bluuebunny/crossref_metadata_2025 huggingface dataset:
Echinomycin Decreases Induction of Vascular Endothelial Growth Factor and Hepatocyte Regeneration in Acetaminophen Toxicity in Mice
Authors: Milesi‐Hallé Alessandra , McCullough Sandra , Hinson Jack A. , Kurten Richard C. , Lamps Laura W. , Brown Aliza , James Laura P.
Published: October 2011

Abstract:  Up‐regulation of vascular endothelial growth factor (VEGF) is important to hepatocyte regeneration in the late stages of acetaminophen (APAP) toxicity in the mouse. This study was conducted to examine the relationship of hypoxia‐inducible factor 1α (HIF‐1α) to VEGF and hepatocyte regeneration in APAP toxicity using an inhibitor of HIF‐1α DNA‐binding activity, echinomycin (EC). B6C3F1 male mice were treated with APAP (200 mg/kg IP), followed by EC (0.15 mg IP) and killed at 4 hr. Serum alanine aminotransferase (ALT), necrosis, hepatic glutathione (GSH) and APAP protein adducts were comparable in the APAP/EC and the APAP/veh mice at 4 hr. Additional studies showed that high dose EC (0.3 mg) reduced hepatic VEGF but also lowered hepatic GSH. Subsequent studies were performed using the 0.15‐mg dose of EC. Although EC 0.15 mg had no effect on hepatic VEGF levels at 8 hr, by 24 hr VEGF levels were decreased by 40%. Toxicity (ALT and histopathology) was comparable in the APAP and APAP/EC groups at 24 and 48 hr. Proliferating cell nuclear antigen expression was reduced by both Western blot analysis and immunohistochemical staining in the APAP/EC mice at 48 hr. The data support the hypothesis that induction of HIF‐1α, its binding to DNA and subsequent expression of VEGF are important factors in hepatocyte regeneration in APAP toxicity in the mouse.
Exploring the Interaction Between siRNA and the SMoC Biomolecule Transporters: Implications for Small Molecule–Mediated Delivery of siRNA
Authors: Gooding Matt , Tudzarova Slavica , Worthington Roberta J. , Kingsbury Sarah R. , Rebstock Anne‐Sophie , Dube Henry , Simone Michela I. , Visintin Cristina , Lagos Dimitris , Quesada Juan‐Manuel Funes , Laman Heike , Boshoff Chris , Williams Gareth H. , Stoeber Kai , Selwood David L.
Published: October 2011

The small molecule carrier class of biomolecule transporters, modeled on the third helix of the Antennapedia homeodomain, has previously been shown to transport active proteins into cells. Here, we show an improved synthetic route to small molecule carriers, including Molander chemistry using trifluoroborate salts to improve the yield of the Suzuki–Miyaura coupling step for the formation of the biphenyl backbone. The required boronic acids could be formed by the reaction of a 2‐(dimethylamino)ethyl ether‐modified aryl Grignard reagent with triisopropyl borate. The potential for the use of small molecule carriers as oligonucleotide‐transporting agents was also explored by characterizing the interactions between small molecule carriers and siRNA. Molecular dynamics and NMR analysis indicated that the small molecule carrier guanidines are stabilized by π‐cation interactions with the biphenyl system, thus not only increasing the basicity or pKa but also shielding the charge. The binding affinities of various small molecule carriers for siRNA were investigated using isothermal calorimetry and gel shift assays. Small molecule carrier‐mediated siRNA delivery to cultured fibroblasts is demonstrated, showing that small molecule carriers possess the ability to transport functional siRNA into cells. Knockdown of Cdc7 kinase, a target for cancer, is achieved.
Exploring SAR Continuity in the Vicinity of Activity Cliffs
Authors: Namasivayam Vigneshwaran , Iyer Preeti , Bajorath Jürgen
Published: October 2011

Activity cliffs are formed by structurally similar compounds with significant differences in potency and represent an extreme form of structure–activity relationships discontinuity. By contrast, regions of structure–activity relationships continuity in compound data sets result from the presence of structurally increasingly diverse compounds retaining similar activity. Previous studies have revealed that structure–activity relationships information extracted from large compound data sets is often heterogeneous in nature containing both continuous and discontinuous structure–activity relationships components. Structure–activity relationships discontinuity and continuity are often represented by different compound series, independent of each other. Here, we have searched different compound data sets for the presence of structure–activity relationships continuity within the vicinity of prominent activity cliffs. For this purpose, we have designed and implemented a computational approach utilizing particle swarm optimization to examine the structural neighborhood of activity cliffs for continuous structure–activity relationships components. Structure–activity relationships continuity in the structural neighborhood of activity cliffs was relatively rarely observed. However, in a number of cases, notable structure–activity relationships continuity was detected in the vicinity of prominent activity cliffs. Exemplary local structure–activity relationships environments displaying these characteristics were analyzed in detail. Thus, the structure–activity relationships environment of activity cliffs must not necessarily be discontinuous in nature, and local structure–activity relationships continuity and discontinuity can occur in a concerted manner in series of structurally related compounds.
The Word and the Way in Mozi
Authors: Loy Hui‐Chieh
Published: October 2011

