bluuebunny/crossref_metadata_2025_split huggingface dataset:
The concentration of oxazepam and oxazepam glucuronide in oral fluid, blood and serum after controlled administration of 15 and 30 mg oxazepam
Authors: Smink Beitske E. , Hofman Berendina J. A. , Dijkhuizen Albert , Lusthof Klaas J. , De Gier Johan J. , Egberts Antoine C. G. , Uges Donald R. A. 
Published: June 2008

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • Concentration–time profiles of drugs in oral fluid generally run parallel to those in blood.• In general, oral fluid contains more parent drug than metabolites.• For some benzodiazepines it has been shown that concentrations are lower in oral fluid than in blood. WHAT THIS STUDY ADDS • The concentration–time profile of oxazepam in oral fluid after a single dose of oxazepam runs parallel to blood and is dose dependent.• Concentration ratios (oral fluid/blood and oral fluid/serum) of oxazepam and oxazepam glucuronide after controlled intake of a single dose of oxazepam are presented.AIMSTo measure and compare the concentration–time profiles of oxazepam and oxazepam glucuronide in blood, serum and oral fluid within the scope of roadside testing.METHODSBiological samples were collected from eight male subjects after ingestion of 15 or 30 mg oxazepam on separate dosing occasions with an interval of 7 days. The concentration–time profiles of oxazepam and oxazepam glucuronide were fitted by using a one‐compartment model.RESULTSFor oxazepam and oxazepam glucuronide, the mean oral fluid/blood ratios were 0.05 (range 0.04–0.07) and 0.004 (range 0.002–0.006), respectively. The concentration–time profiles in oral fluid paralleled those in blood.CONCLUSIONAfter oral administration of therapeutic doses of oxazepam, concentrations in oral fluid are very much lower than those in blood, and those of oxazepam glucuronide are much lower than those of the parent compound. Nevertheless, assay of oral fluid for oxazepam can be used to detect recent ingestion of the drug in drivers suspected of impaired driving performance.
Wide variation in thrombin generation in patients with atrial fibrillation and therapeutic International Normalized Ratio is not due to inflammation
Authors: Gatt A. , Van Veen J. J. , Bowyer A. , Woolley A. M. , Cooper P. , Kitchen S. , Makris M. 
Published: June 2008

SummaryAtrial fibrillation (AF) is a common cardiac arrhythmia with a 5–20% annual risk of stroke. Warfarin reduces this risk by at least 60%. Despite adequate anticoagulation within the target International Normalized Ratio (INR) range of 2·0–3·0, some patients still experience thrombotic and bleeding events. It is now possible to assess the intensity of anticoagulation with automated thrombin generation (TG) tests, such as the calibrated automated thrombogram (CAT). These tests were compared and an inverse relationship was found between the INR and CAT in 143 elderly AF patients. There was equally good correlation between the concentration of factors II, VII, IX and X and the INR and TG parameters. The peak thrombin was most strongly associated with the concentration of prothrombin fragment 1 + 2 in plasma. There was wide variability in TG parameters in patients with identical INR values, sometimes up to a fourfold difference. This TG variability in individuals with the same INR is not due to inflammation, at least when the latter is measured as the concentration of factor VIII coagulant activity, von Willebrand factor antigen, high sensitivity C‐reactive protein and fibrinogen. It was concluded that, although the TG and INR were closely correlated there was wide variability in peak thrombin and endogenous thrombin potential in patients within the INR therapeutic range, the cause of which remains unclear.
A previously unidentified σ factor and two accessory proteins regulate oxalate decarboxylase expression in Bacillus subtilis
Authors: MacLellan Shawn R. , Wecke Tina , Helmann John D. 
Published: June 2008

