bluuebunny/crossref_metadata_2025 huggingface dataset:
How common road salts and organic additives alter freshwater food webs: in search of safer alternatives
Authors: Schuler Matthew S. , Hintz William D. , Jones Devin K. , Lind Lovisa A. , Mattes Brian M. , Stoler Aaron B. , Sudol Kelsey A. , Relyea Rick A.
Published: February 2017

The application of deicing road salts began in the 1940s and has increased drastically in regions where snow and ice removal is critical for transportation safety. The most commonly applied road salt is sodium chloride (NaCl). However, the increased costs of NaCl, its negative effects on human health, and the degradation of roadside habitats has driven transportation agencies to seek alternative road salts and organic additives to reduce the application rate of NaCl or increase its effectiveness. Few studies have examined the effects of NaCl in aquatic ecosystems, but none have explored the potential impacts of road salt alternatives or additives on aquatic food webs.

We assessed the effects of three road salts (NaCl, MgCl2 and ClearLane™) and two road salts mixed with organic additives (GeoMelt™ and Magic Salt™) on food webs in experimental aquatic communities, with environmentally relevant concentrations, standardized by chloride concentration.

We found that NaCl had few effects on aquatic communities. However, the microbial breakdown of organic additives initially reduced dissolved oxygen. Additionally, microbial activity likely transformed unusable phosphorus from the organic additives to usable phosphorus for algae, which increased algal growth. The increase in algal growth led to an increase in zooplankton abundance. Finally, MgCl2 – a common alternative to NaCl – reduced compositional differences of zooplankton, and at low concentrations increased the abundance of amphipods.

Synthesis and applications. Our results indicate that alternative road salts (to NaCl), and road salt additives can alter the abundance and composition of organisms in freshwater food webs at multiple trophic levels, even at low concentrations. Consequently, road salt alternatives and additives might alter ecosystem function and ecosystem services. Therefore, transportation agencies should use caution in applying road salt alternatives and additives. A comprehensive investigation of road salt alternatives and road salt additives should be conducted before wide‐scale use is implemented. Further research is also needed to determine the impacts of salt additives and alternatives on higher trophic levels, such as amphibians and fish.
Grammar Schools, a Policy of Social Mobility and Selection—Why?
Authors: Ware Alan
Published: February 2017

Initially, four plausible reasons for introducing selection in secondary education are examined, three of which are irrelevant to contemporary debates about expanding grammar‐school education. These are: first, to ration education in less advanced economies; second, to increase the supply of skilled labour within an expanded national elite; third, as part of a ‘segmented’ system of education. A fourth—increasing upward social mobility—is open to two objections: first, the May government's proposals are so limited as to have little likely impact on mobility and, second, upward mobility in the twentieth century was possible only because of structural change in the British labour market, and that will probably not continue in this century. Finally, it is argued that attempts to select the ‘best’ in any activity or skill are necessarily highly imperfect, and are far less accurate than testing who does and does not meet some minimum level of competence.
Development and Testing of a Physically Based Model of Streambank Erosion for Coupling with a Basin‐Scale Hydrologic Model SWAT
Authors: Narasimhan B. , Allen P.M. , Coffman S.V. , Arnold J.G. , Srinivasan R.
Published: February 2017

A comprehensive streambank erosion model based on excess shear stress has been developed and incorporated in the hydrological model Soil and Water Assessment Tool (SWAT). It takes into account processes such as weathering, vegetative cover, and channel meanders to adjust critical and effective stresses while estimating bank erosion. The streambank erosion model was tested for performance in the Cedar Creek watershed in north‐central Texas where streambank erosion rates are high. A Rapid Geomorphic field assessment (RAP‐M) of the Cedar Creek watershed was done adopting techniques developed by the Natural Resources Conservation Service (NRCS), and the stream segments were categorized into various severity classes. Based on the RAP‐M field assessment, erosion pin sites were established at seven locations within the severely eroding streambanks of the watershed. A Monte Carlo simulation was carried out to assess the sensitivity of different parameters that control streambank erosion such as critical shear stress, erodibility, weathering depth, and weathering duration. The sensitive parameters were adjusted and the model was calibrated based on the bank erosion severity category identified by the RAP‐M field assessment. The average observed erosion rates were in the range 25‐367 mm year−1. The SWAT model was able to reasonably predict the bank erosion rates within the range of variability observed in the field (R2 = 0.90; E = 0.78). Editor's note: This paper is part of the featured series on SWAT Applications for Emerging Hydrologic and Water Quality Challenges. See the February 2017 issue for the introduction and background to the series.
The Changing Nature of the Australian Electricity Industry
Authors: Nelson Tim , Bashir Stephanie , McCracken‐Hewson Eleanor , Pierce Michael
Published: February 2017

The electricity supply industry has historically offered a homogenous good supplied via economically regulated transmission and distribution networks. Competition was introduced into the contestable generation and retail supply chain components as part of the 1990s Hilmer reform process. After a century of incremental technological developments, the industry is now being transformed by new distributed energy technologies and a global focus on reducing anthropogenic greenhouse gas emissions. Policy‐makers did not anticipate these changes. A number of key reforms are likely to be required. These include: assessing whether the return on capital provided to network operators is appropriate given changing economic conditions; determining the role of competition in the provision of “behind the meter” energy services; and integration of climate change policy with wholesale energy market design.
Establishment of native grasses and their impact on exotic annuals in degraded box gum woodlands
Authors: Cole Ian , Prober Suzanne , Lunt Ian , Koen Terry
Published: February 2017