According to A. C. Graham, ‘the crucial question’ for the early Chinese thinkers was ‘Where is the Way [dao]?’–‘the way to order the state and conduct personal life’ rather than ‘What is the Truth?’1 This observation is most apt when applied to the thinking of Mozi (flor. ca. fifth century to early fourth century BCE) and his followers (the ‘Mohists’) as it is exemplified in the ethical and political chapters of the eponymously named text (Mozi Chapters 1–39, 46–51).2 A striking feature of the Mohists’ thinking, however, is the concern they have with yan (‘sayings’, ‘speeches’, ‘words’, ‘discourses’), and the role they assigned to yan in their ethical project. Part I of this article will outline the nature and scope of the Mohists’ concern with yan. In the Mohists’ conception, right yan is the linguistic counterpart to proper dao. And conduct that follows dao is a matter of affirming the right yan and taking it as a model in one’s actions. The Mohists’ concern with yan is prominently exhibited in their proposing objective standards, or ‘gauges’, by means of which any yan may be assessed. Part II introduces these gauges and discusses how they function as standards for right yan and right conduct. Given the generally pragmatic outlook of their thinking, the question remains as to whether, in their conception of yan, the Mohists conceived of language exclusively in terms of its action guiding function, and whether they deployed the notion of truth at all. Part III discusses this issue, arguing that there is a minimal sense in which yan that are positively assessed by the gauges are true, and that the Mohists are not insensitive to the distinction between descriptive as opposed to action guiding uses of language. Part IV briefly discusses how the Mohists’ attitude towards yan contrasts with those of early Confucian and Daoist thinkers.
Berkeley’s Theory of Mind: Some New Models1
Authors: Bettcher Talia Mae
Published: October 2011

Berkeley didn’t write very much about his ‘philosophy of mind’ and what he did write is rather perplexing and perhaps inconsistent. The most basic problem is that it just isn’t clear what a mind (or, more accurately, a spirit) is for Berkeley. Unsurprisingly, many interpretations tend to understand Berkeleian spirit in models provided by other philosophers – interpretations in which Berkeleian spirit turns out to be a close cousin of the Cartesian ego, Lockean spiritual substratum, Lockean self, and Humean bundle of perceptions. Stephen H. Daniel and I have each offered different interpretations of Berkeley that refuse to reduce Berkeley’s account of spirit to that of other canonical thinkers and, indeed, which place Berkeleian spirit in some tension with the Aristotelian‐Cartesian‐Lockean traditions. In this paper, I argue that Daniel’s account is too extreme in that it implausibly removes Berkeley from this tradition altogether. I show how my account avoids that extreme and I defend it against some objections.
Causation and Explanation in Aristotle
Authors: Stein Nathanael
Published: October 2011

Aristotle thinks that we understand something when we know its causes. According to Aristotle but contrary to most recent approaches, causation and explanation cannot be understood separately. Aristotle complicates matters by claiming that there are four causes, which have come to be known as the formal, material, final, and efficient causes. To understand Aristotelian causation and its relationship to explanation, then, we must come to a precise understanding of the four causes, and how they are supposed to be explanatory. Aristotle’s discussion of the causes, however, is compact, and he typically presents them without arguing for them. He thus leaves us with a number of questions, ranging from the highly specific to the highly general. One question in particular has captured the attention of scholars and philosophers over the last century, and it has had a strong influence on recent treatments of the four causes – namely, whether we are right to understand Aristotle as committed to a plurality of kinds of causation, or rather a plurality of kinds of explanation. Sometimes the question is raised as one of whether it would be more accurate to speak of the four ‘becauses’ rather than the four ‘causes’. This worry is highly general, and there are in fact several ways in which it might be formulated; nonetheless, it is important to clarify the precise nature of the problem, and the possible ways of responding to it. At issue is not just whether Aristotle’s notions are sufficiently like the modern notion of causation to be relevant to our concerns, but, more importantly, whether the distinctions he draws are ultimately metaphysical or epistemological in character.
Some Recent Work in Experimental Epistemology
Authors: Pinillos Nestor Ángel
Published: October 2011

I survey here some recent work on experimental philosophy and its bearing on some current debates in Epistemology. In the first part of the paper, I survey some general methodological issues concerning the relevance of folk judgments (a domain of study of experimental philosophy) to Contextualism and Interest Relative Invariantism (IRI). In the second part, I provide a critical review of several experiments some of which have been thought to disfavor contextualism and IRI, and others which have been thought to favor contrastivism (a type of contextualism).
Rapid onset vasodilatation is blunted in obese humans
Authors: Blain G. M. , Limberg J. K. , Mortensen G. F. , Schrage W. G.
Published: October 2011

Aim:  Conduit artery function in obese humans is frequently assessed at rest, but very little is known about resistance artery function in response to muscle contraction. We tested the hypothesis that obese adults will exhibit reduced contraction‐induced rapid onset vasodilatation. Single and brief forearm contractions were used to isolate the local effects of muscle contraction on the forearm vasodilatory response, independent of systemic haemodynamic and sympathetic neural influence.

