bluuebunny/crossref_metadata_2025 huggingface dataset:
Farm exposure and time trends in early childhood may influence DNA methylation in genes related to asthma and allergy
Authors: Michel S. , Busato F. , Genuneit J. , Pekkanen J. , Dalphin J.‐C. , Riedler J. , Mazaleyrat N. , Weber J. , Karvonen A. M. , Hirvonen M.‐R. , Braun‐Fahrländer C. , Lauener R. , von Mutius E. , Kabesch M. , Tost J. ,   the PASTURE study group
Published: January 2013

Background

Genetic susceptibility and environmental influences are important contributors to the development of asthma and atopic diseases. Epigenetic mechanisms may facilitate gene by environment interactions in these diseases.

Methods

We studied the rural birth cohort PASTURE (Protection against allergy: study in rural environments) to investigate (a) whether epigenetic patterns in asthma candidate genes are influenced by farm exposure in general, (b) change over the first years of life, and (c) whether these changes may contribute to the development of asthma. DNA was extracted from cord blood and whole blood collected at the age of 4.5 years in 46 samples per time point. DNA methylation in 23 regions in ten candidate genes (ORMDL1, ORMDL2, ORMDL3, CHI3L1, RAD50, IL13, IL4, STAT6, FOXP3, and RUNX3) was assessed by pyrosequencing, and differences between strata were analyzed by nonparametric Wilcoxon–Mann–Whitney tests.

Results

In cord blood, regions in ORMDL1 and STAT6 were hypomethylated in DNA from farmers' as compared to nonfarmers' children, while regions in RAD50 and IL13 were hypermethylated (lowest P‐value (STAT6) = 0.001). Changes in methylation over time occurred in 15 gene regions (lowest P‐value (IL13) = 1.57*10−8). Interestingly, these differences clustered in the genes highly associated with asthma (ORMDL family) and IgE regulation (RAD50, IL13, and IL4), but not in the T‐regulatory genes (FOXP3, RUNX3).

Conclusions

In this first pilot study, DNA methylation patterns change significantly in early childhood in specific asthma‐ and allergy‐related genes in peripheral blood cells, and early exposure to farm environment seems to influence methylation patterns in distinct genes.
The adjuvant‐like activity of staphylococcal enterotoxin B in a murine asthma model is independent of IL‐1R signaling
Authors: Krysko O. , Maes T. , Plantinga M. , Holtappels G. , Imiru R. , Vandenabeele P. , Joos G. , Krysko D. V. , Bachert C.
Published: January 2013

Background

Staphylococcal enterotoxin B (SEB) is a superantigen known to be a modulator of chronic airway inflammation in mice and humans, yet little is known about the mechanisms that regulate its interaction with the innate immune system. We investigated this mechanism in a murine model of allergic airway inflammation induced by OVA (ovalbumin) in the presence of SEB.

Methods

Superantigen‐induced allergic inflammation was studied in IL‐1R knockout (KO) mice exposed to OVA+SEB. Multicolor flow cytometry was used to analyze the inflammatory cell profile in airways and lymph nodes. Production of IL‐4, IL‐5, IL‐10, and IL‐13 in lymph nodes was assessed by Luminex technology.

Results

In wild‐type mice, endonasal instillation of OVA+SEB induced a pulmonary inflammation, characterized by an increase in the number of eosinophils, T cells, and dendritic cells and in the production of Th2 cytokines and OVA‐specific IgE. In IL‐1R KO mice exposed to OVA+SEB, attraction of CD4+ cells and production of Th2 cytokines were reduced. However, knocking out IL‐1R did not affect any of the features of allergic airway inflammation, such as bronchial eosinophilia, OVA‐specific IgE production and goblet cell metaplasia.

Conclusion

We provide new insights into the mechanisms of airways allergy development in the presence of bacterial superantigen. The asthma features induced by OVA+SEB, such as bronchial eosinophilia, goblet cell proliferation, production of OVA‐specific IgE and increase in inflammatory dendritic cells, are IL‐1R independent. Yet, IL‐1R signaling is crucial for CD4 cell accumulation and Th2 cytokine production.
Air pollution interacts with past episodes of bronchiolitis in the development of asthma
Authors: Kim B. J. , Seo J. H. , Jung Y. H. , Kim H. Y. , Kwon J. W. , Kim H. B. , Lee S. Y. , Park K. S. , Yu J. , Kim H. C. , Leem J. H. , Lee J. Y. , Sakong J. , Kim S. Y. , Lee C. G. , Kang D. M. , Ha M. , Hong Y. C. , Kwon H. J. , Hong S. J.
Published: January 2013

Background

Exposure to ambient air pollution and bronchiolitis are risk factors for asthma. The aim of this study was to investigate the effect of air pollution on the development of asthma in children with past episodes of bronchiolitis.

Methods

A prospective 2‐year follow‐up survey consisting of parental responses to the International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire, and allergy evaluations were conducted in 1743 children with a mean age of 6.8 years. Recent 5‐year exposure to air pollution was estimated using a geographic information system.

