bluuebunny/crossref_metadata_2025 huggingface dataset:
Barriers faced by adults with intellectual disabilities who experience sexual assault: A systematic review and meta‐synthesis
Authors: McGilloway Connie , Smith David , Galvin Rose
Published: March 2018

Background

Sexual violence is associated with significant morbidity and mortality. The incidence of sexual violence against adults with intellectual disability is significantly higher than in the general population. The aim of this systematic review and qualitative meta‐synthesis was to explore the barriers faced by adults with intellectual disability in reporting sexual assault from the perspective of different stakeholders.

Method

A systematic literature search was conducted to identify relevant studies. A hermeneutic interpretive approach was employed to review and assess the methodological quality of the studies. Findings were meta‐synthesized and juxtaposed to identify themes, concepts and interpretations.

Results

Thirteen studies were included. Three overarching themes emerged from an interpersonal, professional and social context, and within these domains, eight subthemes emerged as barriers to reporting sexual assault, including fear, communication, sexual knowledge and understanding, intellectual disability identification, lack of collaboration between service providers, presumption of capacity/credibility, lack of resources, myths and misconceptions.

Conclusion

The research demonstrates that deficiencies in communication and collaboration among agencies, a lack of appropriate legislation and specific training needs and education programmes are significant barriers in the reporting of sexual assault by people with intellectual disability. These findings are not unique to adults with intellectual disability and have also been identified among people from the general population who experience sexual assault. However, adults with intellectual disability have additional barriers to overcome in order to access equal rights to healthcare, education and the legal system.
A review of research on bridging the gap between formal and informal learning with technology in primary school contexts
Authors: Jagušt T. , Botički I. , So H.‐J.
Published: March 2018

This study reviews empirical research articles published in the field of technology‐enhanced learning in the out‐of‐class contexts in primary schools between the years 2007 and 2016 and explores how the body of research has connected formal and informal learning experiences, referred to in the paper as bridging the gap. The review focuses on 43 selected experiments from 41 research papers, which are in detail examined and classified using the 3 criteria: (a) the Bloom's taxonomy for learning, (b) the intentionality to physical settings classification used to differentiate types of learning in various environments, and (c) the characteristics of seamless learning design. The findings confirm that technology can enhance learning in and out of classroom, especially by impacting student interest, motivation, and engagement. The close examination of the subset of studies with cognitive gains shows that they successfully bridged the gap between learning spaces and that such bridging positively correlates with the number of steps in the learning activity design. The successful bridging of the gap between learning spaces could further benefit from including more online social learning activities into the designed learning process and from involving teachers as cocreators of the learning process and resources.
Usefulness of pace mapping in catheter ablation of left ventricular papillary muscle ventricular arrhythmias with a preferential conduction
Authors: Itoh Taihei , Yamada Takumi
Published: March 2018

Introduction

Preferential conduction from an origin to breakout sites can occur during ventricular arrhythmias (VAs) originating from the left ventricular papillary muscles (LVPMs). The purpose of this study was to investigate the incidence, electrophysiological characteristics, and relevance to radiofrequency catheter ablation (RFCA) of such a preferential conduction demonstrated by pace mapping.

Methods and results

We studied 34 consecutive patients undergoing RFCA of 40 LVPM VAs. Among 78 QRS morphologies during these VAs, pace mapping was performed for 67 QRS morphologies during 37 VAs, and revealed VA‐matched pace maps (M‐PMs) with a latency for 14 QRS morphologies during 11 VAs (30%). Among 47 QRS morphologies with activation mapping, RFCA at the earliest activation site (EAS) was successful in 39, but not successful in 8 despite M‐PMs with no latency. In these cases, RFCA was successful at remote sites of the M‐PMs with latency (n = 6) and a site located between the EAS and site of that with latency (n = 1). Among the remaining 31 QRS morphologies with pace mapping only, RFCA was successful at M‐PM sites with no latency in 17, and at M‐PMs sites with latency in 7. In 3 of those 7 QRS morphologies, M‐PMs were recorded at multiple remote sites, and RFCA was not successful at M‐PM sites with no latency (n = 2) or a shorter latency (n = 1).

Conclusions

When an M‐PM with latency was recorded in LVPM VAs, RFCA at that site was highly successful. Attention should be paid to latency as well as the score during pace mapping of LVPM VAs.
Late potentials abolition reduces ventricular tachycardia recurrence after ablation especially in higher‐risk patients with a chronic total occlusion in an infarct‐related artery
Authors: Di Marco Andrea , Oloriz Sanjuan Teresa , Paglino Gabriele , Baratto Francesca , Vergara Pasquale , Bisceglia Caterina , Trevisi Nicola , Sala Simone , Marzi Alessandra , Gulletta Simone , Cireddu Manuela , Anguera Ignasi , Della Bella Paolo
Published: March 2018

Introduction

Late potentials (LP) abolition is recognized as an effective strategy for substrate ablation of ventricular tachycardia (VT). The presence of a chronic total occlusion in a coronary artery responsible for a previous myocardial infarction (infarct related artery CTO, IRA‐CTO) is emerging as a predictor of ventricular arrhythmias and VT recurrence after ablation. We sought to analyze the effects of LP abolition, focusing on the high‐risk subgroup of patients with IRA‐CTO.

