bluuebunny/crossref_metadata_2025 huggingface dataset:
Profiling of serine protease activities in human stratum corneum and detection of a stratum corneum tryptase‐like enzyme
Authors: Voegeli R. , Rawlings A. V. , Doppler S. , Heiland J. , Schreier T.
Published: May 2007

Synopsis

Seasonal variation in stratum corneum (SC) biophysical and biological characteristics has been described previously. In particular, the winter season has been shown to affect more severely the properties of facial skin compared with forearm skin. Moreover, when compromised, such as in dry skin conditions, facial SC has been shown to contain increased inflammatory cytokines and proteases. Nevertheless, there have been no comparative studies of the activities and depth activity of several proteases in the SC on different body sites and at different times of the year. In this study, we examined the distribution of key serine protease activities (kallikrein 5, kallikrein 7, urokinase, plasmin and a tryptase‐like enzyme) in different layers of the SC on the cheek and the forearm by analysis of consecutive tape strippings of healthy Caucasian subjects during winter and summer. The protein content of the tape strippings was quantified by absorption measurements with a recently developed and novel infrared densitometer SquameScanTM 850A while the SC enzyme activities were determined using fluorogenic peptide substrates. Transepidermal water loss (TEWL), skin pH and skin hydration were higher on the cheek than on the forearm. In the same way, the activity of the inflammatory‐related proteases plasmin, urokinase and tryptase was approximately five to eight times and the activity of the desquamatory‐related proteases kallikrein 5 and kallikrein 7 approximately two to four times higher on the cheek than on the forearm. There were no gender‐related differences in these enzyme activities except for the increased kallikrein 7 in the forearm skin of the female subjects in winter. Reduced kallikrein 5 was associated with increased SC cohesion, as judged by increased protein removal, in forearm skin in the winter months of the year although the skin was clinically normal. It can be concluded that (i) protected skin areas show lower TEWL, skin pH and skin hydration and less protease activities than skin areas that are exposed to the environment, possibly indicating subclinical inflammation on these body sites, (ii) in normal healthy forearm skin, the outer SC exhibits greater serine protease activity than its deeper layers, (iii) compared with the forearm, urokinase‐ and plasmin‐like activities are elevated on SC strippings from the cheek, confirming activation of the plasminogen cascade, and (iv) tryptase‐like activity in the SC is also elevated in samples from the cheek, possibly indicating involvement of mast cells in these barrier‐compromised body sites or the synthesis of a novel tryptase‐like enzyme by keratinocytes. Although elevation of the activities of urokinase, plasmin, kallikrein 5, kallikrein 7 and now a tryptase‐like enzyme was observed on SC derived from skin of clinically normal cheeks, we anticipate even higher activities in skin conditions where the epidermal barrier is further impaired.
Divisions in subjective construction of teasing incidents: Role and social skill level in the teasing function1
Authors: ENDO YUMI
Published: May 2007

Abstract:  Teasing constitutes ambiguous interpersonal behavior that some people perceive to be fun and other people view as hostile. These perspectives might reflect the views of teasers and targets, as well as those of individuals with high levels of social skill and those with low levels of social skill. A group of 182 university students retrieved an incident from their memories in which they had been teased by someone or had teased someone else, and described it. Teasers and targets systematically differed in their perceptions of teasing. Furthermore, targets with high social skills perceived the event as humorous and as relatively less damaging, as did teasers, whereas targets with low social skills tended to report the event as relatively less humorous and to read some indication of the teaser's devaluation of them from statements made during the teasing incident. These results suggest that individual differences with respect to social skills and roles in teasing situations result in different subjective constructions of teasing.
SIRT2 deacetylates FOXO3a in response to oxidative stress and caloric restriction
Authors: Wang Fei , Nguyen Margaret , Qin F. Xiao‐Feng , Tong Qiang
Published: May 2007

The sirtuin family of nicotinamide adenine dinucleotide‐dependant (NAD) deacetylases plays an important role in aging and metabolic regulation. In yeast, the Sir2 gene and its homolog Hst2 independently mediate the action of caloric restriction on lifespan extension. The mammalian Sir2 ortholog, SIRT1, is up‐regulated by caloric restriction and deacetylates a variety of substrates, including histones and the forkhead box O (FOXO) transcription factors. The mammalian ortholog of Hst2, SIRT2, was shown to co‐localize with microtubules and functions as α‐tubulin deacetylase. During G2/M phase, SIRT2 proteins enter nuclei and deacetylate histones. We report here that the expression of SIRT2 is elevated in the white adipose tissue and kidney of caloric‐restricted mice. Oxidative stress, such as hydrogen peroxide treatment, also increases SIRT2 expression in cells. We have demonstrated that SIRT2 binds to FOXO3a and reduces its acetylation level. SIRT2 hence increases FOXO DNA binding and elevates the expression of FOXO target genes, p27Kip1, manganese superoxide dismutase and Bim. As a consequence, SIRT2 decreases cellular levels of reactive oxygen species. Furthermore, as Bim is a pro‐apoptotic factor, SIRT2 promotes cell death when cells are under severe stress. Therefore, mammalian SIRT2 responds to caloric restriction and oxidative stress to deacetylate FOXO transcription factors.
Longevity determined by developmental arrest genes in Caenorhabditis elegans
Authors: Chen Di , Pan Kally Z. , Palter Julia E. , Kapahi Pankaj
Published: May 2007

