLX56 into crops can enhance crop resistance against a wide range of pest insects, and that MLX56 can be utilized in developing pest-resistance GM crops.
Measles-based Zika vaccine induces long-term immunity and requires NS1 antibodies to protect the female reproductive tract in the hCD46 IFNα/β receptor knockout mice
Authors: Kurup Drishya , Wirblich Christoph , Schnell Matthias J.
Published: September 2020

Zika virus (ZIKV) can cause devastating effects in the unborn fetus of pregnant women. To develop a candidate vaccine that can protect human fetuses, we generated a panel of live measles vaccine (MV) vectors expressing ZIKV-E and -NS1. Our MV-based ZIKV-E vaccine, MV-E2, protected mice from the non-lethal Zika Asian strain (PRVABC59) and the lethal African strain (MR766) challenge. Despite 100% survival of the MV-E2 mice, however, complete viral clearance was not achieved in the brain and reproductive tract of the lethally challenged mice. We then tested a combination of two MV-based vaccines, the MV-E2 and a vaccine expressing NS1 (MV-NS1[2]), and we observed durable plasma cell responses, complete clearance of ZIKV from the female reproductive tract, and complete fetal protection in the lethal African challenge model. Our findings suggest that NS1 antibodies are required to enhance the protection achieved by ZIKV-E antibodies in the female reproductive tract.
MicroRNA775 Promotes Intrinsic Leaf Size and Reduces Cell Wall Pectin Level via a Target Galactosyltransferase inArabidopsis
Authors: Zhang He , Guo Zhonglong , Zhuang Yan , Suo Yuanzhen , Du Jianmei , Gao Zhaoxu , Pan Jiawei , Li Li , Wang Tianxin , Xiao Liang , Qin Genji , Jiao Yuling , Cai Huaqing , Li Lei
Published: September 2020

Plants possess unique primary cell walls made of complex polysaccharides that play critical roles in determining intrinsic cell and organ size. How genes responsible for synthesizing and modifying the polysaccharides are regulated by microRNAs (miRNAs) to control plant size remains largely unexplored. Here we identified 23 putative cell wall related miRNAs, termed CW-miRNAs, inArabidopsis thalianaand characterized miR775 as an example. We showed that miR775 post-transcriptionally silencesGALT9, which encodes an endomembrane-located galactosyltransferase belonging to the glycosyltransferase 31 family. Over-expression of miR775 and deletion ofGALT9significantly enlarged leaf-related organs, primarily owing to increases in cell size. Monosaccharide quantification, confocal Raman imaging, and immunolabelling combined with atomic force microscopy (AFM) revealed that theMIR775A-GALT9circuit modulates pectin level and elastic modulus of the cell wall. We further showed thatMIR775Ais directly repressed by the transcription factor ELONGATED HYPOCOTYL 5 (HY5). Genetic analysis confirmed thatHY5is a negative regulator of leaf size and acts through theHY5-MIR775A-GALT9repression cascade to control pectin level. These results demonstrate that miR775-regulated cell wall remodeling is an integral determinant for intrinsic leaf size inA. thalianaand highlight the need to study other CW-miRNAs for more insights into cell wall biology.
Metabolomic Selection for Enhanced Fruit Flavor
Authors: Colantonio Vincent , Ferrão Luis Felipe V. , Tieman Denise , Bliznyuk Nikolay , Sims Charles , Klee Harry , Munoz Patricio R. , Resende Marcio F. R.
Published: September 2020

Although they are staple foods in cuisines globally, commercial fruit varieties have become progressively less flavorful over time. Due to the cost and difficulty associated with flavor phenotyping, many breeding programs have long been challenged in selecting for this complex trait. To address this issue, we leveraged targeted metabolomics of diverse tomato and blueberry accessions and their corresponding consumer panel ratings to create statistical and machine learning models that can predict sensory perceptions of fruit flavor. Using these models, a breeding program can assess flavor ratings for a large number of varieties, previously limited by the low-throughput and high cost of consumer sensory panels. The ability to predict consumer ratings of liking, sweet, sour, umami, and flavor intensity was evaluated by a 10-fold cross-validation and the accuracies of 18 different models are assessed. The best performing models were used to infer the flavor compounds (sugars, acids, and volatiles) that contribute most to each flavor attribute. The prediction accuracies were high for most attributes in both blueberries and tomatoes. We expect that these models will enable an earlier incorporation of flavor as breeding targets and encourage selection and release of more flavorful fruit varieties.
A Volatile Signal Controls Virulence in the Plant PathogenPseudomonas syringaepv.syringaeand a Strategy for Infection Control in Organic Farming
Authors: Sieber Simon , Mathew Anugraha , Jenul Christian , Kohler Tobias , Bär Max , Carrión Víctor J. , Cazorla Francisco M. , Stalder Urs , Hsieh Ya-Chu , Bigler Laurent , Eberl Leo , Gademann Karl
Published: September 2020