Methods and results

This was a single‐center, observational study that screened all patients with prior myocardial infarction and clinical VT, referred for VT ablation at San Raffaele Hospital between 2010 and June 2013. Patients were then included in the study if they had a coronary diagnostic angiography (without revascularization) performed during the index hospitalization. The main endpoint was VT recurrence after ablation. Eighty‐four patients formed the population of the study. An IRA‐CTO was present in 47 patients (56%) and the presence of an IRA‐CTO was a predictor of VT recurrence (HR 3.7, P = 0.005). LP were observed in 51 patients and successfully abolished in 38 cases. LP abolition was associated with lower VT recurrence especially among patients with IRA‐CTO (24% vs. 65%, P = 0.005). The presence of an IRA‐CTO, in combination with no LP abolition, was the strongest predictor of VT recurrence (HR 4.4, P < 0.001).

Conclusions

Late potentials abolition is an effective strategy for substrate ablation of ventricular tachycardia. The additional reduction of VT recurrence achieved with LP abolition on top of noninducibility is especially significant among high‐risk patients with IRA‐CTO.
Intensive blood pressure lowering reduces adverse cardiovascular outcomes among patients with high‐normal glucose: An analysis from the Systolic Blood Pressure Intervention Trial database
Authors: Gong Yan , Smith Steven M. , Handberg Eileen M. , Pepine Carl J. , Cooper‐DeHoff Rhonda M.
Published: March 2018

The objective of this analysis is to determine the effect of intensive (<120 mm Hg) versus standard (<140 mm Hg) systolic blood pressure (SBP) targets on cardiovascular (CV) outcomes among SPRINT participants with low‐normal or high‐normal fasting glucose (FG). We categorized the 5425 SPRINT participants with FG <100 mg/dL into 2 groups: <85 mg/dL (low‐normal) and 85 to <100 mg/dL (high‐normal). Among participants with low‐normal glucose, there was no significant difference in the primary outcome (PO) between the 2 treatment arms (adjusted hazard ratio, HR: 1.27 (95% confidence interval [CI] 0.68‐2.37, P = .46). However, the intensive SBP target was associated with 27% lower risk for the PO compared with the standard SBP target in those with high‐normal glucose (HR 0.73, 0.57‐0.93, P = .01). Our results indicate that hypertensive patients with high‐normal FG may benefit from intensive SBP lowering, whereas benefits were inconclusive among those with low‐normal FG.
Reference intervals and percentiles for carotid‐femoral pulse wave velocity in a healthy population aged between 9 and 87 years
Authors: Diaz Alejandro , Zócalo Yanina , Bia Daniel , Wray Sandra , Fischer Edmundo Cabrera
Published: March 2018

There is little information regarding age‐related reference intervals (RIs) of carotid‐femoral pulse wave velocity (cfPWV) for large healthy populations in South America. The aims of this study were to determine cfPWV RIs and percentiles in a cohort of healthy children, adolescents, and adults and to generate year‐to‐year percentile curves and body‐height percentile curves for children and adolescents. cfPWV was measured in 1722 healthy participants with no cardiovascular risk factors (9–87 years, 60% men). First, RIs were evaluated for males and females through correlation and covariate analysis. Then, mean and standard deviation age‐related equations were obtained for cfPWV using parametric regression methods based on fractional polynomials and age‐specific (year‐to‐year) percentile curves that were defined using the standard normal distribution. Age‐specific first, 2.5th, 5th, 10th, 25th, 50th, 75th, 90th, 95th, 97.5th, and 99th percentile curves were calculated. Finally, height‐related cfPWV percentile curves for children and adolescents (<21 years) were established. After adjusting for age and blood pressure differences with respect to females, males showed higher cfPWV levels (6.60 vs 6.45 m/s; P < .01). Thus, specific RIs for males and females were reported. The study provides the largest database to date concerning cfPWV in healthy people from Argentina. Specific RIs and percentiles of cfPWV are now available according to age and sex. Specific percentiles of cfPWV according to body height were reported for people younger than 21 years.
NDAMDA: Network distance analysis for MiRNA‐disease association prediction
Authors: Chen Xing , Wang Le‐Yi , Huang Li
Published: March 2018

In recent years, microRNAs (miRNAs) are attracting an increasing amount of researchers’ attention, as accumulating studies show that miRNAs play important roles in various basic biological processes and that dysregulation of miRNAs is connected with diverse human diseases, particularly cancers. However, the experimental methods to identify associations between miRNAs and diseases remain costly and laborious. In this study, we developed a computational method named Network Distance Analysis for MiRNA‐Disease Association prediction (NDAMDA) which could effectively predict potential miRNA‐disease associations. The highlight of this method was the use of not only the direct network distance between 2 miRNAs (diseases) but also their respective mean network distances to all other miRNAs (diseases) in the network. The model's reliable performance was certified by the AUC of 0.8920 in global leave‐one‐out cross‐validation (LOOCV), 0.8062 in local LOOCV and the average AUCs of 0.8935 ± 0.0009 in fivefold cross‐validation. Moreover, we applied NDAMDA to 3 different case studies to predict potential miRNAs related to breast neoplasms, lymphoma, oesophageal neoplasms, prostate neoplasms and hepatocellular carcinoma. Results showed that 86%, 72%, 86%, 86% and 84% of the top 50 predicted miRNAs were supported by experimental association evidence. Therefore, NDAMDA is a reliable method for predicting disease‐related miRNAs.
Up‐regulated deubiquitinase USP4 plays an oncogenic role in melanoma
Authors: Guo Weinan , Ma Jinyuan , Pei Tianli , Zhao Tao , Guo Sen , Yi Xiuli , Liu Yu , Wang Shiyu , Zhu Guannan , Jian Zhe , Gao Tianwen , Li Chunying , Liao Wenjun , Shi Qiong
Published: March 2018

