bluuebunny/crossref_metadata_2025_split huggingface dataset:
A six thousand‐year record of climate and land‐use change from Mediterranean seagrass mats
Authors: López‐Merino Lourdes , Colás‐Ruiz Nieves R. , Adame María F. , Serrano Oscar , Martínez Cortizas Antonio , Mateo Miguel A. 
Published: January 2017

Summary

The Mediterranean seagrass Posidonia oceanica maintains a biodiverse ecosystem and it is a world‐wide important carbon sink. It grows for millennia, accumulating organic‐rich soils (mats) beneath the meadows. This marine habitat is protected by the European Union; however, it is declining rapidly due to coastal development. Understanding its response to disturbances could inform habitat restoration, but many environmental impacts predate monitoring programs (<50 years).

This research explores the palaeoecological potential of Posidonia mats to reconstruct six thousand years of environmental change that could have affected Posidonia meadows and, in turn, left an imprint on the mats.

Palynological, microcharcoal, magnetic susceptibility and glomalin‐related soil protein (GRSP) analyses on Posidonia mats enabled us to detect climate‐ and human‐induced environmental processes impacting on the seagrass during the Late Holocene.

The pollen and microcharcoal records reconstructed anthropogenic disturbances attributed to agriculture. The record of GRSP shows that agrarian activities affected continental soil quality. Changes in magnetic susceptibility reveal that enhanced soil erosion was caused by both climate (major flooding events in the NW Mediterranean) and humans (cultivation) which impacted on the Posidonia mat. Finally, increased human impact is linked to eutrophication of coastal waters since Roman‐Medieval times.

Synthesis. This study shows that climate and land‐use changes in the western Mediterranean resulted in enhanced loadings of terrigenous material to the coastal zone since the Late Holocene, likely disturbing the Posidonia meadows and their mat carbon accumulation dynamics. Under the current global change scenario in which CO2 emissions are projected to increase, restoring carbon sinks is a priority. Seagrass habitat restoration should consider not only the coastal perturbations, but also the continental ones at a catchment scale to preserve the socio‐economic ecosystem services provided by seagrasses.
Comparative proteomic analysis of urine and laser microdissected glomeruli in IgA nephropathy
Authors: Ning Xiaoyuan , Yin Zhong , Li Zuoxiang , Xu Jiayun , Wang Linna , Shen Wanjun , Lu Yang , Cai Guangyan , Zhang Xueguang , Chen Xiangmei 
Published: January 2017

SummaryThe purpose of the present study was to identify the differential proteins that synchronously change in urine and glomeruli and could be used to monitor glomerular lesions of IgA nephropathy (IgAN). The proteomes of urine and glomeruli from four IgAN patients who were graded III/IV according to the grading system of Lee et al. were compared to the urine proteomes of four healthy volunteers and the glomeruli proteomes of adjacent normal tissue from four patients with renal tumors, respectively. Western blot, enzyme‐linked immunosorbent assay and immunofluorescence assay were applied to verify the results of the proteomic analysis. In the proteomic analysis of urine from IgAN patients and healthy volunteers, 714 proteins were identified, with 246 proteins identified as differential proteins. In the proteomic analysis of glomeruli from renal biopsy tissue of IgAN patients and from adjacent normal tissue of patients with renal tumors, 161 proteins were identified altogether, and 20 proteins of these were recognized as differential proteins. After comparatively analyzing the differential proteins identified in the urine and glomeruli, five synchronously changed differential proteins were found: complement C9, Ig kappa chain C region and three cytoskeleton proteins. In summary, our findings indicate that certain immunological indices in urine appear to be associated with glomerular lesions of IgAN.
The intrauterine renin–angiotensin system: Sex‐specific effects on the prevalence of spontaneous preterm birth
Authors: Pringle Kirsty G , Zakar Tamas , Lumbers Eugenie R 
Published: January 2017