Restoration goals often involve the addition of new species to resident, degraded communities but in box gum woodlands such restoration is often constrained by competition from persistent exotic annuals that control critical ecological processes. Nutrient reduction (via carbon addition) and seed bank depletion are two approaches to reduce competition from exotic annuals but to be effective these treatments must allow establishment of species such as native grasses. This experiment was conducted in two degraded Austrostipa understoreys in the box gum woodlands of south‐east Australia. It compares the effects of carbon addition (sugar), seed depletion (spring burning or spring grazing) and combinations of carbon addition and seed depletion treatments on the establishment of C3 and C4 native grasses, and measured the effects of their establishment on soil nitrate concentration and exotic annuals. Treatments that reduced exotic annual abundance did not increase initial germination of the C4 native grasses, Bothriochloa or Themeda. However, sugar increased seedling survival of Themeda and Bothriochloa and grazing increased seedling survival of Bothriochloa, presumably by reducing effects of exotic annuals. Poa and Rytidosperma (C3 native grasses) failed to establish. Although we were unable to detect any reduction in soil nitrate concentration, swards with successful recruitment of C4 grasses suppressed exotic annuals more than the Austrostipa‐only swards at one site (the other was affected by wildfire). Further, Austrostipa‐Themeda swards were more effective than Austrostipa‐Bothriochloa for suppressing exotics, pointing to a role for both functional and species identity in the degree of resistance conferred.
The forgotten Grevy's zebra Equus grevyi population along the Kasigau Corridor ranches, SE Kenya: recent records and conservation issues
Authors: Githiru Mwangi
Published: February 2017

Since the 1970s, the globally endangered Grevy's zebra Equus grevyi has suffered a substantial reduction in range and population size. Grevy's zebra was introduced into the Tsavo ecosystem in two translocations: 22 individuals released in Tsavo East National Park in 1964 and 30 individuals released in Tsavo West National Park in 1977. This study focuses on the Tsavo East subpopulation within the Kasigau Corridor REDD+ Project Area. Data were collected from 2011 to 2014 using systematic and ad lib methods, while vegetation stratification was based on tonnes of CO2e per hectare. Cumulatively, 785 Grevy's zebra were seen in 210 encounters. The largest single group comprised of 24 individuals; mean group size was 4 ± 3. Foals comprised 10% of all individuals seen and were recorded across most months, suggesting year‐round breeding. The range core for the Grevy's zebra in this area was estimated to be 400 km2. Its density was estimated at 0.09 ± 0.038 individuals per km2, translating to a population of 36 ± 15 individuals (range: 6–67) based on the estimated core range. Grasslands and sparse Acacia–Commiphora vegetation strata were used significantly more than expected. Despite constituting only about 2–3% of the global Grevy's zebra population, this subpopulation could still play a role as a – disconnected – reserve population.
Effects of Institutional Investors’ Bidding Information on Offer Prices and Initial Returns of IPOs
Authors: Joh Sung Wook , Kim Yoo‐Hwan
Published: February 2017

Using hand‐collected data on all IPOs in Korea from 2001 to 2007 before the global financial crisis, we find that institutional investors’ favorable valuation increases the offer price and initial returns. In particular, when institutional investors’ weighted average bidding price (WAP) increases by 1%, the offer price increases by 0.81%. A higher WAP predicts higher initial returns. While oversubscription ratios yield positive effects on offer prices and predict higher initial returns, their effects are weaker when IPO market conditions or WAP are included in the regression equations. These results suggest that institutional investors’ bidding prices reflect their private valuations of firms more than their oversubscription ratios. In addition, for predicting initial returns, institutional investors’ bidding information outperforms the revised offer price.
A Fleet of Mediterranean Border Humanitarians
Authors: Stierl Maurice
Published: February 2017

EUrope has created a space of human suffering within which military‐humanitarian measures seem urgently required if the mass drowning is to be halted. The framing of migration governance as humanitarian has become commonplace in spectacular border practices in the Mediterranean Sea. Nonetheless, maritime disasters continue to unfold. This article discusses three non‐governmental actors, part of an emerging “humanitarian fleet” that seeks to turn the sea into a less deadly space: the Migrant Offshore Aid Station, Médecins Sans Frontières, and Sea‐Watch. While the rescue of precarious lives and the alleviation of suffering are central concerns, they imagine their humanitarian practices, the subjects of their compassion, and EUrope's role in shaping borderzones in different ways, pointing to a wide humanitarian spectrum. Engaging with the different discursive frames created by the three “border humanitarians”, the article explores what possibilities exist for political dissent to emanate from within humanitarian reason.
Making space for co‐produced research ‘impact’: learning from a participatory action research case study
Authors: Darby Stella
Published: February 2017