Pseudomonas syringaeis an important pathogen of many agriculturally valuable crops. Among the various pathovars describedP. syringaepv.syringae(Pss) has a particularly wide host range, infecting primarily woody and herbaceous host plants. The ability of Pss to cause bacterial apical necrosis of mango trees is dependent on the production of the antimetabolite toxin mangotoxin. The production of this toxin was shown to be regulated by a self-produced signaling molecule. In this study, we determined the structure of the Pss signal molecule belonging to the recently described family of diazeniumdiolate communication molecules. Employing a targeted mass spectrometry-based approach, we provide experimental evidence that the major signal produced by Pss is the volatile compound leudiazen, which controls mangotoxin production and virulence in a detached tomato leaflet infection model. Experimental results demonstrate that KMnO4solution inactivates leudiazen and that treatment of infected leaves with KMnO4abolishes necrosis. This strategy represents the first example of chemically degrading a signaling molecule to interfere with bacterial communication. The application of KMnO4solution, which is regulatorily approved in organic farming, may constitute an environmentally friendly strategy to control Pss infections.
Cardiac glycosides cause selective cytotoxicity in human macrophages and ameliorate white adipose tissue homeostasis
Authors: Olona Antoni , Hateley Charlotte , Guerrero Ana , Ko Jeong-Hun , Johnson Michael R , Thomas David , Gil Jesus , Behmoaras Jacques
Published: September 2020

Cardiac glycosides (CGs) inhibit the Na+,K+-ATPase and are widely prescribed medicines for chronic heart failure and cardiac arrhythmias. Recently, CGs have been described to induce inflammasome activation in human macrophages, suggesting a cytotoxicity that remains to be elucidated in tissues. Here we show that human monocyte-derived macrophages (hMDMs) undergo cell death following incubation with nanomolar concentrations of CGs, and in particular with ouabain (IC50=50 nM). The ouabain-induced cell death is more efficient in hMDMs compared to non-adherent PBMC populations and is through on-target inhibition of Na,K-ATPAse activity, as it causes an intracellular depletion of K+, while inducing accumulation of Na+and Ca2+levels. Consistently, the cell-death caused by these ion imbalances can be rescued by addition of potassium chloride in hMDMs. Strikingly, white adipose tissue (WAT) explants from morbidly obese patients cultured with nanomolar concentrations of ouabain causes depletion of macrophages, decreases type VI collagen levels, and ameliorates insulin-sensitivityex vivo. These results suggest that the usage of nanomolar concentration of CGs can be an attractive therapeutic avenue in metabolic syndrome characterised by pathogenic infiltration and activation of macrophages.
Monothiol and dithiol glutaredoxin-1 from Clostridium oremlandii: identification of domain-swapped structures by NMR, X-ray crystallography and HDX mass spectrometry
Authors: Lee Kitaik , Yeo Kwon Joo , Choi Sae Hae , Lee Eun Hye , Kim Bo Keun , Kim Sulhee , Cheong Hae-Kap , Lee Won-Kyu , Kim Hwa-Young , Hwang Eunha , Woo Ju Rang , Lee Sung-Joon , Hwang Kwang Yeon
Published: September 2020

Protein dimerization or oligomerization resulting from swapping part of the protein between neighboring polypeptide chains is known to play a key role in the regulation of protein function and in the formation of protein aggregates. Glutaredoxin-1 from Clostridium oremlandii (cGrx1) was used as a model to explore the formation of multiple domain-swapped conformations, which were made possible by modulating several hinge-loop residues that can form a pivot for domain swapping. Specifically, two alternative domain-swapped structures were generated and analyzed using nuclear magnetic resonance (NMR), X-ray crystallography, circular-dichroism spectroscopy and hydrogen/deuterium-exchange (HDX) mass spectrometry. The first domain-swapped structure (β3-swap) was formed by the hexameric cGrx1–cMsrA complex. The second domain-swapped structure (β1-swap) was formed by monothiol cGrx1 (C16S) alone. In summary, the first domain-swapped structure of an oxidoreductase in a hetero-oligomeric complex is presented. In particular, a single point mutation of a key cysteine residue to serine led to the formation of an intramolecular disulfide bond, as opposed to an intermolecular disulfide bond, and resulted in modulation of the underlying free-energy landscape of protein oligomerization.
Fast analytical evaluation of intermolecular electrostatic interaction energies using the pseudoatom representation of the electron density. III. Application to crystal structures via the Ewald and direct summation methods
Authors: Nguyen Daniel , Macchi Piero , Volkov Anatoliy
Published: September 2020