Methods:  We measured forearm blood flow (Doppler ultrasound), blood pressure (finger photoplethysmography) and heart rate (electrocardiogram) on a beat‐by‐beat basis in 14 obese (body mass index = 36.2 ± 1.7 kg m−2) and 14 lean (body mass index = 21.6 ± 0.7 kg m−2) young (18–40 years) adults. Percent changes from baseline in forearm vascular conductance (FVC%) were calculated in response to single, brief forearm contractions performed in random order at 15, 20, 25, 30, 40 and 50% of maximal voluntary contraction (MVC).

Results:  In both groups, each single contraction evoked a significant (P < 0.05), immediate (within one cardiac cycle) and graded FVC% increase from one up to six cardiac cycles post‐contraction. Immediate (20–50% MVC), peak (15–50% MVC) and total (area under the curve, 20–50% MVC) vasodilatory responses were reduced with obesity. The degree of impaired vasodilatation increased with increasing workloads.

Conclusions:  These novel findings demonstrate a blunted contraction‐induced rapid onset vasodilatation with obesity that is exercise intensity dependent. Impaired rapid onset vasodilatation may negatively impact haemodynamic responses to everyday intermittent activities performed by obese humans.
Deaf Readers as Bilinguals: An Examination of Deaf Readers’ Print Comprehension in Light of Current Advances in Bilingualism and Second Language Processing
Authors: Piñar Pilar , Dussias Paola E. , Morford Jill P.
Published: October 2011

Much work has examined whether deaf and hearing individuals’ reading strategies are qualitatively different, under the assumption that such differences might account for discrepancies in levels of reading achievement (cf., Allen 1986; Gallaudet Research Institute 2005; Holt 1994; Karchmer and Mitchell 2003; Traxler 2000; Wauters et al. 2006). While generalizing over the performance of deaf readers is not trivial, the evidence seems to converge on the reader’s quality of modality‐independent language experience as the best predictor for reading abilities (Mayberry et al. 2011). In order to better understand the relationship between sign literacy and written literacy, more attention needs to be devoted to the fact that most deaf readers are bilingual in a signed and a written language and that, in most cases, the written language is, effectively, their second language. The growing body of research on bilingualism and L2 processing is rapidly advancing our understanding of the architecture of the bilingual brain and of the individual factors that might affect both production and comprehension in a second language. This body of research has great potential to illuminate aspects of deaf readers’ behavior that have heretofore appeared vexing. In turn, including deaf literacy studies within the larger context of research on bilingualism will contribute to a richer picture of the bilingual experience.
Sentence Comprehension in Aphasia
Authors: Clark David Glenn
Published: October 2011

Aphasia is a disorder of language that sometimes occurs in the setting of brain damage. Aphasic disturbances of syntactic comprehension have been described only in recent decades, and have been characterized as the loss of the ability to understand non‐canonical sentences. Several interesting hypotheses have been advanced to explain this phenomenon. Some of these hypotheses rest on the assumption that heuristics play a role in producing the aphasic comprehension pattern. Evidence from the past decade suggests that heuristic processes do play a role in normal sentence comprehension, and act in concert with slower processes that more closely resemble the syntax of linguistic theory. The slower syntactic mechanisms appear to be more readily disturbed by brain damage, leading to greater difficulty with sentences that cannot be interpreted heuristically. However, the dichotomy between canonical and non‐canonical sentences accounts for little of the variance in the performance of aphasic individuals. Instead, the comprehension of each sentence structure is disrupted according to the complexity of the structure and the severity of the individual’s aphasia. This observation argues against hypotheses that posit a deficit of a specific linguistic operation and favors reduction of a hypothetical cognitive resource that is necessary for normal comprehension. In this case, the chief contribution from linguistic theory is the syntactic tree itself, which affords a concise characterization of the difficulty of parsing and interpreting a given sentence. The field now faces several challenges. The neural basis of heuristic, parsing, and interpretive mechanisms must be elucidated. Achievement of this objective entails a neural characterization of the cognitive resource that is disrupted in sentence comprehension disorders and of the semantic representations onto which morphemes and sentences are mapped.
Small Clauses
Authors: Citko Barbara
Published: October 2011

This paper provides an overview of the empirical and theoretical questions surrounding small clause constructions. After delimiting the range of constructions that have been analyzed as small clauses, it turns to more concrete arguments in favor of the very existence of small clauses. The arguments involve crosslinguistic, acquisition and diachronic considerations. The paper also reviews the main proposals concerning the internal structure, category and typology of small clauses, drawing primarily on data involving copular constructions.
The post‐infection outcomes of influenza and acute respiratory infection in patients above 50 years of age in Japan: an observational study
Authors: Ikematsu Hideyuki , Takeuchi Yuriko , Rosenlund Mats , Kawai Naoki , Shimamura Ryuji , Hirata Miki , Iwaki Norio
Published: October 2011

Please cite this paper as: Ikematsu et al. (2011) The post‐infection outcomes of influenza and acute respiratory infection in patients above 50 years of age in Japan: an observational study. Influenza and Other Respiratory Viruses 6(3), 211–217.

Objectives  Influenza can be a serious illness, especially for older people, and reducing the impact of influenza in elderly is important. The objective of this study was to estimate the prevalence and postinfection outcomes of influenza among the over‐50 population in Japan.

