bluuebunny/crossref_metadata_2025 huggingface dataset:
Regulatory Function of Buckwheat‐Resistant Starch Supplementation on Lipid Profile and Gut Microbiota in Mice Fed with a High‐Fat Diet
Authors: Zhou Yiming , Zhao Shen , Jiang Yue , Wei Yun , Zhou Xiaoli
Published: August 2019

Buckwheat‐resistant starch (BRS) has shown to be a nutrient capable of lowering cholesterol and reducing obesity. In this study, the regulatory effects of tartary buckwheat starch on blood lipid level and gut microbiota (Lactobacillus, Bifidobacterium, Enterococcus, and Escherichia coli) in mice fed with a high‐fat diet was investigated. Male C57BL/6 mice were separately fed with a normal diet (CON), a high‐fat diet (HFD), and high‐fat diet supplemented with buckwheat‐resistant starch (HFD+BRS) for 6 weeks. After the feedings, lipid profile, blood glucose, plasma levels of cytokines, short‐chain fatty acid content in the colon and intestinal flora of fecal were measured. Furthermore, the antioxidant indices of the liver and duodenum tissues were measured to evaluate the antioxidant capacity of mice. Significantly reduced plasma levels of total cholesterol (TC), triglyceride (TG), glucose, and cytokines were observed in the HFD+BRS group, accompanied by an increased antioxidant capacity in the liver and duodenum. In addition, supplementation with BRS significantly inhibited the increase in plasma lipopolysaccharide, tumor necrosis factor‐α, and interleukin‐6 levels. Gut microbiota composition was regulated by the supplement of BRS, which promoted the growth of Lactobacillus, Bifidobacterium, and Enterococcus, as well as inhibited the growth of Escherichia coli. In contrast to the HFD group, the content of short‐chain fatty acids in mice colon increased in the BRS group. In conclusion, BRS benefited the cholesterol and glucose metabolism, as well as optimized gut microbiota composition in mice fed with a high‐fat diet.

Practical Application

This study identified the beneficial effects of tartary buckwheat‐resistant starch on the regulation of blood lipids and intestinal flora in mice fed a high‐fat diet. The result of this study will provide a basis for the development of probiotic products supplemented with tartary buckwheat‐resistant starch and direction for further research.
fMRI‐Based Brain Responses to Olfactory Stimulation with Two Putatively Orexigenic Functional Food Ingredients at Two Different Concentrations in the Pig Model
Authors: Coquery Nicolas , Menneson Sophie , Meurice Paul , Janvier Régis , Etienne Pierre , Noirot Virginie , Val‐Laillet David
Published: August 2019

Natural plant extracts are increasingly used as functional feed ingredients in animal husbandry and food ingredients in human alternative medicine to improve welfare and health. We investigated in 20 growing pigs via functional magnetic resonance imaging (fMRI) the brain blood oxygen level–dependent (BOLD) responses to olfactory stimulation with two sensory functional feed ingredients, A and B, at two different concentrations. Functional ingredient A contained extracts from Citrus sinensis (60% to 80%), and ingredient B contained a mixture of extracts Oreganum vulgarae (40% to 55%) and Cymbopogon flexuosus (20% to 25%). Increased concentration of ingredients induced a higher activation in reward and cognitive areas compared to lower concentrations. Moreover, considering both ingredients at the highest concentration, the ingredient A elicited higher brain responses in brain areas involved in hedonism/pleasantness compared to ingredient B, and more specifically in the caudate nucleus and orbitofrontal cortex. Our findings shed new light in the scope of emotion regulation through olfactory modulation via sensory functional ingredients, which opens the way to further preclinical studies in animal models and translational research in the context of nutrition, welfare, and health.

Practical Application

Functional food/feed ingredients are gaining interest for improving health and welfare in humans and animals. Besides representing an alternative to antibiotics for example, food ingredients and their sensory characteristics might have a positive impact on emotions and consequently on well‐being. Functional brain imaging in large animals such as in the pig model is a promising approach to investigate the central and behavioural effects of food ingredients, and determine the most effective blends and concentrations to modulate internal and emotional states.
Are individual investors liquidity providers around earnings announcements? Evidence from an emerging market
Authors: Chen Zhijuan , Lin William T. , Ma Changfeng , Wang Kent
Published: August 2019

We first document that both buying and selling by individual investors before earnings announcements are negatively correlated with post‐event abnormal returns using a unique dataset that allows us to precisely identify individual investor trading. Next, we show that both buying and selling by individual investors before earnings announcements not only are positively associated with contemporaneous returns, but also respond positively to past returns. This is consistent with the idea that individual investors act as liquidity providers (demanders) when they sell (buy) before earnings announcements. Individual investor buying and individual investor selling after earnings announcements confirm this point.
Guanyin's Limbo: Icons as Demi‐Persons and Dividuating Objects
Authors: Palmer David A. , Tse Martin M. H. , Colwell Chip
Published: August 2019

