bluuebunny/crossref_metadata_2025 huggingface dataset:
Tyrosine Kinase Inhibitor, Vatalanib, Inhibits Proliferation and Migration of Human Pterygial Fibroblasts
Authors: Kim Hong Kyu , Choi Ji-Young , Park Sang Min , Rho Chang Rae , Cho Kyong Jin , Jo Sangmee Ahn
Published: June 2017

Purpose:

Vatalanib is a small-molecule tyrosine kinase inhibitor. We investigated the effects of vatalanib on the proliferation and migration of cultured human pterygial fibroblasts (HPFs).

Methods:

Pterygium tissues were obtained after pterygium excision surgery and subjected to primary culture. HPFs were treated with vatalanib at various concentrations. Mitomycin C (MMC) was used as a positive control. Cell proliferation and migration assays were used to investigate the effects of vatalanib. Cell death was measured using flow cytometry analysis. Western blot analysis was performed to identify signaling molecules associated with the response to vatalanib.

Results:

Vatalanib inhibited both proliferation and migration of HPFs in a dose-dependent manner. Cell proliferation was significantly suppressed by vatalanib (10 and 100 μM) and MMC (0.004% and 0.04%) treatments. Migration assays revealed significant HPF delay when treated with vatalanib (1, 10, and 100 μM) and MMC (0.004% and 0.04%) compared with that in a negative control. Cell death analysis showed that high concentrations of vatalanib (100 μM) and MMC (0.004% and 0.04%) decreased cell numbers. Western blot analysis of vatalanib-treated cells showed vascular endothelial growth factor and transforming growth factor-β significantly reduced, but there was no alteration in p53 protein levels in HPFs.

Conclusions:

These results indicate that vatalanib significantly suppressed the proliferation and migration of HPFs by decreasing vascular endothelial growth factor and transforming growth factor-β. Vatalanib showed less toxicity than that of MMC. Based on these results, vatalanib may potentially serve as a new adjuvant treatment after pterygium excision surgery.
A Multicenter Evaluation of Adherence to 4 Major Elements of the Baveno Guidelines and Outcomes for Patients With Acute Variceal Hemorrhage
Authors: Tapper Elliot B. , Friderici Jennifer , Borman Zachary A. , Alexander Jacob , Bonder Alan , Nuruzzaman Nabiha , Ramdass Sheryl , Ghaoui Rony
Published: June 2017

Goals:

To determine the rate of and outcomes associated with guideline adherence in the care of acute variceal hemorrhage (AVH).

Background:

Four major elements of high-quality care for AVH defined by the Baveno consensus (VI) include timely endoscopy (≤12 h), antibiotics, and somatostatin analogs before endoscopy and band ligation as primary therapy for esophageal varices.

Study:

We retrospectively evaluated 239 consecutive admissions of 211 patients with AVH admitted to 2 centers in Massachusetts from 2010 to 2015. The primary outcome was 6-week mortality; secondary outcomes included treatment failure (shock, hemoglobin drop by 3 g/dL, hematemesis, death ≤5 d), length of stay, and 30-day readmission.

Results:

Guideline adherence was variable: endoscopy ≤12 hours (79.9%), antibiotics (84.9%), band ligation (78.7%), and somatostatin analogs (90.8%). However, only 150 (62.8%) received care that was adherent to all indicated criteria. The 6-week mortality rate was 22.6%. Treatment failure occurred in 50 (21.0%) admissions. Among the 198 patients who survived to discharge, 41 (20.7%) were readmitted within 30 days. Octreotide before endoscopy was associated with a reduction in 30-day readmission (18.4% vs. 42.1%; P=0.03), whereas banding of esophageal varices was associated with a reduced risk of treatment failure (15.0% vs. 50.0%; P≤0.001). However, adherence to quality metrics did not significantly reduce the risk of death within 6 weeks.

Conclusions:

Adherence to quality metrics may not reduce the risk of mortality but could improve secondary outcomes of AVH. Variation in practice should be addressed through quality improvement interventions.
A Stress Coping App for Hospitalized Pregnant Women at Risk for Preterm Birth
Authors: Jallo Nancy , Thacker Leroy R. , Menzies Victoria , Stojanovic Predrag , Svikis Dace S.
Published: June 2017

Background:

Pregnant women hospitalized with preterm labor (PTL) complications experience increased stress. Prior researchers have attempted to provide stress management strategies with use of various media players to deliver stress coping interventions.

Purpose:

The purpose of this study was to examine the efficacy of a mobile device delivered stress coping app designed to reduce stress in a sample of high-risk pregnant women hospitalized with complications of PTL.

Methods:

A descriptive study using a prospective mixed methods one-group pre/posttest design. Fifteen pregnant women used the mobile device app for 8 consecutive days. The app included study measures, educational overview of concepts, four guided imagery audio files to be listened to daily, and a stress self-assessment scale to be used before and after each use. Measures included: Perceived Stress Scale (PSS), Visual Analog Stress Scale (VASS), Coping Self-Efficacy Scale (CSES), and semistructured interviews.

Results:

There was a significant drop in VASS scores when comparing scores before and after listening to the app (p < 0.0001). There were no significant differences between the baseline and Day 8 scores of PSS or CSES. All participants reported benefits from using the app and provided suggestions for improvement.

