bluuebunny/crossref_metadata_2025 huggingface dataset:
The Health and Social Care Act 2008 (Regulated Activities) Regulations 2014: A Litany of Fundamental Flaws?
Authors: Stirton Ruth
Published: March 2017

This article argues that the Health and Social Care Act 2008 (Regulated Activities) Regulations 2014 are fatally flawed notwithstanding the apparent rigour of the process which produced them. These Regulations were the product of considerable deliberation following a sensitively executed public inquiry yet, it is argued, they rely too heavily on the rhetoric of criminal law while failing to take into account the competing norms for compliance and the impact of NHS budget constraints. Further, they push the CQC towards a heavy‐handed deterrence approach to enforcement, which will increase hostility between regulatees and the inspectorate, and ultimately reduce the scope for developing the transparency about failures which is sorely needed in the NHS. This article challenges the contemporary wisdom that it is primarily knee‐jerk regulatory responses that suffer from fatal flaws of this nature.
MWB Business Exchange Centres Ltd: The Practical Benefit Doctrine Marches On
Authors: Roberts Marcus
Published: March 2017

In MWB Business Exchange Centres Ltd v Rock Advertising Ltd the Court of Appeal held that when an ongoing contract is varied so that one party's obligation to pay money is reduced, the variation is binding as long as the other party receives a practical benefit. In doing so, the Court of Appeal effectively confined the rule in Foakes v Beer to one‐off payments. This raises serious questions about the continued survival of Foakes v Beer. On the other hand, the Court of Appeal ensured that Foakes v Beer would not be killed off via equity by moving away from the suggestion in Collier v P & M J Wright (Holdings) Ltd that an agreed part‐payment of a debt by a debtor will always raise an estoppel preventing the creditor from demanding the remainder of the debt.
Editorial: ONO‐2952 in irritable bowel syndrome with diarrhoea
Authors: Nee J. , Lembo A.
Published: March 2017

Linked Content

This article is linked to W. E. Whitehead et al papers. To view these articles visit https://doi.org/10.1111/apt.13957 and https://doi.org/10.1111/apt.13839.
MicroRNA‐122 can be measured in capillary blood which facilitates point‐of‐care testing for drug‐induced liver injury
Authors: Vliegenthart A. D. Bastiaan , Berends Cécile , Potter Carmelita M. J. , Kersaudy‐Kerhoas Maiwenn , Dear James W.
Published: March 2017

Aims

Liver‐enriched microRNA‐122 (miR‐122) is a novel circulating biomarker for drug‐induced liver injury (DILI). To date, miR‐122 has been measured in serum or plasma venous samples. If miR‐122 could be measured in capillary blood obtained from a finger prick it would facilitate point‐of‐care testing, such as in resource‐limited settings that have a high burden of DILI.

Methods

In this study, in healthy subjects, miR‐122 was measured by polymerase chain reaction in three capillary blood drops taken from different fingers and in venous blood and plasma (n = 20). miR‐122 was also measured in capillary blood obtained from patients with DILI (n = 8).

Results

Circulating miR‐122 could be readily measured in a capillary blood drop in healthy volunteers with a median (interquartile range) cycle threshold (Ct) of 32.6 (31.1–34.2). The coefficient of variation for intraindividual variability across replicate blood drops was 49.9%. Capillary miR‐122 faithfully reflected the concentration in venous blood and plasma (Pearson R = 0.89, P < 0.0001; 0.88, P < 0.0001, respectively). miR‐122 was 86‐fold higher in DILI patients [median value 1.0 × 108 (interquartile range 1.89 × 107–3.04 × 109) copies/blood drop] compared to healthy subjects [1.85 × 106 (4.92 × 105–5.88 × 106) copies/blood drop]. Receiver operator characteristic analysis demonstrated that capillary miR‐122 sensitively and specifically reported DILI (area under the curve: 0.96, P = 0.0002).

Conclusion

This work supports the potential use of miR‐122 as biomarker of human DILI when measured in a capillary blood drop. With development across DILI aetiologies, this could be used by novel point‐of‐care technologies to produce a minimally invasive, near‐patient, diagnostic test.
Cis‐Nerolidol Induces Endoplasmic Reticulum Stress and Cell Death in Human Hepatocellular Carcinoma Cells through Extensive CYP2C19 and CYP1A2 Oxidation
Authors: Biazi Bruna Isabela , Zanetti Thalita Alves , Baranoski Adrivanio , Corveloni Amanda Cristina , Mantovani Mário Sérgio
Published: March 2017

Of late, many studies are attempting to find new molecules with anticancer properties, especially those with the capability to inhibit cell growth. The aim of this work was to evaluate nerolidol, a plant‐based compound, as its cytotoxicity, genotoxicity, antiproliferative and apoptotic induction, cell cycle, mitochondrial membrane potential and RT‐qPCR of transcripts related to those pathways in the human hepatocellular carcinoma cell line (HepG2/C3A). Only cis‐nerolidol (C‐NER) demonstrated cytotoxicity (100–250 μM) activity and was selected to conduct the following experiments. C‐NER did not show genotoxic activity, but altered the mitochondrial membrane potential, reduced cell proliferation by arresting cell cycle in G1 phase and induced cell death. RT‐qPCR showed that C‐NER down‐regulated genes related to apoptosis (BAK1, BAX, CAPN1, CASP8, CASP9, PARP1 and TP53), cell cycle (CCND1, CCNE1, CDK1 and CDK2), xenobiotic metabolism (CYP2D6 and CYP3A4) and paraptosis (IGF1R receptor). Up‐regulation was seen in case of genes related to cell survival (BBC3 and MYC) and reticulum stress protein response (EIF2AK3 and ERN1) and xenobiotic metabolism (CYP1A2 and CYP2C19). We deduced that the antiproliferative activity of C‐NER is attributable to its modulation of the cyclins and cyclin‐dependent kinases as these proteins are necessary for G1/S phase transition. EIF2AK3, ERN1, CYP2C19 and CYP1A2 up‐regulation suggests that endoplasmic reticulum stress was induced owing to the increased activity of cytochrome P450 enzymes. Caspase‐independent cell death was also observed, indicating that another type of cell death, paraptosis, was triggered. Our results indicate that C‐NER has considerable potential in anticancer therapy because it modulates important molecular targets of cell survival and proliferation.
Proportional Hazards Model with a Change Point for Clustered Event Data
Authors: Deng Yu , Zeng Donglin , Zhao Jinying , Cai Jianwen
Published: March 2017