Results

Higher exposure to ozone was associated with airway hyper‐responsiveness (PC20 ≤ 16 mg/ml) at enrollment (odds ratio [OR] = 1.60, 95% CI [confidence interval] = 1.13–2.27) and with new episodes of wheezing during the 2‐year period (OR = 1.92, 95% CI = 0.96–3.83). Past episodes of bronchiolitis were associated with both current wheezing and physician‐diagnosed asthma. When the two factors were combined, the prevalence of bronchial hyper‐reactivity (OR = 2.96, 95% CI = 1.41–6.24) and new wheezing (OR = 4.17, 95% CI = 0.89–19.66) as well as current wheezing and physician‐diagnosed asthma was even greater (P for trend <0.05 for all). In children with both risk factors, lung function was significantly decreased, with atopic children being particularly vulnerable.

Conclusion

In children, the interaction between air pollution and past episodes of bronchiolitis resulted in a greater prevalence of asthma and pointed to an association with bronchial hyper‐reactivity and decreased lung function. These results suggest mechanisms underlying the development of asthma.
Identifying the translational gap in the evaluation of drug‐induced QTc interval prolongation
Authors: Chain Anne S.Y. , Dubois Vincent F.S. , Danhof Meindert , Sturkenboom Miriam C.J.M. , Della Pasqua Oscar ,   Cardiovascular Safety Project Team, TI Pharma PKPD Platform
Published: January 2013

Aims

Given the similarities in QTc response between dogs and humans, dogs are used in pre‐clinical cardiovascular safety studies. The objective of our investigation was to characterize the PKPD relationships and identify translational gaps across species following the administration of three compounds known to cause QTc interval prolongation, namely cisapride, d, l‐sotalol and moxifloxacin.

Methods

Pharmacokinetic and pharmacodynamic data from experiments in conscious dogs and clinical trials were included in this analysis. First, pharmacokinetic modelling and deconvolution methods were applied to derive drug concentrations at the time of each QT measurement. A Bayesian PKPD model was then used to describe QT prolongation, allowing discrimination of drug‐specific effects from other physiological factors known to alter QT interval duration. A threshold of ≥10 ms was used to explore the probability of prolongation after drug administration.

Results

A linear relationship was found to best describe the pro‐arrhythmic effects of cisapride, d,l‐sotalol and moxifloxacin both in dogs and in humans. The drug‐specific parameter (slope) in dogs was statistically significantly different from humans. Despite such differences, our results show that the probability of QTc prolongation ≥10 ms in dogs nears 100% for all three compounds at the therapeutic exposure range in humans.

Conclusions

Our findings indicate that the slope of PKPD relationship in conscious dogs may be used as the basis for the prediction of drug‐induced QTc prolongation in humans. Furthermore, the risk of QTc prolongation can be expressed in terms of the probability associated with an increase ≥10 ms, allowing direct inferences about the clinical relevance of the pro‐arrhythmic potential of a molecule.
International Caries Detection and Assessment System (ICDAS) and its International Caries Classification and Management System (ICCMS) – methods for staging of the caries process and enabling dentists to manage caries
Authors: Pitts NB , Ekstrand KR ,   The ICDAS Foundation
Published: January 2013

Objectives

The aim of this article is to provide an overview of the International Caries Detection and Assessment System (ICDAS) and its associated International Caries Classification and Management System (ICCMS™), explain the evolution of these systems over the past decade and outline how they are being used for staging of the caries process in order to enable dentists to manage caries appropriately.

Methods

the article outlines and references the key steps in development of these systems.

Results

ICDAS employs an evidence‐based and preventively oriented approach, is a detection and assessment system classifying stages of the caries process on the basis of histological extent and activity, is designed for use in the four domains of clinical practice, education, research and public health and provides all stakeholders with a common language for staging caries. Over a decade ICDAS has evolved to comprise a number of approved, compatible ‘formats’, supports decision making at both individual and public health levels and has generated the ICCMS™ to enable improved long‐term caries outcomes. A range of further developments are in train, to assist with information capture and making clinical systems simpler and more practice friendly.

Conclusion

ICDAS provides flexible and increasingly internationally adopted methods for classifying stages of the caries process and the activity status of lesions which can be incorporated into the ICCMS™. The ICCMS™ provides options to enable dentists to integrate and synthesize tooth and patient information, including caries risk status, in order to plan, manage and review caries in clinical and public health practice.
Retracted: Crestal bone reactions to immediate implants placed at different levels in relation to crestal bone. A pilot study in Foxhound dogs
Authors: Calvo‐Guirado José L. , Boquete‐Castro Ana , Negri Bruno , Delgado Ruiz Rafael , Gómez‐Moreno Gerardo , Iezzi Giovanna
Published: January 2013

Objectives

The aim of the present study was to evaluate bone‐to‐implant contact (BIC) and bone remodeling dynamics after immediate implant placement at different levels in relation to the crestal bone.

Materials and methods

The mandibular second, third, and fourth premolars of six Foxhound dogs were extracted bilaterally. Randomly, three implants were immediately placed in the hemi‐arches of each dog, crestally or 2 mm subcrestally. Three dogs were allowed an 8‐week submerged healing period, and the other three at 12‐week submerged healing period. The animals were sacrificed at 12 weeks and samples were obtained. Biopsies were processed for ground sectioning. Histomorphometric analysis was carried out to compare BIC, bone neoformation, and bone remodeling.

Results

All implants osseointegrated clinically and histologically. Healing patterns examined microscopically at eight and twelve weeks for both groups (crestal and subcrestal) yielded similar qualitative bone findings. The Total BIC mean value for the crestal group 44.52% at 8 weeks and 39.50% at 12 weeks, and for the subcrestal group was 47.33% at 8 weeks and 53.85% at 12 weeks%. There was less bone resorption in the subcrestal group (test) than in crestal group (control).

