bluuebunny/crossref_metadata_2025_split 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

SynopsisSeasonal 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.
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

SummaryThe 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

SummaryThe 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

AbstractObjective:  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

AbstractObjectives:  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.