In many epidemiology studies, family data with survival endpoints are collected to investigate the association between risk factors and disease incidence. Sometimes the risk of the disease may change when a certain risk factor exceeds a certain threshold. Finding this threshold value could be important for disease risk prediction and diseases prevention. In this work, we propose a change-point proportional hazards model for clustered event data. The model incorporates the unknown threshold of a continuous variable as a change point in the regression. The marginal pseudo-partial likelihood functions are maximized for estimating the regression coefficients and the unknown change point. We develop a supremum test based on robust score statistics to test the existence of the change point. The inference for the change point is based on the m out of n bootstrap. We establish the consistency and asymptotic distributions of the proposed estimators. The finite-sample performance of the proposed method is demonstrated via extensive simulation studies. Finally, the Strong Heart Family Study dataset is analyzed to illustrate the methods.
Frequent downregulation of BTB and CNC homology 2 expression in Epstein–Barr virus‐positive diffuse large B‐cell lymphoma
Authors: Noujima‐Harada Mai , Takata Katsuyoshi , Miyata‐Takata Tomoko , Sakurai Hiroaki , Igarashi Kazuhiko , Ito Etsuro , Nagakita Keina , Taniguchi Kohei , Ohnishi Nobuhiko , Omote Shizuma , Tabata Tetsuya , Sato Yasuharu , Yoshino Tadashi
Published: March 2017

Diffuse large B‐cell lymphoma (DLBCL) is the most common B‐cell lymphoma subtype, and the Epstein–Barr virus (EBV)‐positive subtype of DLBCL is known to show a more aggressive clinical behavior than the EBV‐negative one. BTB and CNC homology 2 (BACH2) has been highlighted as a tumor suppressor in hematopoietic malignancies; however, the role of BACH2 in EBV‐positive DLBCL is unclear. In the present study, BACH2 expression and its significance were studied in 23 EBV‐positive and 43 EBV‐negative patient samples. Immunohistochemistry revealed BACH2 downregulation in EBV‐positive cases (P < 0.0001), although biallelic deletion of BACH2 was not detected by FISH. Next, we analyzed the contribution of BACH2 negativity to aggressiveness in EBV‐positive B‐cell lymphomas using FL‐18 (EBV‐negative) and FL‐18‐EB cells (FL‐18 sister cell line, EBV‐positive). In BACH2‐transfected FL‐18‐EB cells, downregulation of phosphorylated transforming growth factor‐β‐activated kinase 1 (pTAK1) and suppression in p65 nuclear fractions were observed by Western blot analysis contrary to non‐transfected FL‐18‐EB cells. In patient samples, pTAK1 expression and significant nuclear p65, p50, and p52 localization were detected immunohistochemically in BACH2‐negative DLBCL (P < 0.0001, P = 0.006, and P = 0.001, respectively), suggesting that BACH2 downregulation contributes to constitutive activation of the nuclear factor‐κB pathway through TAK1 phosphorylation in BACH2‐negative DLBCL (most EBV‐positive cases). Although further molecular and pathological studies are warranted to clarify the detailed mechanisms, downregulation of BACH2 may contribute to constitutive activation of the nuclear factor‐κB pathway through TAK1 activation.
Immunosuppressive drugs affect interferon (IFN)-γ and programmed cell death 1 (PD-1) kinetics in patients with newly diagnosed autoimmune hepatitis
Authors: Grant C R , Holder B S , Liberal R , Heneghan M A , Ma Y , Mieli-Vergani G , Vergani D , Longhi M S
Published: March 2017

Autoimmune hepatitis (AIH) is characterized by overwhelming effector immune responses associated with defective regulatory T cells (Tregs). Several lines of evidence indicate CD4 as the main effectors involved in autoimmune liver damage. Herein we investigate the in-vitro effects of prednisolone, 6-mercaptopurine, cyclosporin, tacrolimus, mycophenolic acid (MPA) and rapamycin, immunosuppressive drugs (ISDs) used in AIH treatment, on the expression of proinflammatory cytokines, co-inhibitory molecules and ability to proliferate of CD4+CD25– cells, isolated from the peripheral blood of treatment-naive patients with AIH. We note that in healthy subjects (HS) following polyclonal stimulation and in the absence of ISDs, the expression of interferon (IFN)-γ, interleukin (IL)-17 and tumour necrosis factor (TNF)-α by CD4 effectors peaks at 48 h and decreases at 96 h to reach baseline levels. In contrast, in AIH the expression of all these proinflammatory cytokines continue rising between 48 and 96 h. Levels of programmed cell death-1 (PD-1), T cell immunoglobulin and mucin domain-containing molecule-3 (TIM-3) and cytotoxic T lymphocyte antigen-4 (CTLA-4) increase over 96-h culture both in HS and AIH, although with faster kinetics in the latter. Exposure to ISDs contains IFN-γ and PD-1 expression in AIH, where control over CD4+CD25– cell proliferation is also noted upon exposure to MPA. Treatment with tacrolimus and cyclosporin render CD4+CD25– cells more susceptible to Treg control. Collectively, our data indicate that in treatment-naive patients with AIH, all ISDs restrain T helper type 1 (Th1) cells and modulate PD-1 expression. Furthermore, they suggest that tacrolimus and cyclosporin may ameliorate effector cell responsiveness to Tregs.
Play and Children's Museums: A Path Forward or a Point of Tension?
Authors: Luke Jessica J. , Letourneau Susan M. , Rivera Nicole R. , Brahms Lisa , May Sarah
Published: March 2017