There is growing emphasis in the UK on promoting research that creates a positive impact on society. Research Councils UK, the major national research funding agencies, have recently defined a framework for promoting and measuring this impact. This paper contributes to current debates about this developing agenda and, particularly, the problematic intersection of the impact agenda and co‐production research approaches. I argue that processes of negotiating values, aims and power relations are essential to creating relevant, ethical impacts with research participants. In contrast to the emphasis placed on linear and top‐down change by the impact agenda, my experience doing participatory action research with a UK community group shows that co‐produced research produces different kinds of impacts: co‐produced impacts are emergent and non‐linear; responsive and relational; and empowering when rooted in reciprocal collaboration with research partners. This paper questions the implicit values the impact framework imposes on academic researchers and community partners, calling for continued critical engagement with the impact agenda to encourage the value‐rational reflection, deliberation and collaboration needed for creating socially transformative research.
Folate receptors and neural tube closure
Authors: Saitsu Hirotomo
Published: February 2017

Neural tube defects (NTD) are among the most common human congenital malformations, affecting 0.5–8.0/1000 of live births. Human clinical trials have shown that periconceptional folate supplementation significantly decreases the occurrence of NTD in offspring. However, the mechanism by which folate acts on NTD remains largely unknown. Folate receptor (Folr) is one of the three membrane proteins that mediate cellular uptake of folates. Recent studies suggest that mouse Folr1 (formerly referred to as Fbp1) is essential for neural tube closure. Therefore, we examined spatial and temporal expression patterns of Folr1 in developing mouse embryos, showing a close association between Folr1 and anterior neural tube closure. Transient transgenic analysis was performed using lacZ as a reporter; we identified a 1.1‐kb enhancer that directs lacZ expression in the neural tube and optic vesicle in a manner that is similar to endogenous Folr1. The 1.1‐kb enhancer sequences were highly conserved between humans and mice, suggesting that human FOLR1 is associated with anterior neural tube closure in humans. Several experimental studies in mice and human epidemiological and genetics studies have suggested that folate receptor abnormalities are involved in a portion of human NTDs, although the solo defect of FOLR1 did not cause NTD.
Conservation genomics of the endangered Burmese roofed turtle
Authors: Çilingir F. Gözde , Rheindt Frank E. , Garg Kritika M. , Platt Kalyar , Platt Steven G. , Bickford David P.
Published: February 2017

The Burmese roofed turtle (Batagur trivittata) is one of the world's most endangered turtles. Only one wild population remains in Myanmar. There are thought to be 12 breeding turtles in the wild. Conservation efforts for the species have raised >700 captive turtles since 2002, predominantly from eggs collected in the wild. We collected tissue samples from 445 individuals (approximately 40% of the turtles’ remaining global population), applied double‐digest restriction‐site associated DNA sequencing (ddRAD‐Seq), and obtained approximately 1500 unlinked genome‐wide single nucleotide polymorphisms. Individuals fell into 5 distinct genetic clusters, 4 of which represented full‐sib families. We inferred a low effective population size (≤10 individuals) but did not detect signs of severe inbreeding, possibly because the population bottleneck occurred recently. Two groups of 30 individuals from the captive pool that were the most genetically diverse were reintroduced to the wild, leading to an increase in the number of fertile eggs (n = 27) in the wild. Another 25 individuals, selected based on the same criteria, were transferred to the Singapore Zoo as an assurance colony. Our study demonstrates that the research‐to‐application gap in conservation can be bridged through application of cutting‐edge genomic methods.
Optimizing the analysis strategy for the CANVAS Program: A prespecified plan for the integrated analyses of the CANVAS and CANVAS‐R trials
Authors: Neal Bruce , Perkovic Vlado , Mahaffey Kenneth W. , Fulcher Greg , Erondu Ngozi , Desai Mehul , Shaw Wayne , Law Gordon , Walton Marc K. , Rosenthal Norm , de Zeeuw Dick , Matthews David R. ,   on behalf of the CANVAS Program collaborative group
Published: February 2017

Two large cardiovascular outcome trials of canagliflozin, comprising the CANVAS Program, will complete in early 2017: the CANagliflozin cardioVascular Assessment Study (CANVAS) and the CANagliflozin cardioVascular Assessment Study–Renal (CANVAS‐R). Accruing data for the sodium glucose co‐transporter 2 (SGLT2) inhibitor class has identified questions and opportunities that were not apparent when the trials were designed. Accordingly, a series of modifications have been made to the planned analyses. These updates will ensure that the data from the CANVAS Program will maximize advances in scientific knowledge and patient care. The specification of the analysis strategy prior to knowledge of the trial results, their design by the independent scientific trial Steering Committee, the detailed a priori definition of the analysis plans, and the external review provided by the US Food and Drug Administration all provide maximally efficient and robust utilization of the data. The CANVAS Program should significantly advance our understanding of the effects of canagliflozin, and the broader SGLT2 inhibitor class, on a range of important efficacy and safety outcomes.
Trends in Life Expectancy by Income and the Role of Specific Causes of Death
Authors: Hederos Karin , Jäntti Markus , Lindahl Lena , Torssander Jenny
Published: February 2017