Conclusions

Within the limitations of this study, our findings suggest that apical positioning of the top of the implant does not jeopardize bone crest and peri‐implant tissue remodeling. However, less resorption of the lingual crest may be expected when implants are placed 2 mm subcrestally. Moreover, higher BIC values were found in implants placed subcrestally.
Coronary Artery Wall Thickness of the Left Anterior Descending Artery Using High Resolution Transthoracic Echocardiography – Normal Range of Values
Authors: Perry Rebecca , Joseph Majo X. , Chew Derek P. , Aylward Philip E. , De Pasquale Carmine G.
Published: January 2013

Recently it has been demonstrated that high resolution transthoracic echocardiography (HRTTE) is able to detect differences in the wall thickness of the left anterior descending coronary artery (LAD) between patients with coronary artery disease (CAD) and normal volunteers. We sought to validate this technique, develop a normal range of values and demonstrate the test–retest variability of each measurement. Two hundred forty‐two volunteer participants had a HRTTE study to measure their LAD wall thickness, luminal, and external diameters. Thirty of these subjects had these measurements taken on 3 separate occasions by 2 different echosonographers. All subjects were free of clinical CAD, hypertension, hyperlipidemia, and diabetes mellitus. The average anterior wall thickness was 1.1 ± 0.2 mm; posterior wall thickness was 1.1 ± 0.2 mm, luminal diameter 2.2 ± 0.6 mm, and external elastic membrane (EEM) diameter 4.5 ± 0.9 mm. The bias of the measurements within the same operator for LAD wall thickness, luminal diameter, and EEM was 0.042, −0.06, and −0.077 mm, respectively. The bias of the measurements between 2 different operators for LAD wall thickness, luminal diameter, and EEM was 0.082, −0.077, and −0.027 mm, respectively. In conclusion, HRTTE measurement of the LAD vessel is reproducible within and between operators in normal volunteers. This technique therefore warrants further study as a potential screening modality for subclinical coronary atherosclerosis.
Novel Simple Approach for Detection of Regional Perturbations of Cardiac Function in Mouse Models of Cardiovascular Disease
Authors: Shao Yangzhen , Redfors Bjorn , Tang Margareta Scharin , Assarsson Ulf , Omerovic Elmir
Published: January 2013

Aims

Transthoracic murine echocardiography is a cornerstone of small animal research, but conventional methods cannot detect regional perturbations in cardiac function. Reliable assessment of regional cardiac function would be of value in transgenic models of myocardial disease. Until now automatized algorithms for achieving this suffers from a number of drawbacks. We developed a simple algorithm for rapidly assessing the relative myocardial radial thickening that occurs between end‐diastole and end‐systole, that is, regional radial transmural end‐systolic strain (RTESS).

Methods and Results

Echocardiographic assessment was performed in mice at baseline (n = 8), 2 hours postintraperitoneal isoprenaline (ISO) injection (n = 8), and 10 days postmyocardial infarction (post‐MI) (n = 6). A >1000 frames/sec cine loop was acquired by the ECG‐gated Kilohertz visualization technique in the parasternal short‐axis projection at 3 mm below the mitral annulus. Endo‐ and epicardial borders were traced at end‐diastole and end‐systole and RTESS was calculated for each of n segments by the algorithm. The intra‐ and inter‐observer coefficients of variation for segmental RTESS assessment were 5.11 and 7.32, respectively. At baseline, average segmental RTESS was 56.75% and RTESS was similar in all cardiac segments regardless of how many segments the heart was divided into. In the akinetic myocardium of MI and ISO mice, 47.36% and 26.22% length of the endocardium, respectively, RTESS was near zero and significantly different from the remaining myocardium.

Conclusion

We describe a simple and straightforward approach to quantify regional myocardial deformation in mouse models of cardiovascular disease.
Testing manual dexterity using a virtual reality simulator: reliability and validity
Authors: Ben‐Gal G. , Weiss E. I. , Gafni N. , Ziv A.
Published: January 2013

Virtual reality dental training simulators, unlike traditional human‐based assessment, have the potential to enable consistent and reliable assessment. The purpose of this study was to determine whether a haptic simulator (IDEA Dental®) could provide a reliable and valid assessment of manual dexterity. A total of 106 participants were divided into three groups differing in dental manual dexterity experience: (i) 63 dental students, (ii) 28 dentists, (iii) 14 non‐dentists. The groups, which were expected to display various performance levels, were required to perform virtual drilling tasks in different geometric shapes. The following task parameters were registered: (i) Time to completion (ii) accuracy (iii) number of trials to successful completion and (iv) score provided by the simulator. The reliability of the tasks was calculated for each parameter. The simulator and its scoring algorithm showed high reliability in all the parameters measured. The simulator was able to differentiate between non‐professionals and dental students or non‐professionals and dentists. Our study suggests that for improved construct validity, shorter working times and more difficult tasks should be introduced. The device should also be designed to provide greater sensitivity in measuring the accuracy of the task.
Clinical, biochemical, and molecular studies in pyridoxine‐dependent epilepsy. Antisense therapy as possible new therapeutic option
Authors: Pérez Belén , Gutiérrez‐Solana Luis González , Verdú Alfonso , Merinero Begoña , Yuste‐Checa Patricia , Ruiz‐Sala Pedro , Calvo Rocio , Jalan Anil , Marín Laura López , Campos Oscar , Ruiz Maria Ángeles , Miguel Marta San , Vázquez Maria , Castro Margarita , Ferrer Isaac , Navarrete Rosa , Desviat Lourdes Ruiz , Lapunzina Pablo , Ugarte Magdalena , Pérez‐Cerdá Celia
Published: January 2013