Play is a central, defining concept for children's museums, yet it's become a hot button issue which is problematic if play is what makes children's museums uniquely valuable. In this article, members of the Children's Museum Research Network share findings from their first research study, focused on elucidating the problem of play in children's museums. Results suggest that children's museums may not have shared definitions and conceptualizations of play.
Climate Change Education at Nature‐Based Museums
Authors: Swim Janet K. , Geiger Nathaniel , Fraser John , Pletcher Nette
Published: March 2017

The status of climate change education at nature‐based museums (i.e., zoos, aquariums and nature centers) was examined, with a particular focus on centers participating in a National Network for Ocean and Climate Change Interpretation (NNOCCI) leadership training program. Study 1 revealed that, relative to nature‐based museums that did not participate in the training, NNOCCI‐participating institutions provided resources for staff to work on the topic and professional development programs and were more likely than non‐participating museums to be comfortable with and provide climate change education programming. Study 2 confirms these results via visitor reports about the exhibits they observed. Study 2 also reveals that, relative to non‐visitors and visitors to non‐participating nature‐based museums, visitors to NNOCCI‐participating nature‐based museums were more knowledgeable about and concerned about climate change and ocean acidification, hopeful about their ability to talk about the topic, and likely to engage in climate change actions than those who did not visit these centers. Importantly, results from both studies indicate that nature‐based museums, especially NNOCCI participating museums, have an institutional culture supportive of climate science education and suggests that NNOCCI interpreter training programming facilitates this culture which in turn is reflected in visitor engagement.
Public Support for Biodiversity After a Zoo Visit: Environmental Concern, Conservation Knowledge, and Self‐Efficacy
Authors: Clayton Susan , Prévot Anne‐Caroline , Germain Laurent , Saint‐Jalme Michel
Published: March 2017

The biodiversity crisis is not salient to many people. A zoo visit not only provides the opportunity to learn about the issue, but also provides direct experiences with animals that may increase public engagement. The present study used a nonequivalent pretest–posttest design to assess the impact of a zoo visit on conservation knowledge and engagement by comparing 88 visitors entering a zoo in Paris and 84 visitors on their way out. Those who had completed their visit scored higher on conservation knowledge, general concern about threats to biodiversity, and perceived self‐efficacy to protect biodiversity. Notably, conservation knowledge was not highly correlated with the other dependent variables, but self‐efficacy was significantly correlated with environmental concern, behaviour, and behavioural intent. We conclude that a zoo visit does have a positive impact on knowledge and concern, and by affecting self‐efficacy, it has the potential to influence future behavior.
The Impact of Decision Types on Revenue Management Decisions: An Experimental Study
Authors: Kocabıyıkoğlu Ayşe , Göğüş Celile Itır , Hekimoğlu Mert Hakan
Published: March 2017

In the standard two‐class revenue management model, the decision maker allocates a fixed resource between two customer classes with hierarchical prices and uncertain demand. The normative (i.e., expected revenue‐maximizing) allocation is given by Littlewood's Rule, but little is known about how decision makers actually form these decisions. We report results of an experimental study that investigates revenue management decision‐making. We find that subjects' behavior is influenced by the decision type. In particular, our subjects reserve more units for the high‐end segment when they are asked to set the protection level (the number of units to set aside for the higher priced class) compared to when they set the booking limit (the number of units available for the lower priced class). We propose that this behavioral pattern can be explained by our subjects’ different valuations of revenues from the high‐ and low‐end sales. We also observe that when there is a change in segment prices, although decision makers adjust allocations in the direction suggested by normative theory, the magnitude of adjustments is greater (and hence closer to the normative level) when the source of the price change matches the class whose allocation they determine.
Tracking independence and merging of prosodic and phonemic processing across infancy
Authors: Becker Angelika , Schild Ulrike , Friedrich Claudia K.
Published: March 2017

Recent evidence suggests division of labor in phonological analysis underlying speech recognition. Adults and children appear to decompose the speech stream into phoneme‐relevant information and into syllable stress. Here we investigate whether both speech processing streams develop from a common path in infancy, or whether there are two separate streams from early on. We presented stressed and unstressed syllables (spoken primes) followed by initially stressed early learned disyllabic German words (spoken targets). Stress overlap and phoneme overlap between the primes and the initial syllable of the targets varied orthogonally. We tested infants 3, 6 and 9 months after birth. Event‐related potentials (ERPs) revealed stress priming without phoneme priming in the 3‐month‐olds; phoneme priming without stress priming in the 6‐month‐olds; and phoneme priming, stress priming as well as an interaction of both in 9‐month‐olds. In general the present findings reveal that infants start with separate processing streams related to syllable stress and to phoneme‐relevant information; and that they need to learn to merge both aspects of speech processing. In particular the present results suggest (i) that phoneme‐free prosodic processing dominates in early infancy; (ii) that prosody‐free phoneme processing dominates in middle infancy; and (iii) that both types of processing are operating in parallel and can be merged in late infancy.
Loss of base‐to‐apex circumferential strain gradient: A specific pattern of Fabry cardiomyopathy?
Authors: Labombarda Fabien , Saloux Eric , Milesi Guillaume , Bienvenu Boris
Published: March 2017

