bluuebunny/crossref_metadata_2025 huggingface dataset:
Pharmacodynamic monitoring of cyclosporine A by NFAT‐regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients
Authors: Billing Heiko , Giese Thomas , Sommerer Claudia , Zeier Martin , Feneberg Reinhard , Meuer Stefan , Tönshoff Burkhard
Published: June 2010

Billing H, Giese T, Sommerer C, Zeier M, Feneberg R, Meuer S, Tönshoff B. Pharmacodynamic monitoring of cyclosporine A by NFAT‐regulated gene expression and the relationship with infectious complications in pediatric renal transplant recipients. Pediatr Transplantation 2010: 14:844–851. © 2010 John Wiley & Sons A/S.

Abstract:  Pharmacokinetic monitoring of CsA is unsatisfactory, because at comparable CsA blood concentrations, the frequency and severity of adverse effects vary considerably among patients. We have therefore recently developed a precise, reliable, and robust whole‐blood pharmacodynamic assay that measures the suppression of CsA‐target genes in T lymphocytes. Because of the different characteristics of CsA pharmacokinetics in children and the higher propensity for infectious complications, this assay requires validation in the pediatric patient population. We therefore quantified in a prospective study of 45 pediatric renal transplant recipients the residual expression of NFAT‐regulated genes in lymphocytes by RT‐PCR and correlated these findings with the frequency of recurrent infections in the maintenance period post‐transplant. Patients with recurrent infections showed a significantly stronger inhibition of NFAT‐regulated gene expression (18.2%) than patients without recurrent infections (31.7%; p = 0.012). This difference was specific, because various PK parameters of CsA and the concomitant immunosuppressive therapy were comparable between patients. Multivariate regression analysis showed that patient age and residual NFAT‐regulated gene expression were the only independent determinants of recurrent infections. By ROC curve analysis, a cutoff value of 23% residual NFAT‐regulated gene expression had the highest sensitivity (71.1%) and specificity (65.4%) for the discrimination of patients with and without recurrent infections. Pharmacodynamic monitoring of CsA by measurement of residual NFAT‐regulated gene expression in T lymphocytes has the potential to identify over‐immunosuppressed pediatric renal transplant recipients and is therefore a useful tool for the optimization of CsA therapy.
Methanogenesis, sulfate reduction and crude oil biodegradation in hot Alaskan oilfields
Authors: Gieg Lisa M. , Davidova Irene A. , Duncan Kathleen E. , Suflita Joseph M.
Published: June 2010

Petrochemical and geological evidence suggest that petroleum in most reservoirs is anaerobically biodegraded to some extent. However, the conditions for this metabolism and the cultivation of the requisite microorganisms are rarely established. Here, we report on microbial hydrocarbon metabolism in two distinct oilfields on the North Slope of Alaska (designated Fields A and B). Signature anaerobic hydrocarbon metabolites were detected in produced water from the two oilfields offering evidence of in situ biodegradation activity. Rate measurements revealed that sulfate reduction was an important electron accepting process in Field A (6–807 µmol S l−1 day−1), but of lesser consequence in Field B (0.1–10 µmol S l−1 day−1). Correspondingly, enrichments established at 55°C with a variety of hydrocarbon mixtures showed relatively high sulfate consumption but low methane production in Field A incubations, whereas the opposite was true of the Field B enrichments. Repeated transfer of a Field B enrichment showed ongoing methane production in the presence of crude oil that correlated with ≥ 50% depletion of several component hydrocarbons. Molecular‐based microbial community analysis of the methanogenic oil‐utilizing consortium revealed five bacterial taxa affiliating with the orders Thermotogales, Synergistales, Deferribacterales (two taxa) and Thermoanaerobacterales that have known fermentative or syntrophic capability and one methanogen that is most closely affiliated with uncultured clones in the H2‐using family Methanobacteriaceae. The findings demonstrate that oilfield‐associated microbial assemblages can metabolize crude oil under the thermophilic and anaerobic conditions prevalent in many petroleum reservoirs.
Bladder outlet obstruction: progression from inflammation to fibrosis
Authors: Metcalfe Peter D. , Wang JianFei , Jiao Haiyan , Huang Yue , Hori Keijiro , Moore Ronald B. , Tredget Edward E.
Published: June 2010

Study Type – Aetiology (case control) Level of Evidence 3b

OBJECTIVE

To investigate the progression of urodynamic changes, as well as histological and biochemical outcomes over a prolonged period of partial bladder outlet obstruction (pBOO) in an animal model with physiologically relevant pBOO.

MATERIALS AND METHODS

Healthy, adult, female Fischer rats underwent surgical creation of a pBOO for either 2, 4, 8, or 13 weeks and were compared with sham‐operated rats. Urodynamic measurements were used to compare bladder volumes and pressure. Tissue was grossly analysed with light microscopy and bladder weights and thicknesses were compared. Reverse transcription‐polymerase chain reaction for collagen, transforming growth factor β (TGF‐β), connective tissue growth factor (CTGF), hypoxia inducible factor 1α (HIF‐1α), and platelet‐derived growth factor (PDGF‐A) was performed on all samples, as well as immunohistochemistry (IHC) for α‐smooth muscle actin (α‐SMA). Finally, mass spectrometry was used to quantify the collagen content of the bladders as a measure of fibrosis.