Purpose

Pyridoxine‐dependent epilepsy seizure (PDE;OMIM266100) is a disorder associated with severe seizures that can be controlled pharmacologically with pyridoxine. In the majority of patients withPDE, the disorder is caused by the deficient activity of the enzyme α‐aminoadipic semialdehyde dehydrogenase (antiquitin protein), which is encoded by theALDH7A1gene. The aim of this work was the clinical, biochemical, and genetic analysis of 12 unrelated patients, mostly fromSpain, in an attempt to provide further valuable data regarding the wide clinical, biochemical, and genetic spectrum of the disease.

Methods

The disease was confirmed based on the presence of α‐aminoadipic semialdehyde (α‐AASA) in urine measured by liquid chromatography tandem mass spectrometry (LC‐MS/MS) and pipecolic acid (PA) in plasma and/or cerebrospinal fluid (CSF) measured by high performance liquid chromatography (HPLC)/MS/MSand by sequencing analysis of messenger RNA (mRNA) and genomicDNAofALDH7A1.

Key Findings

Most of the patients had seizures in the neonatal period, but they responded to vitaminB6 administration. Three patients developed late‐onset seizures, and most patients showed mild‐to‐moderate postnatal developmental delay. All patients had elevatedPAand α‐AASAlevels, even those who had undergone pyridoxine treatment for several years. The clinical spectrum of our patients is not limited to seizures but many of them show associated neurologic dysfunctions such as muscle tone alterations, irritability, and psychomotor retardation. The mutational spectrum of the present patients included 12 mutations, five already reported (c.500A>G, c.919C>T, c.1429G>Cc.1217_1218delAT, and c.1482‐1G>T) and seven novel sequence changes (c.75C>T, c.319G>T, c.554_555delAA, c.757C>T, c.787 + 1G>T, c.1474T>C, c.1093‐?_1620+?). Only one mutation, p.G477R(c.1429G>C), was recurrent; this was detected in four different alleles. Transcriptional profile analysis of one patient's lymphoblasts and ex vivo splicing analysis showed the silent nucleotide change c.75C>Tto be a novel splicing mutation creating a new donor splice site inside exon 1. Antisense therapy of the aberrantmRNAsplicing in a lymphoblast cell line harboring mutation c.75C>Twas successful.

Significance

The present results broaden our knowledge ofPDE, provide information regarding the genetic background ofPDEinSpain, afford data of use when making molecular‐based prenatal diagnosis, and provide a cellular proof‐of concept for antisense therapy application.
The isomerase and hydratase reaction mechanism of the crotonase active site of the multifunctional enzyme (type‐1), as deduced from structures of complexes with 3S‐hydroxy‐acyl‐CoA
Authors: Kasaragod Prasad , Schmitz Werner , Hiltunen Jukka K. , Wierenga Rik K.
Published: January 2013

The multifunctional enzyme, type‐1 (MFE1) is involved in several lipid metabolizing pathways. It catalyses: (a) enoyl‐CoA isomerase and (b) enoyl‐CoA hydratase (EC 4.2.1.17) reactions in its N‐terminal crotonase part, as well as (3) a 3S‐hydroxy‐acyl‐CoA dehydrogenase (HAD; EC 1.1.1.35) reaction in its C‐terminal 3S‐hydroxy‐acyl‐CoA dehydrogenase part. Crystallographic binding studies with rat peroxisomal MFE1, using unbranched and branched 2E‐enoyl‐CoA substrate molecules, show that the substrate has been hydrated by the enzyme in the crystal and that the product, 3S‐hydroxy‐acyl‐CoA, remains bound in the crotonase active site. The fatty acid tail points into an exit tunnel shaped by loop‐2. The thioester oxygen is bound in the classical oxyanion hole of the crotonase fold, stabilizing the enolate reaction intermediate. The structural data of these enzyme product complexes suggest that the catalytic base, Glu123, initiates the isomerase reaction by abstracting the C2‐proton from the substrate molecule. Subsequently, in the hydratase reaction, Glu123 completes the catalytic cycle by reprotonating the C2 atom. A catalytic water, bound between the OE1‐atoms of the two catalytic glutamates, Glu103 and Glu123, plays an important role in the enoyl‐CoA isomerase and the enoyl‐CoA hydratase reaction mechanism of MFE1. The structural variability of loop‐2 between MFE1 and its monofunctional homologues correlates with differences in the respective substrate preferences and catalytic rates.

Database

The structures have been deposited in the Protein Data Bank under accession numbers: 3ZW8 (MFE1 apo), 3ZW9 (MFE1 2S‐methyl‐3S‐hydroxy‐butanoyl‐CoA complex), 3ZWA (MFE1 3S‐hydroxy‐hexanoyl‐CoA complex), 3ZWB (MFE1‐E123A 2E‐hexenoyl‐CoA complex) and 3ZWC (MFE1 3S‐hydroxy‐decanoyl‐CoA complex).

