bluuebunny/crossref_metadata_2025_split huggingface dataset:
Assessing nanoparticle risk poses prodigious challenges
Authors: MacPhail Robert C. , Grulke Eric A. , Yokel Robert A. 
Published: April 2013

AbstractRisk assessment is used both formally and informally to estimate the likelihood of an adverse event occurring, for example, as a consequence of exposure to a hazardous chemical, drug, or other agent. Formal risk assessments in government regulatory agencies have a long history of practice. The precision with which risk can be estimated is inevitably constrained, however, by uncertainties arising from the lack of pertinent data. Developing accurate risk assessments for nanoparticles and nanoparticle‐containing products may present further challenges because of the unique properties of the particles, uncertainties about their composition and the populations exposed to them, and how these may change throughout the particle's life cycle. This review introduces the evolving practice of risk assessment followed by some of the uncertainties that need to be addressed to improve our understanding of nanoparticle risks. Given the clarion call for life‐cycle assessments of nanoparticles, an unprecedented degree of national and international coordination between scientific organizations, regulatory agencies, and stakeholders will be required to achieve this goal. WIREs Nanomed Nanobiotechnol 2013, 5:374–387. doi: 10.1002/wnan.1216This article is a U.S. Government work, and as such, is in the public domain in the United States of America.Disclaimer: This manuscript has been reviewed by the National Health and Environmental Effects Research Laboratory and approved for publication. The approval does not signify that the contents reflect the views of the agency, nor does mention of trade names or commercial products constitute endorsement or recommendation for use.This article is categorized under:

Toxicology and Regulatory Issues in Nanomedicine > Regulatory and Policy Issues in Nanomedicine
Toxicology and Regulatory Issues in Nanomedicine > Toxicology of Nanomaterials
Notch1 Contributes to Chemoresistance to Gemcitabine and Serves as an Unfavorable Prognostic Indicator in Pancreatic Cancer
Authors: Du Xiao , Zhao Yu‐Pei , Zhang Tai‐Ping , Zhou Li , Chen Ge , Cui Quan‐Cai , Shi Jie , Wang Tian‐Xiao , You Lei , Shu Hong 
Published: April 2013

AbstractBackgroundPancreatic cancer (PC) carries frequent chemoresistance and extremely dismal prognosis. The underlying mechanisms remain to be further elucidated. We here report the role of Notch1 in gemcitabine resistance and its prognostic significance in PC.MethodsA small interfering RNA (siRNA) specifically targeting Notch1 was transiently transfected into three PC cell lines (AsPC‐1, BxPC‐3, and MIA PaCa‐2), followed by examination of chemosensitivity to gemcitabine. On the other hand, Notch1 expression was evaluated immunohistochemically and correlated with clinicopathological and prognostic variables.ResultsSuccessful knockdown of Notch1 by specific siRNA induced increased chemosensitivity to gemcitabine in all three cell lines. Immunohistochemical staining revealed that Notch1 was highly expressed in PC tissues (54.8 %), in contrast to that in para‐tumor tissues (16.4 %). In addition, Notch1 positivity was significantly correlated with early‐term metastasis and shortened overall survival. Multivariate Cox regression identified Notch1 as an independent prognostic factor.ConclusionsNotch1 contributes to chemoresistance to gemcitabine, and serves as a significant indicator of unfavorable prognosis in PC.
SPan‐1 Is a Useful Prognostic Marker for Patients with Stage IV Gastric Cancer Who Underwent Palliative Gastrectomy: A Retrospective Multivariate Study
Authors: Kubo Naoshi , Ohira Masaichi , Sakurai Katsunobu , Toyokawa Takahiro , Tanaka Hiroaki , Muguruma Kazuya , Nagahara Hisashi , Kimura Kenjiro , Noda Eiji , Amano Ryosuke , Yamada Nobuya , Yashiro Masakazu , Maeda Kiyoshi , Sawada Tetsuji , Hirakawa Kosei 
Published: April 2013

