bluuebunny/crossref_metadata_2025_split huggingface dataset:
Population pharmacokinetic modelling of aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients
Authors: Kim Jung‐Ryul , Seo Hyo‐Bum , Cho Joo‐Youn , Kang Do‐Hyung , Kim Yong Ku , Bahk Won‐Myong , Yu Kyung‐Sang , Shin Sang‐Goo , Kwon Jun Soo , Jang In‐Jin 
Published: May 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Almost all reported studies have investigated the pharmacokinetics of aripiprazole in healthy volunteers.• The pharmacokinetics of dehydroaripiprazole have not been identified in a combined model with aripiprazole. WHAT THIS STUDY ADDS • The data on aripiprazole and dehydroaripiprazole in psychiatric patients were modelled jointly using a population approach.• The apparent clearance of aripiprazole in cytochrome P450 (CYP) 2D6 intermediate metabolizers (IM) was approximately 60% of that in CYP2D6 extensive metabolizers (EM) having two functional alleles, but the exposure to dehydroaripiprazole in CYP2D6 IM was similar to that in EM.AIMSThe aims of this study were to develop a combined population pharmacokinetic model for both aripiprazole and its active metabolite, dehydroaripiprazole, in psychiatric patients and to identify to what extent the genetic polymorphisms of cytochrome P450 (CYP) enzymes contribute to the variability in pharmacokinetics (PK).METHODSA population pharmacokinetic analysis was performed using NONMEM software based on 141 plasma concentrations at steady state from 80 patients receiving multiple oral doses of aripiprazole (10–30 mg day−1).RESULTSA one‐compartment model with first‐order kinetics for aripiprazole and dehydroaripiprazole each was developed to describe simultaneously the concentration data. The absorption rate constant was fixed to 1.06 h−1. The typical value of apparent distribution volume of aripiprazole was estimated to be 192 l. Covariate analysis showed that CYP2D6 genetic polymorphisms significantly influenced the apparent clearance of aripiprazole (CL/F), reducing the interindividual variability on CL/F from 37.8% CV (coefficient of variation) to 30.5%. The CL/F in the CYP2D6 IMs was approximately 60% of that in CYP2D6 EMs having two functional alleles. Based on the CYP2D6 genotype, the metabolic ratios were calculated at 0.20–0.34. However, the plasma concentration : dose ratios of dehydroaripiprazole were not different across the CYP2D6 genotype.CONCLUSIONSThis population pharmacokinetic model provided an adequate fit to the data for both aripiprazole and dehydroaripiprazole in psychiatric patients. The usefulness of CYP genotyping as an aid to select the starting dose should be further investigated.
Epidermal keratinocytes do not activate peripheral T‐cells: interleukin‐10 as a possible regulator
Authors: Domínguez‐Castillo Rocío Isabel , Sánchez‐Guzmán Erika , Castro‐Muñozledo Federico , Santos‐Argumedo Leopoldo , Kuri‐Harcuch Walid 
Published: May 2008

SummaryThe immunogenicity of allogeneic cultured human epidermal keratinocytes (cHEKs) has been studied in several models with contradictory results. We studied human T‐cell activation in an in vitro assay by incubating, for 4 and 24 hr, cHEK confluent sheets with human peripheral blood mononuclear cells (PBMC); parallel HEK cultures were incubated with interferon (IFN)‐γ to induce the expression of major histocompatibility complex (MHC) molecules before their interaction with PBMC. T‐cell activation was evaluated by flow cytometry. T cells neither expressed the early and late activation markers CD69 and CD25, respectively, nor proliferated after incubation with the epidermal sheets, despite the IFN‐γ‐induced expression of MHC and adhesion molecules in cHEKs. Interleukin (IL)‐10 was detected in the medium from the co‐cultured PBMC and HEK sheets, but not from HEK alone. The results suggest that HEKs are unable to stimulate T lymphocytes through secretion of cytokines that might contribute to the immunosuppressive effect in this in vitro model.
The influence of CD4 T‐cell subsets on control of CD4 T‐cell‐mediated graft‐versus‐host disease
Authors: Moncrieffe Halima , Coles Mark , Stockinger Brigitta 
Published: May 2008