This study explores how life expectancy at age 35 has evolved across the income distribution in Sweden over time. We examine individual income for men 1970–2007 and family income for both men and women 1980–2007. During this period, income inequality increased in most western countries, but especially so in Sweden. Drawing on a large sample of the Swedish population, our results show that the gap in life expectancy between the richest and poorest fifths of the income distribution also increased. This was the case both for individual and family income. The increase was larger for men than for women, but the only group with stagnant life expectancy at age 35 was women in the lowest income quintile group. Between 1986 and 2007, the difference between the lowest and highest family income quintiles increased by about one year for women and by almost two years for men. The causes of death that most significantly contributed to the increased disparities among women were circulatory and respiratory diseases. For men, circulatory disease mortality alone caused most of the increased disparities.
Positive effects of neurofeedback on autism symptoms correlate with brain activation during imitation and observation
Authors: Datko Michael , Pineda Jaime A. , Müller Ralph‐Axel
Published: February 2017

Autism has been characterized by atypical task‐related brain activation and functional connections, coinciding with deficits in sociocommunicative abilities. However, evidence of the brain's experience‐dependent plasticity suggests that abnormal activity patterns may be reversed with treatment. In particular, neurofeedback training (NFT), an intervention based on operant conditioning resulting in self‐regulation of brain electrical oscillations, has shown increasing promise in addressing abnormalities in brain function and behavior. We examined the effects of ≥ 20 h of sensorimotor mu‐rhythm‐based NFT in children with high‐functioning autism spectrum disorders (ASD) and a matched control group of typically developing children (ages 8–17). During a functional magnetic resonance imaging imitation and observation task, the ASD group showed increased activation in regions of the human mirror neuron system following the NFT, as part of a significant interaction between group (ASD vs. controls) and training (pre‐ vs. post‐training). These changes were positively correlated with behavioral improvements in the ASD participants, indicating that mu‐rhythm NFT may be beneficial to individuals with ASD.
Evaluation of an optimized [18F]fluoro‐deoxy‐glucose positron emission tomography voxel‐wise method to early support differential diagnosis in atypical Parkinsonian disorders
Authors: Caminiti S. P. , Alongi P. , Majno L. , Volontè M. A. , Cerami C. , Gianolli L. , Comi G. , Perani D.
Published: February 2017

Background and purpose

Atypical Parkinsonian disorders (APD) frequently overlap in clinical presentations, making the differential diagnosis challenging in the early stages. The present study aimed to evaluate the accuracy of the [18F]fluoro‐deoxy‐glucose positron emission tomography Statistical Parametric Mapping (SPM) optimized procedure in supporting the early and differential diagnosis of APD.

Methods

Seventy patients with possible APD were retrospectively included from a large clinical cohort. The included patients underwent [18F]fluoro‐deoxy‐glucose positron emission tomography within 3 months of the first clinical assessment and a diagnostic follow‐up. An optimized SPM voxel‐wise procedure was used to produce t‐maps of brain hypometabolism in single subjects, which were classified by experts blinded to any clinical information. We compared the accuracy of both the first clinical diagnosis and the SPM t‐map classifications with the diagnosis at follow‐up as the reference standard.

Results

At first diagnosis, 60% of patients were classified as possible APD (progressive supranuclear palsy, corticobasal degeneration, dementia with Lewy bodies, multiple system atrophy) and about 40% as APD with uncertain diagnosis, providing 52% sensitivity, 97% specificity and 86% accuracy with respect to the reference standard. SPM t‐map classification showed 98% sensitivity, 99% specificity and 99% accuracy, and a significant agreement with the diagnosis at follow‐up (P < 0.001).

Conclusions

The SPM t‐map classification at entry predicted the second diagnosis at follow‐up. This indicates its significantly superior role for an early identification of APD subtypes, particularly in cases of uncertain diagnosis. The use of a metabolic biomarker at entry in the instrumental work‐up of APD may shorten the diagnostic time, producing benefits for treatment options and support to the patients.
Real‐world practice and Expectation of Asia‐Pacific physicians and patients in Helicobacter Pylori eradication (REAP‐HP Survey)
Authors: Chuah Yoen‐Young , Wu Deng‐Chyang , Chuah Seng‐Kee , Yang Jyh‐Chin , Lee Tzong‐Hsi , Yeh Hong‐Zen , Chen Chan‐Lin , Liu Yu‐Hwa , Hsu Ping‐I
Published: February 2017

Objective

The aims of the study were: 1, to survey the most popular anti‐H. pylori regimens in Asia‐Pacific region and the real‐world effectiveness of these regimens; and 2, to investigate the expectation gaps of eradication rate between physicians and patients.

Design

A questionnaire was distributed to Asia‐Pacific physicians who attended the Asia‐Pacific Digestive Week 2015 meeting. Reported eradication rates from the literatures were compared with real‐world rates of surveyed popular regimens within the region. In addition, a questionnaire was distributed to H. pylori‐infected patients in three regions of Taiwan.

Results

A total of 691 physicians and 539 patients participated in the survey. The top five most commonly used regimens were 7‐day clarithromycin‐based standard triple therapy (50.4%), 14‐day clarithromycin‐based standard triple therapy (31.0%), 10‐day sequential therapy (6.1%), 14‐day bismuth quadruple therapy (3.9%), and 14‐day hybrid therapy (3.6%). All countries except for China had a significant gap between the expectation of physicians on anti‐H. pylori therapy and the real‐world eradication rate of most commonly adopted regimens (all P value <.05). The expectation on minimal eradication rate among patients was higher than that of physicians (91.4% vs 86.5%, P<.001).