The previously reported exact potential and multipole moment (EP/MM) method for fast and accurate evaluation of the intermolecular electrostatic interaction energies using the pseudoatom representation of the electron density [Volkov, Koritsanszky & Coppens (2004).Chem. Phys. Lett.391, 170–175; Nguyen, Kisiel & Volkov (2018).Acta Cryst.A74, 524–536; Nguyen & Volkov (2019).Acta Cryst.A75, 448–464] is extended to the calculation of electrostatic interaction energies in molecular crystals using two newly developed implementations: (i) the Ewald summation (ES), which includes interactions up to the hexadecapolar level and the EP correction to account for short-range electron-density penetration effects, and (ii) the enhanced EP/MM-based direct summation (DS), which at sufficiently large intermolecular separations replaces the atomic multipole moment approximation to the electrostatic energy with that based on the molecular multipole moments. As in the previous study [Nguyen, Kisiel & Volkov (2018).Acta Cryst.A74, 524–536], the EP electron repulsion integral is evaluated analytically using the Löwdin α-function approach. The resulting techniques, incorporated in theXDPROPmodule of the software packageXD2016, have been tested on several small-molecule crystal systems (benzene, L-dopa, paracetamol, amino acidsetc.) and the crystal structure of a 181-atom decapeptide molecule (Z= 4) using electron densities constructed via the University at Buffalo Aspherical Pseudoatom Databank [Volkov, Li, Koritsanszky & Coppens (2004).J. Phys. Chem. A,108, 4283–4300]. Using a 2015 2.8 GHz Intel Xeon E3-1505M v5 computer processor, a 64-bit implementation of the Löwdin α-function and one of the higher optimization levels in the GNU Fortran compiler, the ES method evaluates the electrostatic interaction energy with a numerical precision of at least 10−5 kJ mol−1in under 6 s for any of the tested small-molecule crystal structures, and in 48.5 s for the decapeptide structure. The DS approach is competitive in terms of precision and speed with the ES technique only for crystal structures of small molecules that do not carry a large molecular dipole moment. The electron-density penetration effects, correctly accounted for by the two described methods, contribute 28–64% to the total electrostatic interaction energy in the examined systems, and thus cannot be neglected.
Crystal structure of 6-azido-6-deoxy-1,2-O-isopropylidene-α-D-glucofuranose
Authors: Wood Adam , Bernhardt Paul V. , van Altena Ian , Simone Michela I.
Published: September 2020

Short syntheses to high Fsp
3 index natural-product analogues such as iminosugars are of paramount importance in the investigation of their biological activities and reducing the use of protecting groups is an advantageous synthetic strategy. An isopropylidene group was employed towards the synthesis of seven-membered ring iminosugars and the title compound, C9H15N3O5, was crystallized as an intermediate, in which the THF ring is twisted and the dioxolane ring adopts an envelope conformation: the dihedral angle between the rings is 67.50 (13)°. In the crystal, the hydroxyl groups participate in O—H...(O,O) and O—H...N hydrogen-bonding interactions, which generate chains of molecules propagating parallel to the a-axis direction. There is a notable non-classical C—H...O hydrogen bond, which cross-links the [100] chains into (001) sheets.
Investigation of the relationship between intensity measures and engineering demand parameters of cable-stayed bridges using intra-plate earthquakes
Authors: He Jin-Hai , Pang Yu-Tao , Dang Xinzhi , Yuan Wan-Cheng
Published: September 2020

Purpose

The purpose of the study is to investigate and reveal this relationship of various engineering demand parameters (EDPs) of this structural type and intensity measures (IMs) under intra-plate earthquakes.

Design/methodology/approach

The nonlinear finite element model used was calibrated first to the existing results of the shaking table test to verify the modeling technique.

Findings

This paper investigated the relationship between intensity measures and various engineering demand parameters of cable-stayed bridges using intra-plate earthquakes. The correlation analysis and Pearson coefficient are used to study the correlation between EDPs and IMs. The results showed that peak ground velocity (PGV)/peak ground acceleration, peak ground displacement and root-mean-square of displacement showed weak correlation with IMs. PGV, sustained maximum velocity, a peak value of spectral velocity, A95 parameter, Housner intensity and spectral acceleration at the fundamental period, the spectral velocity at the fundamental period and spectral displacement at the fundamental period were determined to be better predictors for various EDPs.

Originality/value

This paper investigated the correlation between the intensity measures of intra-plate earthquakes with the seismic responses of a typical long-span cable-stayed bridge in China. The nonlinear finite element model used was calibrated to the existing results of the shaking table test to verify the modeling technique. In total, 104 selected ground motions were applied to the calibrated model, and the responses of various components of the bridge were obtained. This study proposed PGV as the optimal IM.
Disaster Colonialism: A Commentary on Disasters beyond Singular Events to Structural Violence
Authors: Rivera Danielle Zoe
Published: September 2020

Disasters are often, outside disaster studies, viewed as singularities. This characterization of disaster disallows analysis of racial violence and dispossession structurally instituted across multiple disasters. As a result, repeatedly poor pre‐disaster and post‐disaster planning is leveraged to displace and disenfranchise marginalized communities. With climate change, disasters are projected to become more intense and frequent, necessitating a serious inquiry into inequalities occurring across repeated disasters. This essay uses theories of colonialism and coloniality from Puerto Rico to examine how colonialism operates through repeated disaster, in this case hurricanes. Building off of research on environmental colonialism in Puerto Rico, the concept of disaster colonialism is proposed to explain how procedural vulnerability is deepened through disasters and subsequently leveraged to deepen coloniality. To illustrate the utility of this term, a brief overview of Puerto Rico's environmental history with hurricanes is examined through the lens of disaster colonialism. Ultimately, the commentary poses three questions to planners relative to the concept of disaster colonialism.
Identification, in silico characterization, and expression analysis of Tenebrio molitor Cecropin‐2
Authors: Ali Mohammadie Kojour Maryam , Jang Ho Am , Edosa Tariku Tesfaye , Keshavarz Maryam , Kim Bo Bae , Bae Young Min , Patnaik Bharat Bhusan , Han Yeon Soo , Jo Yong Hun
Published: September 2020