Design  An observational study was designed to ascertain the proportion of influenza cases in a population aged ≥50 years with acute respiratory infection (ARI) and to determine the postinfection outcomes of their illness during the 2008–09 influenza season in Japan. Respiratory specimens obtained from a total of 401 patients were tested by PCR for influenza viruses, respiratory syncytial virus (RSV) and human metapneumovirus (hMPV). The effectiveness of the seasonal trivalent influenza vaccine was estimated by a test‐negative case control analysis.

Setting  Seventeen outpatient clinics located in four separate areas of Japan.

Sample  Respiratory swab specimens from the ARI patients aged ≥50 years.

Main outcome measures  Laboratory confirmed influenza in patients presenting with ARI.

Results  In all, 89 (22.2%) of the patients were positive for one of the tested viruses; 70 (78.7%) with influenza, 17 (19.1%) with RSV, and 2 (2.2%) with hMPV. Cough (95.7% vs 73.4%), loss of appetite (67.1% vs 35.5%), absence from work (50.0% vs 23.0%), impact on daily activity (90.0% vs 62.5%), and caregiver absence from work (5.7% vs 0.6%) were observed higher in influenza patients. The duration of feeling weakness (6.3 ± 5.4 vs 3.6 ± 1.9 days) and average days of reduced activity (5.2 vs 3.6 days) were longer for influenza patients. Vaccine effectiveness was estimated to be 32.1% (95% CI: −14.9, 59.9%).

Conclusions  Influenza was the dominant ARI‐causing virus and the clinical and socio‐economic outcomes imposed on patients over 50 years of age was high for influenza.
Invasive bacterial infections following influenza: a time‐series analysis in Montréal, Canada, 1996–2008
Authors: Allard R. , Couillard M. , Pilon P. , Kafka M. , Bédard L.
Published: October 2011

Please cite this paper as: Allard et al. (2012) Invasive bacterial infections following influenza: a time‐series analysis in Montréal, Canada, 1996–2008. Influenza and Other Respiratory Viruses 6(4), 268–275.

Background  Shared seasonal patterns, such as between influenza and some respiratory bacterial infections, can create associations between phenomena not causally related.

Objectives  To estimate the association of influenza with subsequent bacterial infections after full adjustment for confounding by seasonal and long‐term trends.

Methods  Time series of weekly counts of notified cases of invasive infections with Haemophilus influenzae, Neisseria meningitidis, Streptococcus pneumoniae and Streptococcus pyogenes, in Montréal, Canada, 1996–2008, were modelled by negative binomial regression, with terms representing seasonal and long‐term trends and terms for numbers of positive laboratory tests for influenza A and B.

Results  The associations of S. pneumoniae, H. influenzae and N. meningitidis with influenza disappeared after seasonal terms were added to the model. However, the influenza B count remained associated with the S. pyogenes counts for the same week and the following week: S. pyogenes incidence rate ratios were 1.0376 (95% CI: 1.0009–1.0757) and 1.0354 (0.9958–1.0766), respectively, for each increase of 1 in the influenza count.

Conclusions  Influenza B accounts for about 8percnt; of the incidence of invasive S. pyogenes infections, over and above any effect associated with modellable seasonal and long‐term trends. This association of influenza B with S. pyogenes infections can be attributed largely to the years 1997, 2001, 2007 and 2008, when late peaks in influenza B counts were followed by peaks in S. pyogenes notifications. This finding reinforces the case for universal immunization against influenza, as partial protection against the ‘flesh eating disease’.
Management of multiple inter‐implant papillae – a report of two cases with 18–36‐month follow‐up
Authors: McCrea S.J.J.
Published: October 2011

Today, oral rehabilitation with osseointegrated dental implants is considered a routine, being utilised for single‐tooth and partial edentulism tooth replacement, and full edentulism therapy. However, osseointegration does not always result in aesthetic success and patient satisfaction. Numerous surgical and restorative management techniques have been developed to achieve predictable and long‐term stable aesthetic and functional success. However, the periodontally compromised patient remains a challenge to all those techniques. This is a ‘step‐by‐step’ surgical and restorative approach to produce a visibly pleasing result where management had to address:

long‐term chronic adult periodontitis with associated gross horizontal bone loss;

elective, multiple extractions of adjacent anterior maxillary teeth with their immediate implant placement;

maintenance of/or regeneration of interdental and inter‐implant papilla; and

maintenance of the width of keratinised gingival tissue and the associated position of the mucogingival junction.
The trouble with ectopic maxillary canines – a cautionary tale of two cases
Authors: Akram A. , Kerr R.M.
Published: October 2011

Two cases are presented in whom extensive cystic change occurred around ectopic unerupted maxillary canines. These cases highlight the importance of long‐term follow‐up where ectopic canines are left in situ.
Ectopic wisdom tooth in the condyle area
Authors: Mourouzis C. , Igoumenakis D. , Dais P. , Rallis G.
Published: October 2011

Grossly ectopic third molar is a quite rare condition. Only a few cases of wisdom tooth location in the condyle area of the mandible have been reported. A patient with a third molar inclusion in the condylar region is presented. The intra‐oral removal of this tooth is described.
Impact of dental visiting trajectory patterns on clinical oral health and oral health‐related quality of life
Authors: Crocombe Leonard A. , Broadbent Jonathan M. , Thomson W. Murray , Brennan David S. , Poulton Richie
Published: October 2011

Background: Previous studies have shown variation in long‐term dental visiting but little is known about the oral health outcomes of such variation.