Conclusions

It is time for physicians in Asia‐Pacific countries to adopt newer and more efficacious anti‐H. pylori regimens to meet the Kyoto consensus recommendation and their patients’ expectations.
International trends in health science librarianship part 20: Russia
Authors: Murphy Jeannette , Jargin Serge
Published: February 2017

This is the last in a series of articles exploring international trends in health science librarianship in the 21st century. The focus of the present issue is Russia. The next feature column will initiate a new series entitled New Directions in Health Science Librarianship. The first contribution will be from Australia.

JM
Extracellular histones disarrange vasoactive mediators release through a COX‐NOS interaction in human endothelial cells
Authors: Pérez‐Cremades Daniel , Bueno‐Betí Carlos , García‐Giménez José Luis , Ibañez‐Cabellos José Santiago , Hermenegildo Carlos , Pallardó Federico V. , Novella Susana
Published: February 2017

Extracellular histones are mediators of inflammation, tissue injury and organ dysfunction. Interactions between circulating histones and vascular endothelial cells are key events in histone‐mediated pathologies. Our aim was to investigate the implication of extracellular histones in the production of the major vasoactive compounds released by human endothelial cells (HUVECs), prostanoids and nitric oxide (NO). HUVEC exposed to increasing concentrations of histones (0.001 to 100 μg/ml) for 4 hrs induced prostacyclin (PGI2) production in a dose‐dependent manner and decreased thromboxane A2 (TXA2) release at 100 μg/ml. Extracellular histones raised cyclooxygenase‐2 (COX‐2) and prostacyclin synthase (PGIS) mRNA and protein expression, decreased COX‐1 mRNA levels and did not change thromboxane A2 synthase (TXAS) expression. Moreover, extracellular histones decreased both, eNOS expression and NO production in HUVEC. The impaired NO production was related to COX‐2 activity and superoxide production since was reversed after celecoxib (10 μmol/l) and tempol (100 μmol/l) treatments, respectively. In conclusion, our findings suggest that extracellular histones stimulate the release of endothelial‐dependent mediators through an up‐regulation in COX‐2‐PGIS‐PGI2 pathway which involves a COX‐2‐dependent superoxide production that decreases the activity of eNOS and the NO production. These effects may contribute to the endothelial cell dysfunction observed in histone‐mediated pathologies.
Association of leptin and leptin receptor gene polymorphisms with systemic lupus erythematosus in a Chinese population
Authors: Li Hong‐Miao , Zhang Tian‐Ping , Leng Rui‐Xue , Li Xiang‐Pei , Wang De‐Guang , Li Xiao‐Mei , Ye Dong‐Qing , Pan Hai‐Feng
Published: February 2017

To explore the association of LEP and leptin receptor (LEPR) gene single‐nucleotide polymorphisms (SNPs) with susceptibility to systemic lupus erythematosus (SLE) in a Chinese population. Four LEP SNPs (rs11761556, rs12706832, rs2071045 and rs2167270) and nine LEPR SNPs (rs10749754, rs1137100, rs1137101, rs13306519, rs8179183, rs1805096, rs3790434, rs3806318 and rs7518632) were genotyped in a cohort of 633 patients with SLE and 559 healthy controls. Genotyping of SNPs was performed with improved multiple ligase detection reaction (iMLDR). No significant differences were detected for the distribution of allele and genotype frequencies of all 13 SNPs between patients with SLE and controls. The genotype effects of recessive, dominant and additive models were also analysed, but no significant evidence for association was detected. However, further analysis in patients with SLE showed that the TT genotype and T allele frequencies of the LEP rs2071045 polymorphism were nominally significantly higher in patients with pericarditis (P = 0.012, P = 0.011, respectively). In LEPR, the GA/AA genotype and A allele frequencies of the rs1137100 polymorphism were both nominally associated with photosensitivity in patients with SLE (P = 0.043, P = 0.018, respectively). Moreover, the genotype and allele distribution of rs3806318 were also nominally associated with photosensitivity in patients with SLE (P = 0.013, P = 0.008, respectively). No significant differences in serum leptin levels were observed in patients with SLE with different genotypes. In summary, LEP and LEPR SNPs are not associated with genetic susceptibility to SLE, but may contribute to some specific clinical phenotype of this disease; further studies are necessary to elucidate the exact role of LEP and LEPR genes in the pathogenesis of SLE.
Carbenoxolone inhibits TRPV4 channel‐initiated oxidative urothelial injury and ameliorates cyclophosphamide‐induced bladder dysfunction
Authors: Zhang Xiling , Gao Shan , Tanaka Masayoshi , Zhang Zhen , Huang Yanru , Mitsui Takahiko , Kamiyama Manabu , Koizumi Schuichi , Fan Jianglin , Takeda Masayuki , Yao Jian
Published: February 2017