SummaryIn this study, we tested the effect of different T‐cell subpopulations on antigen driven effector cell expansion in lymphopenic hosts, making use of an experimental model of graft‐versus‐host disease (GVHD). Fluorescence‐activated cell sorted (FACS) naïve CD4 T cells from C57BL/6 mice, transferred into lymphopenic F1 (C57BL/6 × BALB/c) Rag‐deficient hosts, proliferated extensively and migrated systemically causing acute GVHD within 4 weeks after transfer. Adoptive hosts of CD4 memory T cells on the other hand developed milder symptoms of GVHD with later onset. T‐cell expansion and migration to peripheral sites as well as development of GVHD were prevented when naïve T cells were transferred together with CD4+ CD25+ T cells, but co‐transfer of memory T cells with naïve T cells could not prevent GVHD, although its onset was delayed. OX40, a costimulatory marker that is upregulated at an early time point after T‐cell activation and enhances T‐cell proliferation, cytokine secretion and survival, was strongly upregulated during GVH responses. Naïve T cells deficient in OX40 expression caused markedly reduced GVH in onset and severity despite some level of expansion in the adoptive host, suggesting an important role of this molecule in the immune pathology of GVHD.
The transformation of human services
Authors: Reinders H. 
Published: May 2008

AbstractBackground  Recent studies in the development of professionalism suggest that western society witnesses a transformation of professional practices in human services that deeply affects how professionals experience their work. This paper describes key aspects of this development and presents an account of how it can be explained.Method  The paper offers a review of the main features of neoliberal managerialism as it is found in the literature. The paper does not assume a meta‐theoretical perspective on this literature but rather presents an account on the level of description of what the literature interprets as a transformation of professional practices. Its method is therefore to report the main features of what the literature describes as neoliberal changes in human services.Results  The review results in an account of the transformation of professionalism in human services that shows two sides. One is that of opposing logics that present the tensions between professionalism and managerialism in terms of conflict. The other side is that of compliance of professionals who seek to find their way in the new realities of a neoliberal service economy.Conclusions  I conclude that neoliberal managerialism presents serious challenges to professionals in human services to remain faithful to the values of their profession, and that these challenges – on the level of neoliberal society – raise a serious issue about social (dis)trust.
Nucleocytoplasmic‐localized acyltransferases catalyze the malonylation of 7‐O‐glycosidic (iso)flavones in Medicago truncatula
Authors: Yu Xiao‐Hong , Chen Min‐Huei , Liu Chang‐Jun 
Published: May 2008

Summary(Iso)flavonoids are commonly accumulated as malonylated or acetylated glycoconjugates in legumes. Sequence analysis on EST database of the model legume Medicago truncatula enabled us to identify nine cDNA sequences encoding BAHD super‐family enzymes that are distinct from the most of the characterized anthocyanin/flavonol acyltransferase genes in other species. Functional characterization revealed that three of these corresponding enzymes, MtMaT1, 2 and 3, specifically recognize malonyl CoA as an acyl donor and catalyze the malonylation of a range of isoflavone 7‐O‐glucosides in vitro. These malonyltransferase genes displayed distinct tissue‐specific expression patterns and responded differentially to biotic and abiotic stresses. Consistent with gene expression, the level of the accumulated malonyl isoflavone glucoside was altered in the roots of M. truncatula grown under normal and drought‐stressed conditions. Overexpression of the MtMaT1 gene in a previously engineered Arabidopsis line that accumulates genistein glycosides (Proc. Natl Acad. Sci. USA, 99, 2002:14578) led to a malonylated product. Confocal microscopy of the transiently expressed MtMaT1–GFP fusion revealed strong fluorescence in both the cytoplasm and nucleus of M. truncatula and tobacco leaf cells. A truncated MtMaT1 lacking the C‐terminal polypeptide of 110 amino acid residues that include the DFGWG motif, the single conserved sequence signature of BAHD super‐family members, retained considerable catalytic efficiency, but showed an altered optimum pH preference for maximum activity. Such C‐terminal polypeptide deletion or deletion of the DFGWG motif alone led to improper folding of the transiently expressed GFP fusion protein in living cells, and impaired nuclear localization of the enzyme.
The AtGenExpress hormone and chemical treatment data set: experimental design, data evaluation, model data analysis and data access
Authors: Goda Hideki , Sasaki Eriko , Akiyama Kenji , Maruyama‐Nakashita Akiko , Nakabayashi Kazumi , Li Weiqiang , Ogawa Mikihiro , Yamauchi Yukika , Preston Jeremy , Aoki Ko , Kiba Takatoshi , Takatsuto Suguru , Fujioka Shozo , Asami Tadao , Nakano Takeshi , Kato Hisashi , Mizuno Takeshi , Sakakibara Hitoshi , Yamaguchi Shinjiro , Nambara Eiji , Kamiya Yuji , Takahashi Hideki , Hirai Masami Yokota , Sakurai Tetsuya , Shinozaki Kazuo , Saito Kazuki , Yoshida Shigeo , Shimada Yukihisa 
Published: May 2008