Antimicrobial peptides (AMPs) are considered to be candidate effectors for eliciting humoral immune responses against infectious pathogens in the host. Cecropins are α‐helical peptides of 30–40 amino acids, which are known to permeabilize bacterial membranes, and play authoritative roles in the innate immune system of insects. In the present study, we identified the full‐length open reading frame (ORF) encoding the Tenebrio molitor cecropin‐2 (TmCec2) gene using the Tribolium castaneum cecropin‐2 (TcCec2) gene to query a T. molitor Rnaseq database. Phylogenetic analysis revealed close identity of TmCec2 with TcCec2. TmCec2 was ubiquitously expressed in the insect during all developmental stages, with the highest expression observed in the adult. Tissue‐specific TmCec2 expression was highest in larval hemocytes and in the adult integument and hemocytes. Microbial challenge experiments revealed that TmCec2 was highly induced in response to gram‐positive and gram‐negative bacteria, and fungi. These data provide credible evidence for a putative role of TmCec2 in insect innate immunity against a plethora of pathogens.
A comprehensive and comparative evaluation of primers for metabarcoding eDNA from fish
Authors: Zhang Shan , Zhao Jindong , Yao Meng
Published: September 2020

Accurate assessments of fish species diversity and community composition are essential for understanding fish ecology and conservation management. Environmental DNA (eDNA) metabarcoding has become an integrated method for monitoring fish species. The accuracy and efficacy of eDNA metabarcoding rely heavily on the choice of primers used for PCR amplification. A wide selection of metabarcoding primers for fish has been developed; however, there exists no comprehensive and comparative evaluation of their amplification or taxonomic classification of a rich diversity of fish species, which hinders informed decisions regarding their suitability for different study systems.

Here we reviewed the literature and compiled a list of 22 primer sets for eDNA‐based metabarcoding analysis of teleost fish, the performance of which was compared using in silico PCR, followed by in vitro metabarcoding analysis using eDNA from waterbodies in Beijing, which harbour a high number of freshwater fish species.

We found that the primers showed considerable differences in the amplified taxonomic ranges and proportions, fish taxa richness, species discrimination power and fish community compositions, both in silico and in vitro. The number of fish taxa detected from eDNA by the primer sets varied from 0 to 66. Primers targeting the 12S rRNA gene generally detected greater fish diversity than those targeting the 16S rRNA or COI genes, while primers targeting the cytochrome b gene amplified the fewest fish taxa in vitro.

Regarding target genes, 12S primers generally outperformed other primers in terms of amplified fish diversity. The results of in silico PCR and in vitro tests were not always in agreement, suggesting that primer choice for biodiversity surveys should not be based solely on in silico evaluation. The use of different primers can qualitatively and quantitatively affect the detected biodiversity and these effects should be considered in experimental design and data interpretation. These results will assist with primer selection for eDNA‐based fish surveys, and consequently support conservation of freshwater biodiversity.
A drop in immigration results in the extinction of a local woodchat shrike population
Authors: Schaub M. , Ullrich B.
Published: September 2020

The demographic reasons of local population extinctions are rarely known which hampers learning for preventing extinction of other populations. Here we study the demography of a population of the endangered woodchat shrike Lanius senator at the edge of its distribution range from 1966 to 1992. We recorded the number of breeding pairs and collected reproduction and capture‐recapture data which were analysed with an integrated population model. Population size and most demographic rates fluctuated, but did not show long‐term trends. The most important demographic driver for the variation in the annual population growth rate was immigration. Despite its dependence on immigration, the local population was not necessarily a sink but may have been part of a balanced dispersal system. A population viability analysis showed that the risk was zero for the population to go extinct due to stochastic events during the 10 years after 1992. Yet, the population went extinct 6 years after the end of the study. The only demographic mechanism that can explain the fast extinction is a stop of immigration. The population was always dependent on immigration due to the strong dispersal of the shrikes and became more isolated due to the overall decline of the species. Our results suggest that the reservoir of potential immigrants may have become insufficient to maintain the local population and highlights that local populations can go extinct without the need of local changes in demography. Successful conservation of bird populations with similar demography as woodchat shrikes need to focus on spatial scales that extend significantly beyond the local one.
System biology analysis reveals the role of voltage‐dependent anion channel in mitochondrial dysfunction during non‐alcoholic fatty liver disease progression into hepatocellular carcinoma
Authors: Zhu Yanping , Zhang Chao , Xu Fuyi , Zhao Miaoqing , Bergquist Jonas , Yang Chunhua , Liu Xiuxiu , Tan Ying , Wang Xiang , Li Shasha , Jiang Wenguo , Ong Qunxiang , Lu Lu , Mi Jia , Tian Geng
Published: September 2020