Clinical Implications:

The intervention reduced immediate stress and provided a respite from the stress response in this population. Maternal child nurses may consider incorporating stress coping interventions as standard care practice.
Periodic Paralysis and Encephalopathy as Initial Manifestations of Graves’ Disease
Authors: Tsironis Theocharis , Tychalas Athanasios , Kiourtidis Dimitrios , Kountouras Jannis , Xiromerisiou Georgia , Rudolf Jobst , Deretzi Georgia
Published: June 2017

Background:

Thyrotoxic periodic paralysis (TPP) is an uncommon complication of Graves’ disease, characterized by the triad of acute hypokalemia without total body potassium deficit, episodic muscle paralysis, and thyrotoxicosis. Graves’ encephalopathy is an extremely rare form of encephalopathy associated with autoimmune thyroid disease (EAATD), characterized by neuropsychiatric symptoms, increased antithyroid antibodies and cerebrospinal fluid protein concentration, nonspecific electroencephalogram abnormalities, and cortico-responsiveness. Coexistence of both these complications in the same patient has not been reported before.

Case Report:

We herein present a 48-year-old white male patient with TPP and encephalopathy as initial presentations of Graves’ disease. Flaccid tetraparesis was reversed a few hours after potassium level correction and the patient did not suffer any relapse with the successful pharmaceutical management of the thyroid function. One month later, the patient presented with dizziness and behavioral symptoms, such as inappropriate laughter and anger. Brain magnetic resonance imaging revealed meningeal enhancement and cerebrospinal fluid analysis showed a mild protein increase, with a blood-brain barrier disruption. With the suspicion of EAATD, the patient was treated with high doses of corticosteroids and improved dramatically.

Conclusions:

To our knowledge this is the first reported coexistence of potentially treatable TPP and EAATD as initial neurological manifestations of Graves’ disease, thereby underscoring the necessity of suspicion of possible underlying Graves’ disease in patients with acute paralysis and encephalopathy of unclear origin.
Cholesterol Levels and Hemorrhagic Stroke Risk in East Asian Versus Non-East Asian Populations
Authors: Xie Liang , Wu Wei , Chen Jin , Tu Jianglong , Zhou Jun , Qi Xueliang , Yin Xiaoping
Published: June 2017

Background:

The aim of this work was to evaluate the relationships between cholesterol levels and risk of hemorrhagic stroke [including intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH)] in East Asian versus non-East Asian populations.

Materials and Methods:

Relevant prospective studies were identified from systematic searches of PubMed and EMBASE. A random-effects model was used to calculate summary relative risks (RRs) and 95% confidence intervals (CIs) that were used to compare the relationships between cholesterol levels and risk of hemorrhagic stroke in East Asian versus non-East Asian populations.

Results:

In terms of overall hemorrhagic stroke risk, both East Asians and non-East Asians displayed no significant difference between high versus low total cholesterol (TC) (RR=1.26, 95% CI, 0.92-1.72; I
2=74.4%, P<0.001; RR=1.69, 95% CI, 1.15-2.49; I
2=92.4%, P<0.001, respectively). In terms of ICH risk, East Asians displayed no significant difference between high versus low TC (RR=1.30, 95% CI, 0.89-1.90; I
2=78.6%, P<0.001), whereas non-East Asians displayed a significant difference between high versus low TC with low TC showing a higher ICH risk (RR=1.70, 95% CI, 1.08-2.67; I
2=91.2%, P<0.001). With respect to SAH risk, East Asians displayed a significant difference between high versus low TC with low TC showing a higher SAH risk (RR=1.48, 95% CI, 1.057-2.08; I
2=0%, P=0.682), whereas non-East Asians displayed no significant difference between high versus low TC (RR=1.14, 95% CI, 0.56-2.31; I
2=89.9%, P<0.001).

Conclusions:

Under low cholesterol conditions, East Asian ethnic status favors SAH development, whereas non-East Asian ethnic status favors ICH development.
Calcitonin Gene-Related Peptide-Targeted Therapies for Migraine and Cluster Headache: A Review
Authors: Schuster Nathaniel M. , Rapoport Alan M.
Published: June 2017

Calcitonin gene-related peptide (CGRP) is a signaling neuropeptide released from activated trigeminal sensory afferents in headache and facial pain disorders. There are a handful of CGRP-targeted therapies currently in phase 3 studies for migraine acute treatment or prevention. Currently, 4 monoclonal antibodies targeting either the CGRP ligand or receptor are being studied for migraine prevention: ALD403 (eptinezumab), AMG 334 (erenumab), LY2951742 (galcanezumab), and TEV-48125 (fremanezumab). Meanwhile, 1 small-molecule CGRP receptor antagonist (ubrogepant, MK-1602) is currently in phase 3 studies for the acute treatment of migraine. Two of these anti-CGRP monoclonal antibodies are in clinical trials for cluster headache prevention as well. Several other small-molecular CGRP receptor antagonists are in earlier stages of development for acute migraine treatment or prevention. In this review, we will discuss the growing body of clinical trials studying CGRP-targeted therapies for migraine and cluster headache.
A chromosome 4 trisomy contributes to increased fluconazole resistance in a clinical isolate of Candida albicans
Authors: Anderson Matthew Z. , Saha Amrita , Haseeb Abid , Bennett Richard J.
Published: June 2017