The antagonistic pleiotropy theory of aging proposes that aging takes place because natural selection favors genes that confer benefit early on life at the cost of deterioration later in life. This theory predicts that genes that impact development would play a key role in shaping adult lifespan. To better understand the link between development and adult lifespan, we examined the genes previously known to be essential for development. From a pool of 57 genes that cause developmental arrest after inhibition using RNA interference, we have identified 24 genes that extend lifespan in Caenorhabditis elegans when inactivated during adulthood. Many of these genes are involved in regulation of mRNA translation and mitochondrial functions. Genetic epistasis experiments indicate that the mechanisms of lifespan extension by inactivating the identified genes may be different from those of the insulin/insulin‐like growth factor 1 (IGF‐1) and dietary restriction pathways. Inhibition of many of these genes also results in increased stress resistance and decreased fecundity, suggesting that they may mediate the trade‐offs between somatic maintenance and reproduction. We have isolated novel lifespan‐extension genes, which may help understand the intrinsic link between organism development and adult lifespan.
Would I Attend Child and Adolescent Mental Health Services (CAMHS)? Fourteen to Sixteen Year Olds Decide
Authors: Paul Moli , Berriman Jo Anne , Evans Joanne
Published: May 2007

Background:  Research indicates minors over 14‐years have capacity, yet, in England and Wales, only over‐16s are legally presumed able to consent. This study compared 14/15‐ and 16‐year‐olds’ decision‐making about attending CAMHS.

Method:  Questionnaire‐based study of 1129 14–16‐year‐olds.

Results:  Fewer 16‐year‐olds think parents contribute to decision‐making. There were no significant differences between 14/15‐ and 16‐year‐olds in relation to thinking they have the final say, voluntariness or information preferences. Four‐fifths wanted a range of information and thought it should be provided to all young people, not just those referred.

Conclusions:  14/15‐year‐olds are as likely as 16‐year‐olds to be able to consent to attending CAMHS.
A Large‐scale Mutagenesis Screen to Identify Seizure‐resistant Zebrafish
Authors: Baraban Scott C. , Dinday Matthew T. , Castro Peter A. , Chege Sally , Guyenet Stephan , Taylor Michael R.
Published: May 2007

Summary:  Methods: Seizures were induced with pentylenetetrazole (PTZ). Zebrafish were analyzed between 3 and 7 days postfertilization (dpf). Genome mutations were induced in founders by using N‐ethyl‐nitrosourea (ENU). Seizure behavior was monitored by using a high‐speed camera and quantified by locomotion‐tracking software. Electrographic activity was monitored by using a field‐recording electrode placed in the optic tectum of agar‐immobilized zebrafish.

Results: Short‐term PTZ exposure elicited a burst‐suppression seizure pattern in 3‐dpf zebrafish and more complex activity consisting of interictal‐ and ictal‐like discharges at 7 dpf. Prolonged exposure to PTZ induced status epilepticus–like seizure activity and fatality in wild‐type zebrafish larvae. With a PTZ survival assay at 6–7 dpf, we identified six zebrafish mutants in a forward‐genetic screen covering nearly 2,000 F2 families. One mutant (s334) also was shown to exhibit reduced behavioral activity on short‐term PTZ exposure and an inability to generate long‐duration ictal‐like discharge.

Conclusions: Zebrafish offers a powerful tool for the identification and study of a genetic basis for seizure resistance.
Analysis of a Quantitative Trait Locus for Seizure Susceptibility in Mice Using Bacterial Artificial Chromosome‐Mediated Gene Transfer
Authors: Ferraro Thomas N. , Golden Gregory T. , Dahl John P. , Smith George G. , Schwebel Candice L. , MacDonald Ross , Lohoff Falk W. , Berrettini Wade H. , Buono Russell J.
Published: May 2007

Summary:  Purpose: Previous quantitative trait loci (QTL) mapping studies from our laboratory identified a 6.6 Mb segment of distal chromosome 1 that contains a gene (or genes) having a strong influence on the difference in seizure susceptibility between C57BL/6 (B6) and DBA/2 (D2) mice. A gene transfer strategy involving a bacterial artificial chromosome (BAC) DNA construct that contains several candidate genes from the critical interval was used to test the hypothesis that a strain‐specific variation in one (or more) of the genes is responsible for the QTL effect.

Methods: Fertilized oocytes from a seizure‐sensitive congenic strain (B6.D2‐Mtv7a/Ty‐27d) were injected with BAC DNA and three independent founder lines of BAC‐transgenic mice were generated. Seizure susceptibility was quantified by measuring maximal electroshock seizure threshold (MEST) in transgenic mice and nontransgenic littermates.

Results: Seizure testing documented significant MEST elevation in all three transgenic lines compared to littermate controls. Allele‐specific RT‐PCR analysis confirmed gene transcription from genome‐integrated BAC DNA and copy‐number‐dependent phenotypic effects were observed.

Conclusions: Results of this study suggest that the gene(s) responsible for the major chromosome 1 seizure QTL is found on BAC RPCI23‐157J4 and demonstrate the utility of in vivo gene transfer for studying quantitative trait genes in mice. Further characterization of this transgenic model will provide new insight into mechanisms of seizure susceptibility.
Glial Activation Links Early‐Life Seizures and Long‐Term Neurologic Dysfunction: Evidence Using a Small Molecule Inhibitor of Proinflammatory Cytokine Upregulation
Authors: Somera‐Molina Kathleen C. , Robin Beverley , Somera Cherie Ann , Anderson Christopher , Stine Christy , Koh Sookyong , Behanna Heather A. , Van Eldik Linda J. , Watterson D. Martin , Wainwright Mark S.
Published: May 2007

Summary: Purpose: Early‐life seizures increase vulnerability to subsequent neurologic insult. We tested the hypothesis that early‐life seizures increase susceptibility to later neurologic injury by causing chronic glial activation. To determine the mechanisms by which glial activation may modulate neurologic injury, we examined both acute changes in proinflammatory cytokines and long‐term changes in astrocyte and microglial activation and astrocyte glutamate transporters in a “two‐hit” model of kainic acid (KA)‐induced seizures.