Structured digital abstract

MFE1 and MFE1 bind by x-ray crystallography (View interaction)
Drought characteristics' role in widespread aspen forest mortality across Colorado, USA
Authors: Anderegg Leander D. L. , Anderegg William R. L. , Abatzoglou John , Hausladen Alexandra M. , Berry Joseph A.
Published: January 2013

Globally documented widespread drought‐induced forest mortality has important ramifications for plant community structure, ecosystem function, and the ecosystem services provided by forests. Yet the characteristics of drought seasonality, severity, and duration that trigger mortality events have received little attention despite evidence of changing precipitation regimes, shifting snow melt timing, and increasing temperature stress. This study draws upon stand level ecohydrology and statewide climate and spatial analysis to examine the drought characteristics implicated in the recent widespread mortality of trembling aspen (Populus tremuloides Michx.). We used isotopic observations of aspen xylem sap to determine water source use during natural and experimental drought in a region that experienced high tree mortality. We then drew upon multiple sources of climate data to characterize the drought that triggered aspen mortality. Finally, regression analysis was used to examine the drought characteristics most associated with the spatial patterns of aspen mortality across Colorado. Isotopic analysis indicated that aspens generally utilize shallow soil moisture with little plasticity during drought stress. Climate analysis showed that the mortality‐inciting drought was unprecedented in the observational record, especially in 2002 growing season temperature and evaporative deficit, resulting in record low shallow soil moisture reserves. High 2002 summer temperature and low shallow soil moisture were most associated with the spatial patterns of aspen mortality. These results suggest that the 2002 drought subjected Colorado aspens to the most extreme growing season water stress of the past century by creating high atmospheric moisture demand and depleting the shallow soil moisture upon which aspens rely. Our findings highlight the important role of drought characteristics in mediating widespread aspen forest mortality, link this aspen die‐off to regional climate change trends, and provide insight into future climate vulnerability of these forests.
Tidal marsh plant responses to elevated CO2, nitrogen fertilization, and sea level rise
Authors: Adam Langley J. , Mozdzer Thomas J. , Shepard Katherine A. , Hagerty Shannon B. , Patrick Megonigal J.
Published: January 2013

Elevated CO2 and nitrogen (N) addition directly affect plant productivity and the mechanisms that allow tidal marshes to maintain a constant elevation relative to sea level, but it remains unknown how these global change drivers modify marsh plant response to sea level rise. Here we manipulated factorial combinations of CO2 concentration (two levels), N availability (two levels) and relative sea level (six levels) using in situ mesocosms containing a tidal marsh community composed of a sedge, Schoenoplectus americanus, and a grass, Spartina patens. Our objective is to determine, if elevated CO2 and N alter the growth and persistence of these plants in coastal ecosystems facing rising sea levels. After two growing seasons, we found that N addition enhanced plant growth particularly at sea levels where plants were most stressed by flooding (114% stimulation in the + 10 cm treatment), and N effects were generally larger in combination with elevated CO2 (288% stimulation). N fertilization shifted the optimal productivity of S. patens to a higher sea level, but did not confer S. patens an enhanced ability to tolerate sea level rise. S. americanus responded strongly to N only in the higher sea level treatments that excluded S. patens. Interestingly, addition of N, which has been suggested to accelerate marsh loss, may afford some marsh plants, such as the widespread sedge, S. americanus, the enhanced ability to tolerate inundation. However, if chronic N pollution reduces the availability of propagules of S. americanus or other flood‐tolerant species on the landscape scale, this shift in species dominance could render tidal marshes more susceptible to marsh collapse.
Minimum resection margin should be based on tumor size in hepatectomy for hepatocellular carcinoma in hepatoviral infection patients
Authors: Sasaki Kazunari , Matsuda Masamichi , Ohkura Yu , Kawamura Yusuke , Hashimoto Masaji , Ikeda Kenji , Kumada Hiromitsu , Watanabe Goro
Published: January 2013

Aim

In patients with hepatoviral infection, although a wide resection margin can eradicate the microsatellite lesions around hepatocellular carcinoma (HCC), a large‐volume hepatectomy may diminish remaining liver function and become an obstacle for treating recurrent HCC. The optimal width of the resection margin for these patients is still controversial. This study was conducted to investigate the optimal resection margin in hepatectomy for hepatoviral infection patients.

Methods

We retrospectively investigated the influences of the resection margin status on recurrence patterns and long‐term prognosis in a group of 311 HCC patients with hepatoviral infection who had a solitary HCC without perioperative anti‐HCC treatment.

Results

The resection margin status did not statistically influence the postoperative recurrence‐free and overall survival rates (3‐year recurrence‐free survival of 61.0% vs 55.1%, P = 0.33; 5‐year overall survival of 74.9% vs 81.5%, P = 0.77 in without a margin vs with a margin, respectively), although resection without a margin increased the local recurrence with marginal significance (P = 0.055). Regarding the width of the resection margin, in 30‐mm or smaller HCC, resection margin did not significantly improve the prognosis among hepatoviral infection patients. However, for tumors larger than 30 mm, a resection margin wider than 3 mm showed significant impacts on the prevention of recurrence in spite of the influence of multicentric carcinogenesis.

Conclusion

The resection margin used for eradication of microsatellite lesions showed differences that were dependent on tumor size in hepatoviral infection patients. Resection margin should be based on not only background liver function but also tumor characteristics.
Quality of life of patients with vitiligo attending the Regional Dermatology Training Center in Northern Tanzania
Authors: Kiprono Samson , Chaula Baraka , Makwaya Cyprian , Naafs Bernard , Masenga John
Published: January 2013

Background  Vitiligo is an acquired, predominantly asymptomatic, depigmenting disorder with profound psychological effects.