Introduction and objectives

Cardiac manifestations in Fabry disease are mainly characterized by left ventricular hypertrophy (LVH). The aims of this study were (1) to describe the pattern of regional strain in patients with Fabry disease and (2) to assess whether this pattern may help differentiate patients with Fabry disease from patients with sarcomeric hypertrophic cardiomyopathy (HCM).

Methods

Seventy‐seven subjects were investigated: patients with Fabry disease (n=37; 57% with LVH), patients with HCM (n=21), and healthy controls (n=19). Global and segmental longitudinal and circumferential strain (CS) analyses were performed by two‐dimensional speckle strain imaging. Base‐to‐apex longitudinal and CS gradient, defined as the peak gradient difference between averaged basal and apical strain, was calculated.

Results

Longitudinal strain gradient did not differ between controls and Fabry patients without hypertrophy (respectively: −10±3.2 vs −8±4.3, P=.41) or between the HCM group and Fabry patients with hypertrophy (respectively: −7.5±4.5 vs −9±4.5, P=.37). The CS gradient was lower in Fabry patients without hypertrophy compared to the controls (respectively: 1±8 vs 14.2±9.5, P<.01), and lower in Fabry patients with hypertrophy compared to the HCM group (respectively: 0.5±8 vs 6±9, P<.01). Base‐to‐apex CS gradient was lost in both Fabry groups.

Conclusion

Loss of base‐to‐apex CS gradient may be a specific left ventricular deformation pattern of Fabry cardiomyopathy in patients with and without LVH.
Chinook salmon emergence phenotypes: Describing the relationships between temperature, emergence timing and condition factor in a reaction norm framework
Authors: Fuhrman Abby E. , Larsen Donald A. , Steel E. Ashley , Young Graham , Beckman Brian R.
Published: March 2017

Water temperature can have a profound influence on development and distribution of aquatic species. Salmon are particularly vulnerable to temperature changes because their reproductive and early development life phases are spent in freshwater river systems where temperature fluctuates widely both daily and seasonally. Flow regulation downstream of dams can also cause temperature regime changes, which in turn may spur local adaptation of early life‐history traits. In a common garden laboratory incubation experiment, we exposed spring Chinook salmon (Oncorhynchus tshawytscha) embryos to four temperature regimes: warm stable, cold stable, daily variation and below dam. We found that fry from warmer thermal regimes emerged earlier than those from colder regimes both in terms of calendar date and temperature units and that warmer temperatures caused fry to emerge less developed. There was also a significant effect of family on both emergence timing and development level at emergence. By combining measurements of physiological and behavioural traits at emergence and interpreting them within a reaction norm framework, we can better understand which populations might be more vulnerable to altered thermal regimes.
Human papillomavirus (HPV)‐independent vulvar squamous cell carcinoma has a worse prognosis than HPV‐associated disease: a retrospective cohort study
Authors: McAlpine Jessica N , Leung Samuel C Y , Cheng Angela , Miller Dianne , Talhouk Aline , Gilks C Blake , Karnezis Anthony N
Published: March 2017

Aims

Vulvar squamous cell carcinoma (VSCC) can be subdivided by human papillomavirus (HPV) status into two clinicopathological entities. Studies on the prognostic significance of HPV in VSCC are discordant.

Methods and results

We performed a retrospective analysis of overall survival (OS), disease‐specific survival (DSS) and progression‐free survival (PFS) in 217 patients with VSCC. Cases were extracted from an era of more aggressive en‐bloc radical dissections (1985–95) and more localized radical surgery through separate vulvar and groin excisions (1996–2005). p16 immunohistochemistry was used as a surrogate for HPV status. HPV status could be determined in 197 tumours, 118 HPV‐independent and 79 HPV‐associated tumours. Patients with HPV‐associated tumours were younger (mean 58.8 versus 71.6 years for HPV‐independent tumours, P < 0.0001) and more likely to have prior abnormal cervical cytology (41.1 versus 5.6% for HPV‐independent tumours, P < 0.0001). In univariable analysis, patients with HPV‐associated tumours had superior PFS [hazard ratio (HR): 0.37, 95% confidence interval (CI): 0.18–0.70], DSS (HR: 0.19, 95% CI: 0.08–0.41) and OS (HR: 0.35, 95% CI: 0.21–0.59). This was driven by worse outcomes (PFS, DSS and OS) for patients with HPV‐independent tumours compared with HPV‐associated tumours who underwent surgery after 1995. After adjusting for age and stage in multivariable analysis, patients with HPV‐associated tumours showed superior PFS (HR: 0.25, 95% CI: 0.07–0.77) and DSS (HR: 0.21, 95% CI: 0.04–0.78).