SummaryWe have investigated the function of a cell envelope stress‐inducible gene, yvrI, which encodes a 22.5 kDa protein that includes a predicted σ70 region 4 domain, but lacks an apparent region 2 domain. YvrI interacts with RNA polymerase and overexpression of YvrI results in induction of OxdC, an oxalate decarboxylase maximally expressed under low‐pH conditions. We have used microarray‐based analyses to define the YvrI regulon. YvrI is required for the transcription of three operons (oxdC‐yvrL, yvrJ and yvrI‐yvrHa) each of which is preceded by a highly similar promoter sequence. Activation of these promoters requires both YvrI and the product of the second gene in the yvrI‐yvrHa operon, YvrHa. YvrI and YvrHa together allow recognition of the oxdC promoter, stimulate DNA melting and activate transcription by core RNA polymerase. Together, these results suggest that YvrI is a previously unrecognized σ factor in Bacillus subtilis and that the 9.5 kDa YvrHa protein acts as a required co‐activator of transcription. A yvrL deletion results in the upregulation of YvrI activity suggesting that YvrL is a negative regulator of YvrI‐dependent transcription, possibly functioning as an anti‐σ factor.
Holin of bacteriophage lambda: structural insights into a membrane lesion
Authors: Krupovič Mart , Bamford Dennis H. 
Published: June 2008

SummaryThe length of the infection cycle of double‐stranded DNA bacteriophages is controlled by phage‐encoded small integral membrane proteins, holins. Holins are the gatekeepers of the lysis process, possessing an intriguing ability to be triggered, at a precise time point, to form large holes in the cytoplasmic membrane of phage‐infected bacteria. The paper by Savva et al. in this issue of Molecular Microbiology invites us to take a closer look at this membrane lesion. For the first time, a structural characterization of large‐diameter rings formed by these peculiar membrane proteins is presented.
The FtsEX ABC transporter directs cellular differentiation in Bacillus subtilis
Authors: Garti‐Levi Sharon , Hazan Ronen , Kain James , Fujita Masaya , Ben‐Yehuda Sigal 
Published: June 2008

SummaryA fundamental challenge in developmental biology is to elucidate the regulatory events that trigger cellular differentiation. Sporulation in the Gram‐positive bacterium Bacillus subtilis serves as a simple experimental model system to address this challenge. The hallmark of sporulation is the formation of an asymmetrically positioned septum that divides the cell into unequally sized progeny. Here we describe the role of an ABC transporter, comprising the FtsE and FtsX proteins, in the initiation of spore formation. We discovered that in the absence of this transporter, entry into sporulation is delayed and an atypical symmetric septum is formed instead of a polar one. We show that this phenotype can be suppressed by artificially activating the master regulator of sporulation, Spo0A, or by activating the histidine kinases that function upstream of Spo0A. Our data indicate that the FtsEX transporter is one of the top components in the hierarchy of factors required to initiate sporulation, and thus it is essential for establishing proper temporal activation of the process.
Interaction of CheY2 and CheY2‐P with the cognate CheA kinase in the chemosensory‐signalling chain of Sinorhizobium meliloti
Authors: Riepl Hubert , Maurer Till , Kalbitzer Hans Robert , Meier Veronika M. , Haslbeck Martin , Schmitt Rüdiger , Scharf Birgit 
Published: June 2008

SummaryAn unusual regulatory mechanism involving two response regulators, CheY1 and CheY2, but no CheZ phosphatase, operates in the chemotactic signalling chain of Sinorhizobium meliloti. Active CheY2‐P, phosphorylated by the cognate histidine kinase, CheA, is responsible for flagellar motor control. In the absence of any CheZ phosphatase activity, the level of CheY2‐P is quickly reset by a phospho‐transfer from CheY2‐P first back to CheA, and then to CheY1, which acts as a phosphate sink. In studying the mechanism of this phosphate shuttle, we have used GFP fusions to show that CheY2, but not CheY1, associates with CheA at a cell pole. Cross‐linking experiments with the purified proteins revealed that both CheY2 and CheY2‐P bind to an isolated P2 ligand‐binding domain of CheA, but CheY1 does not. The dissociation constants of CheA–CheY2 and CheA–CheY2‐P indicated that both ligands bind with similar affinity to CheA. Based on the NMR structures of CheY2 and CheY2‐P, their interactions with the purified P2 domain were analysed. The interacting surface of CheY2 comprises its C‐terminal β4‐α4‐β5‐α5 structural elements, whereas the interacting surface of CheY2‐P is shifted towards the loop connecting β5 and α5. We propose that the distinct CheY2 and CheY2‐P surfaces interact with two overlapping sites in the P2 domain that selectively bind either CheY2 or CheY2‐P, depending on whether CheA is active or inactive.
Cysteine proteases XCP1 and XCP2 aid micro‐autolysis within the intact central vacuole during xylogenesis in Arabidopsis roots
Authors: Avci Utku , Earl Petzold H. , Ismail Ihab O. , Beers Eric P. , Haigler Candace H. 
Published: June 2008