Non‐alcoholic fatty liver disease (NAFLD) is one of the most common causes of hepatocellular carcinoma (HCC), but the underlying mechanisms behind the correlation of NAFLD with HCC are unclear. We aimed to uncover the genes and potential mechanisms that drive this progression. This study uncovered the genes and potential mechanisms through a multiple ’omics integration approach. Quantitative proteomics combined with phenotype‐association analysis was performed. To investigate the potential mechanisms, a comprehensive transcriptome/lipidome/phenome‐wide association analysis was performed in genetic reference panel BXD mice strains. The quantitative proteomics combined with phenotype‐association results showed that VDAC1 was significantly increased in tumor tissues and correlated with NAFLD‐related traits. Gene co‐expression network analysis indicated that VDAC1 is involved in mitochondria dysfunction in the tumorigenic/tumor progression. The association between VDAC1 and mitochondria dysfunction can be explained by the fact that VDAC1 was associated with mitochondria membrane lipids cardiolipin (CL) composition shift. VDAC1 was correlated with the suppression of mature specie CL(LLLL) and elevation level of nascent CL species. Such profiling shift was supported by the significant positive correlation between VDAC1 and PTPMT1, as well as negative correlation with CL remodeling enzyme Tafazzin (TAZ). This study confirmed that the expression of VADC1 was dysregulated in NAFLD‐driven HCC and associated with NAFLD progression. The VDAC1‐driven mitochondria dysfunction is associated with cardiolipin composition shift, which causes alteration of mitochondria membrane properties.
Antioxidant activities and mechanisms of polysaccharides
Authors: Mu Si , Yang Wenjian , Huang Gangliang
Published: September 2020

Polysaccharide, as one of the effective components of traditional Chinese medicine, has the activities of anti‐oxidation, anti‐virus, improving immunity and so on. Chinese herbal polysaccharides have a wide range of sources. It is found that polysaccharides in many plants and microorganisms have significant antioxidant effects, mainly through the endogenous antioxidant stress Nrf2/ARE pathway to regulate the expression of downstream antioxidant enzymes. These antioxidant enzymes can further block the free radical chain reaction, thus reducing the generation of free radicals. Secondly, by inhibiting the expression of iNOS mRNA and reducing NO production, it can significantly increase the antioxidant capacity and reduce oxidative stress injury. Polysaccharides are rich in natural resources, their multi‐channel, multi‐target, multi‐effect, and other characteristics have made great progress in antioxidants.
Patch test results with the European baseline series and additions thereof in the ESSCA network, 2015‐2018
Authors: Uter Wolfgang , Bauer Andrea , Belloni Fortina Anna , Bircher Andreas J. , Brans Richard , Buhl Timo , Cooper Susan M. , Czarnecka‐Operacz Magdalena , Dickel Heinrich , Dugonik Aleksandra , Geier Johannes , Giménez‐Arnau Ana M. , Gonçalo Margarida , Johansen Jeanne D. , Johnston Graham A. , Mahler Vera , Rustemeyer Thomas , Sanchez‐Perez Javier , Schuttelaar Marie L.A. , Simon Dagmar , Spiewak Radoslaw , Valiukevičienė Skaidra , Weisshaar Elke , White Ian R. , Wilkinson Mark ,   ESSCA Working Group
Published: September 2020

Background

Clinical surveillance of the prevalence of contact allergy in consecutively patch tested patients is a proven instrument to continually assess the importance of contact allergens (haptens) assembled in a baseline series.

Objectives

To present current results from the European Surveillance System on Contact Allergies, including 13 countries represented by 1 to 11 departments.

Methods

Anonymized or pseudonymized patch test and clinical data from various data capture systems used locally or nationally as transferred to the Erlangen data centre were pooled and descriptively analysed after quality control.

Results

In the 4 years (2015‐2018), data from 51 914 patients patch tested with the European baseline series (EBS) of contact allergens were analysed. Contact allergy to nickel was most frequent (17.6% positive), followed by contact allergy to fragrance mix I (6.9%), methylisothiazolinone (MI; 6.2%), andMyroxylon pereiraeresin (balsam of Peru; 5.8%).

Conclusions

While the prevalence of MI contact allergy decreased substantially following regulatory intervention, the persistently high levels of allergy to metals, fragrances, other preservatives, and rubber chemicals point to problems needing further research and, potentially, preventive efforts. Results with national additions to the baseline series provide important information on substances possibly to be considered for inclusion in the EBS.
Youth‐oriented outcomes of education, employment and training interventions for upcoming youth: Protocol for a discrete choice experiment
Authors: Hawke Lisa D. , Hayes Em , Iyer Srividya , Killackey Eóin , Chinnery Gina , Gariépy Geneviève , Thabane Lehana , Darnay Karleigh , Alagaratnam Akosua , Tucker‐Kilfoil Stephanie , Moxness Katherine , Hachimi‐Idrissi Najia , Winkelmann Ina , Henderson Joanna
Published: September 2020

Aim

The issue of youth who are not engaged in education, employment or training has been a focus of policymakers for decades. Although interventions exist for these youth, they often measure success in ways that fail to capture what youth seek to gain. The project aims to address this gap by assessing youth‐oriented outcomes for interventions targeting upcoming youth. Acknowledging the stigma attached to the deficit‐based notion of not engaged in education, employment or training, hereafter we refer to ‘upcoming youth’, a term coined by youth partners on the project. This study asks what youth want to achieve by participating in an intervention for upcoming youth, with a view to guiding service and research design.