RESULTS

After induction of pBOO, all rats remained healthy. Initial urodynamics showed an increase in capacity while maintaining normal pressures, but then deteriorated into small capacity, high‐pressure bladders. Haematoxylin and eosin (H&E) staining showed an initial inflammatory response, and this was confirmed with significantly increased mRNA levels of TGF‐β, CTGF, HIF‐1α, and PDGF. The progression to smooth muscle hypertrophy was evident on H&E and confirmed with increased bladder mass and thickness. IHC for α‐SMA showed a progressive increase associated with the elevated bladder pressures. Masson’s trichrome and mass spectrometry showed a progressive increase in collagen to 13 weeks.

CONCLUSION

With this model, we have effectively replicated the clinical scenario, with significant pathophysiological changes occurring insidiously in otherwise healthy rats. We believe that our observed changes represent distinct phases of bladder decompensation; with an initial inflammatory response to the stress of the pBOO, smooth muscle hypertrophy to overcome the increased urethral resistance, and eventual decompensation to fibrosis. The time course of the inflammatory markers implies the need for early intervention to prevent this cascade. Novel strategies targeting these observed physiological responses could lead to improved preventative strategies, with respect to biochemical pathways and the time course of their initiation.
The prevalence of chronic constipation and faecal incontinence among men and women with symptoms of overactive bladder
Authors: Coyne Karin S. , Cash Brooks , Kopp Zoe , Gelhorn Heather , Milsom Ian , Berriman Sandra , Vats Vasudha , Khullar Vik
Published: June 2010

Study Type – Symptom prevalence (non‐consecutive cohort) Level of Evidence 4

What’s known on the subject? and What does the study add?

There have been no previous studies examining the overlap of chronic constipation and overactive bladder in the US population. Limited research to date based on samples of elderly, Asian and pediatric populations suggests that there is substantial overlap. The results of this study suggest that the prevalence of chronic constipation is increased in people with overactive bladder who are ≥40 years and should be considered by healthcare providers treating these patients.

OBJECTIVE

To estimate the prevalence and overlap of overactive bladder (OAB), chronic constipation (CC) and faecal incontinence (FI) among a general population sample of adults in the USA.

PATIENTS AND METHODS

A cross‐sectional internet‐based survey of randomly selected panel members who were ≥40 years of age was conducted. Participants reported how often they experienced symptoms of OAB, CC and FI using Likert scales and modified Rome III criteria. Analyses were conducted to examine the overall prevalence of OAB, CC and FI in men and women separately and to characterize the extent of overlap between these conditions in participants with OAB vs those without OAB, and those participants with continent vs incontinent OAB.

RESULTS

The response rate for the survey was 62.2% and the final sample (N= 2000) included 927 men and 1073 women. The overall prevalence of OAB [defined as a response of ≥‘sometimes’ to urinary urgency (i.e. ‘sometimes’ or more often) or ‘yes’ to urinary urgency incontinence (UUI)] was 26.1% in men and 41.2% in women. The overall prevalence of CC was significantly lower in men than in women (15.3 vs 26.3%), but both men and women with OAB were significantly more likely to report CC (22.3 and 35.9% vs 5.7 and 6.7%, respectively, P < 0.0001). The overall prevalence of FI reported ‘rarely’ or more was 16.7% of men and 21.9% of women. Men and women with OAB were significantly more likely to report FI than those without OAB. FI was also more common in participants with incontinent OAB than in those with continent OAB. Logistic regressions controlling for demographic factors and comorbid conditions suggest that OAB status is a very strong predictor of CC, FI and overlapping CC and FI (odds ratios, range 3.55–7.96).

CONCLUSIONS

Chronic constipation, FI and overlapping CC and faecal incontinence occur more frequently in patients with OAB and should be considered when evaluating and treating patients with OAB. These findings suggest a shared pathophysiology among these conditions. Additional study is needed to determine if successful treatment of one or more of these conditions is accompanied by commensurate improvement in symptoms referable to the other organ system.
The impact of preoperative erectile dysfunction on survival after radical prostatectomy
Authors: Han Misop , Trock Bruce J. , Partin Alan W. , Humphreys Elizabeth B. , Bivalacqua Trinity J. , Guzzo Thomas J. , Walsh Patrick C.
Published: June 2010

Study Type – Prognosis (case series) Level of Evidence 4

PURPOSE

Erectile dysfunction (ED) and cardiovascular disease (CVD) share etiology and pathophysiology. The underlying pathology for preoperative ED may adversely affect survival following radical prostatectomy (RP). We examined the association between preoperative ED and survival following RP.

MATERIALS AND METHODS

Between 1983 and 2000, a single surgeon performed RP on 2511 men, with preoperative ED (ED group, n= 231, 9.2%) or without ED (No ED group, n= 2280, 90.8%). We retrospectively analysed their CVD‐specific survival (CVDSS), prostate cancer‐specific survival (PCSS), non‐PCSS (NPCSS) and overall survival (OS) from time of surgery.

RESULTS

With median follow‐up of 13 years after RP, 449 men (18%) died (140 from prostate cancer, 309 from other causes). Kaplan–Meier analyses demonstrated significant differences in CVDSS (P < 0.001), NPCSS (P < 0.001) and OS (P < 0.001), but not in PCSS (P= 0.12), between the ED group vs No ED group. In univariate proportional hazards analyses, preoperative ED was associated with a significant decrease in OS, hazard ratio (HR), 1.71 (95% CI, 1.34–2.23), P < 0.001. However, in multivariable analyses, the association of ED with survival became non‐significant (HR, 1.25 (95% CI, 0.97–1.66), P= 0.111) after adjusting for other prognostic factors, such as age, preoperative prostate‐specific antigen (PSA) level, Gleason score, pathologic stage, body mass index and Charlson Comorbidity Index.