Objective: The objective of this study is to determine the association of different dental visiting trajectories with dental clinical and oral health‐related quality of life (OHRQoL) indicators.

Methods: This study utilized data from the Dunedin Multidisciplinary Health and Development Study, a continuing longitudinal study of 1,037 babies born in Dunedin (New Zealand) between April 1, 1972 and March 31, 1973. Data presented here were collected at ages 15, 18, 26, and 32 years. Three categories of dental attendance were identified in earlier research, namely: regulars (n = 285, 30.9 percent of the cohort), decliners (441, 55.9 percent), and opportunistic users (107, 13.1 percent).

Results: There was a statistically significant association between opportunistic dental visiting behavior and decayed missing and filled surfaces score (Beta = 3.9) as well as missing teeth because of caries (Beta = 0.7). Nonregular dental visiting trajectories were associated with higher Oral Health Impact Profile (OHIP‐14) scores (Beta = 2.1) and lower self‐rated oral health scores (prevalence ratio = 0.8).

Conclusion: Long‐term, postchildhood dental attendance patterns are associated with oral health in adulthood, whether defined by clinical dental indicators or OHRQoL. Improving dental visiting behavior among low socioeconomic status groups would have the greatest effect on improving oral health and reducing oral health impacts.
Factors associated with preventive dental care‐seeking behavior among people living with HIV
Authors: Tobias Carol R. , Lemay Celeste A. , Jeanty Yves , Umez‐Eronini Amarachi A. , Reznik David A.
Published: October 2011

Objectives: This study examined factors associated with preventive dental care‐seeking behavior among HIV‐positive adults who participated in a federally funded demonstration project to expand access to oral health care.

Methods: Two thousand one hundred eighty‐seven adults living with human immunodeficiency virus (HIV) in the United States were enrolled in free dental care and were interviewed about their reasons for seeking care, their oral health, and overall health status. Multivariate analysis using Generalized Estimating Equations to control for clustering by site was conducted to identify factors associated with preventive care‐seeking behavior.

Results: Forty‐one percent of participants reported the only reason they sought dental care was for preventive care, to receive a checkup or cleaning. Factors associated with preventive care‐seeking behavior in multivariate analysis included no unmet need for dental care since testing HIV positive, no dental insurance, taking HIV medications and better overall oral health.

Conclusions: Many HIV‐positive adults may seek preventive care when it is offered at no cost. Interventions that address unmet needs and target individuals who are not taking HIV medications or have poorer oral health may improve preventive practices.
Prenatal nutrition intervention to reduce mutans streptococci among low‐income women
Authors: Reisine Susan , Douglass Joanna , Aseltine Robert , Shanley Ellen , Thompson Colleen , Thibodeau Edward
Published: October 2011

Objectives: The objective of this study is to assess the effectiveness of a prenatal nutrition intervention to reduce sugar intake and mutans streptococci (mutans) among low‐income women.

Methods: Pregnant women were recruited from the obstetrics service at a community health center in Connecticut. Inclusion criteria were ≥18 years of age; mutans levels >10 000 colony forming units/ml as determined by Dentocult SM® kits (Orion Diagnostica Oy, Espoo, Finland); and >3 months pregnant. Women were randomized to receive education alone [education intervenion (EI)] or education and a 1‐hour nutrition group session at 9 months and 6 weeks postpartum [education and nutrition intervention (EIN)]. Mutans and questionnaire data were collected at baseline, 9 months, 6 weeks, and 3 months postpartum. One hundred twenty completed the baseline visit and 93 (77%) completed all four visits. Sugar intake was assessed by the Food Frequency Questionnaire and clinical information was abstracted from medical charts.

Results: Mean age was 26.3 years [standard deviation (SD) = 6], 73% were Hispanic, 29% had lived in the United States < 6 years; 48% completed high school; 27% were married; mean total sugar intake at baseline was 149 g (SD = 85). Repeated measures analysis of variance showed that mutans levels declined significantly in both groups, but that the EI group had significantly lower mutans levels at the final assessment compared with EIN. Sugar intake also declined significantly, but there were no significant differences between groups.

Conclusions: The study demonstrated the following: a) the feasibility of conducting the intervention at community health center sites among low‐income pregnant women; b) the effectiveness of education to reduce mutans/sugar intake; and c) the need to improve the nutrition intervention to obtain additional gains in mutans reduction.
Factors affecting children's oral health: perceptions among Latino parents
Authors: Cortés Dharma E. , Réategui‐Sharpe Ludmila , Spiro, III Avron , García Raul I.
Published: October 2011

Objective: The objective of this study is to understand factors that influence the oral health‐related behaviors of Latino children, as reported by their parents.

Methods: Focus groups and in‐depth interviews assessed parental perceptions, experiences, attributions, and beliefs regarding their children's oral health. Guiding questions focused on a) the participant's child dental experiences; b) the impact of dental problems on the child's daily activities, emotions, self‐esteem; c) parental experiences coping with child's dental problems; and d) hygienic and dietary habits. Participants were purposively sampled from dental clinics and public schools with a high concentration of Latinos; 92 urban low‐income Latino Spanish‐speaking parents participated. Transcriptions of the audio files were thematically analyzed using a grounded theory approach.