Candida albicans is an important opportunistic fungal pathogen capable of causing both mucosal and disseminated disease. Infections are often treated with fluconazole, a front-line antifungal drug that targets the biosynthesis of ergosterol, a major component of the fungal cell membrane. Resistance to fluconazole can arise through a variety of mechanisms, including gain-of-function mutations, loss of heterozygosity events and aneuploidy. The clinical isolate P60002 was found to be highly resistant to azole-class drugs, yet lacked mutations or chromosomal rearrangements known to be associated with azole resistance. Transcription profiling suggested that increased expression of two putative drug efflux pumps, CDR11 and QDR1, might confer azole resistance. However, ectopic expression of the P60002 alleles of these genes in a drug-susceptible strain did not increase fluconazole resistance. We next examined whether the presence of three copies of chromosome 4 (Chr4) or chromosome 6 (Chr6) contributed to azole resistance in P60002. We established that Chr4 trisomy contributes significantly to fluconazole resistance, whereas Chr6 trisomy has no discernible effect on resistance. In contrast, a Chr4 trisomy did not increase fluconazole resistance when present in the standard SC5314 strain background. These results establish a link between Chr4 trisomy and elevated fluconazole resistance, and demonstrate the impact of genetic background on drug resistance phenotypes in C. albicans.
The Centrosome Controls the Number and Spatial Distribution of Microtubules by Negatively Regulating Alternative MTOCs
Authors: Gavilan Maria P. , Gandolfo Pablo , Balestra Fernando R. , Arias Francisco , Bornens Michel , Rios Rosa M.
Published: June 2017

In this work, we have investigated in mammalian cells how microtubule nucleation at centrosome and Golgi apparatus are coordinated, using genetic ablation of three γ-TuRC binding proteins -AKAP450, Pericentrin and CDK5Rap2- and the PLK4 inhibitor centrinone. We show that centrosomal microtubule nucleation is independent of Golgi activity whereas the converse is not true: nucleation on the Golgi negatively correlates with the number of centrosomes. In addition, depleting AKAP450 in cells lacking centrioles, that abolishes Golgi nucleation activity, leads to microtubule nucleation from numerous cytoplasmic Golgi-unbound acentriolar structures containing Pericentrin, CDK5Rap2 and y-tubulin. Strikingly, centrosome-less cells display twice higher microtubule density than normal cells, suggesting that the centrosome controls the spatial distribution of microtubules, not only by nucleating them, but also by acting as a negative regulator of alternative MTOCs. Collectively, the data reveals a hierarchical control of microtubule nucleation, with the centrosome regulating this process in a more complex manner than usually thought. It also unveils mechanisms that could help understanding MT network reorganization during cell differentiation.
A method to minimize condenser lens-induced hysteresis effects in a JEOL JEM-3200FSC microscope to enable stable cryoEM low-dose operations
Authors: Jason de la Cruz M. , Martynowycz Michael , Hattne Johan , Shi Dan , Gonen Tamir
Published: June 2017

Low dose imaging procedures are key for a successful cryoEM experiment (whether by electron cryotomography, single particle analysis, electron crystallography, or MicroED). We present a method to minimize magnetic hysteresis of the condenser lens system in the JEOL JEM-3200FSC transmission electron microscope (TEM) in order to maintain a stable optical axis for the beam path of low-dose imaging. The simple procedure involves independent voltage ramping of the CL1 and CL2 lenses immediately before switching to the focusing and exposure beam settings for data collection.

Highlights

Enables consistent horizontal beam position during low-dose mode switching

Facilitates EM automated data collection for the JEOL JEM-3200FSC

Improves beam stability in both TEM imaging and diffraction modes
Molecular chaperones maximize the native state yield per unit time by driving substrates out of equilibrium
Authors: Chakrabarti Shaon , Hyeon Changbong , Ye Xiang , Lorimer George H. , Thirumalai D.
Published: June 2017

Molecular chaperones have evolved to facilitate folding of proteins and RNAin vivowhere spontaneous self-assembly is sometimes prohibited. Folding ofTetrahymenaribozyme, assisted by the RNA chaperone CYT-19, surprisingly shows that at physiological Mg2+ion concentrations, increasing the chaperone concentration reduces the yield of native ribozymes. In contrast, the more extensively investigated protein chaperone GroEL works in exactly the opposite manner—the yield of native substrate increases with the increase in chaperone concentration. Thus, the puzzling observation on the assisted-ribozyme folding seems to contradict the expectation that a molecular chaperone acts as an efficient annealing machine. We suggest a resolution to this apparently paradoxical behavior by developing a minimal stochastic model that captures the essence of the Iterative Annealing Mechanism (IAM), providing a unified description of chaperone mediated-folding of proteins and RNA. Our theory provides a general relation involving the kinetic rates of the system, which quantitatively predicts how the yield of native state depends on chaperone concentration. By carefully analyzing a host of experimental data onTetrahymena(and its mutants) as well as the protein Rubisco and Malate Dehydrogenase, we show that although the absolute yield of native states decreases in the ribozyme, the rate of native state production increases in both the cases. By utilizing energy from ATP hydrolysis, both CYT-19 and GroEL drive their substrate concentrations far out of equilibrium, in an endeavor to maximize the native yield in a short time. Our findings are consistent with the general expectation that proteins or RNA need to be folded by the cellular machinery on biologically relevant timescales, even if the final yield is lower than what equilibrium thermodynamics would dictate. Besides establishing the IAM as the basis for functions of RNA and protein chaperones, our work shows that cellular copy numbers have been adjusted to optimize the rate of native state production of the folded states of RNA and proteins under physiological conditions.