SummaryWe analyzed global gene expression in Arabidopsis in response to various hormones and in related experiments as part of the AtGenExpress project. The experimental agents included seven basic phytohormones (auxin, cytokinin, gibberellin, brassinosteroid, abscisic acid, jasmonate and ethylene) and their inhibitors. In addition, gene expression was investigated in hormone‐related mutants and during seed germination and sulfate starvation. Hormone‐inducible genes were identified from the hormone response data. The effects of each hormone and the relevance of the gene lists were verified by comparing expression profiles for the hormone treatments and related experiments using Pearson’s correlation coefficient. This approach was also used to analyze the relationships among expression profiles for hormone responses and those included in the AtGenExpress stress‐response data set. The expected correlations were observed, indicating that this approach is useful to monitor the hormonal status in the stress‐related samples. Global interactions among hormones‐inducible genes were analyzed in a pairwise fashion, and several known and novel hormone interactions were detected. Genome‐wide transcriptional gene‐to‐gene correlations, analyzed by hierarchical cluster analysis (HCA), indicated that our data set is useful for identification of clusters of co‐expressed genes, and to predict the functions of unknown genes, even if a gene’s function is not directly related to the experiments included in AtGenExpress. Our data are available online from AtGenExpressJapan; the results of genome‐wide HCA are available from PRIMe. The data set presented here will be a versatile resource for future hormone studies, and constitutes a reference for genome‐wide gene expression in Arabidopsis.
What do patients really want? Patients’ preferences for treatment for angina
Authors: Bowling Ann , Culliford Lucy , Smith David , Rowe Gene , Reeves Barnaby C. 
Published: May 2008

AbstractObjective  To measure preferences for angina treatments among patients admitted from accident and emergency with acute coronary syndrome.Background  Evidence suggests variability in treatment allocations amongst certain socio‐demographic groups (e.g. related to age and sex), although it is unclear whether this reflects patient choice, as research on patients’ treatment preferences is sparse. Given current policy emphasis on ‘patient choice’, providers need to anticipate patients’ preferences to plan appropriate and acceptable health services.Design  Self‐administered questionnaire survey.Setting  In‐patients in a UK hospital.Participants  A convenience sample of 53 newly admitted patients with acute coronary syndrome. Exclusion criteria were: a previous cardiologist consultation (including previous revascularization); a clinical judgement of too ill to participate; post‐admission death; non‐cardiac reasons for chest pain.Main outcome measures  Patients’ preferences for coronary artery bypass graft (CABG); angioplasty; and two medication alternatives.Results  Angioplasty was the preferred treatment (for 80% of respondents), and CABG was second (most preferred by 19%, but second most preferred for 60%). The two least preferred (and least acceptable) treatments were medications. The majority of patients (83%) would ‘choose treatment based on the extent of benefits’ and ‘accept any treatment, no matter how extreme, to return to health’. There were some differences in preference related to age (>70 years preferred medication to a greater degree than <70 years) and sex (males preferred CABG surgery more than females).Conclusions  There was general preference for procedural interventions over medication, but most patients would accept any treatment, however extreme, to return to former health. There was some evidence of differences in preferences related to age and sex. Furthermore, most patients preferred to have some input into treatment choice (e.g. nearly half wanted to share decision responsibility with their doctor), with only 4% preferring to leave the decision entirely to their doctor. Given these findings, and past findings that suggest there may be variability in treatment allocation according to certain socio‐demographic factors, this study suggests a need to develop and use preference measures, and makes a step towards this.
Exploring patient perceptions of larval therapy as a potential treatment for venous leg ulceration
Authors: Spilsbury Karen , Cullum Nicky , Dumville Jo , O’Meara Susan , Petherick Emily , Thompson Carl 
Published: May 2008