Methods: Postnatal day (P) 15 male rats were administered KA or phosphate buffered saline (PBS). On P45 animals either received a second treatment of KA or PBS. On P55, control (PBS‐PBS), early‐life seizure (KA‐PBS), adult seizure (PBS‐KA), and “two‐hit” (KA‐KA) groups were examined for astrocyte and microglial activation, alteration in glutamate transporters, and expression of the glial protein, clusterin.

Results: P15 seizures resulted in an acute increase in hippocampal levels of IL‐1β and S100B, followed by behavioral impairment and long‐term increases in GFAP and S100B. Animals in the “two‐hit” group showed greater microglial activation, neurologic injury, and susceptibility to seizures compared to the adult seizure group. Glutamate transporters increased following seizures but did not differ between these two groups. Treatment with Minozac, a small molecule inhibitor of proinflammatory cytokine upregulation, following early‐life seizures prevented both the long‐term increase in activated glia and the associated behavioral impairment.

Conclusions:These data suggest that glial activation following early‐life seizures results in increased susceptibility to seizures in adulthood, in part through priming microglia and enhanced microglial activation. Glial activation may be a novel therapeutic target in pediatric epilepsy.
Seizure‐Free Outcome in Randomized Add‐on Trials of the New Antiepileptic Drugs
Authors: Gazzola Deana M. , Balcer Laura J. , French Jacqueline A.
Published: May 2007

Summary:  Purpose: The goal of this study is to (1) provide clinically useful, previously unpublished comparative analyses of seizure‐freedom rates for newer antiepileptic drugs (AEDs), and (2) recommend a standard for data presentation and analysis.

Methods: Data were reviewed from placebo‐controlled adjunctive trials in refractory patients of gabapentin (GPN), lamotrigine (LTG), topiramate (TOP), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), zonisamide (ZNS), and pregabalin (PGB). Seizure‐freedom analyses in these publications, if included at all, consistently included both patients who completed the trial, and those who dropped out prior to completion (last observation carried forward, LOCF). This has the potential to increase reported seizure‐free outcomes. Pharmaceutical companies were contacted for the provision of unpublished seizure‐free data in the patients who completed the entire study.

Results: In most cases, LOCF analysis produced a higher rate of seizure freedom compared to completer analysis. A total of 0%–1.1% of the LOCF population was seizure‐free in the GPN trials (completer data not available). For the remaining AEDs, seizure‐freedom results in the LOCF versus completer populations were: 0.7% versus 0.8% (LTG trial); 12% versus 2.6% (OXC trial); 3.6%–6.4% versus 3.9%–7.1% (LEV trial); 3.7%–7.9% versus 1.3%–1.4% (PGB trial); and 6.0% versus 3.0% (ZNS trial, minus titration period).

Conclusions: By employing LOCF, a clinically unrealistic picture of seizure‐free rates may be reported. Access to completer data is informative, as it includes only those patients who were able to tolerate the drug at doses that produced seizure freedom. Ideally, data from both ITT and completer analyses should be made available.
Do Recent Seizures and Recent Changes in Antiepileptic Drugs Impact Performances on Neuropsychological Tests in Subtle Ways that Might Easily Be Missed?
Authors: Dodrill Carl B. , Ojemann George A.
Published: May 2007

Summary:  Purpose: The possibility that a recent seizure or a recent change in antiepileptic medication might produce an occult change in neuropsychological performance is of interest, and especially so in the context of evaluation for epilepsy surgery. Such an evaluation is often done in a setting of video‐EEG monitoring where a strong effort is made to produce seizures as quickly as possible with abrupt changes in medication, alterations in sleep, etc., which could impact the validity of neuropsychological findings.

Methods: A total of 126 adults were studied who had seizures of strictly temporal origin (47 right, 79 left) and whose recent medication history and seizure occurrence prior to testing was as clear as possible. All were tested with an extensive neuropsychological battery with great attention to giving tests only when the patients appeared clinically not to be suffering from recent seizures (seizures occurring on the day of testing or on the day prior to testing) or medication change effects. The cognitive correlates of side of seizures were also evaluated in order to provide a strength‐of‐effect comparison with recency of AED changes and seizures.

Results: Findings from three‐way ANOVA showed a possible slight adverse effect of recent AED change, no effects of recent seizures, and a sizeable relationship with side of seizures. A simultaneous consideration of all three of these variables did not provide additional findings of interest.

Conclusions: Although it is not possible to completely rule out some subtle cognitive effects of recent changes in medication or recent seizures, this investigation does not provide evidence for such effects when the neuropsychological evaluation is conducted carefully with no testing during any questionable or definite postictal periods.
Dental caries and childhood obesity: roles of diet and socioeconomic status
Authors: Marshall Teresa A. , Eichenberger‐Gilmore Julie M. , Broffitt Barbara A. , Warren John J. , Levy Steven M.
Published: May 2007

Objective:  Our objective was to determine (a) if caries and obesity were associated in a pediatric population and (b) if so, then to explore diet and socioeconomic status as additional risk factors.