Methods

A mixed‐methods discrete choice experiment will be conducted with youth engaged as partners. A qualitative (focus group) stage will be conducted to design discrete‐choice experiment attributes and levels. The experiment will be piloted and administered online to approx. 500 youth (aged 14‐29) across Canada to identify the outcomes that youth prioritize for interventions. Latent class analyses will then be conducted to explore clusters of outcomes that different groups of youth prioritize.

Conclusions

From a strengths‐based recovery‐oriented framework, hearing the voices of the target population is important in designing and evaluating services. This youth‐oriented research project will identify the intervention outcomes that are the highest priority for upcoming youth. Findings will inform the development, implementation and testing of interventions targeting relevant outcomes for youth who are not engaged in education, employment or training.
Anticoagulation strategies in extracorporeal circulatory devices in adult populations
Authors: Kato Catherine , Oakes Michael , Kim Morris , Desai Anish , Olson Sven R. , Raghunathan Vikram , Shatzel Joseph J.
Published: September 2020

Extracorporeal circulatory devices such as hemodialysis and extracorporeal membrane oxygenation can be lifesaving; however, they are also prone to pathologic events including device failure, venous and arterial thrombosis, hemorrhage, and an accelerated risk for atherosclerotic disease due to interactions between blood components and device surfaces of varying biocompatibility. While extracorporeal devices may be used acutely for limited periods of time (eg, extracorporeal membrane oxygenation, continuous venovenous hemofiltration, therapeutic apheresis), some patients require chronic use of these technologies (eg, intermittent hemodialysis and left ventricular assist devices). Given the substantial thrombotic risks associated with extracorporeal devices, multiple antiplatelet and anticoagulation strategies—including unfractionated heparin, low‐molecular‐weight heparin, citrate, direct thrombin inhibitors, and direct oral anticoagulants, have been used to mitigate the thrombotic milieu within the patient and device. In the following manuscript, we outline the current data on anticoagulation strategies for commonly used extracorporeal circulatory devices, highlighting the potential benefits and complications involved with each.
Efficacy and safety of Fenfluramine hydrochloride for the treatment of seizures in Dravet syndrome: A real‐world study
Authors: Specchio Nicola , Pietrafusa Nicola , Doccini Viola , Trivisano Marina , Darra Francesca , Ragona Francesca , Cossu Alberto , Spolverato Silvia , Battaglia Domenica , Quintiliani Michela , Luigia Gambardella Maria , Rosati Anna , Mei Davide , Granata Tiziana , Dalla Bernardina Bernardo , Vigevano Federico , Guerrini Renzo
Published: September 2020

Objective

Dravet syndrome (DS) is a drug‐resistant, infantile onset epilepsy syndrome with multiple seizure types and developmental delay. In recently published randomized controlled trials, fenfluramine (FFA) proved to be safe and effective in DS.

Methods

DS patients were treated with FFA in the Zogenix Early Access Program at four Italian pediatric epilepsy centers. FFA was administered as add‐on, twice daily at an initial dose of 0.2 mg/kg/d up to 0.7 mg/kg/d. Seizures were recorded in a diary. Adverse events and cardiac safety (with Doppler echocardiography) were investigated every 3 to 6 months.

Results

Fifty‐two patients were enrolled, with a median age of 8.6 years (interquartile range [IQR] = 4.1‐13.9). Forty‐five (86.5%) patients completed the efficacy analysis. The median follow‐up was 9.0 months (IQR = 3.2‐9.5). At last follow‐up visit, there was a 77.4% median reduction in convulsive seizures. Thirty‐two patients (71.1%) had a ≥50% reduction of convulsive seizures, 24 (53.3%) had a ≥75% reduction, and five (11.1%) were seizure‐free. The most common adverse event was decreased appetite (n = 7, 13.4%). No echocardiographic signs of cardiac valvulopathy or pulmonary hypertension were observed. There was no correlation between type of genetic variants and response to FFA.

Significance

In this real‐world study, FFA provided a clinically meaningful reduction in convulsive seizure frequency in the majority of patients with DS and was well tolerated.
Glutathione affects rheology and water distribution of wheat dough by changing gluten conformation and protein depolymerisation
Authors: Guo Lunan , Fang Fang , Zhang Yao , Xu Dan , Jin Zhengyu , Xu Xueming
Published: September 2020

The effects of reduced glutathione (GSH) on dough rheology, water state and distribution, gluten conformation, and protein molecular weight distribution were investigated. Addition of GSH (0.02−0.04%) resulted in a more viscous and less elastic dough with decreased G′ and increased tanδ values, which suggested decreased cross‐links in gluten network and a weakened dough structure. The molecular weight of proteins was reduced by the GSH‐induced cleavage of intermolecular disulphide bonds. Fourier transform infrared spectroscopy showed a high fraction of β‐sheet formation at the expense of α‐helix and β‐turns, indicating a destabilised secondary structure and protein depolymerisation. GSH increased water release from the gluten network in dough resulting in an increase in freezable water content and caused water redistributed from bound water to weakly bound water. This study provided insights into correlation between wheat dough rheological properties and gluten structure influenced by GSH.
In vitro and in vivo effects of carrot on human blood platelet aggregation
Authors: Herath Thanuja D. , Paturi Gunaranjan , Butts Christine A. , Sansom Catherine E. , Morgenstern Marco P.
Published: September 2020