How do objects and humans relationally constitute one another? In this article, we examine statues of Guanyin, the bodhisattva of compassion, in Hong Kong to illuminate the forms of personhood and agency that arise through human–icon relations in a modern metropolis. We follow the life course of Guanyin statues, investigating their production, circulation, animation, and disposal—teasing out worshippers’ contradictory discourses on whether the deity is present in the statue or in the mind of the worshipper. These ethnographic observations lead us to consider how anthropological debates about the nature of cultural objects asrepresentationsor asagentsparallel Guanyin practices and discourses in Hong Kong. We suggest how the ambivalent status of Guanyin statues is negotiated for practitioners as “demi‐persons” and can be understood for anthropologists through the concept of the “dividuating object.” [material religion, animism, agency, personhood, icon, Hong Kong]
Effect of terminal arrangement of tryptophan on biological activity of symmetric α‐helix‐forming peptides
Authors: Shao Changxuan , Li Weizhong , Lai Zhenheng , Akhtar Muhammad Usman , Dong Na , Shan Anshan , Ma Deying
Published: August 2019

It is traditionally believed that the distribution of tryptophan (Trp) residues is critical for the novo design of antimicrobial peptides (AMPs). However, there is scarce knowledge regarding Trp residues arrangement at the head group level. Thus, a set of α‐helical AMPs containing different Trp residue arrangements at the N‐/C‐terminal of sequence were designed to increase the strategy database and analyze their biological activities. The arrangement of the N‐terminal Trp residue significantly improved the bacteriostatic activity of the peptides, but the C‐terminal Trp residue arrangement reduced the biocompatibility of them. WL and LW were effective against Gram‐negative microbes and had high selectivity for bacteria as compared to human erythrocytes and mammalian cells. They both maintained a relatively desirable activity in the presence of physiological salts and serum. It is observed through electron microscope, flow cytometry and fluorescence spectroscopy that target peptides can penetrate bacterial cell membrane and kill it by damaging cell membrane integrity. Collectively, we determined the structure–activity relationship of Trp residue distributions in a symmetric sequence structure and filled the gap in knowledge related to Trp arrangements at the head group level. The obtained results will be helpful in designing of artificial peptide‐based antimicrobials.
Differential associations of allergic disease genetic variants with developmental profiles of eczema, wheeze and rhinitis
Authors: Clark Hannah , Granell Raquel , Curtin John A. , Belgrave Danielle , Simpson Angela , Murray Clare , Henderson A. John , Custovic Adnan , Paternoster Lavinia
Published: August 2019

Background

Allergic diseases (eczema, wheeze and rhinitis) in children often present as heterogeneous phenotypes. Understanding genetic associations of specific patterns of symptoms might facilitate understanding of the underlying biological mechanisms.

Objective

To examine associations between allergic disease‐related variants identified in a recent genome‐wide association study and latent classes of allergic diseases (LCADs) in two population‐based birth cohorts.

Methods

Eight previously defined LCADs between birth and 11 years: “No disease,” “Atopic march,” “Persistent eczema and wheeze,” “Persistent eczema with later‐onset rhinitis,” “Persistent wheeze with later‐onset rhinitis,” “Transient wheeze,” “Eczema only” and “Rhinitis only” were used as the study outcome. Weighted multinomial logistic regression was used to estimate associations between 135 SNPs (and a polygenic risk score, PRS) and LCADs among 6345 individuals from The Avon Longitudinal Study of Parents and Children (ALSPAC). Heterogeneity across LCADs was assessed before and after Bonferroni correction. Results were replicated in Manchester Asthma and Allergy Study (MAAS) (n = 896) and pooled in a meta‐analysis.

Results

We found strong evidence for differential genetic associations across the LCADs; pooled PRS heterogeneity P‐value = 3.3 × 10−14, excluding “no disease” class. The associations between the PRS and LCADs in MAAS were remarkably similar to ALSPAC. Two SNPs (a protein‐truncating variant in FLG and a SNP within an intron of GSDMB) had evidence for differential association (pooled P‐values ≤ 0.006). The FLG locus was differentially associated across LCADs that included eczema, with stronger associations for LCADs with comorbid wheeze and rhinitis. The GSDMB locus in contrast was equally associated across LCADs that included wheeze.

Conclusions and clinical relevance

We have shown complex, but distinct patterns of genetic associations with LCADs, suggesting that heterogeneous mechanisms underlie individual disease trajectories. Establishing the combination of allergic diseases with which each genetic variant is associated may inform therapeutic development and/or predictive modelling.
BRAF mutation analysis by ARMS‐PCR refines thyroid nodule management
Authors: Li Xinyang , Li Enling , Du Jing , Wang Jiadong , Zheng Bing
Published: August 2019

Background

Fine‐needle aspiration (FNA) of thyroid nodules leads to nearly 25% indeterminate nodules, while BRAFV600E mutation helps to predicting papillary thyroid carcinoma (PTC). However, the clinical validity and utility of the BRAFV600E mutation detected using preoperative FNA samples in a large cohort were rarely reported.

Aim

To explore the clinical significance of the BRAFV600E mutation on preoperative diagnosis and decision‐making in a large FNA cohort in China.

Design

This was a prospective study of BRAFV600E mutation analysis using an amplification refractory mutation system‐polymerase chain reaction (ARMS‐PCR) in FNA samples.

Patients

The study involved 2640 samples from 2307 patients undergoing FNA procedures in a Chinese medical centre.