Methods:  Subjects were recruited at birth and are members of the Iowa Fluoride Study. Data such as parental age, parental education levels and family incomes were obtained by questionnaire at recruitment. Children's primary dentition was examined and their weight and height measured at 4.5–6.9 years of age. Parental weight and height were measured when children were 7.6–10.9 years of age. Beverage and nutrient intake patterns were obtained from 3‐day food and beverage diaries completed at 1, 2, 3, 4 and 5 years of age.

Results:  Children with caries had lower family incomes, less educated parents, heavier mothers and higher soda‐pop intakes at 2, 3 and for 1–5 years than children without caries (P < 0.05). ‘Overweight’ children had less educated fathers and heavier parents than ‘normal’ weight children (P < 0.05). Children ‘at risk’ of overweight had higher caries rates than ‘normal’ or ‘overweight’ children (P < 0.05). In stepwise logistic regression models to predict caries experience, soda‐pop intakes were displaced by mother's education, leaving ‘at risk’ of overweight and mother's education in the final model.

Conclusion:  Caries and obesity coexist in children of low socioeconomic status. Public health measures to improve dietary education and access to appropriate foodstuffs could decrease the risk of both diseases.
Influences of market competition on dental care utilization under the global budget payment system
Authors: Tsai Wen‐Chen , Kung Pei‐Tseng , Chang Wei‐Chieh
Published: May 2007

Objectives:  The degrees of market competition usually influence providers’ behaviors. This study investigated the influence of medical market competition on the utilization of dental care under the global budget payment system. This study also examined the relative factors that influence the utilization of dental care.

Methods:  This study used the healthcare sub‐regions (HCSRs) in the healthcare net as the observation units. The dataset was the National Health Insurance dental care claim data from 1999 to 2002. The degree of market competition of dental care was measured by the Herfindahl Index (HI). The influences of medical market competition on the utilization of dental care were analyzed by multiple linear regression analysis.

Results:  When the market had a higher degree of competition, people had a higher number of dental utilizations after controlling for the other variables. When market competition increased by 1%, annual expenditures and frequencies of dental care as well as frequencies of tooth‐filling per person increased by 0.4%. Thirty‐three percent of dental expenditures could be explained by increases in the degree of market competition. Females or highly educated people had a positive correlation with dental utilization. However, the agricultural population negatively correlated with dental utilization. Average household income had no significant relationship with the frequency of dental care but had a significant negative association with dental expenditures when dental care was covered by health insurance.

Conclusions:  After the global budget payment system for dental care was implemented, increases in dental care market competition led to the increase in utilization of dental care services.
Assessment of orthodontic treatment need: a comparison of study models and facial photographs
Authors: Sherlock Joseph M. , Cobourne Martyn T. , McDonald Fraser
Published: May 2007

Abstract –  Objectives:  The current study aims to examine how orthodontic treatment need is prioritized depending upon whether dental study models or facial photographs are used as the means of assessment.

Methods:  A group of three orthodontists and three postgraduate orthodontic students assessed: (i) dental attractiveness; and (ii) need for orthodontic treatment in 40 subjects (19 males, 21 females). The 40 subjects displayed a range of malocclusions. Separate assessments were made from study models and facial photographs.

Results:  There was a bias towards higher scores for dental attractiveness from facial photographs compared with assessment of study casts, for all examiners. This was statistically significant for five of the six examiners (P = 0.001–0.101). The need for orthodontic treatment was rated as 20% higher from study models compared with facial photographs (P < 0.001); overall the level of need for orthodontic treatment was rated as 18.9% higher from study models compared with facial photographs (P < 0.001). Reproducibility analyses showed that there was a considerable variation in the intra‐ and inter‐examiner agreement.

Conclusions:  This study shows that a group of three orthodontists and three postgraduate students in orthodontics: (i) rated orthodontic treatment need higher from study models compared with facial photographs and; (ii) rated dental attractiveness higher from facial photographs compared with study models. It is suggested that the variable intra‐examiner agreement may result from the assessment of orthodontic treatment need and dental attractiveness in the absence of any specific assessment criteria. The poor reproducibility of assessment of orthodontic treatment need and dental attractiveness in the absence of strict criteria may suggest the need to use an appropriate index.
Maternal periodontitis and adverse pregnancy outcomes
Authors: Pitiphat Waranuch , Joshipura Kaumudi J. , Gillman Matthew W. , Williams Paige L. , Douglass Chester W. , Rich‐Edwards Janet W.
Published: May 2007

Abstract –  Objectives:  Maternal periodontal diseases have been associated with increased risk of preterm birth and restricted fetal growth among relatively low socioeconomic groups. Whether the association can be generalized to middle‐class populations remains uncertain. We evaluated periodontitis in relation to preterm birth (<37 weeks’ gestation) and small‐for‐gestational‐age (SGA, birth weight below the 10th percentile of birth weight for gestational age) among a group of medically insured women.

Methods:  We conducted a prospective study among participants of Project Viva, a US cohort study of pregnant women and their offspring from 1999 to 2002. Pregnancy outcomes were obtained from medical records. Self‐reported periodontitis was assessed during the second trimester of pregnancy, and validated against radiographs. Logistic regression analyses were employed to evaluate the association of periodontitis with pregnancy outcomes adjusted for age, race/ethnicity, smoking status, income, frequency of dental check‐ups, prepregnancy body mass index, pregnancy weight gain, gravidity, prior history of preterm birth and history of genitourinary infection.