SummaryPreterm birth (PTB) is the single largest cause of death in infants and young children. The rate of PTB is significantly higher in male infants, particularly those that are born very preterm. Here we present evidence to suggest that the decidual renin–angiotensin system may play a role in inhibiting inflammation and maintaining the integrity of the fetal membranes during pregnancy, and that sex‐specific alterations in the intrauterine RAS could contribute to the increased risk of PTB in male babies. Women carrying female fetuses have high levels of expression of decidual prorenin at term. Decidua from ‘female’ pregnancies also have greater expression of the anti‐inflammatory angiotensin (Ang)‐(1‐7) pathway, than decidua from ‘male’ pregnancies, and have lower levels of the pro‐inflammatory Ang II pathway. We propose that in ‘female’ pregnancies, the very high levels of decidual prorenin drive the anti‐inflammatory Ang‐(1‐7) pathway, thus reducing the likelihood of PTB. In addition, the high levels of prorenin produced by the decidua in ‘female’ pregnancies are able to diffuse into the amnion and bind to the PRR. We postulate that PRR/prorenin interactions, possibly through both angiotensin dependent and independent pathways, stimulate the production of ECM proteins, inhibit ECM degradation and prevent apoptosis, thus strengthening the amnion. Thus control of the inflammatory signature and the integrity of the fetal membranes prior to parturition may partly depend on the sexually determined activity of the decidual and amniotic renin–angiotensin system pathways.
University foodservices’ potential for providing environmental education to students
Authors: Slobbé Chelsea , Mirosa Miranda , Thomson Carla 
Published: January 2017

AimsUniversity foodservices are potentially well placed to foster environmental education in a non‐classroom setting and so could have the power to benefit communities through producing environmentally literate graduates. Buy‐in from foodservice staff is critical for realising this potential, so understanding what foodservice staff think about their foodservice engaging in the provision of environmental education is essential. The aim of this study was to identify the dominant perspectives held by university foodservice staff about the desirability and realities of fostering environmental education in their workplaces.MethodsThe study design integrated two phases: (i) 36 foodservice staff conducted a card‐sorting activity that revealed four dominant viewpoints; (ii) 60 foodservice staff completed a survey where they identified with one of these viewpoints. The study was conducted in Dunedin, New Zealand.ResultsThe four main perspectives were The ‘Believer’, the ‘Relatively Positive Integrator’, the ‘Uncertain Contender’ and the ‘Sceptic’. All of the perspective groups, except for Sceptic, believed environmental education in their workplace was desirable. In the survey, 25% of the 60 participants self‐identified with the Believer narrative, 40% with the Relatively Positive Integrator, 25% with the Uncertain Contender and 10% with the Sceptic. There were no significant differences between factors for sociodemographic characteristics.ConclusionsA paradigm shift in foodservice framework thinking could unlock the potential university foodservice has to assist universities whose strategic mission is to embed environmental education in both curricular and co‐/extracurricula activities.
A Quality Improvement Initiative to Decrease the Rate of Solitary Blood Cultures in the Emergency Department
Authors: Choi Joseph , Ensafi Sahand , Chartier Lucas Brien , Van Praet Oliver 
Published: January 2017

AbstractObjectivesBest practice guidelines recommend that at least two sets of blood cultures (BCs) be sent when blood cultures are required. However, high rates of solitary BCs are still common in the emergency department (ED). The aim of this study was to evaluate the efficacy of different quality improvement initiatives aimed at reducing the rate of solitary blood cultures being sent to the laboratory on patients ultimately discharged from our ED.MethodsThis was a multicenter, multiphase, prospective study evaluating a comprehensive education‐based intervention and a second intervention that combined a computerized forcing function (FF) along with a brief education‐based intervention. The results were analyzed using segmented regression analysis, as well as statistical process control charts.ResultsThe baseline rate of solitary sets of BCs was 41.1%. The education intervention reduced this rate to 30.3%. The introduction of a FF with a brief educational intervention further reduced the rate to 11.6%. This represents an absolute reduction of 29.5% from baseline (relative reduction of 71.8%). According to segmental regression analyses, the education intervention alone did not produce a statistically significant change when factoring possible background time‐related trends (p = 0.071). However, the FF produced a statistically significant improvement (p < 0.0005), which was maintained for 6 months.ConclusionThe combination of a brief education‐based intervention and a computerized FF was more effective than education alone in reducing solitary BC collection in our ED in this time series study. FFs can be a powerful tool in modifying behaviors and processes in the clinical setting.
Prenatal Alcohol Consumption Between Conception and Recognition of Pregnancy
Authors: McCormack Clare , Hutchinson Delyse , Burns Lucy , Wilson Judy , Elliott Elizabeth , Allsop Steve , Najman Jake , Jacobs Sue , Rossen Larissa , Olsson Craig , Mattick Richard 
Published: January 2017