Results

A high mutation rate of 86.7% was found in the PTC population. For indeterminate thyroid nodules, the malignant rate of BRAFV600E+ and BRAFV600E− was 87.8% and 39.5% in the Bethesda System for Reporting Thyroid Cytopathology (BSRTC) III, and 88.2% and 31.8% in the BSRTC IV, respectively. A cost‐effective diagnostic model combining both BSRTC grading and BRAFV600E mutation status showed the highest sensitivity of 82.9% and specificity of 85.4%. Central lymph node metastasis (CLNM) was independent of the BRAF mutation status and accounted for 34.2% of the patients with PTC. CT values of BRAFV600E of patients with PTMC were significantly lower in young patients and patients with CLNM.

Conclusions

The combined analysis of cytological results and BRAFV600E mutation is highly recommended in BRAFV600E high‐prevalence regions, including China. Prophylactic central neck dissection should be performed in selected patients without regard to the BRAF mutation status.
Heterogeneous consumers and differentiated food markets: Implications for quality signaling in food supply chains
Authors: Hobbs Jill E.
Published: August 2019

The Fellow's address begins by noting several recent consumer food trends and the changing way in which we perceive value‐added. I then focus on the topic of heterogeneity in consumer behavior, reviewing contributions from the literature that enhance our ability as economists to model and measure heterogeneity. Supply chain responses to consumer heterogeneity are examined, including a discussion of information flows within supply chains and the role of certification and verification. I close with a consideration of policy implications flowing from consumer heterogeneity.
Making structured decisions for reintroduced populations in the face of uncertainty
Authors: Panfylova Julia , Ewen John G. , Armstrong Doug P.
Published: August 2019

Structured decision‐making (SDM) has become popular in natural resource management but has been underused in reintroduction programs. We illustrate how conservation managers can use SDM to guide management decisions after initial reintroduction, when data are still limited and uncertainty around vital rates estimates is high. In 2013, the hihi (Notiomystis cincta), an endangered New Zealand forest bird, was reintroduced to Bushy Park (BP), a managed conservation reserve. High post‐release mortality in females led to the population remaining small after 2 years, raising the question of whether more females should be released. We built a model to evaluate three management alternatives, including no further translocation and translocations of 15 additional females (from the only possible source population) in either 2015 or 2016. The fundamental objectives identified were to maximize the number and persistence of female hihi in BP, minimize the impact on the source population, and minimize costs. Our decision analysis incorporated uncertainties in parameter estimation, model selection, and demographic stochasticity. It produced distributions of final scores for each management alternative based on population projections for both the BP population and source population, and objective weights assigned by stakeholders. Although the distributions of final scores overlapped greatly, the “no translocation” alternative was largely stochastically dominant over other management options, that is, it was clearly the best choice in most projections and the choice was ambiguous in the remaining projections. The decision was also unaffected by variation in stakeholder values. Although the underlying modeling was complex, the output provided a simple visualization of outcomes that allowed the recovery group to make an informed decision (no further translocation) that fully considered the uncertainties.
Pregnancy as a transition: First‐time expectant couples′ experience with alcohol consumption
Authors: Gouilhers Solène , Meyer Yvonne , Inglin Sophie , Pfister Boulenaz Stéphanie , Schnegg Céline , Hammer Raphaël
Published: August 2019

Introduction and Aims

Most official healthcare guidelines apply the precautionary principle by recommending that pregnant women abstain from any alcohol consumption. However, a number of women continue drinking alcohol while pregnant. The aim of this study was to investigate couples′ experiences of the issue of alcohol consumption during pregnancy as a transitional process.

Design and Methods

Thirty semi‐directive joint interviews were conducted with couples expecting their first child in Switzerland. Interviews were analysed thematically with the help of ATLAS.ti.

Results

Couples endorsed the imperative of changing drinking habits and all the women reduced their alcohol consumption, although some reported difficulties. First, we identified three themes describing how couples experienced the woman′s change of drinking habits as a smooth transition: Internalisation of risk discourses, abstinence as a social norm and embodiment of alcohol aversion. Second, we emphasised four kinds of difficulties that couples encountered in their everyday lives: burden of risk discourses, conflicting advice, social occasions and desire for alcohol.

Discussion and Conclusions

This paper makes a significant contribution by examining prenatal drinking change as a transition. In this conceptualisation, the change of alcohol consumption is a relational process that is shaped by multiple changes and social norms. Our findings have important implications for practice. First, health professionals should be aware of the difficulties women experience when they abstain from alcohol during pregnancy. Second, our findings suggest the importance of a patient‐centred approach that considers the role of the partner in supporting a pregnant woman′s change of alcohol consumption.
Longitudinal evaluation of myocardial function in preterm infants with respiratory distress syndrome
Authors: Poon Chuen Y. , Wilson Dirk G. , Joshi Suchita , Fraser Alan G. , Kotecha Sailesh
Published: August 2019

Aim

Preterm births and respiratory distress syndrome (RDS) are associated with pulmonary vascular disease and altered myocardial function. We serially assessed up to 1 year of age the effects of RDS on global and regional myocardial function of preterm infants, compared to preterm and term controls using conventional echocardiography parameters, tissue Doppler velocities and deformation analysis.