Results:  Of the 1635 women, 72.7% were Caucasian, 65.0% had annual household income >$70 000, 3.8% reported having periodontitis, 6.4% delivered preterm, 5.4% delivered SGA babies, and 11.0% had poor pregnancy outcome (either preterm birth or SGA). The odds ratio (OR) associated with periodontitis was 1.74 (95% CI 0.65–4.66) for preterm delivery and 2.11 (95% CI 0.76–5.86) for SGA individually. When preterm delivery and/or SGA were combined, the OR was 2.26 (95% CI 1.05–4.85) relating periodontitis with poor pregnancy outcome.

Conclusion:  Within the limitations of the study, the results suggest that periodontitis is an independent risk factor for poor pregnancy outcome among middle‐class women.
Effect of reducing the number of items of the Oral Health Impact Profile on responsiveness, validity and reliability in edentulous populations
Authors: Awad Manal , Al‐Shamrany Muneera , Locker David , Allen Finbarr , Feine Jocelyne
Published: May 2007

Abstract –  Background:  The 49‐item Oral Health Impact Profile (OHIP) has shown strong responsiveness, reliability and validity. However, the large number of items included may limit its use in clinical trials, clinical practice and surveys.

Objective:  The main objective of this study is to assess the effect of reducing the number of items in each domain, one at a time, on responsiveness, reliability and validity of the OHIP in edentulous populations.

Materials and methods:  Data used in this study were obtained from two randomized clinical trials comparing mandibular implant overdentures and conventional dentures among 102 subjects between 35 and 65 years of age, and 60 subjects over the age of 65 years. Participants were edentulous individuals who wished to replace their current prostheses. Subjects in both trials were asked to complete the 49‐item OHIP prior to treatment and at 2 months post‐treatment. Within the study, effect sizes were computed at each stage of item reduction using the impact method. Intraclass correlation coefficients and Pearson's correlation coefficients were also assessed at each stage of item reduction. In addition, receiver‐operating characteristic (ROC) curves were used to indicate the accuracy with which measurement changes corresponded to judgements of important changes in Oral Health Related Quality of Life (OHRQL).

Results:  The results indicated that, in general, domain responsiveness was not affected by the reduction of the number of items used per domain. However, there was a decrease in reliability, especially within the ‘psychological’ and ‘social’ disabilities and ‘handicap’ domains (35‐ to 65‐year group). In addition, there was a decrease in construct validity of the ‘physical pain’, ‘psychological’ and ‘social disabilities’ domains (35‐ to 65‐year group), as well as on ‘physical pain’, ‘psychological discomfort’, ‘physical’ and ‘psychological’ disabilities in the 65‐year and older group. This occurred primarily, when reducing from two to one item per domain. Among the 35‐ to 65‐year group, there were consistencies in patients’ ratings of the importance of similarly measured changes in oral health.

Conclusion:  The results indicate that although the 49‐item OHIP responsiveness could be maintained with item reduction, this will lead to compromises in reliability and validity.
Self‐reported efficacy of an online dental anxiety support group: a pilot study
Authors: Coulson Neil S. , Buchanan Heather
Published: May 2007

Abstract –  Objectives:  This study aimed to explore the self‐reported effectiveness of an existing online dental anxiety support group in terms of perceived level of anxiety since accessing the group.

Methods:  An online questionnaire was completed by 91 individuals who accessed the Dental Fear Central, an online support group bulletin board, during an 8‐week period in 2005. Participants reported background demographic information, their own self‐reported evaluation of the efficacy of the support group, as well as completing the Modified Dental Anxiety Scale (MDAS).

Results:  In total, 60% of the sample considered that the support group had ‘somewhat’ or ‘greatly lessened’ their anxiety. Overall MDAS scores were significantly lower in the ‘greatly lessened’ group.

Conclusions:  The results of this nonrandomised pilot study suggest some individuals retrospectively considered that, since accessing the online group, they experienced a reduction in dental anxiety. Future research should employ a randomised controlled design in order to determine the contribution of the online group to self‐reported changes in dental anxiety over time.
Eighteenth‐Century Cartographic Studies: A Brief Survey
Authors: Sills Adam
Published: May 2007

Eighteenth‐century cartographic studies is a interdisciplinary field that has been and continues to be shaped by the Foucauldian approach popularized by J. B. Harley, who argues for a decidedly political and ideological interpretation of the map and its history. Within this theoretical paradigm, the map is seen as a form of knowledge that facilitates the hegemonic and unilateral exercise of power, especially as it relates to the formation of the British nation‐state and its colonies. Recent work, however, has called this approach to the history of cartography into question by arguing for a more expansive and pluralistic understanding of the map and its place within eighteenth‐century British society. Works exploring the intersection of cartographic and literary studies have broadened the field by moving away from the previous model in which the map was seen only as an expression of British national and imperial power.
Walter Ralegh and the Arts of Memory
Authors: Hiscock Andrew
Published: May 2007