Melanoma is the most malignant skin cancer with increasing incidence worldwide. Although innovative therapies such as BRAF inhibitor and immune checkpoint inhibitor have gained remarkable advances, metastatic melanoma remains an incurable disease for its notorious aggressiveness. Therefore, further clarification of the underlying mechanism of melanoma pathogenesis is critical for the improvement of melanoma therapy. Ubiquitination is an important regulatory event for cancer hallmarks and melanoma development, and the deubiquitinating enzymes including ubiquitin‐specific peptidase (USP) families are greatly implicated in modulating cancer biology. Herein, we first found that the expression of the deubiquitinase USP4 was significantly up‐regulated in melanoma tissues and cell lines. Furthermore, although USP4 knockdown had little impact on melanoma cell proliferation, it could increase the sensitivity to DNA damage agent cisplatin. We subsequently showed that USP4 regulated cisplatin‐induced cell apoptosis via p53 signalling. More importantly, USP4 could accentuate the invasive and migratory capacity of melanoma cells by promoting epithelial‐mesenchymal transition. Altogether, our results demonstrate that the up‐regulated USP4 plays an oncogenic role in melanoma by simultaneously suppressing stress‐induced cell apoptosis and facilitating tumour metastasis.
Diabetic neuropathy and the sensory neuron: New aspects of pathogenesis and their treatment implications
Authors: Kobayashi Masaki , Zochodne Douglas W
Published: March 2018

Diabetic polyneuropathy (DPN) continues to be generally considered as a “microvascular” complication of diabetes mellitus alongside nephropathy and retinopathy. The microvascular hypothesis, however, might be tempered by the concept that diabetes directly targets dorsal root ganglion sensory neurons. This neuron‐specific concept, supported by accumulating evidence, might account for important features of DPN, such as its early sensory neuron degeneration. Diabetic sensory neurons develop neuronal atrophy alongside a series of messenger ribonucleic acid (RNA) changes related to declines in structural proteins, increases in heat shock protein, increases in the receptor for advanced glycation end‐products, declines in growth factor signaling and other changes. Insulin is recognized as a potent neurotrophic factor, and insulin ligation enhances neurite outgrowth through activation of the phosphoinositide 3‐kinase–protein kinase B pathway within sensory neurons and attenuates phenotypic features of experimental DPN. Several interventions, including glucagon‐like peptide‐1 agonism, and phosphatase and tensin homolog inhibition to activate growth signals in sensory neurons, or heat shock protein overexpression, prevent or reverse neuropathic abnormalities in experimental DPN. Diabetic sensory neurons show a unique pattern of microRNA alterations, a key element of messenger RNA silencing. For example, let‐7i is widely expressed in sensory neurons, supports their growth and is depleted in experimental DPN; its replenishment improves features of DPN models. Finally, impairment of pre‐messenger RNA splicing in diabetic sensory neurons including abnormal nuclear RNA metabolism and structure with loss of survival motor neuron protein, a neuron survival molecule, and overexpression of CWC22, a splicing factor, offer further novel insights. The present review addresses these new aspects of DPN sensory neurodegeneration.
Application of functional magnetic resonance imaging in psychiatric clinical evaluation: Controversies and avenues
Authors: Kandilarova Sevdalina , Stoyanov Drozdstoy , Popivanov Ivo D. , Kostianev Stefan
Published: March 2018

Rationale, aims, and objectives

In this study, we have attempted to replicate the findings of altered emotional processing in depressed patients compared with healthy controls by means of functional magnetic resonance imaging during passive viewing of positive, negative, and neutral pictures from the International Affective Pictures System.

Methods

Nineteen medicated depressed patients and 19 sex and age‐matched healthy controls underwent functional magnetic resonance imaging during presentation of affective pictures in a block design. The differences between the blood oxygen level dependent signal elicited in the tree conditions were compared. Within‐group and between‐group analyses were performed with stringent criteria for statistical inference (P < .05 with family‐wise error correction).

Results

In medicated depressed patients, positive pictures compared with neutral pictures activated predominantly the posterior cingulate cortex and precuneus, as well as occipital and middle temporal areas mainly on the left side, while in healthy controls, only the occipito‐temporal areas demonstrated significant activation. The negative pictures elicited stronger activation of occipital and temporal regions in both groups and of inferior frontal gyrus only in control subjects. The difference between the groups did not reach statistical significance. Positive correlation was demonstrated between activation levels of clusters located in left precuneus/posterior cingulate cortex and left inferior/middle occipital gyrus and Montgomery‐Asberg Depression Rating Scale scores in patients while viewing positive compared with neutral pictures.