SummaryEstablishing the mechanisms regulating the autolysis of xylem tracheary elements (TEs) is important for understanding this programmed cell death process. These data demonstrate that two paralogous Arabidopsis thaliana proteases, XYLEM CYSTEINE PROTEASE1 (XCP1) and XCP2, participated in micro‐autolysis within the intact central vacuole before mega‐autolysis was initiated by tonoplast implosion. The data acquisition was aided by the predictable pattern of seedling root xylogenesis, the availability of single and double total knock‐out T‐DNA lines, anti‐sera that recognized XCP1 and XCP2, and the microwave‐assisted processing of whole seedlings prior to immunolabeling and observation in the transmission electron microscope. During secondary wall thickening, XCP1 and XCP2 (in wild type), XCP1 (in xcp2 seedlings) or XCP2 (in xcp1 seedlings) were imported into the TE central vacuole. Both XCP1 and XCP2 heavily labeled dense aggregates of material within the vacuole. However, because of XCP1 deficiency in xcp1 and xcp1 xcp2 TEs, non‐degraded cellular remnants first accumulated in the vacuole and then persisted in the TE lumen (longer than in the wild type) after the final mega‐autolysis was otherwise complete. This delayed TE clearing phenotype in xcp1 was rescued by complementation with wild‐type XCP1. Although TEs in the xcp2 single knock‐out cleared comparably with wild type, the non‐degraded remnants in xcp1 xcp2 TEs were more densely packed than in xcp1 TEs. Therefore, XCP2 has a minor but distinct role in micro‐autolysis. After tonoplast implosion, XCP1 and XCP2 remained associated with disintegrating cellular material as mega‐autolysis, aided by additional lytic enzymes, destroyed the bulk of the cellular contents.
Profile of vitiligo in the south of Tunisia
Authors: Akrem Jalel , Baroudi Aicha , Aichi Taher , Houch Fethi , Hamdaoui Mohamed Hédi 
Published: June 2008

AbstractBackground  Vitiligo is a depigmentation disorder characterized by the loss of melanocytes from cutaneous cells. Its pathogenesis has not yet been clarified.Objective  To study the epidemiologic profile of vitiligo in Tunisia and analyze its characteristics.Methods  The clinical presentation of vitiligo was examined in 60 patients [27 males (45%) and 33 females (55%)] attending the Médenine Hospital Center, a large hospital in the south of Tunisia.Results  The lower limbs were the initial site of onset of vitiligo in the majority of patients (29.8%), followed by the upper limbs, head and neck, trunk, and mucosae. The most common clinical pattern observed was vitiligo vulgaris, followed by focal, acrofacial, mucosal, segmental, and universal types. Leukotrichia was observed in 23%, koebnerization in 18.5%, and a positive family history in 18%.Conclusion  This study indicates that vitiligo vulgaris is the most common clinical type observed in the south of Tunisia. There were associated endocrine disorders in some patients, including diabetes, hypothyroidism, and alopecia.
Kindler syndrome: a study of five Egyptian cases with evaluation of severity
Authors: Nofal Eman , Assaf Magda , Elmosalamy Khaled 
Published: June 2008

AbstractBackground  Kindler syndrome (KS) is a rare genodermatosis characterized by four major features (acral blisters, photosensitivity, poikiloderma, and cutaneous atrophy) and many associated findings. The diagnosis of KS includes clinical features, ultrastructural findings, and, recently, immunostaining and genetic studies. Varying degrees of severity of the syndrome have been described.Methods  Five patients with clinical features consistent with KS were included in this study. All patients were subjected to histopathologic and ultrastructural studies.Results  Cases 1 and 2 presented with severe major features, severe mucosal involvement, and many other associated findings. Case 3 presented with severe major features, but mild and limited mucosal involvement and other associated findings. Cases 4 and 5 showed mild major features and few other findings. Histopathology revealed nonspecific poikiloderma. Marked thickening of the lamina densa and splitting of the lamina lucida were the main ultrastructural findings.Conclusion  KS may be classified into mild, moderate, and severe according to the severity of the major features and mucosal involvement. Because histopathologic and ultrastructural findings are not pathognomonic, clinical features remain the mainstay for the diagnosis of KS, and the need for immunostaining with kindlin antibody and genetic studies may be restricted to early cases with incomplete features.
Clinical reasoning in neurology: Use of the repertory grid technique to investigate the reasoning of an experienced occupational therapist
Authors: Kuipers Kathy , Grice James W. 
Published: June 2008