Results: Parents' explanations of their children's dental experiences were categorized under the following themes: caries and diet, access to dental care, migration experiences, and routines.

Conclusions: Findings revealed fundamental multilevel (i.e., individual/child, family, and community) factors that are important to consider for future interventions to reduce oral health disparities: behaviors leading to caries, parental knowledge about optimal oral health, access to sugary foods within the living environment and to fluoridated water as well as barriers to oral health care such as lack of health insurance or limited health insurance coverage, among others.
PHGDH amplification and altered glucose metabolism in human melanoma
Authors: Mullarky Edouard , Mattaini Katherine R. , Vander Heiden Matthew G. , Cantley Lewis C. , Locasale Jason W.
Published: October 2011

The metabolic requirements of cancer cells differ from that of their normal counterparts. To support their proliferation, cancer cells switch to a fermentative metabolism that is thought to support biomass production. Instances where metabolic enzymes promote tumorigenesis remain rare. However, an enzyme involved in the de novo synthesis of serine, 3‐phosphoglycerate dehydrogenase (PHGDH), was recently identified as a putative oncogene. The potential mechanisms by which PHGDH promotes cancer are discussed.
Impacts of land use change due to biofuel crops on carbon balance, bioenergy production, and agricultural yield, in the conterminous United States
Authors: Qin Zhangcai , Zhuang Qianlai , Chen Min
Published: October 2011

Growing concerns about energy and the environment have led to worldwide use of bioenergy. Switching from food crops to biofuel crops is an option to meet the fast‐growing need for biofuel feedstocks. This land use change consequently affects the ecosystem carbon balance. In this study, we used a biogeochemistry model, the Terrestrial Ecosystem Model, to evaluate the impacts of this change on the carbon balance, bioenergy production, and agricultural yield, assuming that several land use change scenarios from corn, soybean, and wheat to biofuel crops of switchgrass and Miscanthus will occur. We found that biofuel crops have much higher net primary production (NPP) than soybean and wheat crops. When food crops from current agricultural lands were changed to different biofuel crops, the national total NPP increased in all cases by a range of 0.14–0.88 Pg C yr−1, except while switching from corn to switchgrass when a decrease of 14% was observed. Miscanthus is more productive than switchgrass, producing about 2.5 times the NPP of switchgrass. The net carbon loss ranges from 1.0 to 6.3 Tg C yr−1 if food crops are changed to switchgrass, and from 0.4 to 6.7 Tg C yr−1 if changed to Miscanthus. The largest loss was observed when soybean crops were replaced with biofuel crops. Soil organic carbon increased significantly when land use changed, reaching 100 Mg C ha−1 in biofuel crop ecosystems. When switching from food crops to Miscanthus, the per unit area croplands produced a larger amount of ethanol than that of original food crops. In comparison, the land use change from wheat to Miscanthus produced more biomass and sequestrated more carbon. Our study suggests that Miscanthus could better serve as an energy crop than food crops or switchgrass, considering both economic and environmental benefits.
Using imaging spectroscopy to estimate integrated measures of foliage nutritional quality
Authors: Youngentob Kara N. , Renzullo Luigi J. , Held Alex A. , Jia Xiuping , Lindenmayer David B. , Foley William J.
Published: October 2011

1. Integrated measures of foliage nutritional quality that consider the influence of fibre and tannins on the digestibility of nitrogen (N) may provide a more meaningful estimate of forage quality than total foliar N for many herbivorous species. The ability to estimate available nitrogen (AvailN) on a landscape scale could have important applications for herbivore conservation and management. However, AvailN has never been modelled with imaging spectroscopy.

2. We collected hyperspectral remote sensing data (HyMap) over Eucalyptus trees in south‐eastern Australia. Using a combination of laboratory near infrared spectrophotometry, a recently developed in vitro assay for AvailN and two powerful spectral transformation methods, continuum removal and derivative analysis, we developed linear regression models to scale concentrations of total foliar N, AvailN and digestible dry matter (DDM) from leaf to canopy‐level.

3. The model estimates achieved R2‐values between 0·55 and 0·64 for AvailN, 0·54–0·60 for N and 0·75–0·78 for DDM. Ninety‐five per cent of the wavebands selected by the models corresponded to known absorption features. This and the large contribution of a small number of wavebands suggest that it may be possible to develop prediction algorithms based on a few wavelengths that could be extrapolated to other landscape types.