CONCLUSIONS

Preoperative ED is associated with decreased overall survival and survival from causes other than prostate cancer following RP. However, preoperative ED was not an independent predictor of overall survival after adjusting for other predictors of survival. Urologists should carefully assess pretreatment ED status to enhance appropriate treatment recommendation for men with prostate cancer.
Phase II study of docetaxel re‐treatment in docetaxel‐pretreated castration‐resistant prostate cancer
Authors: Di Lorenzo Giuseppe , Buonerba Carlo , Faiella Adriana , Rescigno Pasquale , Rizzo Mimma , Autorino Riccardo , Perdonà Sisto , Riccardi Nando , Scagliorini Sarah , Scognamiglio Florinda , Masala Daniele , Ferro Matteo , Palmieri Giovannella , Aieta Michele , Marinelli Alfredo , Altieri Vincenzo , De Placido Sabino , Cartenì Giacomo
Published: June 2010

Study Type – Therapy (cohort) Level of Evidence 2b

What’s known on the subject? and What does the study add?

We show that (i) docetaxel re‐treatment, after a treatment‐free interval, preserves activity; (ii) the treatment is especially well tolerated in patients who were effectively pretreated with docetaxel; and (iii) it could be speculated that combining docetaxel with other agents in this setting might be safe and result in greater activity.

OBJECTIVE

To determine the activity and tolerability of docetaxel re‐treatment after first‐line therapy with docetaxel in castration‐resistant prostate cancer (CRPC).

PATIENTS AND METHODS

Between November 2005 and January 2009, 45 patients initially responding to docetaxel and then experiencing disease progression after a period of biochemical remission of at least 5 months were enrolled in a prospective multicenter study and re‐treated with docetaxel. The primary endpoint was the biochemical response (biochemical partial response defined as >50% prostate‐specific antigen [PSA] decline); secondary endpoints were objective response, toxicity, progression‐free survival (PFS) and overall survival (OS).

RESULTS

Partial PSA responses were observed in 11 patients (24.5%), 4 (25%) of whom also had an objective response. The treatment was well tolerated, with grade 1–2 neutropenia, thrombocytopenia, vomiting and peripheral neuropathy noted in 18 (40%), 11 (24.5%), 8 (17.8%), and 6 (13.3%) patients, respectively. The most common grade 3 toxicity was neutropenia, which was observed in 8 patients (17.8%). Median PFS was 5 months and median OS was 13 months.

CONCLUSIONS

Docetaxel re‐treatment preserves anti‐tumour activity and is well tolerated in a selected population of pretreated patients with CRPC. Further randomized trials are needed to confirm our preliminary results.
Power Relations and International Migration: The Case of Italy and Libya
Authors: Paoletti Emanuela
Published: June 2010

Building upon the scholarly discussion concerning the growing blurring of domestic and foreign policy domains and the changing spheres of competences of states both within and outside their borders, this article focuses on inter-state cooperation in the field of migration and international relations. I attempt to answer two interrelated questions: how does collaboration on migration affect the bargaining dynamics between migrant-sending and migrant-receiving countries? And specifically, how does the contested process of externalisation of border control practices to third countries influence power relations between the two? Particular attention is paid to the agreements on migration between Italy and Libya, mainly between the late 1990s and 2009, and I examine how the putative process of externalisation of migration policies from Italy to Libya impacts upon their negotiations. I argue that this case of externalisation does not merely consist of a univocal delegation of sovereignty. Therefore I conclude that the theoretical debate is still open, both with regard to the applicability of the externalisation concept to this particular case, and to its broader representativeness.
An application of belief‐importance theory with reference to trait emotional intelligence, mood, and somatic complaints
Authors: PETRIDES K. V.
Published: June 2010

Petrides, K.V. (2011). An application of belief‐importance theory with reference to trait emotional intelligence, mood, and somatic complaints. Scandinavian Journal of Psychology 52, 161–167.

This article describes the basic principles of belief‐importance (belimp) theory and tests them in two empirical studies. Belimp theory hypothesizes that personality traits confer a propensity to perceive convergences and divergences between our belief that we can attain goals and the importance that we place on these goals. Belief and importance are conceptualized as two coordinates, together defining the belimp plane. Four distinct quadrants can be identified within the belimp plane (Hubris, Motivation, Depression and Apathy), broadly corresponding to the personality dimensions of trait emotional intelligence, conscientiousness, neuroticism and introversion. Study 1 (N = 365) defines the four quadrants in relation to goals about financial security and shows that they score differently on trait emotional intelligence, mood and somatic complaints. Study 2 (N = 230) defines the quadrants in relation to goals about appearance and, separately, in relation to goals about popularity, and replicates the findings of the first study. Strategies and requirements for testing belimp theory are presented, as are a number of theoretical and practical advantages that it can potentially offer.
On EPP effects*
Authors: Sigurðsson Halldór Ármann
Published: June 2010

Abstract. In this paper I argue that EPP effects are of two different types, NP‐movement and the Filled Left Edge Effect. While NP‐movement is driven in Narrow Syntax by the computation of Person, some Filled Left Edge phenomena, including Icelandic Stylistic Fronting, seem to take place in PF. Even so, these phenomena also reflect the clausal computation, that is, the matching processes that value clause internal elements in relation to features of the speech event.
A GRASP algorithm for a capacitated, fixed charge, multicommodity network flow problem with uncertain demand and survivability constraints
Authors: Olivera Alfredo , Amoza Franco Robledo , Testuri Carlos E.
Published: June 2010