This article explores both the poetic and prose writing of Sir Walter Ralegh (Raleigh) in the context of early modern cultural debates surrounding memory. Particular attention is paid to the ways in which Platonic and Aristotelian thinking focused upon the faculty may be seen to have influenced Ralegh's ideas on sovereignty (most especially that of James VI/I), the role of the courtier and the undertakings of history and poetry (especially ‘The Ocean's Love to Scinthia/Cynthia’). Whether it was in the narration of the voyage to Guiana, the lyrical evocations of the travails of the courtly lover, the dramatic gestures described in his correspondence, his chronicling of the history of the world, or his arresting final performance on the scaffold, Ralegh gives evidence of a consuming interest in how memory may be seen as a strategic resource with which to formulate identity, to interrogate cultural données and to re‐configure the possibilities of human epistemology. Ralegh is considered in the course of this discussion not only in the contexts of contemporary writers (e.g. Foxe, Jonson, Donne, Bacon), but also as an object of memorialisation by later generations of critics and readers. Directly linked to this consideration of how Ralegh was remembered, this article also reflects upon modern critical controversies surrounding the limits of his authorship and the (insurmountable) difficulties involved in trying to piece together a Ralegh canon.
EFFECT OF ULTIMATE pH ON THE QUALITY CHARACTERISTICS OF PORK
Authors: BIDNER B.S. , ELLIS M. , BREWER M.S. , CAMPION D. , WILSON E.R. , McKEITH F.K.
Published: May 2007

A study was conducted to characterize the relationship between Longissimus thoracis ultimate pH(LTpH) and pork quality. Animals (n = 47) were selected based on LTpH measured at 24 h postmortem. Data were analyzed using regression procedures with ultimate pH as the independent variable, and relationships were determined to be linear (L), quadratic (Ql or cubic (C). Ultimate pH explained 79% (C) of the variation in subjective color, which increased as pH increased. Drip loss, purge loss and L* value decreased as LTpH increased (R2= 0.57C, 0.77 Q and 0.68 Q, respectively). Shear force decreased and sensory juiciness increased as LTpH increased (R2= 0.26Q and 0.46C, respectively). However, of flavor intensity increased as LTpH fell below pH 5.2 or exceeded 6.1(R2=0.52C). Increasing LTpH, up to a point, will improve fresh pork quality and processed meat properties, whereas, above approximately 6.1, of‐flavor may increase.
Validation and Reproducibility Assessment of Tigecycline MIC Determinations by Etest
Authors: Bolmström Anne , Karlsson Åsa , Engelhardt Anette , Ho Phion , Petersen Peter J. , Bradford Patricia A. , Jones C. Hal
Published: May 2007

A multicenter study was conducted to validate Etest tigecycline compared to the Clinical Laboratory Standards Institute reference broth microdilution and agar dilution methodologies. A large collection of gram-negative (
n
= 266) and gram-positive (
n
= 162) aerobic bacteria, a collection of anaerobes (
n
= 385), and selected collections of nonpneumococcal streptococci (
n
= 369),
Streptococcus pneumoniae
(
n
= 372), and
Haemophilus influenzae
(
n
= 372) were tested. Strains with reduced susceptibility to tigecycline were used with all test methods. The Etest showed excellent inter- and intralaboratory reproducibility for all organism groups tested regardless of the test methodology. The essential agreement values with the reference method (±1 dilution) were >99% for the collection of gram-negative and gram-positive aerobes; >98% for the
S. pneumoniae
,
H. influenzae
, and anaerobe collections; and 100% for the group of nonpneumococcal streptococci. These results validate the performance accuracy and utility of Etest tigecycline and verify the reproducibility of this convenient predefined gradient methodology for tigecycline susceptibility determination.
Systems Approach to Improving Antimicrobial Susceptibility Testing in Clinical Laboratories in the United States
Authors: Counts Jon M. , Astles J. Rex , Tenover Fred C. , Hindler Janet
Published: May 2007

Laboratory practice in the preanalytical phase of antimicrobial susceptibility testing (AST) was evaluated in 102 hospital, reference, physician office-clinic, and public health laboratories in Washington state. Surveys were sent to evaluate (i) use of NCCLS/CLSI (formerly NCCLS) AST performance standards, (ii) technical competence in AST case studies, challenging knowledge of contemporary testing issues, and (iii) choice of antimicrobial agents to test for
Streptococcus pneumoniae
. Numerous deficiencies were identified in the survey: (i) initially only 40% of the laboratories surveyed used current NCCLS/CLSI AST performance standards, (ii) the rate of accurate responses for three different case studies ranged from 29% to 69%, and (iii) variation was noted in the choice of antimicrobials tested against invasive isolates of
S. pneumoniae
. These deficiencies could affect therapy and detection of antimicrobial resistance. Several educational programs were implemented to improve AST policies and practices, and a follow-up survey indicated that four intervention strategies were most effective: (i) regional technical workshops, (ii) National Laboratory Training Network teleconferences, (iii) use of the Centers for Disease Control and Prevention (CDC) CD-ROM on AST, and (iv) the CDC Multilevel Antimicrobial Susceptibility Testing Resource website. The interventions could be implemented more widely in the United States to improve AST knowledge and practices.
Rapid Identification of
Staphylococcus aureus
in Blood Cultures by Use of the Direct Tube Coagulase Test
Authors: Qian Qinfang , Eichelberger Karen , Kirby James E.
Published: May 2007

Direct tube coagulase testing for identification of
Staphylococcus aureus
from BACTEC culture broth showed a sensitivity, a specificity, and positive and negative predicative values of 34%, 100%, 100%, and 80.2% with 2 h of incubation and 65%, 98.7, 99.7%, and 88.6% with 4 h of incubation. Anaerobic blood culture contributed significantly to the detection of
S. aureus
.
Isolation and Molecular Characterization of Aichi Viruses from Fecal Specimens Collected in Japan, Bangladesh, Thailand, and Vietnam
Authors: Pham Ngan Thi Kim , Khamrin Pattara , Nguyen Tuan Anh , Kanti Dey Shuvra , Phan Tung Gia , Okitsu Shoko , Ushijima Hiroshi
Published: May 2007