Carrots are a good source of essential nutrients and bioactive phytochemicals including carotenoids, phenolic compounds and polyacetylenes such as falcarinol. In this study, we investigated the inhibitory effect of a carrot extract on blood platelet aggregation in vitro and the effect of raw diced or juiced carrots on platelet aggregation in a human study. Carrot extract significantly reduced the platelet aggregation in vitro in blood obtained from healthy donors. In a randomised crossover human study, healthy volunteers consumed either 100 g of freshly diced carrots or 100 mL of freshly juiced carrots (with pulp). There was no significant effect on blood platelet aggregation in the participants at 2, 5, 8 and 24 h after the carrot meal due to wide interindividual variations. Further research is required to understand diet, genetics and lifestyle factors that may impact the physiological effects of falcarinol on platelet aggregation and blood flow.
Clusterin regulates macrophage expansion, polarization and phagocytic activity in response to inflammation in the kidneys
Authors: Weng Xiaodong , Zhao Haimei , Guan Qiunong , Shi Ganggang , Feng Shijian , Gleave Martin E , Nguan Christopher CY , Du Caigan
Published: September 2020

Clusterin (CLU) is a multifunctional protein localized extracellularly and intracellularly. Although CLU‐knockout (KO) mice are more susceptible to renal ischemia‐reperfusion injury (IRI), the mechanisms underlying the actions of CLU in IRI are not fully understood. Macrophages are key regulators of IRI severity and tissue repair. Therefore, we investigated the role of CLU in macrophage polarization and phagocytosis. Renal IRI was induced in wild‐type (WT) or CLU‐KO C57BL/6 mice by clamping the renal pedicles for 30 min at 32°C. Peritoneal macrophages were activated via an intraperitoneal injection of lipopolysaccharide (LPS). Renal tissue damage was examined using histology, whereas leukocyte phenotypes were assessed using flow cytometry and immunohistochemistry. We found that monocytes/macrophages expressed the CLU protein that was upregulated by hypoxia. The percentages of macrophages (F4/80+, CD11b+ or MAC3+) infiltrating the kidneys of WT mice were significantly less than those in CLU‐KO mice after IRI. The M1/M2 phenotype ratio of the macrophages in WT kidneys decreased at day 7 post‐IRI when the injury was repaired, whereas that in KO kidneys increased consistently as tissue injury persisted. In response to LPS stimulation, WT mice produced fewer M1 macrophages, but not M2, than the control did. Phagocytosis was stimulated by CLU expression in macrophages compared with the CLU null controls and by the exogenous CLU protein. In conclusion, CLU suppresses macrophage infiltration and proinflammatory M1 polarization during the recovery period following IRI, and enhances phagocytic activity, which may be partly responsible for tissue repair in the kidneys of WT mice after injury.
miR‐34a‐5p Attenuates EMT through targeting SMAD4 in silica‐induced pulmonary fibrosis
Authors: Qi Yuanmeng , Zhao Ahui , Yang Peiyan , Jin Luheng , Hao Changfu
Published: September 2020

Silicosis is an incurable occupational disease, and its pathological feature is diffuse pulmonary fibrosis. Pulmonary epithelial‐mesenchymal transition (EMT) is one of the important events in the pathogenesis of silicosis. Previous studies found that abnormal expression of various microRNAs (miRNAs) involved in the development of lung fibrosis. However, their roles in silicosis have not been elucidated. To research the biological effects of miR‐34a in EMT process in silica‐induced lung fibrosis, we established the silicosis model in mouse and miR‐34a intervention in a cell model of TGF‐β1 stimulated lung epithelial cells (A549). The results showed that miR‐34a expression was down‐regulated in the fibrotic lung tissue after silica treatment, and it was similarly expressed in A549 cells stimulated by TGF‐β1. Meanwhile, silica‐induced EMT process can increase expression of two mesenchymal markers, α‐SMA and vimentin. Furthermore, overexpression miR‐34a markedly inhibited EMT stimulated by TGF‐β1. Mechanistically, SMAD4 was identified as the target of miR‐34a. SMAD4 levels decreased in mRNA and protein levels in A549 cells upon miR‐34a overexpression. In addition, the knockdown of SMAD4 blocked the EMT process. Taken together, miR‐34a regulated EMT, which might be partially realized by targeting SMAD4. Our data might provide new insight into treatment targets for silica‐induced pulmonary fibrosis.
MFGE8 is down‐regulated in cardiac fibrosis and attenuates endothelial‐mesenchymal transition through Smad2/3‐Snail signalling pathway
Authors: Wang Bo , Ge Zhuowang , Wu Yan , Zha Yafang , Zhang Xuan , Yan Yexiang , Xie Yuquan
Published: September 2020