Carbenoxolone (CBX) is a clinically prescribed drug for the treatment of digestive ulcer and inflammation. It is also a widely used pharmacological inhibitor of several channels in basic research. Given that the overactivity of several channels, including those inhibitable by CBX, underlies bladder dysfunction, we tested the potential therapeutic application and mechanism of CBX in the treatment of voiding dysfunction. In a mouse model of cystitis induced by cyclophosphamide (CYP), CBX administration prevented the CYP‐elicited increase in bladder weight, oedema, haemorrhage, and urothelial injury. CBX also greatly improved micturition pattern, as manifested by the apparently decreased micturition frequency and increased micturition volume. Western blot results showed that CBX suppressed CYP‐induced increase in protein carbonyls, COX‐2, and iNOS. Further analysis using cultured urothelial cells revealed that acrolein, the major metabolite of CYP, caused protein oxidation, p38 activation, and urothelial injury. These effects of acrolein were reproduced by TRPV4 agonists and significantly prevented by antioxidant NAC, p38 inhibitor SB203580, TRPV4 antagonist RN‐1734, and CBX. Further studies showed that CBX potently suppressed TRPV4 agonist‐initiated calcium influx and subsequent cell injury. CBX attenuated CYP‐induced cystitis in vivo and reduced acrolein‐induced cell injury in vitro, through mechanisms involving inhibition of TRPV4 channels and attenuation of the channel‐mediated oxidative stress. CBX might be a promising agent for the treatment of bladder dysfunction.
Obesity and metabolic dysfunction severely influence prostate cell function: role of insulin and IGF1
Authors: L‐López Fernando , Sarmento‐Cabral André , Herrero‐Aguayo Vicente , Gahete Manuel D. , Castaño Justo P. , Luque Raúl M.
Published: February 2017

Obesity is a major health problem that courses with severe comorbidities and a drastic impairment of homeostasis and function of several organs, including the prostate gland (PG). The endocrine–metabolic regulatory axis comprising growth hormone (GH), insulin and IGF1, which is drastically altered under extreme metabolic conditions such as obesity, also plays relevant roles in the development, modulation and homeostasis of the PG. However, its implication in the pathophysiological interplay between obesity and prostate function is still to be elucidated. To explore this association, we used a high fat–diet obese mouse model, as well as in vitro primary cultures of normal‐mouse PG cells and human prostate cancer cell lines. This approach revealed that most of the components of the GH/insulin/IGF1 regulatory axis are present in PGs, where their expression pattern is altered under obesity conditions and after an acute insulin treatment (e.g. Igfbp3), which might have some pathophysiological implications. Moreover, our results demonstrate, for the first time, that the PG becomes severely insulin resistant under diet‐induced obesity in mice. Finally, use of in vitro approaches served to confirm and expand the conception that insulin and IGF1 play a direct, relevant role in the control of normal and pathological PG cell function. Altogether, these results uncover a fine, germane crosstalk between the endocrine–metabolic status and the development and homeostasis of the PG, wherein key components of the GH, insulin and IGF1 axes could play a relevant pathophysiological role.
Up‐regulation of glycolysis promotes the stemness and EMT phenotypes in gemcitabine‐resistant pancreatic cancer cells
Authors: Zhao Hengqiang , Duan Qingke , Zhang Zhengle , Li Hehe , Wu Heshui , Shen Qiang , Wang Chunyou , Yin Tao
Published: February 2017

Cancer stem cells (CSCs) and epithelial–mesenchymal transition (EMT)‐type cells are considered as underlying causes of chemoresistance, tumour recurrence and metastasis in pancreatic cancer. We aimed to describe the mechanisms – particularly glycolysis – involved in the regulation of the CSC and EMT phenotypes. We used a gemcitabine‐resistant (GR) Patu8988 cell line, which exhibited clear CSC and EMT phenotypes and showed reliance on glycolysis. Inhibition of glycolysis using 2‐deoxy‐D‐glucose (2‐DG) significantly enhanced the cytotoxicity of gemcitabine and inhibited the CSC and EMT phenotypes in GR cells both in vitro and in vivo. Intriguingly, the use of the reactive oxygen species (ROS) scavenger N‐acetylcysteine (NAC) restored the CSC and EMT phenotypes. H2O2 produced changes similar to those of 2‐DG, indicating that ROS were involved in the acquired cancer stemness and EMT phenotypes of GR cells. Moreover, doublecortin‐like kinase 1 (DCLK1), a pancreatic CSC marker, was highly expressed and regulated the stemness and EMT phenotypes in GR cell. Both 2‐DG and H2O2 treatment suppressed DCLK1 expression, which was also rescued by NAC. Together, these findings revealed that glycolysis promotes the expression of DCLK1 and maintains the CSC and EMT phenotypes via maintenance of low ROS levels in chemoresistant GR cells. The glycolysis‐ROS‐DCLK1 pathway may be potential targets for reversing the malignant behaviour of pancreatic cancer.
Reduced hair cortisol after maltreatment mediates externalizing symptoms in middle childhood and adolescence
Authors: White Lars O. , Ising Marcus , von Klitzing Kai , Sierau Susan , Michel Andrea , Klein Annette M. , Andreas Anna , Keil Jan , Quintero Leonhard , Müller‐Myhsok Bertram , Uhr Manfred , Gausche Ruth , Manly Jody T. , Crowley Michael J. , Kirschbaum Clemens , Stalder Tobias
Published: February 2017

Background

The enduring impact of childhood maltreatment on biological systems and ensuing psychopathology remains incompletely understood. Long‐term effects of stress may be reflected in cumulative cortisol secretion over several months, which is now quantifiable via hair cortisol concentrations (HCC). We conducted a first comprehensive investigation utilizing the potential of hair cortisol analysis in a large sample of maltreated and nonmaltreated children and adolescents.