Significance statement

Molecular chaperones have evolved to assist the folding of proteins and RNA, thus avoiding the deleterious consequences of misfolding. Thus, it is expected that increasing chaperone concentration should lead to an enhancement in native yield. While this has been observed in GroEL-mediated protein folding, experiments onTetrahymenaribozyme folding assisted by CYT-19, surprisingly show the opposite trend. Here, we reconcile these divergent experimental observations by developing a unified stochastic model of chaperone assisted protein and RNA folding. We show that chaperones drive their substrates out of equilibrium, and in the process maximize the rate of native substrate production rather than the absolute yield or the folding rate.In vivothe number of chaperones is regulated to optimize their functions.
Crystal structure of 5-[2-(9H-carbazol-9-yl)ethyl]-1,3,4-oxadiazole-2(3H)-thione
Authors: Simpson Jim , Mohamed Shaaban K. , El-Emary Talaat I. , Albayati Mustafa R.
Published: June 2017

The title compound, C16H13N3OS, comprises an oxadiazolethione ring bound to the N atom of an almost planar carbazole ring system (r.m.s. deviation = 0.0088 Å) through an ethylene chain. The oxadiazole ring is inclined to the the carbazole ring system by 40.71 (6)°. In the crystal, N—H...O, N—H...S, C—H...N and C—H...S hydrogen bonds combine with C—H...π(ring) and π–π contacts to stack the molecules along theb-axis direction.
Meet the (media) producers: artists, composers, and gamemakers
Authors: Herro Danielle C. , Lin Lorraine , Fowler Michelle
Published: June 2017

Purpose

The purpose of this paper is to detail the perceived influence of early gaming habits toward media production from seven students enrolled at a university in the Southeastern US. Participants identified as heavily involved in creating media such as anime, videos, fanfiction, webcomics, games, and digital music.

Design/methodology/approach

This exploratory study used qualitative research, thus data collection and analysis included questionnaires, interviews, and artifacts identifying and categorizing six main themes: game play preferences, persistence, early connections between game play and media, support and feedback, creations inspired by games, and significance of games in current lives.

Findings

The study found that most participants believed game play in childhood influenced increasingly complex media production habits. Six of the seven believed game play influenced their career path. The paper concludes with implications for education including games as conduits to personalized learning and career paths.

Originality/value

Results from this study extend prior research on the value of games to promote media production and meet personal and professional goals. This is significant as prior research linking early game play to media production influencing career goals is sparse.
Students’ collaborative patterns in a wiki-authoring project
Authors: Jimoyiannis Athanassios , Roussinos Dimitrios
Published: June 2017

Purpose

The purpose of this paper is to present a case study investigating students’ patterns of collaborative content creation in a wiki project that was designed to promote self-directed and collaborative learning in the context of a university course. In addition, it proposes a new organizational and analysis framework of students’ constructive and collaborative activities in wiki-authoring projects.

Design/methodology/approach

The key notion, around which the present conceptual and research framework was built, is that a wiki integrates a content space and a social (discussion) space both considered in collaborative manner. The analysis of student contributions to their wiki was organized along two dimensions: interaction and refection posts were analyzed using the framework of Community of Inquiry; content contributions to the wiki pages were classified into five categories: creating a new page, content expansion, content reorganization, content enrichment (with video, images or hyperlinks) and editing and grammatical corrections.

Findings

The analysis of the research data revealed important information that could help to depict an overall representation of individual interactions and contributions, students’ collaborative performance within wiki groups as well as the overall evolution of the wiki content. The findings showed that properly designed wiki projects can be effectively introduced in higher education with the aim to support students to improve their authoring and collaborative skills through critical thinking, peer interaction and reflection.

Research limitations/implications

The findings of this study are limited by the specific sample and the context of implementation. Future research will be directed to various educational contexts and to include in the analysis students’ experiences and learning outcomes of wiki-authoring activities.

Practical implications

The results provided supportive evidence that successful wiki-based projects in higher education depend on the way students’ individual and collaborative authoring contributions are interwoven. Effective wiki-based interventions should consider students’ learning as the outcome of both, individual and collaborative work, determined by self and peer reflection in wiki groups.

Originality/value

The originality and the significance of the present study are justified by the conceptual framework proposed which can guide both aspects of students’ learning presence within self-directed wiki-authoring projects, i.e. research and educational practice (design and monitoring).
Autonomy and accountability in schools serving disadvantaged communities
Authors: Klein Esther Dominique
Published: June 2017

Purpose

Increased school autonomy and accountability have been a common denominator of national reforms in otherwise heterogeneous governance systems in Europe and the USA. The paper argues that because schools serving disadvantaged communities (SSDCs) often have lower average performance, they are more often sanctioned or under closer scrutiny, but might also receive more additional resources. The purpose of this paper is to therefore analyze whether SSDCs have more or less autonomy than schools with a more advantageous context in four countries with heterogeneous autonomy and accountability policies.