An extension of the capacitated, fixed charge, multicommodity network flow problem with an uncertain demand of services and survivability constraints was designed and modeled as a stochastic programming problem. A polynomial algorithm based on the GRASP metaheuristic with a construction phase of a survivable topology and a local search phase based on a key‐path decomposition of the graph and a feasible key‐path replacement was proposed to solve it. The heuristic algorithm was tested for several problem instances, and its solutions were compared with a branch‐and‐cut solver. The heuristic reached good quality solutions for the tested cases.
Improving the discrimination of data envelopment analysis models in multiple time periods
Authors: Alirezaee M. R. , Afsharian M.
Published: June 2010

The trade‐offs approach is an advanced tool for the improvement of the discrimination of data envelopment analysis (DEA) models; this can improve the traditional meaning of efficiency as a radial improvement factor for inputs or outputs. Therefore, the Malmquist index – the prominent index for measuring the productivity change of decision making units (DMUs) in multiple time periods that use DEA models with variable returns to scale and constant returns to scale technologies – can be improved by using the trade‐offs technology. Hence, an expanded Malmquist index can be defined as an improved method of a traditional Malmquist index that uses the production possibility set, which could present more discrimination of DMUs, in the presence of the trade‐offs technology. In addition, similar to a traditional Malmquist index, it breaks down into different components. An illustrative example is presented to show the ability of the suggested method of presenting the Malmquist index from a computational point of view.
Solving scalarized multi‐objective network flow problems using an interior point method
Authors: Fonseca Margarida , Figueira José Rui , Resende Mauricio G.C.
Published: June 2010

In this paper, we present a primal‐dual interior‐point algorithm to solve a class of multi‐objective network flow problems. More precisely, our algorithm is an extension of the single‐objective primal infeasible dual feasible inexact interior point method for multi‐objective linear network flow problems. Our algorithm is contrasted with standard interior point methods and experimental results on bi‐objective instances are reported. The multi‐objective instances are converted into single objective problems with the aid of an achievement function, which is particularly adequate for interactive decision‐making methods.
Markov‐Switching Mean Reversion in Short‐Term Interest Rates: Evidence from East Asian Economies*
Authors: CHUA CHEW LIAN , SUARDI SANDY
Published: June 2010

This paper employs a Markov‐switching approach to model the dynamics of East Asian short rates. Regime changes are incorporated in standard unit root test to reveal periodic changes in the stationarity property of interest rates. There is evidence that three of the five short rates follow a random walk process in tranquil and low rates episodes but mean‐revert in periods when rates are high and volatile. Singapore short rates are characterised by a random walk process, whereas the Philippines rates behave as a mean‐reverting process in both regimes. Factors such as exchange rates, monetary policy and interest rate differentials vis‐à‐vis US interest rates influence the likelihood of short rates being in a volatile state. The regime switching dynamics of interest rates carry important implications for policy‐makers.
Unemployment, Government Spending and the Laffer Effect*
Authors: Linnemann Ludger
Published: June 2010

The paper studies the effects of income tax rate changes in a general equilibrium model with frictional unemployment. Laffer curve effects, by which a tax rate reduction may increase the level of government spending or its share in output, are shown to be possible under certain conditions. These are the presence of unemployment benefit payments, government budget balance through fiscal spending adjustment and limited quantitative importance of labour reallocation costs. Endogenous government spending acts as a fiscal accelerator if the fiscal burden of unemployment benefit payments is large, but reduces the employment effects of tax rate cuts if it is low.
Predicting efficacy and safety outcomes in patients with hepatitis C virus genotype 1 and persistently ‘normal’ alanine aminotransferase levels treated with peginterferon α‐2a (40KD) plus ribavirin
Authors: Snoeck Eric , Hadziyannis Stephanos J. , Puoti Claudio , Swain Mark G. , Berg Thomas , Marcellin Patrick , Zarski Jean‐Pierre , Jorga Karin , Zeuzem Stefan
Published: June 2010

Background: Currently, the approved dosage of ribavirin has not been studied in patients with ‘normal’ alanine aminotransferase (ALT) levels.

Methods: Modelling and simulations were performed using generalised additive models (GAMs) to predict the incidence of anaemia and rate of sustained virological response (SVR) in patients with hepatitis C virus (HCV) genotype 1 and persistently ‘normal’ ALT levels treated with peginterferon α‐2a (40KD) 180 μg/week plus ribavirin 1000/1200 mg/day for 48 weeks.

Results: Model‐based simulations predicted that SVR rates would increase from 39 to 48% if patients with genotype 1 and persistently ‘normal’ ALT levels had received the standard weight‐adjusted dose of ribavirin. This was similar to the predicted 49% SVR rate for genotype 1 patients with elevated ALT levels. The incidence of anaemia was predicted to increase from 13% to 23% in patients with persistently ‘normal’ ALT activity and was higher than that predicted for patients with elevated ALT levels; however, the difference appeared to be largely explained by the higher proportion of women in the former group.