Endothelial‐mesenchymal transition (EndMT) is a major source of transformed cardiac fibroblasts, which is reported to play a key role in cardiac fibrosis (CF), a pathogenesis of cardiovascular diseases such as heart failure, myocardial infarction and atrial fibrillation. Nonetheless, the specific mechanism underlying the progression of EndMT to CF is still largely unknown. In this study, we aimed to investigate the role of milk fat globule‐EGF factor 8 (MFGE8), a kind of soluble glycoprotein, in TGF‐β1‐induced EndMT. In animal experiments, the expression of MFGE8 was found down‐regulated in the left ventricle and aorta of rats after transverse aortic constriction (TAC) compared with the sham group, especially in endothelial cells (ECs). In in vitro cultured ECs, silencing MFGE8 with small interfering RNA (siRNA) was found to promote the process of TGF‐β1‐induced EndMT, whereas administration of recombinant human MFGE8 (rh‐MFGE8) attenuated the process. Moreover, activated Smad2/3 signalling pathway after TGF‐β1 treatment and EndMT‐related transcription factors, such as Snail, Twist and Slug, was potentiated by MFGE8 knock‐down but inhibited by rh‐MFGE8. In conclusion, our experiments indicate that MFGE8 might play a protective role in TGF‐β1‐induced EndMT and might be a potential therapeutic target for cardiac fibrosis.
Glucocorticoid levels are linked to lifetime reproductive success and survival of adult barn owls
Authors: Béziers Paul , Korner‐Nievergelt Fränzi , Jenni Lukas , Roulin Alexandre , Almasi Bettina
Published: September 2020

Glucocorticoid hormones, such as corticosterone, are crucial in regulating daily life metabolism and energy expenditure, as well as promoting short‐term physiological and behavioural responses to unpredictable environmental challenges. Therefore, glucocorticoids are considered to mediate trade‐offs between survival and reproduction. Relatively little is known about how selection has shaped glucocorticoid levels. We used 15 years of capture–recapture and dead recovery data combined with 13 years of corticosterone and breeding success data taken on breeding barn owls (Tyto alba) to investigate such trade‐offs. We found that survival was positively correlated with stress‐induced corticosterone levels in both sexes, whereas annual and lifetime reproductive success (i.e. the sum of young successfully fledged during the entire reproductive career) was positively correlated with both baseline and stress‐induced corticosterone levels in females only. Our results suggest that, in the barn owl, the stress‐induced corticosterone response is a good proxy for adult survival and lifetime reproductive success. However, selection pressure appears to act differently on corticosterone levels of males and females.
Blood Pressure Control in Older Adults: Toward a More Personalized Medicine Approach
Authors: Williamson Jeff D.
Published: September 2020

This editorial comments on the article by Sheppard et al. in this issue.
Preoperative Depressive Symptoms Associated with Poor Functional Recovery after Surgery
Authors: Tang Victoria L. , Cenzer Irena , McCulloch Charles E. , Finlayson Emily , Cooper Zara , Silvestrini Molly , Ngo Sarah , Schmitt Eva M. , Inouye Sharon K.
Published: September 2020

BACKGROUND/OBJECTIVES

Depression screening and treatment for older adults are recommended in Age‐Friendly Health Systems. Few studies have evaluated the association between depressive symptoms and postoperative functioning. We aimed to determine the association between varying levels of depressive symptoms in the preoperative setting with postoperative functional recovery.

DESIGN

Prospective cohort study.

SETTING

Two academic hospitals in Boston, Massachusetts.

PARTICIPANTS

Surgical patients aged 70 and older (N = 560).

MEASUREMENTS

Participants were assessed preoperatively and 1 year postoperatively. Preoperative evaluation included the 15‐item short‐form Geriatric Depression Scale (GDS). Results were categorized as low (GDS = 0–1), moderate (2–5), or high (6–15) symptom burden. Primary outcome was 1‐year instrumental activities of daily living functional decline. Secondary outcomes included hospital stay longer than 5 days, discharge to post‐acute care (PAC) facility, and readmission within 30 days.

RESULTS

Mean participant age was 76.6 ± 5 years, 58% were women, 81% underwent an orthopedic operation, 13% gastrointestinal, 6% vascular; 13% had functional decline at 1 year after their operation (by symptom burden: low = 5.5%; moderate = 14.8%, and high = 38.6%). After adjusting for age, sex, and comorbidity, those with moderate or high depressive symptoms demonstrated greater odds of functional decline at 1 year compared with those with a low symptom burden (moderate: adjusted odds ratio [AOR] = 2.7; 95% confidence interval [CI] = 1.3–5.3; high: AOR = 9.3; 95% CI = 4.2–20.6), discharge to PAC facility (moderate: AOR = 1.7; 95%CI = 1.2–2.6; high: AOR = 2.7; 95% CI = 1.4–5.1) but demonstrated no significant association with 30‐day readmission or hospital length of stay longer than 5 days.

CONCLUSION

Greater burden of preoperative depressive symptoms is associated with increased likelihood of functional decline at 1 year after surgery and of discharge to PAC facility. Preoperative assessment of the burden of depressive symptoms in older adults undergoing elective surgery may be helpful in identifying patients at high risk of poor outcomes.