Conclusions

VSCC can be stratified into two prognostically different diseases based on p16 immunostaining. HPV status was associated only with prognosis in the cohort that underwent surgery after 1995, suggesting that more conservative surgery may have led to worse outcomes for patients with HPV‐independent tumours.
Oral lichen planus in childhood: a case series
Authors: Cascone Marco , Celentano Antonio , Adamo Daniela , Leuci Stefania , Ruoppo Elvira , Mignogna Michele D.
Published: March 2017

Background

Although the exact incidence of pediatric oral lichen planus (OLP) is unknown, the oral mucosa seems to be less commonly involved, and the clinical presentation is often atypical. The aim of the study is to present a case series of OLP in childhood.

Methods

From our database, we retrospectively selected and analyzed the clinical data of OLP patients under the age of 18 where the diagnosis had been confirmed by histopathological analysis.

Results

The case series from our database shows eight patients, four males and four females. The mean (±SD) age at the time of diagnosis of the disease was 13.5 (±2.73) years, ranging in age from 9 to 17. Clinically, a reticular pattern was present in six patients (75%), and the tongue was the most commonly involved oral site (six cases, 75%). We also report the first case of OLP in a 9‐year‐old girl affected by autoimmune polyendocrinopathy‐candidiasis‐ectodermal dystrophy.

Conclusions

We report the largest case series of pediatric OLP published in literature thus far. Differences in the disease between adults and pediatric patients have been detected, but further investigation and a larger case series are needed to establish any detailed differences in clinical outcomes.
Hyperleptinemia Exacerbates High‐Fat Diet‐Mediated Atrial Fibrosis and Fibrillation
Authors: FUKUI AKIRA , IKEBE‐EBATA YUKI , KONDO HIDEKAZU , SAITO SHOTARO , AOKI KOHEI , FUKUNAGA NAOYA , SHINOHARA TETSUJI , MASAKI TAKAYUKI , TESHIMA YASUSHI , TAKAHASHI NAOHIKO
Published: March 2017

Hyperleptinemia and Atrial Fibrillation

Background

Obesity including metabolic syndrome is an independent risk factor of atrial fibrillation (AF). Although hyperleptinemia is usually a characteristic of obese subjects, the relationship with atrial fibrosis and AF is unknown. We tested the hypothesis that high‐fat diet (HFD)‐induced hyperleptinemia exacerbates atrial fibrosis and AF.

Methods and Results

Eight‐week‐old male C57BL/6 (WT) and leptin‐deficient ob/ob (Ob) mice were treated with a normal‐fat diet (NFD) or 60% HFD. After 8 weeks, transesophageal burst pacing and electrophysiological study using isolated perfused hearts were performed and left atrial (LA) tissues were collected for histological analysis, hydroxyproline assay, and reverse transcription‐polymerase chain reaction. HFD treatment increased body weight in both WT and Ob mice compared with NFD (both P < 0.01). In WT‐HFD mice, hyperleptinemia was observed as expected. While transesophageal burst pacing invariably induced AF (8/8, 100%) in WT‐HFD mice, AF was induced less frequently (1/8, 12.5%) in Ob‐HFD mice (P < 0.01). In isolated perfused hearts, the interatrial conduction time was prolonged in WT‐HFD mice, but not in Ob‐HFD mice (P < 0.05). Masson's trichrome staining and the hydroxyproline assay revealed interstitial LA fibrosis in WT‐HFD mice, which was not observed in Ob‐HFD mice (P < 0.05). Upregulation of collagen1, collagen3, α‐smooth muscle actin, tumor necrosis factor‐α, and monocyte chemoattractant protein‐1 mRNA levels was noted in WT‐HFD mice LA, but attenuated in Ob‐HFD mice LA.

Conclusions

Our findings suggest that hyperleptinemia exacerbates HFD‐mediated atrial fibrosis and AF. Inhibition of leptin signaling may become a novel therapeutic target to prevent obesity‐related AF.
Prediction of temperature distribution in a horizontal high pressure food processing vessel and its impact on process uniformity
Authors: Salvi Deepti , Khurana Meenakshi , Karwe Mukund V.
Published: March 2017

The temperature distributions in HPP vessels should be of particular concern for pressure assisted thermal sterilization (PATS) processes because in PATS temperature plays a major role in microbial inactivation. Numerical simulations were carried out to predict thermal transport in a horizontal HPP vessel with and without insulation. The results showed that the temperature of water added to compensate for the compression of water in the pressure vessel and the addition of insulation on the inner surface of vessel had significant impact on the temperature distribution and on the predicted inactivation of Clostridium botulinum spores. It was concluded that adding insulation to the vessel lead to higher temperature levels but more non‐uniform temperature distribution as compared with without insulation. It was also observed that the water added to compensate for compression did not impact the flow pattern in the vessel significantly due to low inlet velocity but the temperature of added water had a significant impact on the temperature and Clostridium botulinum spore inactivation distributions. The temperature distribution was close to uniform when the temperature of the inlet water was the same as the initial temperature for the process.

Practical applications

The results obtained from this research will be useful in the evaluation of process performance in terms of process validation and process filing with regulatory agencies to develop guidelines for producing high pressure processed foods using PATS, which are safe to consume. The results will also be important for food processors and equipment manufacturers to understand the effects of non‐uniform thermal treatment on foods processed using PATS.
Combined effect of aerosolized malic acid and UV‐C for the inactivation of Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes on fresh‐cut lettuce
Authors: Seong Ji‐Yeong , Kwon Ki‐Hyun , Oh Se‐Wook
Published: March 2017

This study was conducted to investigate the effects of aerosolized malic acid and ultraviolet light (UV‐C) for inhibiting the growth of foodborne pathogens, Escherichia coli O157:H7, Salmonella Typhimurium, and Listeria monocytogenes, on fresh‐cut lettuce. The antimicrobial effects of aerosolized 2% malic acid and UV‐C, alone or in combination, were tested. Ten grams of lettuce were inoculated with three strains of each pathogens and treated with aerosolized malic acid for 20 min and UV‐C for 30 min. After each treatment, lettuce was stored at 5 °C for 15 days. Sequential treatment (aerosolized malic acid after UV‐C) was the most effective for reducing E. coli O157:H7, S. Typhimurium, and L. monocytogenes and resulted in reduction of 2.89, 1.38, and 2.95 log10 CFU/g after treatment and 3.15, 3.00, and 4.58 log10 CFU/g after 15 days, respectively. These results suggested that combined treatment with aerosolized malic acid after UV‐C can be a useful intervention method for improving the microbial safety of fresh‐cut produce.