Conclusions: Simulations based on GAM suggest that regimens for patients with HCV genotype 1 should include the standard weight‐adjusted dose of ribavirin, as similar SVR rates are predicted to be achieved, regardless of patients' ALT status at baseline.
Functioning of patients with multifocal motor neuropathy
Authors: Erdmann Peter G. , Lindeman Eline , Cats Elisabeth A. , Van Den Berg Leonard H.
Published: June 2010

Patients with multifocal motor neuropathy (MMN) have slowly progressive, predominantly distal asymmetric limb weakness without sensory loss. While previous studies have investigated the impact of MMN on body functions and structures, relatively little is known about the impact of patients' weakness on daily functioning. The aim of the present cross‐sectional study, involving 47 patients with MMN, was to evaluate determinants of patients' functioning. Most patients showed not only muscle weakness but also fatigue, limited dexterity, and limited walking ability. Regression models showed that age, hand aids, and muscle strength scores together explained 54% of the variance in dexterity scores, which in turn explained 8% of the variance in patients' scores for autonomy indoors. Age, the use of walking aids, and muscle strength scores together explained 58% of the variance in walking ability scores, which in turn explained 18% of the variance in patients' scores for autonomy indoors and 7% of the variance in patients' scores for autonomy outdoors. Assessment of determinants of patient functioning may make it possible to tailor interventions to address these aspects and thereby improve patients' functioning in daily life.
The cycling hair follicle as an ideal systems biology research model
Authors: Al‐Nuaimi Yusur , Baier Gerold , Watson Rachel E. B. , Chuong Cheng‐Ming , Paus Ralf
Published: June 2010

Please cite this paper as: The cycling hair follicle as an ideal systems biology research model. Experimental Dermatology 2010; 19: 707–713.

Abstract:  In the postgenomic era, systems biology has rapidly emerged as an exciting field predicted to enhance the molecular understanding of complex biological systems by the use of quantitative experimental and mathematical approaches. Systems biology studies how the components of a biological system (e.g. genes, transcripts, proteins, metabolites) interact to bring about defined biological function or dysfunction. Living systems may be divided into five dimensions of complexity: (i) molecular; (ii) structural; (iii) temporal; (iv) abstraction and emergence; and (v) algorithmic. Understanding the details of these dimensions in living systems is the challenge that systems biology aims to address. Here, we argue that the hair follicle (HF), one of the signature features of mammals, is a perfect and clinically relevant model for systems biology research. The HF represents a stem cell‐rich, essentially autonomous mini‐organ, whose cyclic transformations follow a hypothetical intrafollicular “hair cycle clock” (HCC). This prototypic neuroectodermal‐mesodermal interaction system, at the cross‐roads of systems and chronobiology, encompasses various levels of complexity as it is subject to both intrafollicular and extrafollicular inputs (e.g. intracutaneous timing mechanisms with neural and systemic stimuli). Exploring how the cycling HF addresses the five dimensions of living systems, we argue that a systems biology approach to the study of hair growth and cycling, in man and mice, has great translational medicine potential. Namely, the easily accessible human HF invites preclinical and clinical testing of novel hypotheses generated with this approach.
Leishmaniasis, contact hypersensitivity and graft‐versus‐host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance
Authors: Kautz‐Neu Kordula , Meyer Ralf G. , Clausen Björn E. , Von Stebut Esther
Published: June 2010

Please cite this paper as: Leishmaniasis, contact hypersensitivity and graft‐versus‐host disease: understanding the role of dendritic cell subsets in balancing skin immunity and tolerance. Experimental Dermatology 2010; 19: 760–771.

Abstract:  Dendritic cells (DC) are key elements of the immune system. In peripheral tissues, they function as sentinels taking up and processing antigens. After migration to the draining lymph nodes, the DC either present antigenic peptides by themselves or transfer them to lymph node–resident DC. The skin is the primary interface between the body and the environment and host’s various DC subsets, including dermal DC (dDC) and Langerhans cells (LC). Because of their anatomical position in the epidermis, LC are believed to be responsible for induction of adaptive cutaneous immune responses. The functions of LC and dDC in the skin immune system in vivo are manifold, and it is still discussed controversially whether the differentiation of T‐cell subtypes (e.g. effector T cells and regulatory T cells) may be initiated by distinct DC subtypes. As skin DC are able to promote or downmodulate immune responses, we chose different skin diseases (cutaneous leishmaniasis, contact hypersensitivity, UV radiation‐induced suppression, and graft‐versus‐host disease) to describe the biological interactions between different DC subtypes and T cells that lead to the development of efficient or unwanted immune responses. A detailed knowledge about the immune modulatory capacity of different cutaneous DC subsets might be helpful to specifically target these cells through the skin during therapeutic interventions.
Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata
Authors: Hong‐wei Guo , Jun Deng , Xi‐chuan Yang , Bai‐yu Zhong , Zhu Shen , Shao‐yan Yang , Bao‐heng Liu , Fei Hao
Published: June 2010

Please cite this paper as: Melanocortin receptor type 2 (MC2R, ACTH receptor) expression in patients with alopecia areata. Experimental Dermatology 2010; 19: 1020–1022.

Abstract:  Human skin expresses elements of the hypothalamo‐pituitary‐adrenal (HPA) axis that function as a local stress response system. Because adrenocorticotropic hormone (ACTH) is an intermediate in the HPA axis from corticotropin‐releasing hormone (CRH) signal to cortisol secretion, MC2R that binds only ACTH may be important in the stress response of skin. We investigated the local expression of MC2R by immunohistochemistry to identify the role of ACTH/MC2R in stress‐associated alopecia areata (AA). MC2R appeared to be highly compartmentalized in scalp skin including the epidermal cells of hair follicles and epidermis, sebaceous and eccrine glands, as well as dermal fibroblasts. The expression of MC2R was lower in AA lesions than in normal scalp tissue in almost all scalp skin cells, especially in epithelial cells. These findings demonstrate that MC2R expression is aberrant in AA and suggest a deficit in ACTH/MC2R activity may play an important role in the pathophysiology of AA.
Comparative analysis of two methods for wound bed area measurement
Authors: Van Poucke Sven , Nelissen Roald , Jorens Philippe , Vander Haeghen Yves
Published: June 2010