BackgroundCurrent estimates of the rates of alcohol‐exposed pregnancies may underestimate prenatal alcohol exposure if alcohol consumption in early trimester 1, prior to awareness of pregnancy, is not considered. Extant literature describes predictors of alcohol consumption during pregnancy; however, alcohol consumption prior to awareness of pregnancy is a distinct behavior from consumption after becoming aware of pregnancy and thus may be associated with different predictors. The purpose of this study was therefore to examine prevalence and predictors of alcohol consumption by women prior to awareness of their pregnancy, and trajectories of change to alcohol use following pregnancy recognition.MethodsPregnant women (n = 1,403) were prospectively recruited from general antenatal clinics of 4 public hospitals in Australian metropolitan areas between 2008 and 2013. Women completed detailed interviews about alcohol use before and after recognition of pregnancy.ResultsMost women (n = 850, 60.6%) drank alcohol between conception and pregnancy recognition. Binge and heavy drinking were more prevalent than low‐level drinking. The proportion of women who drank alcohol reduced to 18.3% (n = 257) after recognition of pregnancy. Of women who drank alcohol, 70.5% ceased drinking, 18.3% reduced consumption, and 11.1% made no reduction following awareness of pregnancy. Socioeconomic status (SES) was the strongest predictor of alcohol use, with drinkers more likely to be of high rather than low SES compared with abstainers (OR = 3.30, p < 0.001). Factors associated with different trajectories (either cessation, reduction, or continuation of drinking) included level of alcohol use prior to pregnancy recognition, age, pregnancy planning, and illicit substance use.ConclusionsIn this sample of relatively high SES women, most women ceased or reduced drinking once aware of their pregnancy. However, the rate of alcohol‐exposed pregnancies was higher than previous estimates when the period prior to pregnancy recognition was taken into account.
Affordable orphan drugs: a role for not‐for‐profit organizations
Authors: Davies Elin H. , Fulton Emma , Brook Daniel , Hughes Dyfrig A. 
Published: January 2017

AimsThe success of the Regulation on Orphan Medicinal Products in the European Union is evidenced by the 127 orphan drugs that have had market authorization since 2000. However, the incentives aimed at stimulating research and development have had the unintended consequence of increasing drug cost, resulting in many orphan drugs not being cost‐effective. Orphan drugs command an increasing share of the pharmaceutical market and account for a disproportionate amount of healthcare expenditure. Orphan drug ownership by socially motivated, not‐for‐profit organizations may facilitate access to more affordable orphan drugs, for the benefit of patients and healthcare systems alike. This study aims to describe opportunities for such organizations to become orphan drug Market Authorization Holders.MethodsWe reviewed data on the ownership of EMA designated and approved orphan drugs, identified funding opportunities and business models for not‐for‐profit organizations, and summarised relevant legal and policy documents concerning intellectual property rights and drug regulation.ResultsUsing repurposed drugs as a paradigm, this narrative review navigates the regulatory hurdles, describes the legal context and identifies funding opportunities, in a bid to facilitate and encourage not‐for‐profit organizations to lead on the development of affordable orphan drugs.ConclusionsAlthough the regulatory steps required to obtain an MA for an orphan drug are numerous and challenging, they are not insurmountable and can be achieved by not‐for‐profit organizations that are socially motivated to reduce the costs of orphan drugs to the payers of healthcare. Opportunities for orphan drug development resulting in affordable products lie mainly with repurposed drugs.
β‐Caryophyllene protects against alcoholic steatohepatitis by attenuating inflammation and metabolic dysregulation in mice
Authors: Varga Zoltan V. , Matyas Csaba , Erdelyi Katalin , Cinar Resat , Nieri Daniela , Chicca Andrea , Nemeth Balazs Tamas , Paloczi Janos , Lajtos Tamas , Corey Lukas , Hasko Gyorgy , Gao Bin , Kunos George , Gertsch Jürg , Pacher Pal 
Published: January 2017