Practical applications

The experiment suggested new method on the inactivation of foodborne pathogens on lettuce.

Treatment with aerosolized 2% malic acid after UV‐C was the most effective method to inhibit the growth of foodborne pathogens in this study.

This method will be helpful for fresh‐cut lettuce producers to manage the safety and quality of lettuce.
Combined SNPs and miRNAs technologies for beef traceability
Authors: Wu Qiayu , Zhou Guanghong , Yang Sasa , Xu Xinglian , Li Chunbao
Published: March 2017

The independent and highly heterozygous single nucleotide polymorphisms (SNPs) have been shown suitable for meat traceability. The microRNAs (miRNAs) that were differently expressed among regions could be used for meat origin traceability. In the present study, ten SNPs from 148 Chinese beef cattle were screened by HRM. The results showed that these SNPs were all suitable for beef traceability with the probability error rate of .308‰. These cattle could not be clustered into different regions based on the SNP genotyping, which indicated that the SNPs assay was suitable for individual traceability. High throughput sequencing revealed that 16 miRNAs were up‐regulated expression and 18 miRNAs were down‐regulated expression in JL group (eastern part) compared to XJ group (western part). RT‐PCR confirmed that bta‐miR‐2284ab and bta‐miR‐486 were differently expressed in Jilin and Xinjiang samples. Thus, the two miRNAs could be used as biomarkers for origin traceability.

Practical applications

To solve meat safety problems, meat traceability is extremely important. SNPs‐based technology can trace animal individuals and miRNAs‐based technology can do origin traceability. Once suitable primers could be designed for a sufficient number of SNP loci, these primers could be loaded on an array, and then traceability could be realized by HRM. We identified the miRNAs that were differently expressed among regions and beef origin traceability could be realized by analyzing them using RT‐PCR. All the detection methods are rapidly and cost‐effectively. A combination of SNPs‐ and miRNAs‐based technologies can implement traceability management of beef cattle.
Intergranular diffusion rates from the analysis of garnet surfaces: Implications for metamorphic equilibration
Authors: Dempster Tim J. , Symon Shona , Chung Peter
Published: March 2017

Novel approaches to garnet analysis have been used to assess rates of intergranular diffusion between different matrix phases and garnet porphyroblasts in a regionally metamorphosed staurolite‐mica‐schist from the Barrovian‐type area in Scotland. X‐ray maps and chemical traverses of planar porphyroblast surfaces reveal chemical heterogeneity of the garnet grain boundary linked to the nature of the adjacent matrix phase. The garnet preserves evidence of low temperature retrograde exchange with matrix minerals and diffusion profiles documenting cation movement along the garnet boundaries. Garnet–quartz and garnet–plagioclase boundaries preserve evidence of sluggish Mg, Mn and Fe diffusion at comparable rates to volume diffusion in garnet, whereas diffusion along garnet–biotite interfaces is much more effective. Evidence of particularly slow Al transport, probably coupled to Fe3+ exchange, is locally preserved on garnet surfaces adjacent to Fe‐oxide phases. The Ca distribution on the garnet surface shows the most complex behaviour, with long‐wavelength heterogeneities apparently unrelated to the matrix grain boundaries. This implies that the Ca content of garnet is controlled by local availability and is thought likely to reflect disequilibrium established during garnet growth. Geochemical anomalies on the garnet surfaces are also linked to the location of triple junctions between the porphyroblasts and the matrix phases, and imply enhanced transport along these channels. The slow rates of intergranular diffusion and the characteristics of different boundary types may explain many features associated with the prograde growth of garnet porphyroblasts. Thus, minerals such as quartz, Fe‐oxides and plagioclase whose boundaries with garnet are characterized by slow intergranular diffusion rates appear to be preferentially trapped as inclusions within porphyroblasts. As such grain boundary diffusion rates may be a significant kinetic impediment to metamorphic equilibrium and garnet may struggle to maintain chemical and textural equilibrium during growth in pelites.
A quantitative structural and morphometric analysis of the Purkinje network and the Purkinje–myocardial junctions in pig hearts
Authors: Garcia‐Bustos V. , Sebastian R. , Izquierdo M. , Molina P. , Chorro F. J. , Ruiz‐Sauri A.
Published: March 2017