Wound bed area measurements are considered to be an essential part of the wound assessment process. Wound care professionals should be aware of the reliability and validity of the techniques they use. The purpose of this study was to assess whether wound care professionals are able to make as accurate and reproducible a measurement of the wound bed area using two methods for area measurement. Five wound care professionals independently assessed 2285 digital wound images for the wound bed area. Each image was measured in random order, three times, and in four angles by providing the rotated versions of each image (0°, 90°, 180° and 270°). Two techniques were compared: free hand drawing and closed polygon (CP) graph algorithm. Comparison of the two techniques showed differences that are, in our opinion, not acceptable in clinical practice when these techniques are used interchangeably and/or the measurements are carried out by different observers. Variations observed between wounds and observers seem related to the difference in perception of the wound bed margin. Our results indicate that repetition of CP graph area measurement results in the lowest difference in repetitive measurements. Study limitations are related to an incomplete consensus on definitions of wound, wound bed, wound edge and wound border. The development of an ontology related to wound images could aid to reduce these ambiguities.
Single‐stage Matriderm® and skin grafting as an alternative reconstruction in high‐voltage injuries
Authors: Ryssel Henning , Radu Christian Andreas , Germann Günter , Otte Max , Gazyakan Emre
Published: June 2010

This article presents a retrospective analysis of a series of nine patients requiring reconstruction of exposed bone, tendons or joint capsules as a result of acute high‐voltage injuries in a single burn centre. As an alternative to free tissue transfer, the dermal substitute Matriderm® was used in a one‐stage procedure in combination with split‐thickness skin grafts (STSG) for reconstruction. Nine patients, in the period between 2005 and 2009 with extensive high‐voltage injuries to one or more extremities which required coverage of exposed functional structures as bone, tendons or joint capsule, were included. A total of 11 skin graftings and 2 local flaps were performed. Data including regrafting rate, complications, hospital stays, length of rehabilitation and time until return to work were collected. Eleven STSG in combination with Matriderm® were performed on nine patients (success rate 89%). One patient died. One patient needed a free‐flap coverage as a secondary procedure. The median follow‐up was 30 months (range 6–48 months). The clinical results of these nine treated patients concerning skin‐quality and coverage of exposed tendons or joint capsule were very good. In high‐voltage injuries free‐flap failure occurs between 10% and 30% if performed within the first 4–6 weeks after trauma. The use of single‐stage Matriderm® and skin grafting for immediate coverage described in this article is a reliable alternative to selected cases within this period.
Association of the HLA‐G gene polymorphism with multiple sclerosis in a Polish population
Authors: Wiśniewski A. , Bilińska M. , Klimczak A. , Wagner M. , Majorczyk E. , Nowak I. , Pokryszko‐Dragan A. , Kuśnierczyk P.
Published: June 2010

In this study, three polymorphic sites in the HLA‐G gene: −725C>G>T, −716T>G and 14bpindel were genotyped. Significant differences were found between patients and controls in the alleles and genotypes for −725C>G>T and in three‐point haplotypes. We observed also a significant difference in the age of disease onset between patients positive and negative for 14bpins. The results suggest that single nucleotide polymorphisms in the promoter of the HLA‐G gene (mainly −725C>G>T), and 14bpindel, or some genetic marker in tight linkage disequilibrium with them are associated with multiple sclerosis.
Arabidopsis Chloroplast FtsH, var2 and Suppressors of var2 Leaf Variegation: a Review
Authors: Liu Xiayan , Yu Fei , Rodermel Steve
Published: June 2010

Variegation mutants are ideal model systems to study chloroplast biogenesis. We are interested in variegations whose green and white‐sectored leaves arise as a consequence of the action of nuclear recessive genes. In this review, we focus on the Arabidopsis var2 variegation mutant, and discuss recent progress toward understanding the function of VAR2 and the mechanism of var2‐mediated variegation. VAR2 is a subunit of the chloroplast FtsH complex, which is involved in turnover of the Photosystem II reaction center D1 protein, as well as in other processes required for the development and maintenance of the photosynthetic apparatus. The cells in green sectors of var2 have normal‐appearing chloroplasts whereas cells in the white sectors have abnormal plastids that lack pigments and organized lamellae. To explain the mechanism of var2 variegation, we have proposed a threshold model in which the formation of chloroplasts is due to the presence of activities/processes that are able to compensate for a lack of VAR2. To gain insight into these activities, second‐site suppressor screens have been carried out to obtain mutants with non‐variegation phenotypes. Cloning and characterization of several var2 suppressor lines have uncovered several mechanisms of variegation suppression, including an unexpected link between var2 variegation and chloroplast translation.
COMPARATIVE ASSESSMENT OF THE NUTRITIONAL VALUE OF COMMERCIALLY AVAILABLE COCOYAM AND POTATO TUBERS IN SOUTH AFRICA
Authors: LEWU M.N. , ADEBOLA P.O. , AFOLAYAN A.J.
Published: June 2010

Potato (Solanum tuberosum) is a popular staple food in South Africa, whereas cocoyam (Colocasia esculenta) remains unpopular and not well known outside KwaZulu‐Natal Province, where it is cultivated mainly for subsistence. A comparative study of the nutritional compositions of commercially available tubers of both crops in South Africa was carried out. The results showed that the tubers of the two crops were high in carbohydrate and energy but low in lipid contents. Although potato was significantly higher in moisture and ash than the tubers of cocoyam, carbohydrate, caloric and crude protein contents were not significantly different (P < 0.05) in both tubers. Whereas boiling improved the availability of crude protein, fiber and lipid contents for both species, boiling reduced the ash contents in the tubers of both crops. Manganese levels were not detectable, whereas iron contents were appreciably high, but magnesium and copper contents were in the average range in both tubers. Whereas cooking reduced iron level in potato (11.20–9.95 mg/100 g DM), a significant increase in iron was observed for cocoyam (9.08–13.87 mg/100 g DM). Cooking significantly lowered magnesium, potassium and copper contents in both crops. Oxalates and phytate contents were significantly higher in cocoyam when compared with potato. Cooking remarkably reduced the anti‐nutrient contents of both tubers.