Methods and results

A total of 120 infants (30 preterm [PT] with RDS, 30 PT controls without RDS, and 60 term controls) underwent conventional and tissue Doppler echocardiography within 72 hours of birth, at corrected term age for the preterm infants, at 1 month corrected, and at 1 year corrected age. At birth, compared to preterm and term controls, the PT‐RDS group had decreased right ventricular (RV) long‐axis function, systolic velocity, peak systolic strain, shorter pulmonary arterial acceleration time (PAAT), and lower ratio of PAAT to RV ejection time (PAAT:RVET). Preterm infants had left ventricular (LV) diastolic dysfunction at birth (lower early diastolic myocardial velocity, mitral E velocity, and mitral E:A ratio), and reduced long‐axis systolic velocities and shortening. Differences between groups disappeared by 1 month corrected age, except PAAT:RVET which remained lower in the PT‐RDS group. At 1 year, RV function was normal in PT‐RDS apart from systolic strain rate, and LV function was normal apart from lower stroke volume and shortening, relative to body weight.

Conclusion

PT‐RDS had lower left and right ventricular systolic and diastolic function at birth which improved over time, suggesting postnatal maturation of cardiac function and resolution of lung disease.
The postembryonic transformation of the shell in emydine box turtles
Authors: Cordero Gerardo A. , Stearns Samantha , Quinteros Kevin , Berns Chelsea M. , Binz Steven M. , Janzen Fredric
Published: August 2019

A key trend in the 210‐million‐year‐old history of modern turtles was the evolution of shell kinesis, that is, shell movement during neck and limb retraction. Kinesis is hypothesized to enhance predator defense in small terrestrial and semiaquatic turtles and has evolved multiple times since the early Cretaceous. This complex phenotype is nonfunctional and far from fully differentiated following embryogenesis. Instead, kinesis develops slowly in juveniles, providing a unique opportunity to illustrate the postembryonic origins of an adaptive trait. To this end, we examined ventral shell (plastral) kinesis in emydine box turtles and found that hatchling plastron shape differs from that of akinetic‐shelled relatives, particularly where the hinge that enables kinesis differentiates. We also demonstrated shape changes relative to plastron size in juveniles, coinciding with a shift in the carapace‐plastron structural connection, rearrangement of ectodermal plates, and bone repatterning. Furthermore, because the shell grows larger relative to the head, complete concealment of the head and extremities is only achieved after relative shell proportions increase. Structural alterations that facilitate the box turtle's transformation are probably prepatterned in embryos but require function‐induced changes to differentiate in juveniles. This mode of delayed trait differentiation is essential to phenotypic diversification in turtles and perhaps other tetrapods.
Trade‐off between attraction to aggregation pheromones and repellent effects of spike lavender essential oil and its main constituent linalool in the flour beetle Tribolium confusum
Authors: Kheloul Lynda , Kellouche Abdellah , Bréard Dimitri , Gay Marie , Gadenne Christophe , Anton Sylvia
Published: August 2019

Essential oils of aromatic plants and their individual volatile components have been tested in pest management strategies for their toxic and often repellent effects on target insects. When evaluating their possible effects on crucial behaviours of the pest insects, the olfactory environment including intraspecific communication cues has to be considered. We used the flour beetle Tribolium confusum du Val (Coleoptera: Tenebrionidae), a common stored‐product pest, to investigate the influence of oil of spike lavender, Lavandula spica Medik. (Labiaceae), and its main component, linalool, at various doses on olfactory‐guided behaviour. Using four‐way olfactometers, a dose‐dependent repellent effect of L. spica oil and linalool alone was revealed. On the other hand, we confirmed that T. confusum is attracted by conspecifics, by means of an aggregation pheromone and by 10 ng of one of its components, 1‐tetradecene. Twenty‐four hour pre‐exposure to 10 μl of L. spica oil abolished subsequent attraction to 1‐tetradecene and reduced attraction to five conspecifics. Simultaneous exposure to L. spica oil or linalool and five conspecifics reduced the repellent effect of the volatiles in a dose‐dependent manner, whereas simultaneous exposure to 1‐tetradecene at 10 ng abolished the repellent effect of L. spica oil only at a dose of 0.01 mg. These results indicate a dose‐dependent trade‐off between attractive and plant‐derived repellent volatiles, which may influence the effectiveness of such volatiles in their potential use in alternative pest management strategies.
Admirable and delectable gardens: uiridaria in early medieval Italy
Authors: Goodson Caroline
Published: August 2019

This article will chart the usage of a rare term, uiridarium, in the documents of early medieval Italy in order to explore the history of decorative or pleasure gardens between c.600–c.1000. Property documents and placita, alongside a small body of archaeobotanical evidence, suggest a significant change in the planting of cultivated spaces in Italian cities during the early Middle Ages. A few charters refer to enclosed gardens called uiridaria attached to houses of the highest‐status people in Italy: dukes, kings, emperors, and bishops. We have a glimpse of how they were used and this article makes the case that decorative gardens played a role in the urban performance of the highest echelons of power.
Mexican states' business cycles co‐movement over the period 2000–2014. A panel data model estimation
Authors: Mejía‐Reyes Pablo , Díaz‐Carreño Miguel Ángel , Aroca Patricio
Published: August 2019

This paper examines the business cycle co‐movement in Mexican states over the period 2000–2014 by estimating an extended gravitational panel data model. Two different de‐trending filters are used to check the robustness of our results. The estimates suggest that the co‐movement increases as the size of the states’ economies does so as well as with the productive structure similarities and the relative level of development; however, the co‐movement decreases at a diminishing rate with geographical distance. There is also evidence of time‐dependent effects. In addition, the existence of moderate co‐movements among the states’ cycles suggests that common economic policies may not be suitable for all states, which implies there is a need for specific countercyclical policies to mitigate idiosyncratic shocks.
Microscopic investigation of the formation of a thermoset wheat gluten network in a model system relevant for bread making
Authors: Verbauwhede Annelien E. , Lambrecht Marlies A. , Jekle Mario , Lucas Isabelle , Fierens Ellen , Shegay Oksana , Brijs Kristof , Delcour Jan A.
Published: August 2019