The morpho‐functional properties of the distal section of the cardiac Purkinje network (PN) and the Purkinje–myocardial junctions (PMJs) are fundamental to understanding the sequence of electrical activation in the heart. The overall structure of the system has already been described, and several computational models have been developed to gain insight into its involvement in cardiac arrhythmias or its interaction with implantable devices, such as pacemakers. However, anatomical descriptions of the PN in the literature have not enabled enough improvements in the accuracy of anatomical‐based electrophysiological simulations of the PN in 3D hearts models. In this work, we study the global distribution and morphological properties of the PN, with special emphasis on the cellular and architectural characterization of its intramural branching structure, mesh‐like sub‐endocardial network, and the PMJs in adult pig hearts by both histopathological and morphometric evaluation. We have defined three main patterns of PMJ: contact through cell bodies, contact through cell prolongations either thick or piliform, and contact through transitional cells. Moreover, from hundreds of micrographs, we quantified the density of PMJs and provided data for the basal/medial/apical regions, anterior/posterior/septal/lateral regions and myocardial/sub‐endocardial distribution. Morphometric variables, such as Purkinje cell density and thickness of the bundles, were also analyzed. After combining the results of these parameters, a different septoanterior distribution in the Purkinje cell density was observed towards the cardiac apex, which is associated with a progressive thinning of the conduction bundles and the posterolateral ascension of intramyocardial terminal scattered fibers. The study of the PMJs revealed a decreasing trend towards the base that may anatomically explain the early apical activation. The anterolateral region contains the greatest number of contacts, followed by the anterior and septal regions. This supports the hypothesis that thin distal Purkinje bundles create a junction‐rich network that may be responsible for the quick apical depolarization. The PN then ascends laterally and spreads through the anterior and medial walls up to the base. We have established the first morphometric study of the Purkinje system, and provided quantitative and objective data that facilitate its incorporation into the development of models beyond gross and variable pathological descriptions, and which, after further studies, could be useful in the characterization of pathological processes or therapeutic procedures.
Distribution of the characteristics of barbs and barbules on barn owl wing feathers
Authors: Weger Matthias , Wagner Hermann
Published: March 2017

Owls are known for the development of a silent flight. One conspicuous specialization of owl wings that has been implied in noise reduction and that has been demonstrated to change the aerodynamic behavior of the wing is a soft dorsal wing surface. The soft surface is a result of changes in the shape of feather barbs and barbules in owls compared with other bird species. We hypothesized that as the aerodynamic characteristics of a wing change along its chordwise and spanwise direction, so may the shape of the barbs and barbules. Therefore, we examined in detail the shapes of the barbs and barbules in chordwise and spanwise directions. The results showed changes in the shapes of barbs and barbules at the anterior and distal parts of the wing, but not at more posterior parts. The increased density of hook radiates at the distalmost wing position could serve to stiffen that vane part that is subject to the highest forces. The change of pennulum length in the anterior part of the wing and the uniformity further back could mean that a soft surface may be especially important in regions where flow separation may occur.
Rosuvastatin promotes benefits on induced periodontitis in hypertensive rats
Authors: Messora M. R. , Apolinário Vieira G. H. , Vanderlei J. M. T. M. M. , Mariguela V. C. , Fernandes P. G. , Palioto D. B. , Scombatti de Souza S. L. , Novaes A. B. , Furlaneto F. , Taba M.
Published: March 2017

Background and Objective

The potential benefits of statins in modulating periodontal disease is supported by in vitro and clinical studies showing statins can induce a lower expression of proinflammatory cytokines and matrix metalloproteinases. The aim of this study was to evaluate the effects of rosuvastatin (ST) on ligature‐induced periodontitis in spontaneously hypertensive rats (SHR).

Material and Methods

Fifty‐four adult male rats were divided into three groups: SHR‐C, SHR‐L and SHR‐L‐ST (C, control; L, ligature groups). In the SHR‐L‐ST group, animals were treated with daily 2 mg/kg ST administration. In L groups, a ligature remained around mandibular first molars for 10 d. Each group was divided for killing at 10 or 21 d postoperatively. Microtomographic and histometric analyses were performed. Osteoclastogenesis was evaluated by tartrate‐resistant acid phosphatase assay and gene expression of 84 proinflammatory mediators by polymerase chain reaction array.

Results

The SHR‐L‐ST group showed reduced bone loss and attachment loss in comparison with the SHR‐L group at both 10 and 21 d postoperatively (p < 0.05). ST decreased the amount of tartrate‐resistant acid phosphatase‐positive cells compared with the SHR‐L group at both 10 and 21 d (p < 0.05). The SHR‐L‐ST group presented 14 genes differentially expressed when compared with SHR‐L group, featuring a downregulated gene profile at 10 d.

Conclusion

Statin therapy may promote a protective effect against alveolar bone and connective tissue attachment losses attributable to periodontitis in hypertensive rats through inflammatory gene profile modulation.
Vitamin D‐binding protein expression in healthy tooth and periodontium: an experimental study both in monkeys in vivo and in humans in vitro
Authors: Li W. , Zhu W. , Hou J. , Meng H.
Published: March 2017

Background and Objective

Vitamin D‐binding protein (DBP) is a highly expressed plasma protein with many important functions, including transport of vitamin D metabolites, sequestration of actin, control of bone metabolism and modulation of immune and inflammatory responses. Previous results of our study indicated an association between DBP and periodontitis. We hypothesized that periodontium might be another source of DBP in gingival crevicular fluid other than serum.

Material and Methods

DBP expression was examined in dental and periodontal tissues of monkeys by immunohistochemistry, and in primary cells isolated from human dental and periodontal tissues by reverse transcription plus the polymerase chain reaction and immunocytochemistry.

Results

DBP was constitutively expressed and widely distributed in dental and periodontal tissues of primates. Their immunoreaction was evident in gingival epithelium, particularly in junctional epithelium, and in mineralizing areas of the dental pulp, periodontal ligament and bone marrow. Correspondingly, mRNA and protein expression were detected in primary human gingival epithelial cells, dental pulp cells and periodontal ligament cells.