Conclusions

Although the within‐group analysis demonstrated significant activations in both groups with apparent discrepancies, the between‐group analysis did not reach statistical significance under the stringent criteria for statistical inference. These results are further contextualized in the critical debate on the methodological issues of clinical evaluation in psychiatry, more specifically the validity and consistency of the applied methods and the limitations existing in the attempts to provide sound cross‐disciplinary validation of the diagnostic tools by means of neuroscience.
An Optimized Protocol of Protargol Staining for Ciliated Protozoa
Authors: Ji Daode , Wang Yunfeng
Published: March 2018

Protargol staining is a crucial method to reveal the infraciliature of ciliates, which is the most important morphological character for species identification. In the present study, Wilbert's protocol of protargol staining was emended mainly toward the highly happened improper bleaching. Through reciprocal treatments, both insufficient and excessive bleachings were much eliminated from the protargol protocol and the tests performed with four different species of ciliates established that the stainings were considerably improved and more reliable with optimized bleaching. Compared to the original protocol, the optimized method was proved to be more suitable for the groups difficult to stain, and it is also friendlier for the beginners and researchers in related fields.
Gazelletta kashiwaensis sp. nov. (Medusettidae, Phaeodaria, Cercozoa), Its Morphology, Phylogeny, Distribution, and Feeding Behavior
Authors: Nakamura Yasuhide , Somiya Rei , Kanda Masaru , Yamaguchi Atsushi , Tuji Akihiro , Hori Rie S.
Published: March 2018

A phaeodarian morphotype, characterized by the feet surrounded with forked pedal spines with anchor‐like structures, was collected in the subtropical North Pacific. Considering the morphological and phylogenetic uniqueness, this morphotype is described as Gazelletta kashiwaensis sp. nov. The distribution of this new species is possibly affected by the Kuroshio Current. The feeding behavior of living phaeodarians was first filmed: the present new species floated in the water column stretching “protoplasmic webs” and collected diatoms by repeating the expansion and retraction of “pseudopodium‐like tentacles”.
Detection of Weakly Expressed Trypanosoma cruzi Membrane Proteins Using High‐Performance Probes
Authors: Cruz‐Bustos Teresa , Moreno Silvia N.J. , Docampo Roberto
Published: March 2018

Membrane proteins in trypanosomatids are, in general, weakly expressed and confirmation of their subcellular localization frequently requires their overexpression with epitope tags. However, overexpression can lead to mislocalization of the probes. Viswanathan et al. (Nat. Methods, 2015, 12:568) described high performance tags for localization of weakly expressed proteins. We report here the use of these protein tags, named “spaghetti monster,” for CRISPR/Cas9‐mediated C‐terminal endogenous tagging of Trypanosoma cruzi to localize two weakly expressed transient receptor potential channels to acidic compartments. The results indicate that this method will improve the detection of membrane proteins in T. cruzi.
How many daddies: microsatellite genotyping reveals polyandry in a live‐bearing clinid fish Muraenoclinus dorsalis
Authors: Schulze M. J. , Henriques R. , Feldheim K. A. , Bowie R. C. K. , von der Heyden S.
Published: March 2018

Fishes belonging to the family Clinidae in South Africa display super‐embryonation, a rare reproductive mode were females gestate broods at different gestational stages, but little is known regarding the mating systems of this family. Here we tested the hypothesis that multiple males would contribute not only to the offspring of each female, but that several males would contribute to each brood, by sampling Muraenoclinus dorsalis from three sampling locations along the west and south‐west coast of South Africa. Larval (n = 97) and maternal (n = 14) genotpyes, generated with newly developed microsatellites, were used to estimate the number of potential mates per female. Our results show that up to 78% of females displayed multiple mating with an average of 2·1–2·2 males. In addition, 39–42% of females displayed polyandry with an average of 1·5–1·6 sires per brood. This study provides the evidence for multiple mating and polyandry within a clinid fish characterized by super‐embryonation that offers important baseline information regarding rare reproductive strategies, highlighting several gaps in our knowledge concerning clinid reproduction and mating systems.
Nephroblastoma in bester sturgeon, a cultured hybrid of Huso huso × Acipenser ruthenus: Diagnostic imaging, clinical and histopathological study
Authors: Rahmati‐Holasoo H , Soltani M , Masoudifard M , Shokrpoor S , Taheri Mirghaed A , Ahmadpoor M
Published: March 2018

Abdominal distention occurred at an incidence of 1% (15 from 1500 fish) in the population of 1‐year‐old bester (Huso huso × Acipenser ruthenus). Computed tomography (CT) images and radiographs showed a soft tissue mass compressed the posterior part of the swim bladder. Ultrasonography showed that the masses had different patterns. Internal examination revealed the abdominal cavities to be filled with large masses which appeared to encompass most of the visceral organs, including the swim bladder. The masses originated from the posterior kidney. Histologically, the masses were composed of mixtures of embryonal epithelial (tubules and glomeruli), blastema and mesenchymal tissues. The tubules showed cystic, papillary and tubular patterns. Tubules and glomeruloid structures were surrounded by proliferating blastema cells. The primitive mesenchyme was composed of loose streams and whorls of spindle to stellate cells with elongate nuclei. Histological findings in the skeletal muscles, hypoderm and spleen confirmed the metastatic tumour from the kidney in two cases. Immunohistochemically, neoplastic cells of the tubules and glomeruloid structures were positive for cytokeratin AE1/AE3. Sections stained with Masson's trichrome showed blue staining of the stroma. The histopathologic findings were consistent with nephroblastoma.
Association Between Neighborhood Cohesion and Self‐Neglect: Exploring Mental Health in Asian Americans
Authors: Lee Tonya , Woo Benjamin K.P.
Published: March 2018

See the Reply by Hei et al.
Although there is no Physical Short‐Term Scarcity of Phosphorus, its Resource Efficiency Should be Improved
Authors: Scholz Roland W. , Wellmer Friedrich‐Wilhelm
Published: March 2018