Background/aim:  The aim of this paper is to describe the use of a structured interview methodology, the repertory grid technique, for investigating the clinical reasoning of an experienced occupational therapist in the domain of upper limb hypertonia as a result of brain injury. Method:  Repertory grid interviews were completed before and after exposure to a protocol designed to guide clinical reasoning and decision‐making in relation to upper limb neurological rehabilitation. Data were subjected to both qualitative and quantitative analyses. Results:  Qualitative analysis focussed on clinical reasoning content. Common themes across the pre‐ and post‐exposure interviews were the use of theoretical frameworks and practice models, the significance of clinical expertise, and discrimination of ‘broad’ and ‘specific’ aspects, as well as differentiation between ‘therapist and client‐related’ aspects of the clinical situation. Quantitative analysis indicated that for both pre‐ and post‐exposure repertory grids, clinical reasoning was structured in terms of two main concepts. In the pre‐exposure grid, these were related to the therapist's role, and to the ‘scope’ of practice tasks (either broad or specific). In the post‐exposure grid the two main concepts were upper limb performance, and client‐centred aspects of the therapy process. Conclusions:  The repertory grid technique is proposed as an effective tool for exploring occupational therapy clinical reasoning, based on its capacity for accessing personal frames of reference, and elucidating both the meaning and the structure supporting clinical reasoning.
Systematic review of quality of life following laparoscopic and open colorectal surgery
Authors: Dowson H. M. , Cowie A. S. , Ballard K. , Gage H. , Rockall T. A. 
Published: June 2008

AbstractObjective  To compare the health‐related quality of life (HRQoL) of patients following laparoscopic and open colorectal surgery.Method  A systematic review was performed according to Quorum guidelines. Prospective studies comparing the HRQoL of patients after laparoscopic and open colorectal surgery were identified. The primary outcome measure was postoperative quality of life; performance status and cosmesis were secondary outcome measures.Results  Twenty‐three studies were identified that satisfied the inclusion criteria; 18 assessed HRQoL, four performance status, and three cosmesis. It was not possible to perform a meta‐analysis due to study heterogeneity. The studies reported outcomes for 2946 patients. The most frequent HRQoL instruments employed were Short Form 36, European Organization for Research and Treatment of Cancer, and gastrointestinal quality of life index. Six studies, using a total of 12 separate measures, evaluated QoL during the first three postoperative months: 10 of these measures showed no significant difference, and two showed an improved HRQoL with laparoscopy. Twelve further studies evaluated HRQoL up to 5 years postoperatively: nine showed no difference between the two groups, and three demonstrated a benefit for laparoscopy. Three of four studies assessing performance status on discharge, and all three studies assessing cosmesis, reported benefits with the laparoscopic approach.Conclusions  The current evidence suggests there is no significant difference in HRQoL following laparoscopic and open colorectal surgery, although there is a lack of good quality data. There is a trend towards improved quality of life outcomes and performance status with laparoscopy in the early postoperative period. There is a need for further research, particularly assessing quality of life in the early postoperative period.
PLACE‐MAKING AND ‘GREEN’ REUSES OF BROWNFIELDS IN THE RUHR
Authors: FRANZ MARTIN , GÜLES ORHAN , PREY GISELA 
Published: June 2008

ABSTRACTDepending on location, size and former use, brownfields in the Ruhr have different potentials. Besides brownfields where viable regeneration projects are possible there are many sites that are not attractive to the market. One type of use for this category is post‐industrial nature (e.g. industrial forests). Following the overall concept of sustainable development, these sites offer potentials for creative ‘place‐making’ by local residents. The approach of ‘place‐making’ is embedded in the discussion of establishing local governance in urban districts of the Ruhr. Introducing one best‐practice‐case (the Rheinelbe industrial forest in Gelsenkirchen), the paper focuses on the discussion of ‘place‐making’ as a strategy for innovative brownfield development and local governance using the example of the former Lohberg colliery in Dinslaken.
Metastatic Crohn's disease: a review
Authors: Palamaras I , El‐Jabbour J , Pietropaolo N , Thomson P , Mann S , Robles W , Stevens HP 
Published: June 2008