Although the impact of heat on molecular properties of wheat gluten is well understood, changes in its microstructure have rarely been studied. Here, formation of the thermoset gluten network in a model system relevant for bread baking was studied with confocal laser scanning microscopy and protein network analysis. From 65 °C onwards, gluten converts from thick aligned protein strands in a highly branched and homogeneous network of small thin protein threads. Neither gliadin incorporation in the network nor application of aqualysin 1, the thermo‐active serine peptidase from Thermus aquaticus which recently has been reported to hydrolyse gluten proteins in dough only at temperatures exceeding 80 °C, impacts on the gluten microstructure. As starch causes structure setting itself and thereby decreases protein mobility, molecular scale changes in the gluten network at temperatures exceeding 80 °C brought about by aqualysin 1 do not impact its microstructure.
Low expression of TET2 gene in pediatric acute lymphoblastic leukemia is associated with poor clinical outcome
Authors: Zhang Ping , Weng Wen‐Wen , Chen Ping , Zhang Yao , Ruan Jin‐Fei , Ba Dian‐Dian , Xu Wei‐Qun , Tang Yong‐Min
Published: August 2019

Introduction

TET2, a member of the Ten‐Eleven translocation gene family, catalyzes the conversion of 5‐methylcytosine to 5‐hydroxymethylcytosine in DNA. Low expression of TET2 has been reported as a prognostic factor for several types of malignancies in adult patients. However, there have been few data on the effect of TET2 mRNA level on the prognosis of children with ALL so far.

Methods

In this study, TET2 expression of samples cryopreserved in the liquid nitrogen from January 1, 2007 through December 31, 2011 was retrospectively analyzed in 136 newly diagnosed ALL patients by real‐time polymerase chain reaction (PCR) assay. The patients' samples were divided into two groups by the median value of patients group and divided into TET2 low and TET2 high groups.

Results

A total of 136 childhood ALL patients demonstrated lower TET2 expression than control group (P = .038). TET2 mRNA expression levels were correlated with the disease status. In addition, patients with low TET2 expression had lower platelet counts and lower CR rates. Survival analysis showed that low TET2 expression in children with ALL was associated with lower 5‐year overall survival (OS) (63% vs 88%, P = .011) and event‐free survival (EFS) (60% vs 85%, P = .003). Multivariate analysis revealed that low TET2 expression was an independent poor prognostic factor of OS and EFS.

Conclusion

Low expression of TET2 in children with ALL is associated with poor prognosis and can be used as a molecular prognostic marker for risk group stratification.
A comparison of immunoglobulin IGHV, IGHD and IGHJ genes in wild‐derived and classical inbred mouse strains
Authors: Watson Corey T , Kos Justin T , Gibson William S , Newman Leah , Deikus Gintaras , Busse Christian E , Smith Melissa L , Jackson Katherine JL , Collins Andrew M
Published: August 2019

The genomes of classical inbred mouse strains include genes derived from all three major subspecies of the house mouse, Mus musculus. We recently posited that genetic diversity in the immunoglobulin heavy chain (IGH) gene loci of C57BL/6 and BALB/c mice reflects differences in subspecies origin. To investigate this hypothesis, we conducted high‐throughput sequencing of IGH gene rearrangements to document IGH variable (IGHV), joining (IGHJ) and diversity (IGHD) genes in four inbred wild‐derived mouse strains (CAST/EiJ, LEWES/EiJ, MSM/MsJ and PWD/PhJ) and a single disease model strain (NOD/ShiLtJ), collectively representing genetic backgrounds of several major mouse subspecies. A total of 341 germline IGHV sequences were inferred in the wild‐derived strains, including 247 not curated in the international ImMunoGeneTics information system. By contrast, 83/84 inferred NOD IGHV genes had previously been observed in C57BL/6 mice. Variability among the strains examined was observed for only a single IGHJ gene, involving a description of a novel allele. By contrast, unexpected variation was found in the IGHD gene loci, with four previously unreported IGHD gene sequences being documented. Very few IGHV sequences of C57BL/6 and BALB/c mice were shared with strains representing major subspecies, suggesting that their IGH loci may be complex mosaics of genes of disparate origins. This suggests a similar level of diversity is likely present in the IGH loci of other classical inbred strains. This must now be documented if we are to properly understand interstrain variation in models of antibody‐mediated disease.
Asthma control and acute healthcare visits among young adults with asthma—A population‐based study
Authors: Selberg Stina , Hedman Linnea , Jansson Sven‐Arne , Backman Helena , Stridsman Caroline
Published: August 2019

Aims

To study asthma control and acute healthcare visits among young adults with asthma.

Background

Despite the access to effective treatment and nursing interventions, poor asthma control is still common among individuals with asthma. However, studies describing clinical characteristics among young adults with asthma are rare.

Design

A population‐based cohort study.

Methods

In 2015, as a part of the OLIN paediatric cohort I (recruited in 1996 at age 7–8 years), N = 2,291 young adults (27–28 years) completed a postal questionnaire survey including questions on asthma and respiratory symptoms. Of these, N = 280 (12%) were identified as having current asthma and were further studied.

