bluuebunny/crossref_metadata_2025 huggingface dataset:
Asymptotic shape of small cells
Authors: Beermann Mareen , Redenbach Claudia , Thäle Christoph
Published: November 2013

A stationary Poisson line tessellation is considered whose directional distribution is concentrated on two different atoms with some positive weights. The shape of the typical cell of such a tessellation is studied when its area or its perimeter tends to zero. In contrast to known results where the area or the perimeter tends to infinity, it is shown that the asymptotic shape of cells having small area is degenerate. Again in contrast to the case of large cells, the asymptotic shape of cells with small perimeter is not uniquely determined. The results are accompanied by a large scale simulation study.
Gradient estimates and entropy monotonicity formula for doubly nonlinear diffusion equations on Riemannian manifolds
Authors: Wang Yuzhao , Chen Wenyi
Published: November 2013

In the first part of this paper, we prove the sharp global Li‐Yau type gradient estimates for positive solutions to doubly nonlinear diffusion equation(DNDE) on complete Riemannian manifolds with nonnegative Ricci curvature. As an application, one can obtain a parabolic Harnack inequality. In the second part, we obtain a Perelman‐type entropy monotonicity formula for DNDE on compact Riemannian manifolds with nonnegative Ricci curvature. These results generalize some works of Ni (JGA 2004), Lu–Ni–Vázquez–Villani (JMPA 2009) and Kotschwar–Ni (Annales Scientifiques de l'École Normale Supérieure 2009). Copyright © 2013 John Wiley & Sons, Ltd.
Magnetization transfer in lamellar liquid crystals
Authors: Malyarenko Dariya I. , Zimmermann Ellen M. , Adler Jeremy , Swanson Scott D.
Published: November 2013

Purpose

This study examines the relationship between quantitative magnetization transfer (qMT) parameters and the molecular composition of a model lamellar liquid crystal (LLC) system composed of 1‐decyl alcohol (decanol), sodium dodecyl sulfate (SDS), and water.

Methods

Samples were made within a stable lamellar mesophase to provide different ratios of total semisolid protons (SDS + decanol) to water protons. Data were collected as a function of radiofrequency power, frequency offset, and temperature. qMT parameters were estimated by fitting a standard model to the data. Fitting results of four different semisolid line shapes were compared.

Results

A super‐Lorentzian line shape for the semisolid component provided the best fit. The estimated amount of semisolids was proportional to the ratio of decanol‐to‐water protons. Other qMT parameters exhibited nonlinear dependence on sample composition. Magnetization transfer ratio (MTR) was a linear function of the semisolid fraction over a limited range of decanol concentration.

Conclusion

In LLC samples, MT between semisolid and water originates from intramolecular nOe among decanol aliphatic chain protons followed by proton exchange between decanol hydroxyl and water. Exchange kinetics is influenced by SDS, although SDS protons do not participate in MT. These studies provide clinically relevant range of semisolid fraction proportional to detected MTR. Magn Reson Med 72:1427–1434, 2014. © 2013 Wiley Periodicals, Inc.
Phase‐based manganese enhanced MRI, a new methodology to enhance brain cytoarchitectural contrast and study manganese uptake
Authors: Maddage Rajika , Marques José P. , Gruetter Rolf
Published: November 2013

Purpose

As the magnetic susceptibility induced frequency shift increases linearly with magnetic field strength, the present work evaluates manganese as a phase imaging contrast agent and investigates the dose dependence of brain enhancement in comparison to T1‐weighted imaging after intravenous administration of MnCl2.

Methods

Experiments were carried out on 12 Sprague‐Dawley rats. MnCl2 was infused intravenously with the following doses: 25, 75, 125 mg/kg (n=4). Phase, T1‐weighted images and T1 maps were acquired before and 24h post MnCl2 administration at 14.1 Tesla.

Results

Manganese enhancement was manifested in phase imaging by an increase in frequency shift differences between regions rich in calcium gated channels and other tissues, together with local increase in signal to noise ratio (from the T1 reduction). Such contrast improvement allowed a better visualization of brain cytoarchitecture. The measured T1 decrease observed across different manganese doses and in different brain regions were consistent with the increase in the contrast to noise ratio (CNR) measured by both T1‐weighted and phase imaging, with the strongest variations being observed in the dentate gyrus and olfactory bulb.

Conclusion

Overall from its high sensitivity to manganese combined with excellent CNR, phase imaging is a promising alternative imaging protocol to assess manganese enhanced MRI at ultra high field. Magn Reson Med 72:1246–1256, 2014. © 2013 Wiley Periodicals, Inc.
Differences in prostate cancer grade, stage, and location in radical prostatectomy specimens from United States and Japan
Authors: Takahashi Hiroyuki , Epstein Jonathan I. , Wakui Shin , Yamamoto Toshihiro , Furusato Bungo , Zhang Miao
Published: November 2013

BACKGROUND

To compared prostate cancer at radical prostatectomy between men in the United States (US) and Japan in the modern era.