AbstractObjectives  To explore patient preferences and acceptability of two forms of larval therapy (‘bagged’ and ‘loose’).Background  Larval therapy is frequently used to treat patients with leg ulcers. However, patient preferences and acceptability of larval therapy when compared with other treatments is not established.Design  A survey of patient preferences between larvae and standard therapy (hydrogel) using randomized allocation of two questionnaires (‘bagged’ or ‘loose’ questionnaire). The questionnaire contained closed and open‐response questions and was administered by a nurse researcher. Open responses enabled exploration of patients’ preferences and the acceptability of larval therapy when compared with a standard treatment. Qualitative data were analysed for thematic content.Setting and participants  Thirty‐five participants, aged 18 years and above, with at least one venous leg ulcer were recruited from a UK Hospital Vascular Outpatients Clinic.Findings  Majority of participants stated that they would consider larval therapy, irrespective of method of containment. Acceptance of therapy was influenced by length of time with (or recurrence of) ulceration, experiences of other treatments, social contact in hospitals and the experiences of others. Visual imagery was a key influence among participants who would refuse larval therapy. Refusal was mostly among older women (aged 70 years or above).Conclusions  Eliciting patient preferences and increasing patient involvement in treatment decisions is an important part of quality improvement and improved health outcomes. These findings have relevance for practitioners offering larval therapy as a treatment option and for the feasibility of clinical trials.
Selection on multiple QTL with control of gene diversity and inbreeding for long‐term benefit
Authors: Li Y. , Kadarmideen H. N. , Dekkers J. C. M. 
Published: May 2008

SummaryThe purpose of this study was to develop and investigate selection strategies that aim at maximizing long‐term genetic response while conserving gene diversity and controlling inbreeding in populations of limited effective size, assuming complete knowledge of all genes affecting a quantitative trait. Three selection strategies were proposed to select on 100 quantitative trait loci (QTL) and compared with truncation selection on breeding value. Alternative selection strategies aimed at maximizing the average breeding value of parents with a penalty on (1) the number of unfavourable QTL genotypes among parents (OS‐I), (2) the negative of the logarithm of the frequency of the favourable allele at each QTL among parents (OS‐II), and (3) the average pedigree relationship among parents (OS‐III). When all QTL and their effects were known, the strategies examined were able to obtain extra long‐term responses, conserve QTL diversity and reduce inbreeding, compared with truncation selection. Strategy OS‐II was the most effective in conserving QTL diversity and OS‐III in reducing inbreeding. By changing the magnitude of the penalties applied, the impact on long‐term response, inbreeding and diversity can be controlled. Extra long‐term responses over truncation selection of OS‐I and OS‐II were even greater when effects of QTL were estimated rather than assumed known, indicating the applicability of results to practical strategies for marker‐assisted selection. Extra responses are expected to be reduced for larger population sizes.
Genetic variation at the alpha‐1‐fucosyltransferase (FUT1) gene in Asian wild boar and Chinese and Western commercial pig breeds
Authors: Bao W.B. , Wu S.L. , Musa H.H. , Zhu G.Q. , Chen G.H. 
Published: May 2008

Summary Escherichia coli F18 bacteria producing enterotoxins and/or shigatoxin (ETEC/STEC) are main pathogens that cause oedema disease and postweaning diarrhoea in piglets, and alpha‐1‐fucosyltransferase (FUT1) gene has been identified as a candidate gene for controlling the expression of ETEC F18 receptor. The genetic variations at nucleotide position 307 in open reading frame of FUT1 gene in one wild boar breed and 20 western commercial and Chinese native pig breeds were investigated by polymerase chain reaction–restriction fragment length polymorphism. The results showed that the genetic polymorphisms of the FUT1 locus were only detected in western pig breeds and the Chinese Taihu (including Meishan pig, Fengjing pig and Erhualian pig), Huai and Lingao pig breeds; only Duroc and Pietrain possessed the resistant AA genotype, while the wild boar and other Chinese pig breeds only presented the susceptible genotype GG. The results indicated that Chinese native pig breeds lack genetic factors providing resistance to ETEC F18 bacteria. The resistant allele to ETEC F18 might originate from European wild boar. It was inferred that oedema and postweaning diarrhoea caused by ETEC F18 have close relationship with the growth rate, which can explain why on the contrary Chinese native pig breeds have stronger resistance to oedema and postweaning diarrhoea in piglets compared with western pig breeds.
Influence of visual and olfactory cues on field trapping of the pollen beetle, Astylus atromaculatus (Col.: Melyridae)
Authors: Van den Berg J. , Torto B. , Pickett J. A. , Smart L. E. , Wadhams L. J. , Woodcock C. M. 
Published: May 2008