4. This is the first time that integrated measures of foliage nutritional quality have been estimated with imaging spectroscopy. In combination with appropriate crown‐delineation techniques, our methodology will enable users to map variations in these foliar constituents across forest canopies.
Active tension‐extension splints: A novel technique for management of congenital flexural deformities affecting the distal limb in the foal
Authors: Compston P. C. , Payne R. J.
Published: October 2011

A variety of methods are described for managing distal limb flexural deformities in the foal, including intravenous oxytetracycline and splint or cast use. This case series describes a novel technique that creates an ‘active tension‐extension splint’ by wiring the toe into a custom‐made fibreglass splint and therefore into active extension. A dorsal fibreglass splint is made by halving a cast that is set around the affected leg with padding underneath it, so that it is sculpted to a more appropriate anatomical shape. Cerclage wire is placed through the toe and the dorsal aspect of the splint, then tightened to pull the limb into active extension. Foals with distal limb flexural deformities that were treated in this way were followed up by examination of hospital records and telephone questionnaire. Records were examined for 13 foals treated between 2004 and 2010. One foal developed septic osteitis of the distal phalanx due to suspected laminar penetration; other post operative complications seen were bandage sores and minor cosmetic scarring. Out of 10 foals where follow‐up by questionnaire was available, 8 had complete resolution of their deformity following active tension‐extension splinting, one required inferior check ligament desmotomy for complete correction and one had carpal flexural deformities that did not resolve. All that survived to adulthood are sound and have achieved their intended purpose. This previously unpublished technique using a wire through the toe to create an active tension‐extension splint has a high success rate for correction of congenital flexural deformities affecting the distal interphalangeal and metacarpo‐/metatarsophalangeal joints in the foal. The majority of post operative complications are minor and easily managed. This is a simple technique that can improve the management of neonatal distal limb deformities both in a hospital situation and for equine practitioners in the field.
Diagnostic challenges: Equine thoracic neoplasia
Authors: Davis E. G. , Rush B. R.
Published: October 2011

The diagnosis of thoracic neoplasia in the horse can be difficult due to the nonspecific nature of the clinical signs and their overlap with other pulmonary diseases. Haematological and serum biochemical evaluation, thoracic ultrasonography, radiography, endoscopic examination, and, where appropriate, thoracocentesis and pleural fluid cytology may all be helpful in reaching a diagnosis. Granular cell tumours are the most frequently reported primary pulmonary tumours of horses. They occur as single or multiple masses adjacent to bronchi and bronchioles, and the mass typically extends into the airway, resulting in partial or complete occlusion of the lumen. Thymic tumours are classified as benign or metastatic, based on evidence of tissue invasiveness, even though they uniformly appear benign histologically. These tumours are derived from epithelial reticular cells of the thymus and are rare in horses. Other primary thoracic neoplasms originate from various pulmonary tissues and are primarily reported as single case reports: pulmonary and bronchial carcinoma and adenocarcinoma, bronchogenic squamous cell carcinoma, bronchial myxoma, pulmonary chondrosarcoma, pulmonary leiomyosarcoma and pleuropulmonary blastoma. Clinical signs of these primary pulmonary neoplasms are dependent on the tumour type and location, but commonly include chronic cough, weight loss, anorexia, fever and respiratory difficulty; ventral oedema, pleural effusion and epistaxis are also frequently observed. Mesothelioma is a rare primary pleural tumour arising from the mesothelium of the pleura, pericardium and peritoneum. The clinical presentation in horses includes weight loss, respiratory difficulty and large volume pleural effusion. The tumour appears ultrasonographically as multiple small nodules on a thick serosal surface and pleural biopsy is diagnostic. Lymphoma is the most common haematopoietic neoplasm in horses, which can present with 4 main manifestations of lesions: mediastinal, multicentric, alimentary and cutaneous. Common clinical features include chronic weight loss, lethargy, anorexia, subcutaneous oedema, lymphadenopathy, colic, bleeding tendency and diarrhoea. Coughing and laboured respiratory effort are often apparent in individuals suffering from mediastinal masses. In such instances, pleural effusion may result in severe pulmonary atelectasis and pulmonary function is significantly compromised. Haemangiosarcoma is the second most common metastatic thoracic neoplasm in horses. Disseminated haemangiosarcoma is aggressive and rapidly progressive. The clinical presentation often includes tachypnoea, pale or icteric mucous membranes, respiratory distress, epistaxis, and subcutaneous, cutaneous or intramuscular masses. Other tumour types that metastasise to the thoracic cavity include adenocarcinoma, squamous cell carcinoma, fibrosarcoma, metastatic melanoma, mastocytoma and undifferentiated sarcoma. The clinical features of these tumours are generally nonspecific and often relate more to the primary site of tumour formation.
Use of proxy measurements of insulin sensitivity and insulin secretory response to distinguish between normal and previously laminitic ponies
Authors: BORER K. E. , BAILEY S. R. , MENZIES‐GOW N. J. , HARRIS P. A. , ELLIOTT J.
Published: October 2011

Reasons for performing study: Insulin resistance may be a risk factor for pasture‐associated laminitis. Diagnosis of insulin resistance could help identify individuals at increased risk of laminitis.

Objective: To calculate proxy measurements of insulin sensitivity (reciprocal of the square root of insulin: RISQI and quantitative insulin sensitivity check index: QUICKI) and insulin secretory response (modified insulin‐to‐glucose ratio: MIRG) based on basal glucose and insulin concentrations in normal (NP) and previously laminitic (PLP) ponies.

Methods: Proxies were calculated in 7 NP and 5 PLP from 20 separate measurements of insulin and glucose taken in spring, summer and winter when ponies were adapted to eating either pasture or hay. Proxies were RISQI: Insulin‐0.5, QUICKI: 1/(log[fasting Insulin]+ log[fasting Glucose]) and MIRG: (800−0.3×[Insulin‐50]2)/[Glucose‐30]. A modified insulin‐to‐glucose ratio for ponies (MIGRP) was investigated using: (3000−0.012 ×[Insulin‐500]2)/[Glucose‐30]. Statistical analysis used linear mixed models.