Background and Aimsβ‐Caryophyllene (BCP) is a plant‐derived FDA approved food additive with anti‐inflammatory properties. Some of its beneficial effects in vivo are reported to involve activation of cannabinoid CB2 receptors that are predominantly expressed in immune cells. Here, we evaluated the translational potential of BCP using a well‐established model of chronic and binge alcohol‐induced liver injury.MethodsIn this study, we investigated the effects of BCP on liver injury induced by chronic plus binge alcohol feeding in mice in vivo by using biochemical assays, real‐time PCR and histology analyses. Serum and hepatic BCP levels were also determined by GC/MS.ResultsChronic treatment with BCP alleviated the chronic and binge alcohol‐induced liver injury and inflammation by attenuating the pro‐inflammatory phenotypic `M1` switch of Kupffer cells and by decreasing the expression of vascular adhesion molecules intercellular adhesion molecule 1, E‐Selectin and P‐Selectin, as well as the neutrophil infiltration. It also beneficially influenced hepatic metabolic dysregulation (steatosis, protein hyperacetylation and PPAR‐α signalling). These protective effects of BCP against alcohol‐induced liver injury were attenuated in CB2 receptor knockout mice, indicating that the beneficial effects of this natural product in liver injury involve activation of these receptors. Following acute or chronic administration, BCP was detectable both in the serum and liver tissue homogenates but not in the brain.ConclusionsGiven the safety of BCP in humans, this food additive has a high translational potential in treating or preventing hepatic injury associated with oxidative stress, inflammation and steatosis.Linked ArticlesThis article is part of a themed section on Inventing New Therapies Without Reinventing the Wheel: The Power of Drug Repurposing. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.2/issuetoc
Chloride ion transport and overexpression of TMEM16A in a guinea‐pig asthma model
Authors: Kondo M. , Tsuji M. , Hara K. , Arimura K. , Yagi O. , Tagaya E. , Takeyama K. , Tamaoki J. 
Published: January 2017

SummaryBackgroundTMEM16A, a Ca‐activated Cl channel, regulates various physiological functions such as mucin secretion. However, the role of TMEM16A in hyper‐secretion in asthma is not fully understood.ObjectiveThe aim of this study is to evaluate Cl ion transport via TMEM16A and determine the localization of TMEM16A in a guinea‐pig asthma model.MethodsGuinea‐pigs were sensitized with ovalbumin (OVA) i.p. on Days 1 and 8. On Day 22, we assessed OVA challenge‐induced Cl ion transport in the sensitized tracheas ex vivo in an Ussing chamber, compared with the non‐sensitized tracheas. We then examined the effect of T16Ainh‐A01, a TMEM16A inhibitor, on the increase in Cl ion transport. The tracheal epithelium was immunostained with an anti‐TMEM16A antibody. Epithelial cells from guinea‐pig tracheas were cultured at the air–liquid interface in the presence of IL‐13 for in vitro study. We studied the effect of TMEM16A inhibitors on Ca‐dependent agonist, uridine triphosphate (UTP)‐induced increases in Cl ion transport in the cultured cells. The cells were immunostained with an anti‐TMEM16A antibody, an anti‐MUC5AC antibody and an anti‐α‐tubulin antibody.ResultsOVA challenge induced an increase in short circuit current within 1 min in the OVA‐sensitized tracheas but not in the non‐sensitized tracheas, which was inhibited by pretreatment of T16Ainh‐A01. Sensitized tracheas showed goblet cell metaplasia with more positive TMEM16A immunostaining, particularly in the apical portion compared with the non‐sensitized tracheas. The in vitro UTP‐induced increase in Cl ion transport was strongly inhibited by pretreatment with T16Ainh‐A01, benzbromarone, and niflumic acid. TMEM16A was positively immunostained at the apical portion and in the MUC5AC‐positive area in IL‐13‐induced goblet cell metaplasia.ConclusionsAntigen challenge and Ca‐dependent agonist treatment increased Cl ion transport via the overexpression of TMEM16A in goblet cell metaplasia in a guinea‐pig asthma model. TMEM16A inhibitors may be useful for the treatment of hyper‐secretion in asthma.
Assessment of biological, psychological and adherence factors in the prediction of step‐down treatment for patients with well‐controlled asthma
Authors: Saito N. , Kamata A. , Itoga M. , Tamaki M. , Kayaba H. , Ritz T. 
Published: January 2017