Results

Of those with current asthma, women reported respiratory symptoms and smoking to a greater extent than men. Approximately one‐fourth had uncontrolled asthma and acute healthcare visits due to asthma was reported by 15% of women and 8% of men. Uncontrolled asthma was associated with smoking, lower educational level, use of reliever treatment most days, and acute healthcare visits. Acute healthcare visits due to asthma were associated with periodic use of regular controller treatment also after adjustment for uncontrolled asthma.

Conclusion

The result indicate poor adherence to asthma treatment which may lead to decreased asthma control and acute healthcare visits.

Impact

Most young adults with asthma are diagnosed and treated in primary care, ideally in a team with a nurse. The main findings highlight the need for evidenced‐based nursing interventions, contributing to a more efficient asthma management in primary care.
Brain Vitality Enhancement (BRAVE) program to promote brain health among persons with mild cognitive impairment: A study protocol
Authors: Li Polly W.C. , Yu Doris S.F. , Siu Parco M. , Wong Schwinger C.K.
Published: August 2019

Aim

This study aims to evaluate the effects of a community‐based program entitled ‘Brain Vitality Enhancement (BRAVE)’ on the cognitive function, physical and mental well‐being of persons with mild cognitive impairment.

Study design

This is a parallel wait list randomized controlled trial.

Methods

The BRAVE program consists of two phases. Phase 1 is an empowerment workshop for training 50 peer mentors to be the exercise ambassadors, while Phase 2 is a supervised exercise program for 250 persons with mild cognitive impairment. They will be randomly allocated to intervention or wait list control groups. For the intervention group, the peer mentors and mentees will be matched according to gender and residential areas to form mentor–mentee groups to attend an 8‐week supervised exercise training. The mentor–mentee groups will continue to participate mentor‐directed exercise sessions in the community thereafter. A mobile application will be developed for self‐directed learning. We hypothesize that persons with mild cognitive impairment receiving the BRAVE program will demonstrate better cognitive function and health‐related quality of life than the control group who receive usual care. This study is funded by a grant from the Food and Health Bureau of the Government of Hong Kong Special Administrative Region in April 2018.

Discussion

This study will empower a group of golden‐aged adults to be the ambassadors to promote brain health in the community and persons with mild cognitive impairment to integrate moderate‐intensity exercise into their lifestyle to achieve long‐term beneficial effects on their cognition and well‐being.

Impact

Given the population with mild cognitive impairment is growing rapidly and expected to keep escalating in coming decades and limited treatment options for cognitive decline and its significant burden on the health and social care system, this study is timely to promote active ageing in the society and reduce the burden associated with cognitive decline.
Prevention behaviours of oesophageal cancer: Protocol for a mixed‐method study
Authors: Gerayllo Sakineh , Morowatisharifabad Mohammad Ali , Jouybari Leila , Amirbeigy Mohammad Kazem , Fallahzadeh Hossein
Published: August 2019

Aim

The aim was to implement an educational programme for the family members of patients with oesophageal cancer on prevention behaviours in Golestan province, north of Iran.

Design

In this mixed‐method research, qualitative and quantitative studies will be conducted.

Methods

This study will be carried out using an exploratory mixed‐method design in Golestan province, north of Iran in 2018–2019. The research will include three consecutive phases. At first, a qualitative study will be carried out to determine the preventive behaviour and measures of oesophageal cancer. In this phase, the participants will be selected using the purposive sampling method. Later, semi‐structured interviews will be conducted with the relatives of patients with oesophageal cancer to collect the necessary qualitative data. The second phase will include a literature review based on the information collected from the first phase. Later, a researcher‐made questionnaire will be designed based on the extended parallel process model. Furthermore, a comprehensive programme will be proposed about self‐care of the patients with oesophageal cancer. In the third phase, a quantitative quasi‐experimental research will be conducted over two groups of participants to measure the effectiveness of this programme. This research was approved by the Ethics Committee of Yazd Shahid Sadoughi University of Medical Sciences, Iran in November 2017.

Discussion

Educational interventions should be designed purposefully according to the needs of the target group to improve their self‐care behaviours. We also expect that this research can improve the individuals' access to high‐quality preventive behaviours with regard to oesophageal cancer.

Trial registration: The project was registered on the Iranian Registry of Clinical Trials, (registration number: IRCT20180725040588N1, date registered: 2th October 2018).
A coordinated preventive care approach for healthy ageing in five European cities: A mixed methods study of process evaluation components
Authors: Franse Carmen B. , Zhang Xuxi , van Grieken Amy , Rietjens Judith , Alhambra‐Borrás Tamara , Durá Estrella , Garcés‐Ferrer Jorge , van Staveren Rob , Rentoumis Tasos , Markaki Athina , Bilajac Lovorka , Vasiljev Marchesi Vanja , Rukavina Tomislav , Verma Arpana , Williams Greg , Clough Gary , Koppelaar Elin , Martijn Rens , Mattace Raso Francesco , Voorham Antonius J. J. , Raat Hein
Published: August 2019

Aims

To evaluate specific process components of the Urban Health Centres Europe (UHCE) approach; a coordinated preventive care approach aimed at healthy ageing by decreasing falls, polypharmacy, loneliness and frailty among older persons in community settings of five cities in the United Kingdom, Greece, Croatia, the Netherlands and Spain.