Results: Diet did not significantly affect measurements, so values were pooled for further analysis. RISQI (mean ± s.d.) was lower in PLP (0.26 ± 0.15 [mu/l]‐0.5) than NP (0.29 ± 0.12 [mu/l]‐0.5; P = 0.05). QUICKI was lower in PLP (0.31 ± 0.05) than NP (0.33 ± 0.04; P = 0.047). There was no difference in MIRG between NP and PLP. MIGRP (median [interquartile range]) was greater in PLP (4.0 [7.9][muins]2/10·l·mggluc) than NP (2.6 [3.2][muins]2/10·l·mggluc; P = 0.022). In spring, NP had higher RISQI and QUICKI and lower MIGRP than PLP (P<0.001). In PLP, RISQI and QUICKI were higher in summer than spring (P<0.02) and MIGRP was lower in summer than other seasons (P<0.01). In NP, RISQI, QUICKI and MIGRP were each different between seasons (P<0.017). MIRG did not vary with season.

Conclusions: RISQI, QUICKI and MIGRP, but not MIRG, differentiated between NP and PLP. None of the proxies accurately identified individual PLP. Seasonal changes in insulin sensitivity and insulin secretory response were apparent.

Potential relevance: Current proxy measurements cannot determine an individual's laminitis susceptibility. MIGRP may be useful in hyperinsulinaemic animals.
Ergosta-4,6,8(14),22-tetraen-3-one isolated from Polyporus umbellatus prevents early renal injury in aristolochic acid-induced nephropathy rats
Authors: Zhao Ying-Yong , Zhang Li , Mao Jia-Rong , Cheng Xiao-Hong , Lin Rui-Chao , Zhang Yongmin , Sun Wen-Ji
Published: October 2011

Objectives

Aristolochic acid (AA) nephropathy, first reported as Chinese herbs nephropathy, is a rapidly progressive tubulointerstitial nephropathy that results in severe anemia, interstitial fibrosis and end-stage renal disease. Tubulointerstitial injury was studied in a rat model of AA nephropathy to determine whether ergosta-4,6,8(14),22-tetraen-3-one (ergone) treatment prevents early renal injury in rats with aristolochic acid I-induced nephropathy.

Methods

Early renal injury via renal interstitial fibrosis was induced in rats by administration of aristolochic acid I (AAI) solution intragastrically for 8 weeks. Ninety-six rats were randomly divided into four groups (n = 24/group): (1) control (2) AAI (3) AAI + ergone (10 mg/kg) and (4) AAI + ergone (20 mg/kg). Blood and urine samples were collected and rat were sacrificed for histological assessment of the kidneys on at the end of weeks 2, 4, 6 and 8.

Key findings

AAI caused progressive elevation of blood urea nitrogen, creatinine, potassium, sodium, chlorine, proteinuria and urinary N-acetyl-β-D-glucosaminidase (NAG). Ergone suppressed elevation of blood urea, nitrogen, creatinine, proteinuria and urinary NAG to some degree, but the AAI–ergone-treated group did not differ from AAI-treated group for body weight, serum potassium, sodium and chlorine. The progress of the lesions in the kidney after AAI administration was also observed by histopathological examinations, but kidneys from rats of AAI–ergone-treated group displayed fewer lesions.

Conclusions

Ergone treatment conferred protection against early renal injury in a rat model of AA nephropathy. Early administration of ergone may prevent the progression of renal injury and the subsequent renal fibrosis in AA nephropathy.
An investigation on the correlation between drug dissolution properties and the growth behaviour of granules in high shear mixer
Authors: Guo Zhen , Ma Mingxin , Hao Yanru , Jiang Tongying , Wang Siling
Published: October 2011

Objectives

The aim of this study was to investigate the correlation between the growth behaviour and in-vitro dissolution rate of water-insoluble drugs prepared with high-shear wet granulation.

Methods

Granules containing nimodipine, microcrystalline cellulose, low-substituted hydroxypropylcellulose and aqueous solution of hydroxypropylcellulose were prepared and the effects of independent process variables, including impeller speed and liquid-to-solid ratio were taken into consideration. The mean granule size, granule-size distribution (GSD), porosity and surface properties were monitored at different kneading times to identify the granule-growth mechanisms simultaneously. A computer-based method was applied to simulate the dissolution behaviour of polydisperse granules based on the GSD data.

Key findings

The in-vitro dissolution rate of drug was high for the early stages of granulation and sharply decreased when coalescence and consolidation of granules started, approaching a flat and low level when granules were sufficiently consolidated. The simulated dissolution results were in agreement with experimental observations and were significantly affected by the GSD, porosity and surface properties of granules during the granulation process. Moreover the GSD was directly related to the granule-growth behaviour and mechanisms.

Conclusions

In general, it was concluded that the dissolution properties of nimodipine basically correlated with the growth behaviour of granules in a high-shear mixer. The simulation method based on GSD can be used as a convenient and rapid way to predict the dissolution properties for formulation development and granulation optimization.