Aichi virus is a new member of the family
Picornaviridae
, genus
Kobuvirus
, and is associated with human gastroenteritis. This study detected Aichi virus in 28 of 912 fecal specimens which were negative for rotavirus, adenovirus, norovirus, sapovirus, and astrovirus and were collected in Japan, Bangladesh, Thailand, and Vietnam during 2002 to 2005.
Clathrin-Dependent Entry of Severe Acute Respiratory Syndrome Coronavirus into Target Cells Expressing ACE2 with the Cytoplasmic Tail Deleted
Authors: Inoue Yuuki , Tanaka Nobuyuki , Tanaka Yoshinori , Inoue Shingo , Morita Kouichi , Zhuang Min , Hattori Toshio , Sugamura Kazuo
Published: May 2007

The penetration of various viruses into host cells is accomplished by hijacking the host endocytosis machinery. In the case of severe acute respiratory syndrome coronavirus (SARS-CoV) infection, viral entry is reported to require a low pH in intracytoplasmic vesicles; however, little is known about how SARS-CoV invades such compartments. Here we demonstrate that SARS-CoV mainly utilizes the clathrin-mediated endocytosis pathway for its entry to target cells by using infectious SARS-CoV, as well as a SARS-CoV pseudovirus packaged in the SARS-CoV envelope. The SARS-CoV entered caveolin-1-negative HepG2 cells, and the entry was significantly inhibited by treatment with chlorpromazine, an inhibitor for clathrin-dependent endocytosis, and by small interfering RNA-mediated gene silencing for the clathrin heavy chain. Furthermore, the SARS-CoV entered COS7 cells transfected with the mutant of ACE2 with the cytoplasmic tail deleted, SARS-CoV receptor, as well as the wild-type ACE2, and their entries were significantly inhibited by treatment with chlorpromazine. In addition, ACE2 translocated into EEA1-positive early endosomes immediately after the virus attachment to ACE2. These results suggest that when SARS-CoV binds ACE2 it is internalized and penetrates early endosomes in a clathrin-dependent manner and that the cytoplasmic tail of ACE2 is not required for the penetration of SARS-CoV.
Differential Requirements of NS4A for Internal NS3 Cleavage and Polyprotein Processing of Hepatitis C Virus
Authors: Kou Yi-Hen , Chang Ming-Fu , Wang Yi-Ming , Hung Tzu-Min , Chang Shin C.
Published: May 2007

The NS3 protein of hepatitis C virus (HCV) possesses protease activity responsible for the proteolytic cleavage of the viral polyprotein at the junctions of nonstructural proteins downstream of NS3. The NS3 protein was also found to be internally cleaved. In this study, we demonstrated that internal cleavages occurred on the NS3 protein of genotype 1b in the presence of NS4A, both in culture cells and with a mouse model system. No internal cleavage products were detected with the NS3 and NS4A proteins of genotype 2a. Three potential cleavage sites were detected in the NS3 protein (genotype 1b), with IPT
402
|S being the major one. The internal cleavage requires the polyprotein processing activity of NS3 protease, but when supplemented in
trans
, the internal cleavage efficiency is reduced. In addition, several mutations in NS4A disrupted the internal cleavage of NS3 but did not affect polyprotein processing, indicating that NS4A contributes differently to these two proteolytic activities. Furthermore, Ile-25, Val-26, and Ile-29 of the NS4A protein, important for the NS4A-dependent internal cleavages, were also shown to be critical for the transforming activity of NS3, but mutations at these critical residues resulted only in a slight increase of HCV replicating efficiency. The internal cleavage-associated enhancement of the transforming activity of NS3 was reduced when a T402A substitution at the major internal cleavage site was introduced. The multiple roles of NS4A in viral multiplication and pathogenesis make NS4A an ideal molecular target for HCV therapy.
Identification of Two Distinct Human Immunodeficiency Virus Type 1 Vif Determinants Critical for Interactions with Human APOBEC3G and APOBEC3F
Authors: Russell Rebecca A. , Pathak Vinay K.
Published: May 2007

Human cytidine deaminases APOBEC3G (A3G) and APOBEC3F (A3F) inhibit replication of Vif-deficient human immunodeficiency virus type 1 (HIV-1). HIV-1 Vif overcomes these host restriction factors by binding to them and inducing their proteasomal degradation. The Vif-A3G and Vif-A3F interactions are attractive targets for antiviral drug development because inhibiting the interactions could allow the host defense mechanism to control HIV-1 replication. It was recently reported that the Vif amino acids D
14
RMR
17
are important for functional interaction and degradation of the previously identified Vif-resistant mutant of A3G (D128K-A3G). However, the Vif determinants important for functional interaction with A3G and A3F have not been fully characterized. To identify these determinants, we performed an extensive mutational analysis of HIV-1 Vif. Our analysis revealed two distinct Vif determinants, amino acids Y
40
RHHY
44
and D
14
RMR
17
, which are essential for binding to A3G and A3F, respectively. Interestingly, mutation of the A3G-binding region increased Vif's ability to suppress A3F. Vif binding to D128K-A3G was also dependent on the Y
40
RHHY
44
region but not the D
14
RMR
17
region. Consistent with previous observations, subsequent neutralization of the D128K-A3G antiviral activity required substitution of Vif determinant D
14
RMR
17
with SEMQ, similar to the SERQ amino acids in simian immunodeficiency virus SIV
AGM
Vif, which is capable of neutralizing D128K-A3G. These studies are the first to clearly identify two distinct regions of Vif that are critical for independent interactions with A3G and A3F. Pharmacological interference with the Vif-A3G or Vif-A3F interactions could result in potent inhibition of HIV-1 replication by the APOBEC3 proteins.
Lambda Interferon (IFN-λ) in Serum Is Decreased in Hantavirus-Infected Patients, and In Vitro-Established Infection Is Insensitive to Treatment with All IFNs and Inhibits IFN-γ-Induced Nitric Oxide Production
Authors: Stoltz Malin , Ahlm Clas , Lundkvist Åke , Klingström Jonas
Published: May 2007