Method

Participants included 537 children and adolescents (3–16 years; 272 females) with maltreatment (n = 245) or without maltreatment histories (n = 292). Maltreated subjects were recruited from child protection services (CPS; n = 95), youth psychiatric services (n = 56), and the community (n = 94). Maltreatment was coded using the Maltreatment Classification System drawing on caregiver interviews and complemented with CPS records. Caregivers and teachers reported on child mental health. HCC were assessed in the first 3 cm hair segment.

Results

Analyses uniformly supported that maltreatment coincides with a gradual and dose‐dependent reduction in HCC from 9 to 10 years onwards relative to nonmaltreated controls. This pattern emerged consistently from both group comparisons between maltreated and nonmaltreated subjects (27.6% HCC reduction in maltreated 9–16‐year‐olds) and dimensional analyses within maltreated subjects, with lower HCC related to greater maltreatment chronicity and number of subtypes. Moreover, both group comparisons and dimensional analyses within maltreated youth revealed that relative HCC reduction mediates the effect of maltreatment on externalizing symptoms.

Conclusions

From middle childhood onwards, maltreatment coincides with a relative reduction in cortisol secretion, which, in turn, may predispose to externalizing symptoms.
‘Mixed blessings’: parental religiousness, parenting, and child adjustment in global perspective
Authors: Bornstein Marc H. , Putnick Diane L. , Lansford Jennifer E. , Al‐Hassan Suha M. , Bacchini Dario , Bombi Anna Silvia , Chang Lei , Deater‐Deckard Kirby , Di Giunta Laura , Dodge Kenneth A. , Malone Patrick S. , Oburu Paul , Pastorelli Concetta , Skinner Ann T. , Sorbring Emma , Steinberg Laurence , Tapanya Sombat , Tirado Liliana Maria Uribe , Zelli Arnaldo , Alampay Liane Peña
Published: February 2017

Background

Most studies of the effects of parental religiousness on parenting and child development focus on a particular religion or cultural group, which limits generalizations that can be made about the effects of parental religiousness on family life.

Methods

We assessed the associations among parental religiousness, parenting, and children's adjustment in a 3‐year longitudinal investigation of 1,198 families from nine countries. We included four religions (Catholicism, Protestantism, Buddhism, and Islam) plus unaffiliated parents, two positive (efficacy and warmth) and two negative (control and rejection) parenting practices, and two positive (social competence and school performance) and two negative (internalizing and externalizing) child outcomes. Parents and children were informants.

Results

Greater parent religiousness had both positive and negative associations with parenting and child adjustment. Greater parent religiousness when children were age 8 was associated with higher parental efficacy at age 9 and, in turn, children's better social competence and school performance and fewer child internalizing and externalizing problems at age 10. However, greater parent religiousness at age 8 was also associated with more parental control at age 9, which in turn was associated with more child internalizing and externalizing problems at age 10. Parental warmth and rejection had inconsistent relations with parental religiousness and child outcomes depending on the informant. With a few exceptions, similar patterns of results held for all four religions and the unaffiliated, nine sites, mothers and fathers, girls and boys, and controlling for demographic covariates.

Conclusions

Parents and children agree that parental religiousness is associated with more controlling parenting and, in turn, increased child problem behaviors. However, children see religiousness as related to parental rejection, whereas parents see religiousness as related to parental efficacy and warmth, which have different associations with child functioning. Studying both parent and child views of religiousness and parenting are important to understand the effects of parental religiousness on parents and children.
Nutritional, microbiological and psychosocial implications of the low FODMAP diet
Authors: Staudacher Heidi Maria
Published: February 2017

Dietary restriction of certain fermentable carbohydrates (low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet) is effective for managing symptoms of irritable bowel syndrome (IBS). However, there are potential consequences of this diet that relate to its impact on nutritional, microbiological, and health‐related quality of life outcomes. Evidence suggests that the low FODMAP diet leads to some alterations in nutrient intake. For example, carbohydrate intake is reduced, and there is a decrease in the proportion of patients meeting the recommended intake for calcium. Intake of other macro and micro‐nutrients appears to be adequate in the short term. As well as the impact on nutrient intake, extensive dietary modification can have a pronounced impact on the gastrointestinal microbiota. Indeed, recent data suggests the diet markedly reduces luminal Bifidobacteria concentration, and there is limited evidence that it reduces total bacteria abundance and concentration of other bacterial groups, for example, Faecalibacterium prausnitzii. Finally, despite the evidence for its clinical effectiveness in patients with IBS, the restrictive nature of the diet could pose a significant burden on patients, thereby limiting improvements, or indeed worsening health‐related quality of life. In conclusion, while robust evidence supports the clinical effectiveness of the low FODMAP diet, it is important, considering the likelihood of its continued widespread use in IBS and other functional bowel disorders, that we extend our understanding of the impact of the diet on endpoints that may have potential consequences for long term health.
FODMAPs: food composition, defining cutoff values and international application
Authors: Varney Jane , Barrett Jacqueline , Scarlata Kate , Catsos Patsy , Gibson Peter R , Muir Jane G
Published: February 2017