Design

Mixed methods evaluation of specific process components of the UHCE approach: reach of the target population, dose of the intervention actually delivered and received by participants and satisfaction and experience of main stakeholders involved in the approach.

Methods

The UHCE approach intervention consisted of a preventive assessment, shared decision‐making on a care plan and enrolment in one or more of four coordinated care‐pathways that targeted falls, polypharmacy, loneliness and frailty. Quantitative data from a questionnaire and quantitative/qualitative data from logbooks were collected among older persons involved in the approach. Qualitative data from focus groups were collected among older persons, informal caregivers and professionals involved in the approach. Quantitative data were analysed by means of descriptive statistics and multilevel logistic regression models. Qualitative data were analysed through thematic analysis.

Results

Having limited function was associated with non‐enrolment in falls and loneliness care‐pathways (both p < .01). The mean rating of the approach was 8.3/10 (SD 1.9). Feeling supported by a care professional and meeting people were main benefits for older persons. Mistrust towards unfamiliar care providers, lack of confidence to engage in care activities and health constraints were main barriers towards engagement in care.

Conclusions

Although the UHCE approach was received generally positively, health constraints and psychosocial barriers prevented older person's engagement in care.

Impact

Coordinated preventive care approaches for older community‐dwelling persons should address health constraints and psychosocial barriers that hinder older person's engagement in care. Trial registration: ISRCTN registry number is ISRCTN52788952. Date of registration is 13/03/2017.
Hoxa5 alleviates obesity‐induced chronic inflammation by reducing ER stress and promoting M2 macrophage polarization in mouse adipose tissue
Authors: Cao Weina , Zhang Tiantian , Feng Ruonan , Xia Tianyu , Huang Hongtao , Liu Chenlong , Sun Chao
Published: August 2019

Obesity‐induced chronic inflammation is associated with endoplasmic reticulum stress (ERS) in adipocytes and changes in both the number and phenotype of adipose tissue macrophages (ATMs). In addition, ERS enhances macrophage activation. So far, the function of Hoxa5 in obesity‐induced chronic inflammation has been poorly understood. Herein, we demonstrate the importance of the transcription factor, Hoxa5, in determining adipose tissue macrophage (ATM) polarity and ERS. Hoxa5 decreased bodyweight, reduced inflammatory cytokine secretion and corresponded with an increased number of M2 macrophages in the adipose tissue of high‐fat diet (HFD) mice. Transcriptome sequencing data showed that overexpression of Hoxa5 in adipocytes changed expression of endoplasmic reticulum (ER) protein processing‐related genes. Based on transcriptome sequencing data and bioinformatics prediction, we have been suggested that Hoxa5 alleviated inflammatory responses by inhibiting ERS and by activating PPARγ pathway in mouse adipose tissue. Hoxa5 alleviated ERS and inflammatory responses by inhibiting the eIF2α/PERK signalling pathway in adipocytes. Hoxa5 also inhibited chronic inflammation of adipocytes by promoting M2 macrophage polarization. In addition, Hoxa5 transcriptionally activated the PPARγ pathway to promote polarization of M2 macrophages, which in turn alleviated chronic inflammation of adipocytes. Taken together, these results shed light on the mechanisms underlying Hoxa5‐dependent inhibition of obesity‐induced chronic inflammation by reducing ERS and promoting polarization of M2 macrophages. These results suggest that Hoxa5 may be a potential therapeutic target for obesity and other metabolic syndromes.
Burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa: a hospital‐based cohort study
Authors: Jørgensen A.‐H.R. , Yao Y. , Ghazanfar M.N. , Ring H.C. , Thomsen S.F.
Published: August 2019

Aim

To examine the burden, predictors and temporal relationships of comorbidities in patients with hidradenitis suppurativa (HS).

Methods

Information on HS and ten systemic comorbidities was obtained by interview and clinical examination, including blood pressure, body mass index (BMI) and blood samples, in a cohort of consecutive HS outpatients.

Results

A total of 302 patients were included. About 86.6% had at least one comorbidity. The mean number of comorbidities per patient was 2.1. One or more cardiovascular comorbidities were observed in 76.5% with evidence of substantial unawareness and undertreatment; 48.4% had hypertension, 9.3% had diabetes, 57.7% had dyslipidaemia and 36.7% were obese. About 6.6% had inflammatory bowel disease, 6.3% had arthritis, 29.5% had a psychiatric diagnosis, 5.6% had psoriasis, 7.9% had obstructive lung disease, and 6.6% had polycystic ovary syndrome. These comorbidities occurred at different time points in relation to the onset of HS with evidence of shared as well as differential risk factors. Age (per year), HR = 0.87 (0.79–0.96), P < 0.006, age of onset of HS (per year), HR = 1.26 (1.14–1.40), P < 0.001, male sex, HR = 2.51 (0.88–7.16), P = 0.086, Hurley stage III (vs. Hurley I + II), HR = 3.46 (1.25–9.58), P = 0.017, BMI (per unit), HR = 1.12 (1.04–1.20), P = 0.002, and blood glucose (per unit), HR = 1.27 (1.16–1.39), P < 0.001 were significant predictors for onset of diabetes.