Conclusion

DBP is highly expressed and widely distributed in dental and periodontal tissues, which may take an active part in local host defense and hard tissue metabolism.
From substrate specificity to promiscuity: hybrid ABC transporters for osmoprotectants
Authors: Teichmann Laura , Chen Chiliang , Hoffmann Tamara , Smits Sander H.J. , Schmitt Lutz , Bremer Erhard
Published: March 2017

The ABC‐transporters OpuB and OpuC fromBacillus subtilisfunction as osmoprotectant import systems. Their structural genes have most likely evolved through a duplication event but the two transporters are remarkably different in their substrate profile. OpuB possesses narrow substrate specificity, while OpuC is promiscuous. We assessed the functionality of hybrids between these two ABC‐transporters by reciprocally exchanging the coding regions for the OpuBC and OpuCC substrate‐binding proteins between the correspondingopuBandopuCoperons. Substantiating the critical role of the binding protein in setting the substrate specificity of ABC transporters, OpuB::OpuCC turned into a promiscuous system, while OpuC::OpuBC now exhibited narrow substrate specificity. Both hybrid transporters possessed a high affinity for their substrates but the transport capacity of the OpuB::OpuCC system was moderate due to the synthesis of only low amounts of the xenogenetic OpuCC protein. Suppressor mutations causing single amino acid substitutions in the GbsR repressor controlling the choline to glycine betaine biosynthesis pathway greatly improved OpuB::OpuCC‐mediated compatible solute import through transcriptional up‐regulation of the hybridopuB::opuCCoperon. Collectively, we demonstrate for the first time that one can synthetically switch the substrate specificity of a given ABC transporter by combining its core components with a xenogenetic ligand‐binding protein.
The Jewish diaspora and Israel: belonging at distance?
Authors: Dieckhoff Alain
Published: March 2017

The involvement of diasporas in the advent of modern nationalism is not a new phenomenon: already in the 19th century some diasporas wanted to ‘normalise’ their national existence by building a state of their own. However, with the growing globalisation trend in the 199'0s , especially in the areas of transportation and communication, Benedict Anderson put forward the idea of long‐distance nationalism (LDN), as a new way of linking diasporas and the national project and thus creating a more intense sense of belonging. LDN has been characterised by him as having two main features: its unaccountability which allows for intense political radicalism, and its instrumental function for strengthening ethnic identity in the diaspora and thus a sense of belonging. I will test those hypotheses in the case of the archetypal Jewish diaspora.
Dreaming as a critical discourse of national belonging: China Dream, American Dream and world dream
Authors: Callahan William A.
Published: March 2017

This article explores the normative politics of national belonging through an analysis of the ‘China Dream’ and the ‘American Dream’. It traces how politicians and public intellectuals employ such slogans to highlight how national dreams emerge in times of crisis and involve a combination of aspirations and anxieties. It compares parallel rhetorical strategies – ‘patriotic worrying’ in China and the American Jeremiad in the US – to examine how belonging to these two nations involves a nostalgic longing for the past as a model for the future. Debates about the meaning of these national dreams highlight the tension between freedom and equality in the US, between the individual and the collective in China, and between longing for the true nation, and belonging in the actual nation for both countries. It concludes that while this quest for redemption through past models limits opportunities for critical discourse in China, the American Dream still contains much ‘promise’. The China Dream and the American Dream thus are, at the same time, 1) familiar expressions of nationalism and national belonging, and 2) ongoing self/Other coherence‐producing performances that help us to question received notions of nationalism and national belonging.
Pharyngeal stimulus‐induced reflexes are impaired in infants with perinatal asphyxia: Does maturation modify?
Authors: Jensen P. S. , Gulati I. K. , Shubert T. R. , Sitaram S. , Sivalingam M. , Hasenstab K. A. , El‐Mahdy M. A. , Jadcherla S. R.
Published: March 2017

Background

Development of pharyngo‐esophageal protective reflexes among infants with hypoxic ischemic encephalopathy (HIE) is unclear. Our aim was to distinguish these reflexes from controls and examine the maturational changes in HIE infants.

Methods

We evaluated 14 HIE infants (seven males) at 41.4±0.6 (HIE Time‐1) and 46.5±0.6 (HIE Time‐2) weeks postmenstrual age (PMA). Seven controls (three males) were evaluated at 43.5±1.3 weeks PMA. Graded pharyngeal stimulation with liquids (0.1, 0.3, 0.5 mL in triplicate) concurrent with high‐resolution manometry was used to analyze sensory‐motor components of pharyngeal reflexive swallowing (PRS), upper esophageal sphincter (UES), contractile reflex (PUCR), and esophageal body characteristics. Linear mixed and generalized estimating equation models were used for comparison among groups.

Key Results

Compared to controls, HIE infants (Time‐1 and Time‐2) exhibited decreased number of pharyngeal peaks and latency to terminal swallow. HIE Time‐1 infants showed increased UES resting tone and distal latency, compared to controls and HIE Time‐2. Contractile vigor was increasingly abnormal during maturation, compared to healthy controls. Threshold volumes and frequency distribution of primary responses (PRS: PUCR: None) were not significant among all groups.

Conclusions & Inferences

Compared to controls, HIE infants display significant hypertonicity of skeletal muscle components, impairment of pharyngeal provocation‐induced reflexes and smooth muscle contractile vigor, reflecting poor propagation with maturation. These mechanisms may be responsible for inadequate clearance of secretions, ascending refluxate, and oropharyngeal bolus in HIE infants.