Hantaviruses, causing hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS), are known to be sensitive to nitric oxide (NO) and to pretreatment with type I and II interferons (alpha interferon [IFN-α]/IFN-β and IFN-γ, respectively). Elevated serum levels of NO and IFN-γ have been observed in HFRS patients, but little is known regarding the systemic levels of other IFNs and the possible effects of hantaviruses on innate antiviral immune responses. In Puumala virus-infected HFRS patients (
n
= 18), we report that the levels of IFN-α and IFN-β are similar, whereas the level of IFN-λ (type III IFN) is significantly decreased, during acute (day of hospitalization) compared to the convalescent phase. The possible antiviral effects of IFN-λ on the prototypic hantavirus Hantaan virus (HTNV) replication was then investigated. Pretreatment of A549 cells with IFN-λ alone inhibited HTNV replication, and IFN-λ combined with IFN-γ induced additive antiviral effects. We then studied the effect of postinfection treatment with IFNs. Interestingly, an already-established HTNV infection was insensitive to subsequent IFN-α, -β, -γ, and -λ stimulation, and HTNV-infected cells produced less NO compared to noninfected cells when stimulated with IFN-γ and IL-1β. Furthermore, less phosphorylated STAT1 after IFN treatment was observed in the nuclei of infected cells than in those of noninfected cells. The results suggest that hantavirus can interfere with the activation of antiviral innate immune responses in patients and inhibit the antiviral effects of all IFNs. We believe that future studies addressing the mechanisms by which hantaviruses interfere with the activation and shaping of immune responses may bring more knowledge regarding HFRS and HCPS pathogenesis.
Early Blood Profiles of Virus Infection in a Monkey Model for Lassa Fever
Authors: Djavani Mahmoud M. , Crasta Oswald R. , Zapata Juan Carlos , Fei Zhangjun , Folkerts Otto , Sobral Bruno , Swindells Mark , Bryant Joseph , Davis Harry , Pauza C. David , Lukashevich Igor S. , Hammamieh Rasha , Jett Marti , Salvato Maria S.
Published: May 2007

Acute arenavirus disease in primates, like Lassa hemorrhagic fever in humans, begins with flu-like symptoms and leads to death approximately 2 weeks after infection. Our goal was to identify molecular changes in blood that are related to disease progression. Rhesus macaques (Macaca mulatta) infected intravenously with a lethal dose of lymphocytic choriomeningitis virus (LCMV) provide a model for Lassa virus infection of humans. Blood samples taken before and during the course of infection were used to monitor gene expression changes that paralleled disease onset. Changes in blood showed major disruptions in eicosanoid, immune response, and hormone response pathways. Approximately 12% of host genes alter their expression after LCMV infection, and a subset of these genes can discriminate between virulent and nonvirulent LCMV infection. Major transcription changes have been given preliminary confirmation by quantitative PCR and protein studies and will be valuable candidates for future validation as biomarkers for arenavirus disease.
Identification of the Optimal DC-SIGN Binding Site on Human Immunodeficiency Virus Type 1 gp120
Authors: Hong Patrick W.-P. , Nguyen Sandra , Young Sophia , Su Stephen V. , Lee Benhur
Published: May 2007

Human immunodeficiency virus type 1 (HIV-1) envelope (gp120) binding to DC-SIGN, a C-type lectin that can facilitate HIV infection incisand intrans, is largely dependent on high-mannose-content moieties. Here, we delineate the N-linked glycosylation (N-glycan) sites in gp120 that contribute to optimal DC-SIGN binding. Soluble DC-SIGN was able to block 2G12 binding to gp120, but not vice versa, suggesting that DC-SIGN binds to a more flexible combination of N-glycans than 2G12. Consistent with this observation, HIV strain JRCSF gp120 prebound to 2G12 was 10-fold more sensitive to mannan competition than gp120 that was not prebound in a DC-SIGN cell surface binding assay. The analysis of multiple mutant forms of the 2G12 epitope revealed one triple glycosylation mutant form, termed 134mut (carrying N293Q, N382Q, and N388Q mutations), that exhibited a significant increase in sensitivity to both mannan competition and endoglycosidase H digestion compared to that of the 124mut form (carrying N293Q, N328Q, and N388Q mutations) and wild-type gp120 in a DC-SIGN binding assay. Importantly, no such differences were observed when binding toGalanthus nivaliswas assessed. The 134mut form of gp120 also exhibited decreased binding to DC-SIGN in the context of native envelope spikes on a virion, and virus bearing 134mut exhibited less efficient DC-SIGN-mediated infection intrans. Significantly, 124mut and 134mut differed by only one glycosylation site mutation in each construct, and both 124mut and 134mut viruses exhibited wild-type levels of infectivity when used in a direct infection assay. In summary, while DC-SIGN can bind to a flexible combination of N-glycans on gp120, its optimal binding site overlaps with specific N-glycans within the 2G12 epitope. Conformationally intact envelopes that are DC-SIGN binding deficient can be used to probe the in vivo biological functions of DC-SIGN.