The German government has adopted a law that requires sewage plants to go beyond the recovery of phosphorus from wastewater and to promote recycling. We argue that there is no physical global short‐ or mid‐term phosphorus scarcity. However, we also argue that there are legitimate reasons for policies such as those of Germany, including: precaution as a way to ensure future generations’ long‐term supply security, promotion of technologies for closed‐loop economics in a promising stage of technology development, and decrease in the current supply risk with a new resource pool.
Automatic deformable registration of histological slides to μCT volume data
Authors: Chicherova N. , Hieber S.E. , Khimchenko A. , Bikis C. , Müller B. , Cattin P.
Published: March 2018

Localizing a histological section in the three‐dimensional dataset of a different imaging modality is a challenging 2D‐3D registration problem. In the literature, several approaches have been proposed to solve this problem; however, they cannot be considered as fully automatic. Recently, we developed an automatic algorithm that could successfully find the position of a histological section in a micro computed tomography (μCT) volume. For the majority of the datasets, the result of localization corresponded to the manual results. However, for some datasets, the matching μCT slice was off the ground‐truth position. Furthermore, elastic distortions, due to histological preparation, could not be accounted for in this framework.

In the current study, we introduce two optimization frameworks based on normalized mutual information, which enabled us to accurately register histology slides to volume data. The rigid approach allocated 81 % of histological sections with a median position error of 8.4 μm in jaw bone datasets, and the deformable approach improved registration by 33 μm with respect to the median distance error for four histological slides in the cerebellum dataset.
Effects of a Web‐Based Antenatal Care System on Maternal Stress and Self‐Efficacy During Pregnancy: A Study in Taiwan
Authors: Tsai Yi‐Jing , Hsu Yu‐Yun , Hou Ting‐Wei , Chang Chiung‐Hsin
Published: March 2018

Introduction

Women may experience significant stress during pregnancy, and antenatal care and education provide a means to address this. E‐health, the use of computer and information technology for health care, has been incorporated into antenatal care and education, but e‐health has not been evaluated for its usefulness in addressing stress. The objective of this study was to investigate the effectiveness of a web‐based antenatal care and education system on pregnancy‐related stress, general self‐efficacy, and satisfaction with antenatal care.

Methods

A quasi‐experimental design enrolled pregnant women at 16 to 24 weeks’ gestation with a low‐risk pregnancy. Women in the control group (n = 67) received routine antenatal care; women in the experimental group (n = 68) also received a web‐based antenatal care and education program in the second trimester. Pregnancy stress and general self‐efficacy were assessed at study entry and again at 36 to 38 weeks’ gestation; satisfaction with care was assessed at the study endpoint.

Results

When the pretest scores were controlled, the women in the experimental group reported significantly lower pregnancy‐related stress (F  =  12.9, P < .001) and significantly higher self‐efficacy (F = 17.61, P < .001) than did the women in the control group. Women in the experimental group reported lower pregnancy‐related stress (t = 5.09, P < .001) and a higher general self‐efficacy (t = −3.17, P = .001) at posttest compared to pretest. However, the women in the control group reported a lower general self‐efficacy at posttest compared to pretest (t = 2.86, P = .006). Women in the experimental group reported significantly higher satisfaction levels with antenatal care than those in the control group.

Discussion

A web‐based antenatal care and education system can improve pregnancy‐related stress and general self‐efficacy among pregnant women. Integrating health care with web‐based or internet‐based interventions may improve the quality of antenatal care.
Corticosterone and serotonin similarly influence GABAergic and purinergic pathways to affect cortical inhibitory networks
Authors: Wotton C. A. , Quon E. F. , Palmer A. C. , Bekar L. K.
Published: March 2018

Both serotonin (5‐HT) and stress exert changes in cortical inhibitory tone to shape the activity of cortical networks. Because astrocytes are also known to affect inhibition through established purinergic pathways, we assessed the role of GABA and purinergic pathways with respect to the effects of rapid corticosterone (CORT) and 5‐HT on cortical inhibition. We used a paired‐pulse paradigm (P1 and P2) in acutely isolated mouse brain slices to evaluate changes in cortical evoked inhibition. Normally, 5‐HT decreases the amplitude of the first pulse P1, whereas it increases the amplitude of P2 (increasing frequency transmission). Interestingly, it was observed that CORT application decreased P1 and increased P2 similar to that of 5‐HT application. Given that CORT and 5‐HT are known to modulate inhibition, we applied the GABAA antagonist bicuculline in the presence of both and found that the increase in P2 and the P2/P1 was lost, providing evidence for a common mechanism involving GABAA receptor signalling. Additional occlusion experiments (ie, 5‐HT in presence of CORT and CORT in presence of 5‐HT) provide further support for a common mechanism. Because both 5‐HT and CORT blocked the increase in P2 and P2/P1 with respect to the other, we suggest 5‐HT/CORT already utilise the shared mechanism to affect cortical inhibition. Using low concentrations of the GAPDH inhibitor iodoacetate, as commonly used to selectively disrupt astrocyte metabolism, we found that the increase in P2 and P2/P1 was similarly blocked in response to both CORT and 5‐HT. Because astrocyte signalling depends in large part on purinergic pathways, the purinergic contribution was assessed using Ab129 (P2Y antagonist) and SCH 58261 (A2A antagonist). Once again, P2Y and A2A receptor blockade similarly disrupted 5‐HT‐ or CORT‐mediated increases in P2 and P2/P1. Taken together, these results support the common involvement of GABAergic and purinergic pathways in the effects of CORT and 5‐HT that may also involve astrocytes.
Chemical fertilizer in transformations in world agriculture and the state system, 1870 to interwar period
Authors: Dixon Marion W.
Published: March 2018