Design/methodology/approach

The paper is based on the data from the Programme for International Student Assessment 2012 school and student questionnaires from Finland, Germany, the UK, and the USA. The choice of countries is based on different governance models described by Glatter et al. (2003). The data are used to identify SSDCs and analyze the reported autonomy in resource allocation and curriculum and assessment. Using regression analyses, patterns are analyzed for each country individually. They are then juxtaposed and compared. Differences are related back to the governance models of the respective countries.

Findings

The results indicate an association between the communities the schools are serving and the autonomy either in the allocation of resources, or the curriculum and assessment. SSDCs appeared to have a little more autonomy than schools with a more advantageous context in Finland, Germany, and the UK, but less autonomy in the USA. The comparison suggests that in the USA, autonomy is rather a reward for schools that have the least amount of need, whereas in the other three countries it could be a result of strategies to improve schools in need. The paper discusses possible explanations in the policies and support structures for SSDCs.

Originality/value

The effects of increased school autonomy and accountability on student achievement have been discussed at length. How different accountability policies affect the autonomy of schools with the highest needs has so far not been studied. The study can be understood as a first step to unravel this association. Following steps should include in-depth investigations of the mechanisms underlying increased or diminished autonomy for SSDCs, and the consequences for school improvement in these schools.
Prioritizing cost management system considerations for Nigerian housing projects
Authors: Obi Lovelin Ifeoma , Arif Mohammed , Kulonda Dennis J.
Published: June 2017

Purpose

This study aims to develop a success factor model to understand and facilitate improved cost management system (CMS) implementation in low-cost housing (LcH) project delivery in Nigeria.

Design/methodology/approach

Literature findings highlight 13 drivers affecting effective implementation within the CMS and uses series of brainstorming sessions and questionnaire surveys to validate the drivers. Factor analysis (FA) identifies possible contextual relationships among the validated drivers and groups them into three success factors. The results of the FA are refined using interpretive structural modelling (ISM). The ISM identifies and models the influential drivers and aids the development of the success factor model.

Findings

Effective team qualities, information and management actions and a stable operational environment are the three essential success factors for effective CMS implementation.

Practical implications

The paper highlights effective team qualities as the most important CMS considerations for Nigerian LcH project delivery. This finding creates the needed awareness to guide project sponsors and project managers in the appropriate selection of the project management team (PMT) as well as the procurement system that facilitates their collaboration.

Originality/value

This study is a novel research using FA and ISM to investigate the influence of success factors needful for effective implementation within the CMS. It further develops a hierarchy model that aids the PMT with better understanding of the drivers and factors interrelationships for use on LcH projects within the Nigerian context.
São Paulo’s office market: scenario for the next years
Authors: Tavares de Alencar Claudio , Rocha Lima João , Monetti Eliane
Published: June 2017

Purpose

The purpose of this paper is to simulate possoble scenarios of São Paulo’s office market recovering. In 2006, a previous paper that dealt with the same issue was published which the authors propose to analyse here. After eight years, the São Paulo office market is starting a new phase within its cycle. Then, the first part of this paper, as in Rocha-Lima and Alencar (2006), describes the economic scenario in which investment decisions are made for developing office buildings in the Brazilian market. Afterward, the authors simulated both the necessary period of time for investments in the São Paulo office market to recover attractiveness and time for the increase in the occupation rate to absorb the current vacant spaces.

Design/methodology/approach

These simulations were carried out using simple linear regressions models using the Brazilian gross domestic product (GDP) as explanatory variable to prices and vacancy rates dependent ones.

Findings

The authors have found that the vacant space can be fully re-occupied in the beginning of 2021 or mid of 2022, according to the GDP growth rate, and, from this moment on, the demand for new spaces may grow, and, moreover around 2019, investments may become attractive again in this market.

Originality/value

This paper offers an alternative approach for estimating office building scenarios, especially when the database of the market is scarce. It also permits to evaluate an investment strategy for emerging markets within next years, particularly in São Paulo, Brazil.
Ferulic acid alleviates symptoms of preeclampsia in rats by upregulating vascular endothelial growth factor
Authors: Gong Weiyan , Wan Jipeng , Yuan Qing , Man Quanzhan , Zhang Xiaojing
Published: June 2017

Preeclampsia is a complication affecting pregnant women worldwide, which leads to maternal and fetal morbidity and mortality. In this study, we evaluated the efficacy of ferulic acid (FA) on an Nω‐nitro‐L‐arginine methyl ester hydrochloride (L‐NAME) induced rat model of preeclampsia. L‐NAME was administered to pregnant rats to induce preeclampsia. 48 rats were divided into three experimental groups (n=16 each): control group, preeclampsia group and preeclampsia with FA treatment (preeclampsia+FA). Physiological characteristics such as urine volume, total urine protein and blood pressure were assessed. Expressions levels of urinary nephrin and podocin mRNAs were analyzed by RT‐PCR. Levels of renal vascular endothelial growth factor (VEGF), renal soluble fms‐like tyrosine kinase‐1 (sFlt‐1) and serum placenta growth factor (PlGF) were also examined. Urine volume, total urine protein and blood pressure were markedly increased in preeclampsia group rats compared to control (P<.05), which were then significantly reduced in preeclampsia+FA group (P<.05). Expressions of urinary nephrin and podocin mRNAs, levels of VEGF, sFlt‐1 and PlGF were also reversed in preeclampsia+FA group compared to preeclampsia rats (P<.05). We hereby report for the first time, FA alleviates preeclampsia symptoms in a rat preeclampsia model, supporting its potential value in treating preeclampsia.
The Effect of Incentive Framing and Descriptive Norms on Internal Whistleblowing
Authors: Chen Clara Xiaoling , Nichol Jennifer E. , Zhou Flora H.
Published: June 2017