Methods  This was a cross‐sectional study conducted at the Regional Dermatology Training Center in Moshi, Tanzania. All 88 patients with vitiligo older than 15 years of age who attended the skin clinic from October 2009 to April 2010 were recruited. Data were collected using a structured questionnaire, Dermatology Life Quality Index questionnaire (DLQI), and Vitiligo European Task Force form.

Results  Vitiligo moderately affects patient’s quality of life, as indicated by a DLQI mean score of 7.2 ± 4.8. The mean age was 41 years with a male/female ratio of 1:1.7. The mean age of disease onset was 33.5 years (range 16–83 years); vitiligo vulgaris was the most common disease form seen (n = 49). None of the factors considered were found to be significantly associated with impaired quality of life on multivariate analysis. The majority of patients (73.8%) perceived that their disease was moderate to severe in contrast to the clinical grading in which only 49.2% patients were classified as having mild disease. This difference in classification of disease severity was statistically significant (Fishers exact test = 0.001).

Conclusion  Patients with vitiligo of African descent have a moderate impairment of quality of life.
Long‐term outcome of small, organ‐confined renal cell carcinoma (RCC) is not always favourable
Authors: Shindo Tetsuya , Masumori Naoya , Kobayashi Ko , Fukuta Fumimasa , Hirobe Megumi , Tonooka Akiko , Hasegawa Tadashi , Kitamura Hiroshi , Tsukamoto Taiji
Published: January 2013

What's known on the subject? and What does the study add?

Small, organ‐confined renal cell carcinoma (RCC) generally has favourable pathological characteristics and a good prognosis. However, late recurrence is a known characteristic of the biological behaviour of RCC and no consensus has been established for surveillance protocols from 5 years after radical or partial nephrectomy.

In the present study with long‐term follow‐up of patients with small RCCs, 18 of 172 patients (10.5%) with pT1a RCC developed recurrence and eight of these (4.7%) died from cancer. Patients with microvascular invasion had a higher risk for cancer death than those without (P < 0.001, Log‐rank test). Therefore long‐term follow‐up is required after surgery, particularly when the disease has microvascular invasion.

Objectives

To identify the long‐term clinical course of small, organ‐confined renal cell carcinoma (RCC).

To detect the risk factors of recurrence and of cancer death in small RCC.

Patients and Methods

Retrospectively reviewed 172 patients who were pathologically diagnosed as having pT1a RCC without metastasis at our institution from 1980 to 2005.

All pathology slides were re‐reviewed by a single experienced pathologist.

Associations of microvascular invasion (MVI), development of metastasis, and cancer death were evaluated using Cox proportional hazards analysis.

Results

During a median (range) follow‐up of 104.5 (8–308) months, 18 patients (10.5%) developed progression and eight patients (4.7%) died from cancer.

Kaplan–Meier curves showed higher cancer‐specific survival (CSS) in patients without MVI (P < 0.001).

In multivariate analysis, MVI was the only factor that reached statistical significance (P = 0.006).

The 10‐year CSS rates were 85.1% and 96.5% in patients with and without MVI, respectively.

Conclusions

Patients with MVI have worse survival than those without MVI.

This suggests that long‐term follow‐up of patients with small RCCs is needed because of the risk of recurrence and cancer death even 10 years after surgery, particularly when the disease has apparent MVI.
Orthographic learning during reading: the role of whole‐word visual processing
Authors: Bosse Marie‐line , Chaves Nathalie , Largy Pierre , Valdois Sylviane
Published: January 2013

The self‐teaching hypothesis suggests that knowledge about the orthographic structure of words is acquired incidentally during reading through phonological recoding. The current study assessed whether visual processing skills during reading further contribute to orthographic learning. French children were asked to read pseudowords. The whole pseudoword letter string was available at once for half of the targets while the pseudoword's sub‐lexical units were discovered in turn for the other half. Then memorisation of the targets’ orthographic form was assessed. Although most pseudowords were accurately decoded, target orthographic forms were recognised more often when the pseudowords entire orthographic sequence was available at once during the learning phase. The whole‐word presentation effect was significant and stable from third to fifth grades. This effect was affected neither by target reading accuracy nor by target reading speed during the learning phase. Results suggest that beyond recoding skills, the ability to process the entire orthographic letter string at once during reading contributes to efficient orthographic learning.
Occupational stereotypes: activation of male bias in a gender‐neutral world
Authors: Lassonde Karla A. , O'Brien Edward J.
Published: January 2013

The goal of the present study was to determine whether gender‐neutral language, used to replace male‐biased language, carries an implicit male bias. Participants read passages in which a target occupation was introduced using either male‐biased or gender‐neutral nouns. A target sentence followed defining the gender of the occupational character. In Experiment 1, participants read target sentences defining the character as a woman more slowly following passages that contained male‐biased nouns and gender‐neutral nouns. In Experiment 2, an additional sentence was added that defined the occupational character as a woman. This information eliminated the reading disruption in Experiment 1 demonstrating that gender‐neutral language can moderate against activation of gender stereotypes when combined with an explicit mention that the occupational character is female.
Assessing five decades of change in a high Arctic parasitoid community
Authors: Timms Laura L. , Bennett Andrew M. R. , Buddle Christopher M. , Wheeler Terry A.
Published: January 2013