The role of fertilizer in spreading commercial agriculture during the first food regime (ca 1870 to the First World War) is well established. What is less understood is the role of fertilizer in industry at this time. This paper details superphosphate fertilizer, part of a class of chemical fertilizers that emerged in the metropoles from the 1870s, and its role in the transformations in world agriculture as well as in industry. Superphosphate fertilizer was not just for the soil. The manufacture of superphosphates also provided a base for the growth of chemical industries. This growth was constitutive of industrial transformations in imperial states—the second industrial revolution—in which mass production units became integrated through a handful of chemicals. One of these chemicals is sulphuric acid, of which superphosphates require large amounts in their manufacture. As the main market for sulphuric acid through the interwar period, superphosphate manufacturing created synergies with other industries and thus made sulphuric acid cheaper. By connecting the manufacturing centres of fertilizer to the multiple farming regions undergoing accelerated commodity production, this study shows that the first food regime and the second industrial revolution were mutually constitutive moments to explain transformations in agriculture and the state system in the long 19th century.
Improvement of skin barrier dysfunction by Scutellaria baicalensis GEOGI extracts through lactic acid fermentation
Authors: Lee Hyeon Yong
Published: March 2018

Background

The development of an alternative medicine to treat atopic dermatitis (AD) from natural sources is necessary.

Aims

To improve skin barrier dysfunction by enhancing the differentiation of human keratinocytes with the fermented Scutellaria baicalensis.

Methods

Scutellaria baicalensis was fermented with Lactobacillus plantarum and extracted with 70% ethanol (FE). Antioxidant activities and the regulation of the gene expression related to keratinocyte differentiation were measured as well as its proliferation.

Result

This work first proved that the FE had multiple activities, both increasing keratinocyte differentiation and proliferation: The FE greatly up‐regulated expression of the genes of keratinocyte differentiation such as involucrin, keratin 10, and transglutaminase‐1 (TG‐1) up to 4.06‐fold, which was 3 times higher than the 2 other extracts. The effect of baicalein on keratinocyte differentiation was also first found; however, its efficacy was lower than that of the fermented extract. The FE proved to effectively accelerate keratinocyte differentiation, rather than to initiate the differentiation, and also showed an ability of stimulating keratinocyte proliferation up to 2.8 × 106 viable cells/mL as well as 70.24 ng/mL of collagen production in fibroblasts. High efficacy of the FE was confirmed by synergistic effects of large amounts of various bioactive substances in the extracts as baicalein alone did not show remarkable effects and even positive controls had not much better activities than the FE.

Conclusion

The fermented extract was able to improve skin barrier dysfunction, and the ointment with 1%‐5% (v/v) of the extract be directly used for skin clinical trials to treat AD.
Lactase persistence, milk intake, hip fracture and bone mineral density: a study of 97 811 Danish individuals and a meta‐analysis
Authors: Bergholdt H. K. M. , Larsen M. K. , Varbo A. , Nordestgaard B. G. , Ellervik C.
Published: March 2018

Background

Whether a causal relationship exists between milk intake and reduced risk of fractures is unclear.

Objectives

We tested the hypothesis that genetically determined milk intake reduces the risk of fractures and increases bone mineral density (BMD).

Methods

We investigated the association between milk intake, LCT‐13910 C/T (rs4988235), which is associated with lactase persistence (TT/TC) in Northern Europeans, and hip fractures in three Danish prospective studies (N = 97 811, age ≥20 years). We added meta‐analyses of LCT‐13910 and fractures and BMD from five published Northern European population studies.

Results

In the Danish studies, the adjusted hazard ratio (HR) for hip fracture per one glass per week higher milk intake was 1.00 (95% CI: 0.99–1.01). The per T‐allele milk intake was 0.58 (0.49–0.68) glasses per week, but HR was 1.01 (0.94–1.09) for hip fracture. In meta‐analyses of Danish studies with published Northern European population studies, the random effects odds ratio for any fracture was 0.86 (0.61–1.21; I2 = 73%) for TT vs. CC and 0.90 (0.68–1.21; I2 = 63%) for TC vs. CC. The standardized mean difference in femoral neck BMD was 0.10 (0.02–0.18; I2 = 0%) g cm−2 for TT vs. CC and 0.06 (−0.04 to 0.17; I2 = 17%) g cm−2 for TC vs. CC. There were no differences in lumbar spine or total hip BMD comparing TT or TC with CC.

Conclusion

Genetically lifelong lactase persistence with high milk intake was not associated with hip fracture in Danish population‐based cohorts. A meta‐analysis combining Danish studies with published Northern European population studies also showed that lactase persistence was not associated with fracture risk. Genetic lactase persistence was associated with a higher femoral neck BMD, but not lumbar spine or total hip BMD.
The Effects of Middle School Weight Climate on Youth With Higher Body Weight
Authors: Juvonen Jaana , Lessard Leah M. , Schacter Hannah L. , Enders Craig
Published: March 2018

This study examines whether social‐emotional difficulties associated with higher body weight vary across schools as a function of the school's weight climate. Weight climate, characterized by weight‐policing, was assessed indirectly by examining how strongly self‐reported weight predicts victim reputation within 26 ethnically diverse middle schools. Social‐emotional indicators included self‐reported loneliness, school belonging, and self‐esteem. In schools with stronger weight‐policing at seventh grade, loneliness was intensified by eighth grade among both girls (n = 2,101) and boys (n = 1,985) with higher weight. Similar effects were found for low self‐esteem among girls. Additionally, boys—regardless of their weight—reported lower sense of belonging in schools with stronger weight‐policing. The study offers a new method to estimate school weight climate, and the findings provide insights for interventions.
Resistance to Phytophthora pathogens is dependent on gene silencing pathways in plants
Authors: Guo Na , Zhao Jinming , Yan Qiang , Huang Jing , Ma Huifei , Rajput Nasir Ahmed , Jiang Hua , Xing Han , Dou Daolong
Published: March 2018