METHODS

Three hundred seventy consecutive totally embedded RP cases (159 US; 211 Japan) from 2010 to 2012 were reviewed.

RESULTS

US men were significantly younger (mean age 58.8 years) than Japanese men (mean age 64.6 years; P < 0.00001). Japanese patients presented with higher PSA levels (mean = 10.9 ng/ml) compared to US patients (mean = 5.8 ng/ml, P < 0.00001) and higher clinical stage (P = 0.003). Japanese tumors were: higher grade; larger; more advanced stage; with increased lymphovascular invasion; and more commonly TZ in location (P < 0.00001). In multivariate analysis, independent predictors of high tumor volume were PSA level, clinical stage, TZ location, Gleason grade, and country of origin (Japan). Independent predictors of TZ location were clinical stage, tumor volume, and country of origin (Japan).

CONCLUSION

A major factor for larger, higher grade and stage tumors in Japanese patients is the lower prevalence of screening for prostate cancer in Japan. Another contributing factor may be their TZ location, where they are not palpable until advanced and where they are difficult to sample on needle biopsy possibly leading to a delay in diagnosis. The finding of a difference in zonality of prostate cancer between US and Japanese cases is novel and may reflect differences in biology rather than different health care practice between the groups. If this data is confirmed, consideration should be given to TZ sampling as part of routine needle biopsies in Japanese men. Prostate 74:321–325, 2014. © 2013 Wiley Periodicals, Inc.
Time, Modality, and the Unbearable Lightness of Being
Authors: Frischhut Akiko M. , Skiles Alexander ,   Philosophy Documentation Center
Published: November 2013

We develop a theory about the metaphysics of time and modality that combines the conceptual resources devised in recent sympathetic work on ontological pluralism (the thesis that there are fundamentally distinct kinds of being) with the thought that what is past, future, and merely possible is less real than what is present and actual (albeit real enough to serve as truthmakers for statements about the past, future, and merely possible). However, we also show that despite being a coherent, distinctive, and prima facie appealing position, the theory succumbs to what we call the ‘‘problem of mixed ontological status’’. We conclude that the proponents of the theory can only evade these problems by developing ontological pluralism in a radically different way than it has been by its recent sympathizers.
Wood smoke exposure induces a decrease in respiration parameters and in the activity of respiratory complexes I and IV in lung mitochondria from guinea pigs
Authors: Granados‐Castro Luis Fernando , Rodríguez‐Rangel Daniela Sarai , Montaño Martha , Ramos Carlos , Pedraza‐Chaverri José
Published: November 2013

Domestic exposure to biomass smoke represents the second cause of chronic obstructive lung disease. Previous studies have shown that exposure of guinea pigs to wood smoke is capable of generating oxidative stress in lung tissue, and this may involve a failure at a mitochondrial level, given its close relation with the production of reactive oxygen species (ROS). The purpose of this study was to evaluate, in guinea pigs exposed to wood smoke, the lung mitochondrial functionality through O2 consumption measurement and the determination of the mitochondrial complexes enzymatic activity. We found that normal and maximum respiration decreased at 15 and 30 min of wood smoke exposure, recovering its normal values at 180 min. The same behavior was observed for the respiratory control rate (RCR) and the ADP/O value. Complex I activity decreased significantly after 30 min of exposure and it returned to baseline after 180 min. The greatest alteration was observed by the decrease of 85% on complex IV activity at 30 min of exposure, which returned to control values after 180 min of exposure. It is concluded that even when wood smoke exposure induces severe mitochondrial respiration alterations at the first 30 min, it seems that there is one or many ways by which mitochondria can reinstate its normal function after 180 min of exposure. © 2013 Wiley Periodicals, Inc. Environ Toxicol 30: 461–471, 2015.
Diverse high-risk B2 and D Escherichia coli clones depicted by Fourier Transform Infrared Spectroscopy
Authors: Sousa Clara , Novais Ângela , Magalhães Ana , Lopes João , Peixe Luísa
Published: November 2013