PRACTICAL APPLICATIONS

This study provides evidence that commercially available cocoyam (Colocasia esculenta) and potato (Solanum tuberosum) in South Africa have very close nutritional values. Cocoyam compared favorably with potato and even excelled in some nutrients. Thus, cocoyam consumption could be encouraged and popularized as an additional tuber crop.
OPTIMIZATION OF A HS‐SPME/GC‐MS METHOD FOR DETERMINATION OF VOLATILE COMPOUNDS IN SOME CUBAN UNIFLORAL HONEYS
Authors: CEBALLOS LIENA , PINO JORGE A. , QUIJANO‐CELIS CLARA E. , DAGO ANGEL
Published: June 2010

A headspace (HS)/solid phase microextraction (SPME)/gas chromatography‐mass spectrometry (GC‐MS) method was developed to determine the profiles of volatile compounds from three Cuban unifloral honeys: Turbina corymbosa (L.) Raf., Ipomoea triloba L. and Gouania polygama (Jacq.) Urb. The optimization of the extraction conditions was carried out by response surface methodology. The analytical conditions of the optimized HS‐SPME method were: 65 µm PDMS/DVB fiber, 6 g honey, 3 mL water and 20% w/w sodium chloride, 20 min for pre‐extraction, 30 min for extraction at 60C and 4 min for GC desorption. The GC‐MS analysis allowed the identification of 181 volatile compounds in these honeys. Possible markers for the floral classification of honeys were for the T. corymbosa type: 4‐methyl methoxysalicylate, trans‐pinocarveol, chavicol, methyl anisate, trans‐α‐bergamotene and α‐bisabolol. In I. triloba honey, 2,5,5‐trimethyl‐3‐tetrahydrofuranone and 1,2‐diphenylethanol were found, while4‐methyl‐1‐pentanol and isopentyl acetate were only present in G. polygama honey. With the use of the HS‐SPME method in combination with multivariate analysis techniques such as Principal Component Analysis and K‐nearest neighbor, it was possible to discriminate the different honeys according to their floral origin.

PRACTICAL APPLICATIONS

Honey is a natural product produced by Apis mellifera bees from nectar and secretions of the living parts of the plants. According to the nectar source, honeys can be multifloral (nectars from diverse flowers) or unifloral (nectar from only one flower). The floral origin of honey is an important characteristic in the evaluation of its quality. Control and characterization of the volatile compounds of unifloral honeys is highly important in Cuban apiculture, and has not been carried out so far. The objective of this work was to develop and optimize a method to determine origin of some Cuban unifloral honeys, by means of a headspace‐solid phase microextraction.
Exercise training‐induced improvements in insulin action
Authors: Hawley J. A. , Lessard S. J.
Published: June 2010

Individuals with insulin resistance are characterized by impaired insulin action on whole‐body glucose uptake, in part due to impaired insulin‐stimulated glucose uptake into skeletal muscle. A single bout of exercise increases skeletal muscle glucose uptake via an insulin‐independent mechanism that bypasses the typical insulin signalling defects associated with these conditions. However, this ‘insulin sensitizing’ effect is short‐lived and disappears after ∼48 h. In contrast, repeated physical activity (i.e. exercise training) results in a persistent increase in insulin action in skeletal muscle from obese and insulin‐resistant individuals. The molecular mechanism(s) for the enhanced glucose uptake with exercise training have been attributed to the increased expression and/or activity of key signalling proteins involved in the regulation of glucose uptake and metabolism in skeletal muscle. Evidence now suggests that the improvements in insulin sensitivity associated with exercise training are also related to changes in the expression and/or activity of proteins involved in insulin signal transduction in skeletal muscle such as the AMP‐activated protein kinase (AMPK) and the protein kinase B (Akt) substrate AS160. In addition, increased lipid oxidation and/or turnover is likely to be another mechanism by which exercise improves insulin sensitivity: exercise training results in an increase in the oxidative capacity of skeletal muscle by up‐regulating lipid oxidation and the expression of proteins involved in mitochondrial biogenesis. Determination of the underlying biological mechanisms that result from exercise training is essential in order to define the precise variations in physical activity that result in the most desired effects on targeted risk factors, and to aid in the development of such interventions.
Inhibiting Leukocytosis
Authors: Mueller Kristen L.
Published: June 2010

Pathways that reduce cholesterol in atherosclerosis also suppress increased immune cell numbers associated with the disease.
Addicts Lose Plasticity
Authors: Stern Peter R.
Published: June 2010

Loss of glutamate receptor–dependent synaptic plasticity in the brain is associated with the transition to cocaine addiction.
The Promise of Evolutionary Systems Biology: Lessons from Bacterial Chemotaxis
Authors: Soyer Orkun S.
Published: June 2010