RNA silencing is one of the main defence mechanisms employed by plants to fight pathogens. p19 protein encoded by the tomato bushy stunt virus (TBSVp19) is known as a suppressor of RNA silencing via siRNA sequestration to prevent the assembly of RISC. To better understand the impact of TBSVp19 on silencing and its roles in Phytophthora pathogens, we used the transient expression assay in Nicotiana benthamiana and found that the leaves expressing TBSVp19 were more susceptible to Phytophthora parasitica. Furthermore, we demonstrated that TBSVp19‐mediated plant susceptibility in N. benthamiana is dependent on RNA‐dependent RNA polymerase 6 (RDR6). We also tested the role of RNA silencing in resistance of soybean hairy roots to Phytophthora. The lesion size induced by P. sojae on TBSVp19‐expressing soybean hairy roots was slightly, but significantly larger than GFP‐expressing soybean hairy roots. Finally, the Arabidopsis gene silencing mutants ago1‐27, zip‐1, sgs3‐11 and rdr6‐11 were also examined for their resistance to P. parasitica. The results clearly showed that resistance levels of the mutants were visibly reduced compared with the wild type. Taken together, these results suggest that the gene silencing system in plants is essential for resistance to Phytophthora pathogens.
Glucantime reduces mechanical hyperalgesia in cutaneous leishmaniasis and complete Freund's adjuvant models of chronic inflammatory pain
Authors: da Silva Suelen S , Mizokami Sandra S , Fanti Jacqueline R , Costa Idessania N , Bordignon Juliano , Felipe Ionice , Pavanelli Wander R , Verri Waldiceu A , Conchon Costa Ivete
Published: March 2018

Objectives

To evaluate the analgesic effect of Glucantime (antimoniate N-methylglucamine) in Leishmania amazonensis infection and complete Freund's adjuvant (CFA), chronic paw inflammation model, in BALB/c mice.

Methods

Two models of chronic inflammatory pain in BALB/c mice paw were used: infection with L. amazonensis and CFA stimulation. Both animals models received daily treatment with Glucantime (10 mg/kg, i.p.) and during the treatment was measured the mechanical hyperalgesia with electronic version of von Frey filaments. After the treatment, the paw skin sample was collected for analysis of myeloperoxidase (MPO) and N-acetyl-β-glucosaminidase (NAG) activity, and IL-1β, TNF-α, IL-6, IFN-γ and IL-10 cytokines production by ELISA.

Key findings

Leishmania amazonensis-induced chronic inflammation with significant increase in mechanical hyperalgesia, MPO and NAG activity, and IL-1β, TNF-α and IL-6 production in the paw skin. Glucantime (10 mg/kg, i.p.) inhibited L. amazonensis-induced mechanical hyperalgesia and IL-1β and IL-6 cytokines productions. In chronic inflammatory model induced by CFA, Glucantime treatment during 7 days inhibited CFA-induced mechanical hyperalgesia, MPO and NAG activity, and IL-1β, TNF-α, IL-6 and IFN-γ production as well as increased IL-10 production.

Conclusions

Our data demonstrated that Glucantime reduced the chronic inflammatory pain induced by L. amazonensis and CFA stimuli by inhibiting the hyperalgesic cytokines production.
Development of an enteric nanoparticle of marine sulfated polysaccharide propylene glycol alginate sodium sulfate for oral administration: formulation design, pharmacokinetics and efficacy
Authors: Li Pengli , Hao Jiejie , Li Haihua , Guan Huashi , Li Chunxia
Published: March 2018

Objectives

Propylene glycol alginate sodium sulfate (PSS) is poorly absorbed by oral administration due to its large molecular weight and slightly degradability in stomach acidic environment. Here, a novel enteric-coated nano formulation of PSS (enteric PSS-NP) was prepared to improve its bioavailability and efficacy.

Methods

The enteric PSS-NP was prepared by double (W1/O/W2) emulsion and solvent evaporation method. The drug release characteristics in vitro were studied in artificial gastrointestinal fluid. And the pharmacokinetics and efficacy of enteric PSS-NP were separately investigated in normal rats and type 2 diabetic db/db mice.

Key findings

The enteric PSS-NP were in spherical shape and exhibited negative zeta potential. The releasing characteristics of enteric PSS-NP in vitro showed that it possessed a strong pH-sensitive release character. Single-dose (50 mg/kg) oral pharmacokinetic study in rat plasma showed that enteric PSS-NP could improve the relative bioavailability significantly compared with PSS solution. Furthermore, the efficacy of enteric PSS-NP in vivo was better than that of PSS solution at equivalent doses.