We aimed to develop a reliable method based on Fourier transform infrared spectroscopy with attenuated total reflectance (FTIR-ATR) to discriminateEscherichia coliclones from B2(n = 9) and D(n = 13) phylogenetic groups. Eighty-eightE. coliisolates belonging to phylogenetic groups B2(n = 39) and D(n = 49), including particularly widespread high risk clones or clonal complexes (HiRCC) ST131, ST69, ST393 and ST405 were studied. Spectra were analysed by unsupervised (hierarchical cluster analysis-HCA) and supervised methods (soft independent modelling of class analogy-SIMCA and partial least square discriminant analysis-PLSDA). B2-ST131 isolates were discriminated from B2 non-ST131 and D phylogroup isolates (ST69, ST393, ST405) by HCA, SIMCA and PLSDA. D-ST69, D-ST393 and D-ST405 isolates were also distinguished from each other and from other STs from phylogroup D by the three methods. We demonstrate that FTIR-ATR coupled with chemometrics is a reliable and alternative method to accurately discriminate particularE. coliclones. Its validation towards an application at a routine basis could revolutionize high-throughput bacterial typing.
Selective synthesis of [7]- and [8]cycloparaphenylenes
Authors: Sibbel Friederike , Matsui Katsuma , Segawa Yasutomo , Studer Armido , Itami Kenichiro
Published: November 2013

We report a size-selective synthesis of [7]- and [8]CPP by a modular approach and present the first X-ray crystal structure of [7]CPP.
Design and formulation of functional pluripotent stem cell-derived cardiac microtissues
Authors: Thavandiran Nimalan , Dubois Nicole , Mikryukov Alexander , Massé Stéphane , Beca Bogdan , Simmons Craig A. , Deshpande Vikram S. , McGarry J. Patrick , Chen Christopher S. , Nanthakumar Kumaraswamy , Keller Gordon M. , Radisic Milica , Zandstra Peter W.
Published: November 2013

Significance

Robust and predictive in vitro models of human cardiac tissue function could have transformative impact on our ability to test new drugs and understand cardiac disease. Despite significant effort, the generation of high-fidelity adult-like human cardiac tissue analogs remains challenging. In this paper, we systematically explore the design criteria for pluripotent stem cell-derived engineered cardiac tissue. Parameters such as biomechanical stress during tissue remodeling, input-cell composition, electrical stimulation, and tissue geometry are evaluated. Our results suggest that a specified combination of a 3D matrix-based microenvironment, uniaxial mechanical stress, and mixtures of cardiomyocytes and fibroblasts improves the performance and maturation state of in vitro engineered cardiac tissue.
Movement Patterns and Size‐Class Influence Entrainment Susceptibility of Lake Sturgeon in a Small Hydroelectric Reservoir
Authors: McDougall C. A. , Blanchfield P. J. , Peake S. J. , Anderson W. G.
Published: November 2013

Hydroelectric development is considered a threat to the recovery of Lake Sturgeon Acipenser fulvescens populations, in part because of injury and mortality concerns caused by interaction with hydroelectric facilities. Lake Sturgeon resident in small impoundments may be particularly susceptible to entrainment, depending on movement and habitat usage patterns. Using acoustic telemetry, we monitored coarse‐scale movements of 99 juvenile, subadult and adult Lake Sturgeon captured throughout a 10‐km‐long hydroelectric reservoir. Overall, adults moved over larger ranges than did smaller size‐classes. However, all size‐classes utilized habitat immediately upstream of hydroelectric facilities, and during the 18‐month study period, 27% of subadults tagged in the lowermost section of the reservoir, and 8.7% of adults tagged throughout the reservoir were entrained. Movements of juveniles and subadults were generally restricted to extended sections (2–6 km) of contiguous deepwater habitat (>15 m), and passage through the two shallow river narrows that subdivide the reservoir were rare. Over half of the tagged adults (52%) moved upstream or downstream through one or both river narrows, albeit infrequently. Initial residency influenced entrainment susceptibility for juveniles and subadults but not for adults. Results suggest that Lake Sturgeon resident in small impoundments are susceptible to entrainment. However, the presence of river narrows, which function as natural movement restrictors, may largely preclude susceptibility of juveniles and subadults resident in upstream sections.
Pregabalin Rectifies Aberrant Brain Chemistry, Connectivity, and Functional Response in Chronic Pain Patients
Authors: Harris Richard E. , Napadow Vitaly , Huggins John P. , Pauer Lynne , Kim Jieun , Hampson Johnson , Sundgren Pia C. , Foerster Bradley , Petrou Myria , Schmidt-Wilcke Tobias , Clauw Daniel J.
Published: November 2013

Background:

Chronic pain remains a significant challenge for modern health care as its pathologic mechanisms are largely unknown and preclinical animal models suffer from limitations in assessing this complex subjective experience. However, human brain neuroimaging techniques enable the assessment of functional and neurochemical alterations in patients experiencing chronic pain and how these factors may dynamically change with pharmacologic treatment.

Methods:

To identify the clinical action of pregabalin, a proven analgesic, the authors performed three complementary brain neuroimaging procedures: (proton magnetic resonance spectroscopy, functional magnetic resonance imaging, and functional connectivity magnetic resonance imaging) in 17 chronic pain patients diagnosed with fibromyalgia.