AbstractBackgroundWe retrospectively investigated prognostic factors to be used in selecting the patients with stage IV gastric cancer (GC) who have an unfavorable prognosis after palliative gastrectomy.MethodsA total of 146 GC patients at stage IV who had undergone palliative gastrectomy were enrolled. Various clinicopathological parameters were evaluated for prognosis.ResultsSurgical morbidity and hospital mortality occurred in 35 (23.9 %) and 4 (2.7 %) patients, respectively. The overall 5‐year survival rate and the median survival time were 11.2 % and 13.2 months, respectively. Of the 146 patients, 64 had uncomfortable symptoms associated with GC and 76 had no such symptoms. Of the 64 patients with uncomfortable symptoms, 60 (93.7 %) experienced relief of these symptoms after palliative surgery. Multivariate analysis for patients without uncomfortable symptoms associated with GC revealed that the number of incurable factors and serum SPan‐1 level were independent prognostic factors.ConclusionsPatients with stage IV GC who had multiple incurable factors and a high level of serum SPan‐1 might not be candidates for palliative gastrectomy for the purpose of prognostic benefit.
Implantation of Prophylactic Nonabsorbable Intraperitoneal Mesh in Patients With Peritonitis Is Safe and Feasible
Authors: Kurmann Anita , Barnetta Corina , Candinas Daniel , Beldi Guido 
Published: April 2013

AbstractBackgroundPatients with peritonitis undergoing emergency laparotomy are at increased risk for postoperative open abdomen and incisional hernia. This study aimed to evaluate the outcome of prophylactic intraperitoneal mesh implantation compared with conventional abdominal wall closure in patients with peritonitis undergoing emergency laparotomy.MethodA matched case‐control study was performed. To analyze a high‐risk population for incisional hernia formation, only patients with at least two of the following risk factors were included: male sex, body mass index (BMI) >25 kg/m2, malignant tumor, or previous abdominal incision. In 63 patients with peritonitis, a prophylactic nonabsorbable mesh was implanted intraperitoneally between 2005 and 2010. These patients were compared with 70 patients with the same risk factors and peritonitis undergoing emergency laparotomy over a 1‐year period (2008) who underwent conventional abdominal closure without mesh implantation.ResultsDemographic parameters, including sex, age, BMI, grade of intraabdominal infection, and operating time were comparable in the two groups. Incidence of surgical site infections (SSIs) was not different between groups (61.9 vs. 60.3 %; p = 0.603). Enterocutaneous fistula occurred in three patients in the mesh group (4.8 %) and in two patients in the control group (2.9 %; p = 0.667). The incidence of incisional hernia was significantly lower in the mesh group (2/63 patients) than in the control group (20/70 patients) (3.2 vs. 28.6 %; p < 0.001).ConclusionsProphylactic intraperitoneal mesh can be safely implanted in patients with peritonitis. It significantly reduces the incidence of incisional hernia. The incidences of SSI and enterocutaneous fistula formation were similar to those seen with conventional abdominal closure.
Glutathione metabolism in cobalamin deficiency type C (cblC)
Authors: Pastore Anna , Martinelli Diego , Piemonte Fiorella , Tozzi Giulia , Boenzi Sara , Di Giovamberardino Gianna , Petrillo Sara , Bertini Enrico , Dionisi‐Vici Carlo 
Published: April 2013

AbstractBackgroundMethylmalonic aciduria with homocystinuria, cblC defect, is the most frequent disorder of vitamin B12 metabolism. CblC patients are commonly treated with a multidrug therapy to reduce metabolite accumulation and to increase deficient substrates. However the long‐term outcome is often unsatisfactory especially in patients with early onset, with frequent progression of neurological and ocular impairment. Recent studies, have shown perturbation of cellular redox status in cblC. To evaluate the potential contribution of oxidative stress into the patophysiology of cblC defect, we have analyzed the in vivo glutathione metabolism in a large series of cblC deficient individuals.MethodsLevels of different forms of glutathione were measured in lymphocytes obtained from 18 cblC patients and compared with age‐matched controls. Furthermore, we also analyzed plasma cysteine and total homocysteine.ResultsWe found an imbalance of glutathione metabolism in cblC patients with a significant decrease of total and reduced glutathione, along with a significant increase of different oxidized glutathione forms.ConclusionsThese findings show a relevant in vivo disturbance of glutathione metabolism underlining the contribution of glutathione pool depletion to the redox imbalance in treated cblC patients. Our study may be helpful in addressing future research to better understanding the pathogenetic mechanism of the disease and in developing new therapeutic approaches, including the use of novel vitamin B12 derivatives.
The Richtmyer–Meshkov instability of a three-dimensional interface with a minimum-surface feature
Authors: Luo Xisheng , Wang Xiansheng , Si Ting 
Published: April 2013