Conclusion

There is a substantial burden, unawareness and undertreatment of several systemic comorbidities in patients with HS. Comorbidities occur at different time points in relation to the onset of HS. This should lead to higher awareness among treating specialists.
Neurokinin 1 receptor antagonists exhibit peripheral effects in prurigo nodularis including reduced ERK1/2 activation
Authors: Agelopoulos K. , Rülander F. , Dangelmaier J. , Lotts T. , Osada N. , Metze D. , Luger T. A. , Loser K. , Ständer S.
Published: August 2019

Background

Aprepitant is a neurokinin 1 receptor (NK1R) antagonist used for its antipruritic properties in dermatoses and systemic diseases. The mode of action is still unclear. A peripheral effect is assumed as aprepitant shows efficacy in inflammatory skin diseases including prurigo nodularis (PN).

Objectives

To investigate the peripheral effects of NK1R antagonism in PN and cell culture models.

Methods

Subjects with PN received an aprepitant treatment. Clinical, morphological and immunohistochemical changes were investigated in skin biopsies before and after treatment. Expression of NK1R was analysed by immunohistochemistry and for downstream pathways ((p)ERK1/2) by Western blotting in PN patients and matched healthy volunteers. Effects of NK1R blocking were analysed in cell cultures of primary keratinocytes by Western blotting for (p)ERK1/2 and by qPCR for NK1R, interleukin (IL)‐1beta, IL‐6, IL‐8 and TNFalpha.

Results

Aprepitant treatment showed significant reduction in pruritus intensity (P < 0.05) in PN and relevant immunohistochemical changes (down: CD5, CD25, up: CD79a, IL4). NK1R expression was higher in keratinocytes of PN patients compared to healthy controls. After treatment, epidermal NK1R expression increased while expression and activation of ERK1/2 decreased. In vitro, receptor up‐regulation and reduced expression and activation of ERK1/2 were confirmed and reduced IL‐expression shown when blocking NK1R.

Conclusion

Our data confirm that NK1R antagonists such as aprepitant exhibit effects in the skin. Epidermal receptor expression, epidermal inflammatory ILs, ERK1/2 MAPK signalling and cutaneous inflammatory infiltrate were targets of NK1R antagonism. This may explain partly the antipruritic effect of NK1R antagonists next to its role in the central nervous system.
Basal cell carcinoma treated with combined ablative fractional laser and ingenol mebutate – an exploratory study monitored by optical coherence tomography and reflectance confocal microscopy
Authors: Banzhaf C.A. , Phothong W. , Suku M.‐L.H. , Ulrich M. , Philipsen P.A. , Mogensen M. , Haedersdal M.
Published: August 2019

Background

Basal cell carcinomas (BCCs) have previously been treated off‐label with ingenol mebutate (IM). Ablative fractional laser (AFL) may improve efficacy of IM by increasing drug uptake in the tumour. Optical coherence tomography (OCT) and reflectance confocal microscopy (RCM) detect BCC non‐invasively. Our aim was to investigate BCC response and tolerability after combined AFL and IM treatment of low‐risk BCCs.

Methods

Twenty patients with histologically verified superficial (n = 7) and nodular (n = 13) BCCs were treated with combined fractional CO2‐laser (10 600 nm) and IM 0.015% or 0.05%, the concentration depending on anatomical location. BCC response was evaluated clinically, by OCT and RCM at day 29 and 90 after first treatment, and histologically at day 90. Treatment was repeated at day 29 if BCC persisted. Local skin reactions (LSRs) were assessed using LSR scale at all visits.

Results

At day 29, 18/20 patients received a second treatment due to residual BCC detected clinically, by OCT or RCM. OCT and RCM presented subclinical BCCs in five of 20 cases (25%). At day 90, overall histological cure rate was 70%, corresponding to clinical (65%) and OCT/RCM (60%) cure rates, and agreement between evaluation methods was substantial (kappa ≥ 0.796, P < 0.0001). Clearance rates were similar for sBCCs and nBCCs (P = 0.354) and for lesions treated with IM 0.015% and 0.05% (P = 0.141). LSRs were tolerable, but scarring was observed in the majority of cleared patients.

Conclusion

Two treatments of combined AFL and IM show potential to treat low‐risk BCCs with acceptable tolerability. OCT and RCM show promise to detect subclinical BCCs at short‐term follow‐up.
Students’ Interpretation of Formative Assessment Feedback: Three Claims for Why We Know So Little About Something So Important
Authors: Leighton Jacqueline P.
Published: August 2019

If K‐12 students are to be fully integrated as active participants in their own learning, understanding how they interpret formative assessment feedback is needed. The objective of this article is to advance three claims about why teachers and assessment scholars/specialists may have little understanding of students’ interpretation of formative assessment feedback. The three claims are as follows. First, there is little systematic research of K‐12 students’ interpretations of feedback. Systematic research requires gathering substantive evidence of students’ cognitive and emotional processes using psychological methods and tools. Second, there is an overemphasis on the external assessment process at the expense of uncovering learners’ internal reasoning and emotional processes. This overemphasis may be due to vestiges of behavioral approaches and lack of training in social cognitive methods. Third, there are psychological tools such as the clinical interview, pioneered by Piaget and used by psychologists to “enter the child's mind,” which may be helpful in uncovering students’ interpretation of feedback and associated behavioral responses. If the purpose of formative assessment is to change student learning, and feedback is delivered as a conduit to help with this long‐term change, understanding students’ interpretation of feedback plays a central role in the validity of the process.