Conclusions

The study showed that enteric-coated formulation of PSS had the intestinal-targeted absorption and improved pharmacodynamics, which indicated that enteric PSS-NP could be developed into a new formulation product in the future.
Intraspecific interactions between algae with different nutritional histories
Authors: Venuleo Marianna , Giordano Mario
Published: March 2018

The diatom Phaeodactylum tricornutum was cultured in five different growth regimes to obtain cells with different composition. Pairs of populations subjected to different treatments were then mixed in a communal culture regime that differed from those of origin. After 6 h, the ratio between the two populations was verified by flow cytometry. Alterations in this ratio were found when cells previously grown at 1 mM NH4+ were mixed with GeO2‐ and 0.5 mM NH4+‐grown cells. The nutritional background may thus make cells differently suited to new environmental conditions and afford advantages in terms of reproductive potential. Competitive interactions between populations may result from the differences in the expressed proteome and/or in the availability of tools for regulatory responses. This may have relevance to the persistence of phenotypically neutral variants present in the population best suited to the new condition, after the interaction of the conspecifics with different nutritional histories.
Detecting Tail Risk Differences in Multivariate Time Series
Authors: Hoga Yannick
Published: March 2018

We derive functional central limit theory for tail index estimates in multivariate time series under mild conditions on the extremal dependence between the components. We use this result to also derive convergence results for extreme value‐at‐risk and extreme expected shortfall estimates. This allows us to construct tests for equality of ‘tail risk’ in multivariate data, which can be useful in a number of empirical contexts. In constructing test statistics, we avoid estimating long‐run variances by using self‐normalization. Size and power of the tests for equal ‘tail risk’ are assessed in simulations. An empirical application to exchange returns illustrates the practical usefulness of the tests.
HBsAg and HBcrAg as predictors of HBeAg seroconversion in HBeAg‐positive patients treated with nucleos(t)ide analogues
Authors: Wang B. , Carey I. , Bruce M. , Montague S. , Dusheiko G. , Agarwal K.
Published: March 2018

HBeAg seroconversion marks an important spontaneous change and treatment end‐point for HBeAg‐positive patients and is a pre‐requisite for HBsAg loss or functional cure. In this retrospective analysis, we aimed to identify predictors of seroconversion using serum quantitative HBsAg and HBcrAg, in HBeAg‐positive patients treated with nucleos(t)ide analogues (NA). Data and samples from 118 HBeAg‐positive adults (genotypes A‐G) started on NA between Jan 2005 and Sept 2016 were retrospectively analysed at several time‐points. The predictive power of on‐treatment levels of HBsAg and HBcrAg was determined using receiver operating curve (ROC) analysis and cut‐off values determined by maximized Youden's index. About 36.4% of patients achieved HBeAg seroconversion after a median of 39 months’ treatment. On treatment kinetics of HBV DNA, HBsAg and HBcrAg differed between HBeAg seroconverters and nonseroconverters. A combination of HBsAg and HBcrAg had the greatest predictive value for HBeAg seroconversion: at 6 months, HBsAg of 3.9 log10 IU/mL and HBcrAg of 5.7 log10 U/mL had a sensitivity of 71.4%, specificity of 79.5%, positive predictive value (PPV) of 65.2% and negative predictive value (NPV) of 83.8%, with AUROC of 0.769 (0.668, 0.869; 95%CI), and at 12 months, HBsAg 3.8 log10 IU/mL and HBcrAg 5.5 log10 U/mL had a sensitivity of 73.7%, specificity of 79.5%, PPV of 63.6% and NPV of 86.1%, with AUROC 0.807 (0.713, 0.901; 95% CI). In conclusion, our results may be used to identify patients who are unlikely to achieve treatment end‐points, which will be important as the future management of chronic hepatitis B looks to therapies that offer functional cure.
Effect of hepatitis B virus on steatosis in hepatitis C virus co‐infected subjects: A multi‐centre study and systematic review
Authors: Goossens N. , de Vito C. , Mangia A. , Clément S. , Cenderello G. , Barrera F. , D'Ambrosio R. , Coppola N. , Zampino R. , Stanzione M. , Adinolfi L. E. , Wedemeyer H. , Semmo N. , Müllhaupt B. , Semela D. , Malinverni R. , Moradpour D. , Heim M. , Trincucci G. , Rubbia‐Brandt L. , Negro F. ,   on behalf of the BOSTIC Study Group
Published: March 2018

It remains unclear whether hepatitis B virus (HBV) infection may modify the severity of viral steatosis in patients coinfected with chronic hepatitis C virus (HCV). We examined the influence of coinfection with HBV on prevalence of steatosis in chronic hepatitis C in a multi‐centre cohort of HBV‐HCV subjects, and by performing a systematic review and meta‐analysis of the literature. We centrally and blindly assessed steatosis prevalence and severity in a cohort of HBV‐HCV coinfected subjects compared to HCV and HBV monoinfected controls and we performed a systematic review of studies addressing the prevalence of steatosis in HBV‐HCV subjects compared to HCV controls. In the clinical cohort, we included 85 HBV‐HCV, 69 HBV and 112 HCV subjects from 16 international centres. There was no significant difference in steatosis prevalence between the HBV‐HCV and the HCV groups (33% vs 45%, P = .11). In subgroup analysis, lean HBV‐HCV subjects with detectable HBV DNA had less steatosis than lean HCV subjects matched for HCV viremia (15% vs 45%, P = .02). Our literature search identified 5 additional studies included in a systematic review. Overall, prevalence of steatosis > 5% was similar in HBV‐HCV infection compared to HCV (pooled odds ratio [OR] 0.91, 95% CI 0.53‐1.6) although there was significant heterogeneity (I2 69%, P = .007). In conclusion, although the prevalence of steatosis is similar in HBV‐HCV compared to HCV subjects, our analysis suggests that there may be an inhibitory effect of HCV‐induced steatogenesis by HBV in certain subgroups of patients.