SummaryBackground and ObjectiveInhaled corticosteroids (ICS) and inhaled corticosteroids combined with long‐acting beta2‐agonist (ICS/LABA) are standard treatments for asthma. However, factors that might help reduce medication in well‐controlled asthma are unknown. We classified problems of asthma patients into biological, psychological and adherence factors, and investigated factors associated with the indication and failure of a medication step‐down treatment.MethodsTwo hundred twenty two well‐controlled asthma patients receiving ICS or ICS/LABA were assessed for physical and psychiatric problems and followed up for one year from adjustment of their treatment step. Factor B was defined as a presence of chronic upper airway complications. Factor P was defined as presence of psychiatric complications such as sleep disorder, depression, anxiety and somatoform disorders. Factor A was defined as poor adherence to ICS or ICS/LABA inhaler of 75% or less. Success in step‐down treatment was defined as maintenance of well‐controlled status for over one year after step‐down.ResultsFactor B was the most important single negative predictive factor for indication for step‐down treatment (Odds ratio; 0.19). Factor A increased the risk of failure to maintain step‐down treatment most significantly by 23‐fold, and factor B increased it by 11‐fold. The combination of factors B and A increased failure by 24‐fold, factors P and A by 21‐fold, all three factors by 36‐fold. Factor P only interacted with the other factors to reduce chances of stepping down, but did not constitute a problem factor when present alone.Conclusion and Clinical RelevanceThe evaluation of biological, psychological and adherence problems may lead to a more proactive and targeted approach to step‐down treatment for patients with well‐controlled asthma.
Maternal psychiatric symptoms during pregnancy and risk of childhood atopic diseases
Authors: Elbert N. J. , Duijts L. , den Dekker H. T. , de Jong N. W. , Nijsten T. E. C. , Jaddoe V. W. V. , de Jongste J. C. , van Wijk R. Gerth , Tiemeier H. , Pasmans S. G. M. A. 
Published: January 2017

SummaryBackgroundMaternal psychiatric symptoms during pregnancy might affect the developing immune system and subsequent risk of childhood atopic diseases.ObjectiveOur aim was to examine the associations of maternal psychiatric symptoms during pregnancy with allergic sensitization, allergy and eczema in children until age 10 years.MethodsThis study among 5205 children was performed in a population‐based prospective cohort from foetal life onwards. We assessed maternal and paternal psychiatric symptoms (overall, depressive, anxiety) during pregnancy and at 36 months after delivery, and maternal psychiatric symptoms at 2 and 6 months after delivery using the Brief Symptom Inventory. Inhalant and food allergic sensitization were measured by skin prick tests, and physician‐diagnosed inhalant and food allergy or eczema by questionnaires from birth until age 10 years. We used multivariate logistic regression, multinomial logistic regression or generalized estimating equation models where appropriate.ResultsWe observed no association of maternal psychiatric symptoms during pregnancy with allergic sensitization. Maternal overall psychiatric, depressive and anxiety symptoms during pregnancy were associated with an increased risk of inhalant allergy only (adjusted odds ratio (95% confidence interval) 1.96 (1.44, 2.65), 1.58 (1.25, 1.98) and 1.61 (1.27, 2.03), respectively, per 1‐unit increase). Maternal overall psychiatric and anxiety symptoms during pregnancy were associated with an increased risk of eczema (1.21 (1.05, 1.39) and 1.15 (1.02, 1.29), respectively, per 1‐unit increase). Effect estimates did not materially change when maternal psychiatric symptoms after delivery, or paternal psychiatric symptoms during pregnancy and after delivery were taken into account.Conclusions and Clinical RelevanceMaternal psychiatric symptoms during pregnancy were associated with increased risks of childhood inhalant allergy and eczema, independent of maternal psychiatric symptoms after delivery and of paternal psychiatric symptoms.
The influence of macrophages on mesenchymal stromal cell therapy: passive or aggressive agents?
Authors: Carty F , Mahon B P , English K 
Published: January 2017

SummaryMesenchymal stromal cells (MSC) have emerged as promising cell therapies for multiple conditions based on demonstrations of their potent immunomodulatory and regenerative capacities in models of inflammatory disease. Understanding the effects of MSC on T cells has dominated the majority of work carried out in this field to date; recently, however, a number of studies have shown that the therapeutic effect of MSC requires the presence of macrophages. It is timely to review the mechanisms and manner by which MSC modulate macrophage populations in order to design more effective MSC therapies and clinical studies. A complex cross-talk exists through which MSC and macrophages communicate, a communication that is not controlled exclusively by MSC. Here, we examine the evidence that suggests that MSC not only respond to inflammatory macrophages and adjust their secretome accordingly, but also that macrophages respond to encounters with MSC, creating a feedback loop which contributes to the immune regulation observed following MSC therapy. Future studies examining the effects of MSC on macrophages should consider the antagonistic role that macrophages play in this exchange.