AbstractField trapping experiments investigated the response of the pollen beetle Astylus atromaculatus to visual and olfactory cues during a 3‐year period, 1999–2001. The visual preference of the pollen beetle was determined using yellow, white, blue, green and red water traps. The yellow trap was most attractive, capturing 56% of the total beetles trapped, with 30% caught by the blue and white traps, while 14% was caught by the red and green traps. The response of the beetle to olfactory cues was then evaluated by using the yellow water trap with three antennally active components identified in the volatiles of sorghum panicles by coupled gas chromatography (GC)–electroantennographic detection and GC–mass spectrometry. These components were 2‐phenylethanol, benzyl alcohol and linalool. There were no significant colour × chemical compound interactions and traps baited with 2‐phenylethanol captured significantly more beetles than unbaited traps, irrespective of trap colour, demonstrating the effectiveness of olfactory cues in trapping the pollen beetle. Traps baited with 2‐phenylethanol were more attractive than and caught more beetles than traps baited with linalool. 2‐Phenylethanol had the greatest effect on the relatively unattractive blue trap, confirming the importance of olfactory cues mediating A. atromaculatus attraction.
Candida endocarditis: role of new antifungal agents
Authors: Talarmin J. P. , Boutoille D. , Tattevin P. , Abgueguen P. , Ansart S. , Roblot F. , Raffi F. 
Published: May 2008

SummaryDespite the relative high frequency of Candida bloodstream infection, Candida endocarditis is a rare entity. We report seven cases, which occurred during a period of 1 year in western France. Six cases were because of Candida albicans, and one pacemaker endocarditis was because of Candida parapsilosis. All patients were men and presented risk factors for candidaemia. Of the six patients with valvular involvement, five received caspofungin and two had surgical valve replacement. Three patients treated with caspofungin antifungal therapy without valve replacement were cured from endocarditis. Antifungal and surgical strategies are discussed, in particular, the possible role of new antifungal therapies and long‐term suppression therapy without surgery. One patient died in the acute phase of endocarditis, three patients died of causes unrelated to infective endocarditis and three patients had a favourable outcome.
Glans penis and prepuce colonisation of yeast fungi in a paediatric population: pre‐ and postcircumcision results
Authors: Aridogan I. A. , Ilkit Macit , Izol Volkan , Ates Aylin , Demirhindi Hakan 
Published: May 2008

SummaryThe members of the genera Candida and Malassezia comprise opportunistic yeast with a natural habitat on the skin of humans and warm‐blooded animals. This study aimed to compare the prevalence of these yeast fungi in samples from the glans penis and prepuce 3–5 min prior to circumcision and after 1‐month follow‐up by mycological examination. A total of 77 children aged between 0.01 and 13.0 years (mean age 5.8 ± 3.4) were included in the study. Impression preparations were made on modified Dixon and Leeming‐Notman agars without cycloheximide. The isolates were identified by morphological, biochemical and physiological characteristics. The frequency of yeast colonisation was found to be significantly decreased from 11.7% to 1.3% following circumcision (P = 0.008). The glans penis and prepuce were colonised with especially Candida albicans (50%) followed by Malassezia furfur (40%) and Malassezia sympodialis (10%). This study highlighted the potential medical benefits of circumcision as a significant factor decreasing the colonisation rate of yeast fungi. We suggest that circumcision, rather than age, plays an important part in the reduction of yeast fungi in genitalia.
Rhino‐cerebral zygomycosis resistant to antimycotic treatment: a case report
Authors: Vyzantiadis Timoleon‐Achilleas , Kioumi Anna , Papadakis Emmanouil , Braimi Margarita , Dermitzakis Emmanouil , Tsitouridis Ioannis , Antoniadis Antonios 
Published: May 2008

SummaryWe report a fatal case of a rhino‐cerebral zygomycosis, caused by Rhizopus arrhizus (oryzae). The patient was suffering from idiopathic thrombopenic purpura, diagnosed 1 year earlier. He was already treated with methylprednisolone 5 months prior to his admission to the hospital for a loss of vision and pain in the left eye as well as left orbital cellulitis. After an initial empirical treatment with broad spectrum antibiotics and voriconazole (infection of unknown origin), the patient was treated with liposomal amphotericin as soon as a positive fungal culture revealed a zygomycete. Unfortunately, the mould was resistant to amphotericin B (MIC: 16 μg ml−1) and probably to posaconazole (MIC: 4 μg ml−1), which was co‐administrated a few days later.