The low‐FODMAP diet is a new dietary therapy for the management of irritable bowel syndrome that is gaining in popularity around the world. Developing the low‐FODMAP diet required not only extensive food composition data but also the establishment of “cutoff values” to classify foods as low‐FODMAP. These cutoff values relate to each particular FODMAP present in a food, including oligosaccharides (fructans and galacto‐oligosaccharides), sugar polyols (mannitol and sorbitol), lactose, and fructose in excess of glucose. Cutoff values were derived by considering the FODMAP levels in typical serving sizes of foods that commonly trigger symptoms in individuals with irritable bowel syndrome, as well as foods that were generally well tolerated. The reliability of these FODMAP cutoff values has been tested in a number of dietary studies. The development of the techniques to quantify the FODMAP content of foods has greatly advanced our understanding of food composition. FODMAP composition is affected by food processing techniques and ingredient selection. In the USA, the use of high‐fructose corn syrups may contribute to the higher FODMAP levels detected (via excess fructose) in some processed foods. Because food processing techniques and ingredients can vary between countries, more comprehensive food composition data are needed for this diet to be more easily implemented internationally.
Prebiotic inulin‐type fructans and galacto‐oligosaccharides: definition, specificity, function, and application in gastrointestinal disorders
Authors: Wilson Bridgette , Whelan Kevin
Published: February 2017

Prebiotics are non‐digestible selectively fermented dietary fibers that specifically promote the growth of one or more bacterial genera in the gastrointestinal tract and thus provide health benefit to the host. The two most investigated prebiotics being the inulin‐type fructans and galacto‐oligosaccharides. Prebiotic specificity is mediated through species‐specific gene clusters within saccharolytic bacteria controlled by signaling sensors for various substrates. Prebiotic health benefits are attributed to immune regulation and bacterial metabolite production. In humans, prebiotic supplementation leads to increased growth of specific gut microbiota (e.g., bifidobacteria), immune modulation, and depending on the bacterial augmentation, short‐chain fatty acid production. Irritable bowel syndrome and Crohn's disease are gastrointestinal disorders associated with reductions in some gut bacteria and greater mucosal inflammation. Prebiotic supplementation studies have shown some promise at low doses for modulation of the gut bacteria and reduction of symptoms in IBS; however, larger doses may have neutral or negative impact on symptoms. Studies in Crohn's disease have not shown benefit to bacterial modulation or inflammatory response with prebiotic supplementation. Dietary restriction of fermentable carbohydrates (low FODMAP diet), which restricts some naturally occurring prebiotics from the diet, has shown efficacy in improving symptoms in irritable bowel syndrome, but it lowers the numbers of some key gut microbiota. Further research is required on the effect of prebiotics in gastrointestinal disorders and, in particular, on their use in conjunction with the low FODMAP diet.
Non‐coeliac gluten sensitivity
Authors: Gibson Peter R , Skodje Gry I , Lundin Knut E A
Published: February 2017

Irritable bowel syndrome‐like symptoms in response to wheat ingestion is common and well described, but whether the reaction is due to gluten (i.e., non‐coeliac gluten sensitivity), other wheat proteins, or FODMAPs (mostly fructans) alone or in combinations has not been clearly defined. Exclusion of coeliac disease in the presence of negative serology, and normal villous architecture but increased density of intraepithelial lymphocytes on duodenal biopsies, is difficult. Furthermore, the confidence by which a positive diagnosis is made or non‐coeliac gluten sensitivity is excluded by blinded placebo‐controlled rechallenge with wheat protein is reduced by strong nocebo responses generally found in patients with self‐reported non‐coeliac gluten sensitivity. The absence of a clear biological mechanism of action and difficulties with the design and interpretation of research studies have plunged this entity into even deeper controversy. In the absence of clarity in its diagnosis, the epidemiology, prognosis, and therapeutic approaches to a patient who may be gluten sensitive remain to be determined. Adequate understanding of the issues surrounding the controversy and further research will slowly unravel the truth behind the problem.
Gluten‐induced cognitive impairment (“brain fog”) in coeliac disease
Authors: Yelland Gregory W
Published: February 2017

Much is known about the serious neurological effects of gluten ingestion in coeliac disease patients, such as sporadic ataxia and peripheral neuropathy, although the causal links to gluten are still under debate. However, such disorders are observed in only a small percentage of coeliac patients. Much less is known about the transient cognitive impairments to memory, attention, executive function, and the speed of cognitive processing reported by the majority of patients with coeliac disease. These mild degradations of cognitive functions, referred to as “brain fog,” are yet to be formally recognized as a medical or psychological condition. However, subtle tests of cognitive function are measurable in untreated patients with coeliac disease and improve over the first 12 months' therapy with a gluten‐free diet. Such deficits also occur in patients with Crohn's disease, particularly in association with systemic inflammatory activity. Thus, cognitive impairments associated with brain fog are psychologically and neurologically real and improve with adherence to a gluten‐free diet. There is not yet sufficient evidence to provide a definitive account of the mechanism by which gluten ingestion causes the impairments to cognitive function associated with brain fog, but current evidence suggests that it is more likely that the causal factor is not directly related to exposure to gluten.