Firms are under increasing pressure to implement effective internal whistleblowing systems. While firms can provide incentives to encourage internal whistleblowing, it remains controversial how such incentives should be structured. We examine whether the effectiveness of incentives encouraging internal whistleblowing is a joint function of the framing of such incentives (reward or penalty) and the strength of descriptive norms supporting internal whistleblowing. We predict and find in a lab experiment that penalties lead to a greater increase in internal whistleblowing (compared to rewards) when descriptive norms supporting whistleblowing are stronger. Our study contributes to the previous accounting literature on dishonesty and the role of management control systems design in promoting honesty and ethical norms in organizations. We also contribute to an emerging accounting literature on the links between controls, norms, and individual behavior by distinguishing between descriptive norms and injunctive norms and by highlighting the interplay between these two types of norms. Our results have important implications for organizations considering adopting incentives to encourage internal whistleblowing.
Uterine natural killer cells in patients with idiopathic recurrent miscarriage
Authors: Kuon Ruben‐J. , Weber Maja , Heger Julia , Santillán Isabel , Vomstein Kilian , Bär Christin , Strowitzki Thomas , Markert Udo R. , Toth Bettina
Published: June 2017

Problem

Uterine natural killer (uNK) cells are major players during implantation and early pregnancy. The aim of our study was to analyze uNK cell concentration in the endometrium of idiopathic recurrent miscarriage (iRM) patients and fertile controls.

Method of study

Out of n=130 couples with ≥3 consecutive, clinical RM screened according to a standardized diagnostic protocol, n=58 patients with iRM were identified. Endometrial biopsies were investigated in patients and n=17 fertile women (controls) via immunohistochemistry.

Results

Compared to controls, the concentration of uNK cells was significantly higher in iRM patients (257±212 vs. 148±73 uNK cells/mm², P=.04). IRM patients showed a higher prevalence of >300 uNK cells/mm² than controls (34.5% vs. 5.9%, P=.02). In 88% of controls and 62% of iRM patients, uNK cells were detected within the range of 40‐300/mm².

Conclusion

Idiopathic recurrent miscarriage patients showed higher uNK cell levels than controls supporting the possible impact of uNK cells in the pathophysiology of miscarriage. Our cutoff levels might help to select RM patients which may benefit from immunomodulatory treatment.
Understanding Indigenous patient attendance: A qualitative study
Authors: Copeland Stephen , Muir Josephine , Turner Angus
Published: June 2017

Objective

To better understand Indigenous patient non‐attendance at medical specialty appointments by learning from the patients attending their scheduled outreach ophthalmology clinic appointment.

Design, setting and participants

A qualitative study using face‐to‐face, semi‐structured interviews with 69 Indigenous Australian ophthalmology patients and 8 clinic workers at one urban and one rural Aboriginal Medical Service (AMS) over the period from April 2015 to November 2015.

Main outcome measures

Explored motivations and enablers for attending patients to guide best practice for specialist outreach clinics.

Results

The main themes emerging from the interviews included: clinic staff are persistent in their efforts to organise outreach ophthalmology clinics; both motivated and reluctant patients attend medical appointments; and reluctant patients are more likely to be unaware of their referral pathway. Health literacy and clinic staff triggered the reluctant patient to attend.

Conclusion

Indigenous patients attend their outreach ophthalmology appointments based on various motivations. Clinic staff who recognise reluctant patients can communicate through a sensitive, patient‐centred approach that helps the patient realise the importance of the appointment thus creating motivation and promoting attendance. The efforts of the clinic staff, through their patient reminding, transport provision and patient‐centred communication suggest that they are the enablers of Indigenous patient attendance at AMS outreach ophthalmology clinics.
Adipokines played a limited role in predicting temporary growth differences between very low birthweight infants with and without bronchopulmonary dysplasia
Authors: Lehtinen A , Korhonen P , Hyödynmaa E , Koivisto AM , Peltola T , Hämäläinen M , Moilanen E , Tammela O
Published: June 2017

Aims

This study explored whether growth was poorer among very low birthweight (VLBW) infants with bronchopulmonary dysplasia (BPD) and assessed adipokine levels as predictors of early growth.

Methods

We studied 53 VLBW infants born in Tampere University Hospital up to 12 months of corrected age (CA). The median gestational age of the 21 infants with BPD and 32 infants without BPD was 29 weeks, and the median birthweights were 930 (635–1470) and 1185 (650–1470) grams. Growth parameters, macronutrients intake and plasma levels of adipokines were measured.