AbstractA novel method to create a discontinuous gaseous interface with a minimum-surface feature by the soap film technique is developed for three-dimensional (3D) Richtmyer–Meshkov instability (RMI) studies. The interface formed is free of supporting mesh and the initial condition can be well controlled. Five air/SF6 interfaces with different amplitude are realized in shock-tube experiments. Time-resolved schlieren and planar Mie-scattering photography are employed to capture the motion of the shocked interface. It is found that the instability at the linear stage in the symmetry plane grows much slower than the predictions of previous two-dimensional (2D) impulsive models, which is ascribed to the opposite principal curvatures of the minimum surface. The 2D impulsive model is extended to describe the general 3D RMI. A quantitative analysis reveals a good agreement between experiments and the extended linear model for all the configurations including both the 2D and 3D RMIs at their early stages. An empirical model that combines the early linear growth with the late-time nonlinear growth is also proposed for the whole evolution process of the present configuration.
THE STRONG DUAL OF MEASURE ALGEBRAS WITH CERTAIN LOCALLY CONVEX TOPOLOGIES
Authors: JAVANSHIRI HOSSEIN , NASR-ISFAHANI RASOUL 
Published: April 2013

AbstractFor a locally compact group$ \mathcal{G} $, we introduce and study a class of locally convex topologies$\tau $on the measure algebra$M( \mathcal{G} )$of$ \mathcal{G} $. In particular, we show that the strong dual of$(M( \mathcal{G} ), \tau )$can be identified with a closed subspace of the Banach space$M\mathop{( \mathcal{G} )}\nolimits ^{\ast } $; we also investigate some properties of the locally convex space$(M( \mathcal{G} ), \tau )$.
A maternal high-protein diet predisposes female offspring to increased fat mass in adulthood whereas a prebiotic fibre diet decreases fat mass in rats
Authors: Hallam Megan C. , Reimer Raylene A. 
Published: April 2013

The negative effects of malnourishmentin uterohave been widely explored; the effects of increased maternal macronutrient intake are not known in relation to high fibre, and have been inconclusive with regard to high protein. In the present study, virgin Wistar dams were fed either a control (C), high-protein (40 %, w/w; HP) or high-prebiotic fibre (21·6 %, w/w; HF) diet throughout pregnancy and lactation. Pups consumed the C diet from 3 to 14·5 weeks of age, and then switched to a high-fat/sucrose diet for 8 weeks. A dual-energy X-ray absorptiometry scan and an oral glucose tolerance test were performed and plasma satiety hormones measured. The final body weight and the percentage of body fat were significantly affected by the interaction between maternal diet and offspring sex: weight and fat mass were higher in the female offspring of the HPv. HF dams. No differences in body weight or fat mass were seen in the male offspring. There was a significant sex effect for fasting and total AUC for ghrelin and fasting GIP, with females having higher levels than males. Liver TAG content and plasma NEFA were lower in the offspring of high-prebiotic fibre dams (HF1) than in those of high-protein dams (HP1) and control dams (C1). Intestinal expression ofGLUT2was decreased in HF1 and HP1v. C1. The maternal HP and HF diets had lasting effects on body fat and hepatic TAG accumulation in the offspring, particularly in females. Whereas the HP diet predisposes to an obese phenotype, the maternal HF diet appears to reduce the susceptibility to obesity following a high-energy diet challenge in adulthood.
Novel amidines and analogues as promising agents against intracellular parasites: a systematic review
Authors: SOEIRO M. N. C. , WERBOVETZ K. , BOYKIN D. W. , WILSON W. D. , WANG M. Z. , HEMPHILL A. 
Published: April 2013