AbstractMetastatic Crohn's disease (MCD) indicates the presence of non‐caseating granuloma of the skin at sites separated from the gastrointestinal tract by normal tissue and is the least common dermatologic manifestation of CD. In adults, MCD usually appears after the initial diagnosis of CD in 70% of cases, whereas in children, it appears at the same time as CD in almost half of the cases. The most frequent skin lesions in adults are nodules, plaques with or without ulceration on the extremities and ulcers on the genitals. In children, genital swelling with or without erythema is the most frequent presentation of MCD. Simultaneous presence of perianal CD affects more females (60%) and particularly children. Associated gastrointestinal symptoms are present in one third of the cases in adults and in half of the cases in children. Treatment is often unsatisfactory. Randomised controlled trials are lacking. Various chemotherapeutic agents have been used such as oral metronidazole, topical and/or oral steroids, azathioprine, cyclosporine, sulfasalazine, tetracyclines, topical or systemic tacrolimus, infliximab alone or with methotrexate, and surgical treatment with oral zinc sulphate. MCD represents another ‘great imitator’. This reviews the most relevant characteristics of this disease, in order to increase awareness and to avoid delay in diagnosis and improve management of the whole CD complex.
A Bayesian Spatial Multimarker Genetic Random‐Effect Model for Fine‐Scale Mapping
Authors: Tsai M.‐Y. , Hsiao C. K. , Wen S.‐H. 
Published: June 2008

SummaryMultiple markers in linkage disequilibrium (LD) are usually used to localize the disease gene location. These markers may contribute to the disease etiology simultaneously. In contrast to the single‐locus tests, we propose a genetic random effects model that accounts for the dependence between loci via their spatial structures. In this model, the locus‐specific random effects measure not only the genetic disease risk, but also the correlations between markers. In other words, the model incorporates this relation in both mean and covariance structures, and the variance components play important roles. We consider two different settings for the spatial relations. The first is our proposal, relative distance function (RDF), which is intuitive in the sense that markers nearby are likely to correlate with each other. The second setting is a common exponential decay function (EDF). Under each setting, the inference of the genetic parameters is fully Bayesian with Markov chain Monte Carlo (MCMC) sampling. We demonstrate the validity and the utility of the proposed approach with two real datasets and simulation studies. The analyses show that the proposed model with either one of two spatial correlations performs better as compared with the single locus analysis. In addition, under the RDF model, a more precise estimate for the disease locus can be obtained even when the candidate markers are fairly dense. In all simulations, the inference under the true model provides unbiased estimates of the genetic parameters, and the model with the spatial correlation structure does lead to greater confidence interval coverage probabilities.
Three‐Dimensional Culture Environments Enhance Osteoblast Differentiation
Authors: Boehrs Jessica , Zaharias Rebecca S. , Laffoon John , Ko Y. Joon , Schneider Galen B. 
Published: June 2008

Abstract Purpose: In previous work from our laboratory, we demonstrated that the three‐dimensional (3D) cell cultures developed in simulated microgravity environments enhanced osseous‐like aggregate formation and accelerated preosteoblast cell differentiation. Thus, as described here, we hypothesize that aggregate formation and mineralization would occur with fewer than 10 × 106 cells as previously described. Materials and Methods: Human preosteoblastic cells were cultured at different concentrations in a rotary wall vessel to simulate microgravity for 7 days. Aggregate size was assessed, and mineralization and collagen expression detected using Von Kossa and Masson Trichrome staining. Scanning electron microscopy was used for structural and elemental analysis. Immunohistochemistry was used to detect expression of the osteogenic markers BSPII and osteopontin (OP). Results: Size and calcium expression were dependent upon cultured cell number (p < 0.01). Calcium and collagen expression were detected throughout the aggregate, but organization was independent of cell number. Aggregates had similar microscopic structural patterns demonstrating organized development. Presence of BSPII and OP showed that the aggregates share common differentiation proteins with in vivo bone formation. Conclusions: These results may lead to novel bone engineering techniques associated with dental treatment.