Genomic analysis reveals missing links in the evolution of chemotaxis systems.
Pharmacokinetics of Rifampin and Clarithromycin in Patients Treated for
Mycobacterium ulcerans
Infection
Authors: Alffenaar J. W. C. , Nienhuis W. A. , de Velde F. , Zuur A. T. , Wessels A. M. A. , Almeida D. , Grosset J. , Adjei O. , Uges D. R. A. , van der Werf T. S.
Published: June 2010

In a randomized controlled trial in Ghana, treatment of
Mycobacterium ulcerans
infection with streptomycin (SM)-rifampin (RIF) for 8 weeks was compared with treatment with SM-RIF for 4 weeks followed by treatment with RIF-clarithromycin (CLA) for 4 weeks. The extent of the interaction of RIF and CLA combined on the pharmacokinetics of the two compounds is unknown in this population and was therefore studied in a subset of patients. Patients received CLA at a dose of 7.5 mg/kg of body weight once daily, rounded to the nearest 125 mg. RIF was administered at a dose of 10 mg/kg, rounded to the nearest 150 mg. SM was given at a dose of 15 mg/kg once daily as an intramuscular injection. Plasma samples were drawn at steady state and analyzed by liquid chromatography-tandem mass spectroscopy. Pharmacokinetic parameters were calculated with the MW/Pharm (version 3.60) program. Comedication with CLA resulted in a 60% statistically nonsignificant increase in the area under the plasma concentration-time curve (AUC) for RIF of 25.8 mg·h/liter (interquartile ratio [IQR], 21.7 to 31.5 mg·h/liter), whereas the AUC of RIF was 15.2 mg·h/liter (IQR, 15.0 to 17.5 mg·h/liter) in patients comedicated with SM (
P
= 0.09). The median AUCs of CLA and 14-hydroxyclarithromycin (14OH-CLA) were 2.9 mg·h/liter (IQR, 1.5 to 3.8 mg·h/liter) and 8.0 mg·h/liter (IQR, 6.7 to 8.6 mg·h/liter), respectively. The median concentration of CLA was above the MIC of
M. ulcerans
, but that of 14OH-CLA was not. In further clinical studies, a dose of CLA of 7.5 mg/kg twice daily should be used (or with an extended-release formulation, 15 mg/kg should be used) to ensure higher levels of exposure to CLA and an increase in the time above the MIC compared to those achieved with the currently used dose of 7.5 mg/kg once daily.
First Report of the Multidrug Resistance Gene
cfr
and the Phenicol Resistance Gene
fexA
in a
Bacillus
Strain from Swine Feces
Authors: Dai Lei , Wu Cong-Ming , Wang Ming-Gui , Wang Yang , Wang Yu , Huang Si-Yang , Xia Li-Ning , Li Bei-Bei , Shen Jian-Zhong
Published: June 2010

A multidrug resistance gene,
cfr
, and a phenicol resistance gene,
fexA
, were detected in a
Bacillus
strain, BS-01, isolated from swine feces. The
cfr
gene was carried on a novel 16.5-kb plasmid, designated pBS-01. A complete Tn
917
structure, which harbors the macrolide-lincosamide-streptogramin B resistance gene
erm
(B), was located downstream of the
cfr
gene. The
fexA
gene was discovered in the chromosomal DNA of the BS-01 strain and identified in a Tn
558
variant.
Plasmid-Mediated Resistance to Cephalosporins in
Salmonella enterica
Serovar Typhi
Authors: Morita Masatomo , Takai Nobuko , Terajima Jun , Watanabe Haruo , Kurokawa Manabu , Sagara Hiroko , Ohnishi Kenji , Izumiya Hidemasa
Published: June 2010

This study characterized a cephalosporin-resistant
Salmonella enterica
serovar Typhi isolate. The organism possessed a plasmid encoding the CTX-M-15 extended-spectrum-β-lactamase. This plasmid is the determinant for the phenotype of cephalosporin resistance and is transferrable among
Enterobacteriaceae
.
In Vitro
Antimicrobial Activity and Mutant Prevention Concentration of Colistin against
Acinetobacter baumannii
Authors: Cai Yun , Li Ran , Liang Beibei , Bai Nan , Liu Youning , Wang Rui
Published: June 2010

The antimicrobial activities of colistin and other antibiotics against clinical
Acinetobacter baumannii
and the mutant prevention concentration (MPC) of colistin against multidrug-resistant
A. baumannii
were studied. All 70 stains tested were sensitive to colistin. The MPC range of colistin against 30 multidrug-resistant
A. baumannii
stains was approximately 32 to >128 μg/ml, and the MPC at which 90% of the isolates tested were prevented (MPC
90
) exceeded 128 μg/ml, which was much higher than the plasma concentration of colistin at the current recommended dosage. So, combination therapy for colistin treatment of
A. baumannii
would be prudent to slow the emergence of resistance.
Antimicrobial Susceptibility Patterns for Recent Clinical Isolates of Anaerobic Bacteria in South Korea
Authors: Lee Yangsoon , Park Yongjung , Kim Myung Sook , Yong Dongeun , Jeong Seok Hoon , Lee Kyungwon , Chong Yunsop
Published: June 2010

We determined the antimicrobial susceptibilities of 255 clinical isolates of anaerobic bacteria collected in 2007 and 2008 at a tertiary-care hospital in South Korea. Piperacillin-tazobactam, cefoxitin, imipenem, and meropenem were highly active β-lactam agents against most of the isolates tested. The rates of resistance of
Bacteroides fragilis
group organisms and anaerobic Gram-positive cocci to moxifloxacin were 11 to 18% and 0 to 27%, respectively.