SUMMARYParasitic protozoa comprise diverse aetiological agents responsible for important diseases in humans and animals including sleeping sickness, Chagas disease, leishmaniasis, malaria, toxoplasmosis and others. They are major causes of mortality and morbidity in tropical and subtropical countries, and are also responsible for important economic losses. However, up to now, for most of these parasitic diseases, effective vaccines are lacking and the approved chemotherapeutic compounds present high toxicity, increasing resistance, limited efficacy and require long periods of treatment. Many of these parasitic illnesses predominantly affect low-income populations of developing countries for which new pharmaceutical alternatives are urgently needed. Thus, very low research funding is available. Amidine-containing compounds such as pentamidine are DNA minor groove binders with a broad spectrum of activities against human and veterinary pathogens. Due to their promising microbicidal activity but their rather poor bioavailability and high toxicity, many analogues and derivatives, including pro-drugs, have been synthesized and screened in vitro and in vivo in order to improve their selectivity and pharmacological properties. This review summarizes the knowledge on amidines and analogues with respect to their synthesis, pharmacological profile, mechanistic and biological effects upon a range of intracellular protozoan parasites. The bulk of these data may contribute to the future design and structure optimization of new aromatic dicationic compounds as novel antiparasitic drug candidates.
Rapid visual information processing as a cognitive endophenotype of attention deficit hyperactivity disorder
Authors: Gau S. S.-F. , Huang W.-L. 
Published: April 2013

BackgroundDeficits in sustained attention and reaction time are core features of attention deficit hyperactivity disorder (ADHD). However, little is known about attention performance in unaffected siblings. Hence, we examined sustained attention and reaction time in youths with ADHD, unaffected siblings and controls to test whether impaired performance in attention tasks can be a potential endophenotype of ADHD.MethodWe recruited 438 probands with clinical diagnosis of ADHD according to DSM-IV criteria, 180 unaffected siblings, and 173 healthy controls without lifetime ADHD. They were assessed using psychiatric interviews, Conners’ Continuous Performance Test, and the tasks involving attention performance of the Cambridge Neuropsychological Test Automated Battery (CANTAB): Rapid Visual Information Processing (RVP), Reaction Time (RTI) and Match to Sample Visual Search (MTS). Multi-level models were used for data analysis.ResultsCompared with the controls, probands with ADHD and unaffected siblings had significantly higher total misses, lower probability of hits in the RVP task and probands with ADHD performed worse in the RTI and MTS tasks after controlling for sex, age, co-morbidity, parental educational levels and IQ. The duration of methylphenidate use and IQ but not psychiatric co-morbidity or current use of methylphenidate were associated with deficits in sustained attention in probands with ADHD.ConclusionsOur findings suggest that attention performance assessed by the RVP task, but not the RTI or MTS tasks, of the CANTAB may be a useful cognitive endophenotype for ADHD genetic studies.
Prolegomena to any future non-doxastic religion
Authors: CHIGNELL ANDREW 
Published: April 2013

AbstractI discuss some trends in recent philosophy of religion, focusing on J. L. Schellenberg'sProlegomena to a Philosophy of Religion. I pay special attention to Schellenberg's dual emphases on ‘the Ultimate’ as metaphysical object of inquiry and various non-doxastic states (‘faith that’, ‘faith in’) as psychological objects of inquiry. This view is contrasted throughout to what might be called a ‘liturgical’ orientation in philosophy of religion.
The conceptual focus of ultimism: an object of religious concern for the nones and somes
Authors: DILLER JEANINE 
Published: April 2013

AbstractIn his recent trilogy, J. L. Schellenberg presents a new religious option: to have beliefless faith in a general object of religious concern that he thinks is referenced at the core of most sectarian religions – the axiological, soteriological, and metaphysical ultimate, which I call ‘UUU’. After explaining what UUU is more fully, I argue that the claim that UUU exists should not be, as Schellenberg says, the only focus for philosophy of religion. Still, I argue that such a claim is a good basis for a new form of religion, especially if it is modified in a couple of ways.
Addressing the Social Determinants of Subjective Wellbeing: The Latest Challenge for Social Policy
Authors: DEEMING CHRISTOPHER 
Published: April 2013

AbstractThe idea that the happiness and wellbeing of individuals should shape government policy has been around since the enlightenment; today such thinking has growing practical policy relevance as governments around the world survey their populations in an effort to design social policies that promote wellbeing. In this article, we consider the social determinants of subjective wellbeing in the UK and draw lessons for social policy. Survey data are taken from the ‘Measuring National Wellbeing Programme’ launched by the UK's Office for National Statistics in 2010. For the empirical strategy, we develop bivariate and multivariate logistic regression models, as well as testing for interaction effects in the data. The findings show that wellbeing is not evenly distributed within the UK. Socio-demographic characteristics such as age, gender, ethnicity, employment, household composition and tenure all matter, as does health status. Influencing population wellbeing is inherently complex, though, that said, there is a clear need to place greater emphasis on thesocial, given the direction of current policy.
Aetiology and clinical features of dysentery in children aged <5 years in rural Bangladesh
Authors: FERDOUS F. , AHMED S. , DAS S. K. , FARZANA F. D. , LATHAM J. R. , CHISTI M. J. , FARUQUE A. S. G. 
Published: April 2013