Results

Bronchopulmonary dysplasia infants were lighter than controls until 36 weeks of CA, with catch‐up growth achieved by three months of CA. Adipsin levels were lower in BPD infants at 28 days of postnatal age. High leptin levels seemed protective for low weight for height at nine months of CA. The duration of ventilator therapy predicted low weight for height, length for age and body mass index and BPD predicted low length for age at 12 months of CA.

Conclusions

Catch‐up growth in VLBW infants with BPD was achieved by three months of CA, but adipokines played a limited role in predicting growth. Shortening ventilator therapy could help growth in VLBW infants.
First environmental sample containing plasmid‐mediated colistin‐resistant ESBL‐producing Escherichia coli detected in Norway
Authors: Jørgensen Silje Bakken , Søraas Arne , Arnesen Lotte Stenfors , Leegaard Truls , Sundsfjord Arnfinn , Jenum Pål A.
Published: June 2017

We hereby report the detection of the plasmid borne mcr‐1 gene conferring colistin resistance in an extended‐spectrum β‐lactamase (ESBL) producing Escherichia coli ST10 strain retrieved from seawater at a public beach in Norway. The sample was collected in September 2010 and was investigated by whole‐genome sequencing in 2016. This report illustrates that E. coli strains carrying plasmid‐mediated colistin resistance genes have also reached areas where this drug is hardly used at all. Surveillance of colistin resistance in environmental, veterinary, and human strains is warranted also in countries where colistin resistance is rare in clinical settings.
Case of ileal herniation through the foramen of Winslow diagnosed preoperatively by CT and treated with laparoscopic surgery
Authors: Ichikawa Yoshitoshi , Kanazawa Akifumi , Dan Nobuhiro , Ishikawa Satoshi , Hagi Takaomi , Mizojiri Gaku , Tsubakimoto Mituo , Oka Hiroshi
Published: June 2017

A previously healthy 35‐year‐old man visited the emergency room complaining of epigastric pain and vomiting. The pain was sudden in onset. His blood tests were within normal limits except for a mild neutrophilia of 14 300/μL. Enhanced abdominal CT scan showed the small intestine dilated into the space between the portal vein and inferior vena cava from the foramen of Winslow. Under the diagnosis of herniation through the foramen of Winslow (HFW), we performed emergency laparoscopic surgery. Laparoscopy revealed an internal herniation of the dilated small intestine through the foramen of Winslow. Because the herniated small intestine was viable, intestinal resection was unnecessary. We released the incarceration under laparoscopy. HFW is very rare and often overlooked, but abdominal CT examination enabled a precise preoperative diagnosis because of characteristic findings. We should consider the possibility of HFW in patients with internal herniation of unknown origin. Laparoscopic surgery for HFW is effective.
Vascular Calcification, Vitamin K and Warfarin Therapy – Possible or Plausible Connection?
Authors: Siltari Aino , Vapaatalo Heikki
Published: June 2017

Atherosclerosis is a pathological process underpinning many cardiovascular diseases; it is the main cause of global mortality. Atherosclerosis is characterized by an invasion of inflammatory cells, accumulation of lipids and the formation of fatty streaks (plaques) which subsequently allow accumulation of calcium and other minerals leading to a disturbance in the vascular endothelium and its regulatory role in arterial function. Vascular calcification is a different process, stringently regulated mainly by local factors, in which osteoblast‐like cells accumulate in the muscular layer of arteries ultimately taking on the physiological appearance of bone. The elevated stiffness of the arteries leads to severe vascular complications in brain, heart and kidneys. Recently, evidence from animal experiments as well as clinical and epidemiological results suggests that long‐term treatment with warfarin, but not with the novel direct anticoagulants, can increase the risk or even induce vascular calcification in some individuals. Gamma‐carboxylation is an enzymatic process not only needed for activation of vitamin K but also other proteins which participate in bone formation and vascular calcification. Thus, reduced expression of the vitamin K‐dependent proteins which physiologically inhibit calcification of cellular matrix could be postulated to lead to vascular calcification. Published clinical data, describing at present a few thousand patients, need to be supplemented with controlled studies to confirm this interesting hypothesis.
The Pharmacokinetics of Enalapril in Relation to CES1 Genotype in Healthy Danish Volunteers
Authors: Stage Claus , Jürgens Gesche , Guski Louise Schow , Thomsen Ragnar , Bjerre Ditte , Ferrero‐Miliani Laura , Lyauk Yassine Kamal , Rasmussen Henrik Berg , Dalhoff Kim ,   The INDICES Consortium (for members of this consortium‐see Supplementum)
Published: June 2017