Arctic ecosystems are fragile, and are particularly sensitive to the pressures of climate change. Both average temperature and precipitation have increased over the past five decades on Ellesmere Island, Nunavut, Canada in the high Arctic. Altered growth forms and increased biomass in dominant plant species on Ellesmere Island have been observed concurrent with the changing climate, but shifts in the diversity or rank abundance of plant and bird species have not been detected. Changes in diversity may take longer to appear, or may be assessed better using organisms with shorter generation times such as insects. We explored the ecological impacts of climate change on Ellesmere Island using historical and contemporary communities of ichneumonid wasps. We compared community diversity, functional composition, and body size of two common species using ichneumonid specimens collected in 1961–1965, 1980–1982, 1989–1992, and 2010. We found high compositional similarity between collections, overlapping estimates of species richness, no change in the proportion of idiobiont genera in the community, and no clear pattern in body size over time. The greatest amount of variation over time was detected in parasitoids of herbivores; proportionally fewer herbivore‐parasitizing genera were found in 2010 than in historical collections, and the two genera that were only found in one of the four collections were both parasitoids of herbivores. Our results point to the need to assess climate change effects in Arctic systems using a range of taxa, and responses to large‐scale environmental disturbances may be idiosyncratic and difficult to predict.
Abelmoschus enbeepeegearense sp. nov. (Malvaceae), an endemic species of okra from Western Ghats, India
Authors: John K. Joseph , Scariah Sheen , Nissar V. A. Muhammed , Bhat K. V. , Yadav S. R.
Published: January 2013

Abelmoschus enbeepeegearense J. John et al. is a new species occurring at low elevations in the Western Ghats of India, comprising Kerala, Karnataka and Tamil Nadu. The taxon is morphologically allied to A. moschatus subsp. moschatus, A. moschatus subsp. tuberosus and A. crinitus, but easily distinguishable by virtue of its orthotropic branching, 3–5‐angled leaves, glandular hairy plant body with whitish waxy secretions, glandular non‐setose epiclayx segmens which is more than eight in number and ovate hirsute fruits with a short mucro at the apex. It can be crossed with all three taxa with varying degree of success, but the hybrids are sterile. The material belonging to it was earlier identified as and placed under A. moschatus Medik. The taxon is described and illustrated with notes on its phenology, ecology and distribution. In additions, a key to all Abelmoschus taxa occurring in India is provided.
Fire regimes of Australia: a pyrogeographic model system
Authors: Murphy Brett P. , Bradstock Ross A. , Boer Matthias M. , Carter John , Cary Geoffrey J. , Cochrane Mark A. , Fensham Roderick J. , Russell‐Smith Jeremy , Williamson Grant J. , Bowman David M. J. S.
Published: January 2013

Aim

Comparative analyses of fire regimes at large geographical scales can potentially identify ecological and climatic controls of fire. Here we describe Australia's broad fire regimes, and explore interrelationships and trade‐offs between fire regime components. We postulate that fire regime patterns will be governed by trade‐offs between moisture, productivity, fire frequency and fire intensity.

Location

Australia.

Methods

We reclassified a vegetation map of Australia, defining classes based on typical fuel and fire types. Classes were intersected with a climate classification to derive a map of ‘fire regime niches’. Using expert elicitation and a literature search, we validated each niche and characterized typical and extreme fire intensities and return intervals. Satellite‐derived active fire detections were used to determine seasonal patterns of fire activity.

Results

Fire regime characteristics are closely related to the latitudinal gradient in summer monsoon activity. Frequent low‐intensity fires occur in the monsoonal north, and infrequent, high‐intensity fires in the temperate south, demonstrating a trade‐off between frequency and intensity: that is, very high‐intensity fires are only associated with very low‐frequency fire regimes in the high biomass eucalypt forests of southern Australia. While these forests occasionally experience extremely intense fires (> 50,000 kW m−1), such regimes are exceptional, with most of the continent dominated by grass fuels, typically burning with lower intensity (< 5000 kW m−1).

Main conclusions

Australia's fire regimes exhibit a coherent pattern of frequent, grass‐fuelled fires in many differing vegetation types. While eucalypts are a quintessential Australian entity, their contribution as a dominant driver of high‐intensity fire regimes, via their litter and bark fuels, is restricted to the forests of the continent's southern and eastern extremities. Our analysis suggests that the foremost driver of fire regimes at the continental scale is not productivity, as postulated conceptually, but the latitudinal gradient in summer monsoon rainfall activity.
Fascicular and Nonfascicular Left Ventricular Tachycardias in the Young: An International Multicenter Study
Authors: COLLINS KATHRYN K. , SCHAFFER MICHAEL S. , LIBERMAN LEONARDO , SAAREL ELIZABETH , KNECHT MARIA , TANEL RONN E. , BRADLEY DAVID , DUBIN ANNE M. , PAUL THOMAS , SALERNO JACK , BAR‐COHEN YANIV , SREERAM NARAYANSWAMI , SANATANI SHUBHAYAN , LAW IAN H. , BLAUFOX ANDREW , BATRA ANJAN , MOLTEDO JOSE M. , VAN HARE GEORGE F. , REED JOHN , RO PAMELA S. , KUGLER JOHN , ANDERSON CHRIS , TRIEDMAN JOHN K. ,   on behalf of members of the Pediatric and Congenital Electrophysiology Society
Published: January 2013

Left Ventricular Tachycardia in Pediatrics

Introduction

The aim of this study was to evaluate the clinical presentation and outcomes of pediatric patients with ventricular tachycardia (VT) originating from left heart structures.