SUMMARYThe study identified the common aetiological agents and prominent clinical features of dysentery cases in children aged <5 years and compared this to non-dysentery diarrhoeal cases from the same population. From January 2010 to December 2011, 2324 children aged <5 years received treatment at Kumudini Hospital, of which 682 (29%) presented with dysentery. Of the dysenteric children, aetiology could not be determined for over half (61%). Shigella spp. accounted for 32% of dysentery cases. Significant associations were found between presence of blood in stool and: child age (24–59 months) [odds ratio (OR) 2·21, 95% confidence interval (CI) 1·49–3·27], no treatment of drinking water at home (OR 2·00, 95% CI 1·09–3·67), vomiting (OR 0·19, 95% CI 0·14–0·25), abdominal pain (OR 4·68, 95% CI 3·24–6·77), straining (OR 16·45, 95% CI 11·92–22·69), wasting (OR 1·66, 95% CI 1·15–2·41), and presence of Shigella in stool (OR 6·25, 95% CI 4·20–9·29) after controlling for confounders. This study makes it clear that appropriate public health strategies are needed to reduce the burden of dysentery in Bangladesh.
An insight into the public acceptance of nutrigenomic-based personalised nutrition
Authors: Fallaize R. , Macready A. L. , Butler L. T. , Ellis J. A. , Lovegrove J. A. 
Published: April 2013

It is predicted that non-communicable diseases will account for over 73 % of global mortality in 2020. Given that the majority of these deaths occur in developed countries such as the UK, and that up to 80 % of chronic disease could be prevented through improvements in diet and lifestyle, it is imperative that dietary guidelines and disease prevention strategies are reviewed in order to improve their efficacy. Since the completion of the human genome project our understanding of complex interactions between environmental factors such as diet and genes has progressed considerably, as has the potential to individualise diets using dietary, phenotypic and genotypic data. Thus, there is an ambition for dietary interventions to move away from population-based guidance towards ‘personalised nutrition’. The present paper reviews current evidence for the public acceptance of genetic testing and personalised nutrition in disease prevention. Health and clear consumer benefits have been identified as key motivators in the uptake of genetic testing, with individuals reporting personal experience of disease, such as those with specific symptoms, being more willing to undergo genetic testing for the purpose of personalised nutrition. This greater perceived susceptibility to disease may also improve motivation to change behaviour which is a key barrier in the success of any nutrition intervention. Several consumer concerns have been identified in the literature which should be addressed before the introduction of a nutrigenomic-based personalised nutrition service. Future research should focus on the efficacy and implementation of nutrigenomic-based personalised nutrition.
Play to Learn, Learn to Play: Language Learning through Gaming Culture
Authors: Ryu Dongwan 
Published: April 2013

AbstractMany researchers have investigated learning through playing games. However, after playing games, players often go online to establish and participate in the online community where they enrich their game experiences, discuss game-related issues, and create fan-fictions, screenshots, or scenarios. Although these emerging activities are an essential part of gaming culture, they have not attracted much attention from researchers and only a few empirical studies have been done on learning through beyond-game culture. Language learning in particular has not been extensively researched despite the proliferation of game players who speak English as a foreign language within this community. To address how non-native English speaking (NNE) game players participate in language learning through game play and beyond-game culture, three generations of activity theories and a multiple-case study design were employed in this study. The asynchronous computer-mediated discourses were repeatedly reviewed, and email interviews with participants were conducted over three stages. The discourse analysis of interaction data and interview scripts showed how participants were engaged in language learning through gaming culture. First, words or phrases used in game play could be learned while playing games. Second, sentences or discourses could be practiced through interaction with native or more fluent peers in the online community after playing games. Third, these two types of engagement in gaming culture were closely related to influencing language learning through repeated practices and collaborative interactions. In conclusion, language learning through gaming is appropriately understood when ecological perspectives are adopted to look at both sides of gaming culture.