This study investigated the influence of variations in the carboxylesterase 1 gene (CES1) on the pharmacokinetics of enalapril. Forty‐three healthy, Danish, Caucasian volunteers representing different pre‐defined genotypes each received 10 mg of enalapril. At specified time‐points, plasma concentrations of enalapril and the active metabolite enalaprilat were measured. The volunteers were divided into six different groups according to their genetic profile of CES1: group 1 (control group, n = 16) with two CES1 copies without non‐synonymous SNPs in the exons; group 2 (n = 5) with four copies of CES1; group 3 (n = 6) harbouring the G143E polymorphism; group 4 (n = 2) with three CES1 copies and increased transcriptional activity of the duplication (CES1A2); group 5 (n = 4) harbouring the CES1A1c variant; and group 6 (n = 10) with three CES1 copies and the common promoter with low transcriptional activity of the duplication. The median AUC of enalaprilat in the control group was not significantly different from any of the other five groups (297 ng/ml x h in the control group versus 310, 282, 294, 344 and 306 ng/ml x h in groups 2–6, respectively). The terminal half‐life of enalaprilat was significantly longer in group 6 compared with the control group (26.7 hr versus 12.7 hr, respectively). However, this was not considered clinically relevant. In conclusion, none of the selected variations of CES1 had a clinically relevant impact on the metabolism of enalapril.
The mechanism of coupling between oxido‐reduction and proton translocation in respiratory chain enzymes
Authors: Papa Sergio , Capitanio Giuseppe , Papa Francesco
Published: June 2017

The respiratory chain of mitochondria and bacteria is made up of a set of membrane‐associated enzyme complexes which catalyse sequential, stepwise transfer of reducing equivalents from substrates to oxygen and convert redox energy into a transmembrane protonmotive force (PMF) by proton translocation from a negative (N) to a positive (P) aqueous phase separated by the coupling membrane. There are three basic mechanisms by which a membrane‐associated redox enzyme can generate a PMF. These are membrane anisotropic arrangement of the primary redox catalysis with: (i) vectorial electron transfer by redox metal centres from the P to the N side of the membrane; (ii) hydrogen transfer by movement of quinones across the membrane, from a reduction site at the N side to an oxidation site at the P side; (iii) a different type of mechanism based on co‐operative allosteric linkage between electron transfer at the metal redox centres and transmembrane electrogenic proton translocation by apoproteins.

The results of advanced experimental and theoretical analyses and in particular X‐ray crystallography show that these three mechanisms contribute differently to the protonmotive activity of cytochrome c oxidase, ubiquinone‐cytochrome c oxidoreductase and NADH‐ubiquinone oxidoreductase of the respiratory chain.

This review considers the main features, recent experimental advances and still unresolved problems in the molecular/atomic mechanism of coupling between the transfer of reducing equivalents and proton translocation in these three protonmotive redox complexes.
How Do Macroeconomic and Bank‐specific Variables Influence Profitability in the Austrian Banking Sector? Evidence from a Panel Vector Autoregression Analysis
Authors: Sigmund Michael , Gunter Ulrich , Krenn Gerald
Published: June 2017

We examine the determinants of the net interest margin (NIM) and the net fee and commission income ratio (NFCIR) of Austrian banks as well as their interrelationship and whether portfolio separation between loan and deposit categories holds. We describe a conceptual framework for the profit optimization problem faced by banks as a Bertrand game with differentiated products and intrafirm product interactions. We contribute to the literature by factoring in banks’ business models in terms of their balance sheet structure. We empirically assess the implications of our conceptual framework using a unique supervisory data set of around 48,000 observations between 1998 and 2014. We estimate two panel vector autoregression models with a novel panel vector autoregression code. Apart from quantifying the contributions of the determinants (e.g., risk weighted assets, leverage ratio, loan loss provision ratio) to NIM and NFCIR, the empirical results show that interest income and fee and commission income should be regarded as strategic complements within a bank. We further conclude that portfolio separation between different loan and deposit categories does not hold.
Growth or stagnation? Farming in England, 1200–1800
Authors: Clark Gregory
Published: June 2017

Estimates of English income in Broadberry et al.’s British economic growth, 1270–1870 are founded upon a fourfold growth of farm output, and output per farm worker, over this interval. This article shows, using four separate tests, that farm output growth must have been much more limited. The tests are, first, whether in 1300 there was enough work at harvest to employ all the labour force; second, whether the value of output per worker in agriculture was greater than the annual earnings of workers; third, whether the implied relative outputs per acre of arable versus pasture were reasonable; and fourth, whether a much shorter medieval work year was possible. An alternative index of farm output consistent with the labour supply, wages, and farm rents is derived. This shows much less growth during the period 1270–1800. Overall economic growth in England during these years must consequently have been far less than Broadberry et al. estimate.
Road transport productivity in the sixteenth‐century Low Countries: the case of Brabant, 1450–1650†
Authors: Ballaux Bart , Blondé Bruno
Published: June 2017

Though there is a consensus that transport plays a central role in economic development, for the period before the eighteenth century there is a lack of strategic information for assessing the importance of road transport productivity changes in economic development. Transport prices in particular are crucial missing pieces of the puzzle. Sources rarely reveal information that meets the standards of reliable price history. However, it is possible to create a reliable transport price series on the basis of the transport of millstones to ducal mills in Brabant. Assessing the impact of the ‘transport productivity changes’ that can be inferred from this transport price series is a hazardous exercise. Moreover, as Masschaele has observed, land transport prices closely match general agricultural price trends. Land transport was essentially an agricultural service, determined both by cost (especially horse provender) and income effects. Transport price inflation was not demand‐led. However, while transport did not impede urbanization and economic growth, conversely, in sixteenth‐century Brabant—a highly urbanized region that experienced considerable growth in the volume of land transport—no significant land transport productivity gains were achieved.