Methods and Results

This international multicenter retrospective study including 152 patients (age 10.0 ± 5.1 years, 62% male), divided into those with fascicular VT (85%, 129/152) and nonfascicular LV VT (15%, 23/152). All patients had a normal heart structure or only a minor cardiac abnormality. Adenosine was largely ineffective in both groups (tachycardia termination in 4/74 of fascicular VT and 0/5 of nonfascicular LV VT). In fascicular VT, calcium channel blockers were effective in 80% (74/92); however, when administered orally, there was a 21% (13/62) recurrence rate. In nonfascicular LV VT, a variety of antiarrhythmic therapies were used with no one predominating. Ablation procedures were successful in 71% (72/102) of fascicular VT and 67% (12/18) of nonfascicular LV VT on an intention to treat analysis. Major complications occurred in 5 patients with fascicular VT and 1 patient with nonfascicular LV VT. After a follow‐up period of 2 years (1 day to 15 years), 72% of all patients with fascicular VT were off medications with no tachycardia recurrence. One patient died of noncardiac causes. In nonfascicular LV VT, follow‐up was 3.5 years (0.5–15 years), P = 0.38. A total of 65% of these patients were free from arrhythmias. Two patients died suddenly (P < 0.01).

Conclusion

The clinical course and outcomes of pediatric patients with fascicular VT and nonfascicular LV VT are varied. Catheter ablation procedures can be curative.
A Large‐Scale Study on Storage Stability of Cloudy Apple Juice Treated by N2 and Ascorbic Acid
Authors: Tetik Nedim , Karhan Mustafa , Turhan Irfan , Aksu Mehmet , Oziyci Hatice Reyhan
Published: January 2013

The effect of ascorbic acid and N2 usage in large‐scale cloudy apple juice production was investigated. Samples were stored at 5 and 20C for 6 months. The quality of the initial cloudy apple juice samples was evaluated by characteristic properties (pH, total titratable acidity, total dry matter, soluble solids and total phenolic content) and storage stability was evaluated by turbidity and color parameters, which were analyzed on a monthly basis. According to the results, change in total phenolic content of the samples was considerable (minimal values were recorded in N2‐treated groups). However, ascorbic acid and N2 usage alone or in combination was not enough to prevent turbidity loss during storage. Only the lower temperature (5C) chosen was effective to decelerate this loss. In terms of color stability, the most stable group was the N2 and ascorbic acid‐treated one (ΔE: 3.59 at 5C).

Practical Applications

Color and cloud stability are important attributes of cloudy apple juice during storage. Many laboratory studies have been conducted to improve these quality parameters. However, there is no large‐scale study about the storage stability of cloudy apple treated by N2 and ascorbic acid during the production stages. Therefore, in this study, a large‐scale cloudy apple juice production was performed using N2 and ascorbic acid during the juice processing stage and the storage stability of the final products was investigated for 6 months. The results of this large‐scale study could be useful for fruit juice processors and retailers.
THE CAUSAL LINK BETWEEN FINANCIAL INCENTIVES AND WEIGHT LOSS: AN EVIDENCE‐BASED SURVEY OF THE LITERATURE
Authors: Paloyo Alfredo R. , Reichert Arndt R. , Reinermann Holger , Tauchmann Harald
Published: January 2013

Obesity and overweight are linked to diseases that cost society a significant amount of resources. While behavior modification can reduce the problem, instigating such lifestyle changes is an uneasy task. One potential way to reduce the problem is through the use of financial incentives. In this survey, we review the available evidence, properly emphasizing studies that credibly yield meaningful estimates of the effect of financial incentives on weight loss. We find that the scientific literature on the subject has not yet satisfactorily settled whether such a mechanism is effective at eliciting the desired behavioral and health outcomes. We therefore advocate a rigorous large‐scale randomized experiment to provide reliable estimates of the effect.
Can questions about social interaction correctly identify preschool aged children with autism?
Authors: Williams Katrina , Perkins Deborah , Wheeler Danielle , Hayen Andrew , Bayl Vivian
Published: January 2013

Aim

We developed a questionnaire to assess social development (SIQ) in preschool children. Social development is often not included in medical assessment, though it may assist in early identification of autism spectrum disorder (ASD).

Methods

Parents of 108 children with ASD, speech and language disorders, or ‘developmental concerns’, recruited from a clinical developmental assessment and community child health service, completed the SIQ, and also a Childhood Autism Rating Scale (CARS) assessment. Receiver Operator Characteristic (ROC) curves were generated to assess the performance of different questionnaire score thresholds in correctly identifying children with a CARS score of 30 or more. Logistic regression models were used to identify the questions which had the most predictive value for a CARS score of 30 or more.

Results

An SIQ score of 14 or more correctly identified children with a CARS ≥30 with a sensitivity of 85%, specificity 85%, positive likelihood ratio (LR) 8.3 and negative LR 0.2. Two questions were identified as most predictive of ASD.

Conclusions

The SIQ may assist clinicians in assessing social development and in making decisions about referral for autism assessment. Evaluation of the SIQ at the point of entry to a clinical service is needed.