Results:

The authors found that pregabalin but not placebo reduces combined glutamate + glutamine levels within the posterior insula (pregabalin P = 0.016; placebo P = 0.71). Interestingly, reductions in clinical pain were associated with reductions in brain connectivity of this structure to brain regions within the default mode network during pregabalin (r = 0.82; P = 0.001) but not placebo (r = −0.13; P = 0.63). Response of default mode network regions to experimental pain was also reduced with pregabalin (P = 0.018) but not placebo (P = 0.182). Perhaps most importantly, baseline values for all three neuroimaging markers predicted subsequent analgesic response to pregabalin but not placebo.

Conclusions:

The results of this study suggest that pregabalin works in part by reducing insular glutamatergic activity, leading to a reduction of the increased functional connectivity seen between brain regions in chronic pain states. The study also supports a role for human brain imaging in the development, assessment, and personalized use of central-acting analgesics.
Brood parasites lay eggs matching the appearance of host clutches
Authors: Honza Marcel , Šulc Michal , Jelínek Václav , Požgayová Milica , Procházka Petr
Published: November 2013

Interspecific brood parasitism represents a prime example of the coevolutionary arms race where each party has evolved strategies in response to the other. Here, we investigated whether common cuckoos (Cuculus canorus) actively select nests within a host population to match the egg appearance of a particular host clutch. To achieve this goal, we quantified the degree of egg matching using the avian vision modelling approach. Randomization tests revealed that cuckoo eggs in naturally parasitized nests showed lower chromatic contrast to host eggs than those assigned randomly to other nests with egg-laying date similar to naturally parasitized clutches. Moreover, egg matching in terms of chromaticity was better in naturally parasitized nests than it would be in the nests of the nearest active non-parasitized neighbour. However, there was no indication of matching in achromatic spectral characteristics whatsoever. Thus, our results clearly indicate that cuckoos select certain host nests to increase matching of their own eggs with host clutches, but only in chromatic characteristics. Our results suggest that the ability of cuckoos to actively choose host nests based on the eggshell appearance imposes a strong selection pressure on host egg recognition.
RESTRICTIVE DETERRENT EFFECTS OF A WARNING BANNER IN AN ATTACKED COMPUTER SYSTEM
Authors: MAIMON DAVID , ALPER MARIEL , SOBESTO BERTRAND , CUKIER MICHEL
Published: November 2013

System trespassing by computer intruders is a growing concern among millions of Internet users. However, little research has employed criminological insights to explore the effectiveness of security means to deter unauthorized access to computer systems. Drawing on the deterrence perspective, we employ a large set of target computers built for the sole purpose of being attacked and conduct two independent experiments to investigate the influence of a warning banner on the progression, frequency, and duration of system trespassing incidents. In both experiments, the target computers (86 computers in the first experiment and 502 computers in the second) were set either to display or not to display a warning banner once intruders had successfully infiltrated the systems; 1,058 trespassing incidents were observed in the first experiment and 3,768 incidents in the second. The findings reveal that although a warning banner does not lead to an immediate termination or a reduction in the frequency of trespassing incidents, it significantly reduces their duration. Moreover, we find that the effect of a warning message on the duration of repeated trespassing incidents is attenuated in computers with a large bandwidth capacity. These findings emphasize the relevance of restrictive deterrence constructs in the study of system trespassing.
Feasibility of Autologous Bone Marrow Mesenchymal Stem Cell–Derived Extracellular Matrix Scaffold for Cartilage Tissue Engineering
Authors: Tang Cheng , Xu Yan , Jin Chengzhe , Min Byoung‐Hyun , Li Zhiyong , Pei Xuan , Wang Liming
Published: November 2013

Extracellular matrix (ECM) materials are widely used in cartilage tissue engineering. However, the currentECMmaterials are unsatisfactory for clinical practice as most of them are derived from allogenous or xenogenous tissue. This study was designed to develop a novel autologousECMscaffold for cartilage tissue engineering. The autologous bone marrow mesenchymal stem cell–derivedECM(aBMSC‐dECM) membrane was collected and fabricated into a three‐dimensional porous scaffold via cross‐linking and freeze‐drying techniques. Articular chondrocytes were seeded into theaBMSC‐dECMscaffold and atelocollagen scaffold, respectively. An in vitro culture and an in vivo implantation in nude mice model were performed to evaluate the influence on engineered cartilage. The current results showed that theaBMSC‐dECMscaffold had a good microstructure and biocompatibility. After 4 weeks in vitro culture, the engineered cartilage in theaBMSC‐dECMscaffold group formed thicker cartilage tissue with more homogeneous structure and higher expressions of cartilaginous gene and protein compared with the atelocollagen scaffold group. Furthermore, the engineered cartilage based on theaBMSC‐dECMscaffold showed better cartilage formation in terms of volume and homogeneity, cartilage matrix content, and compressive modulus after 3 weeks in vivo implantation. These results indicated that theaBMSC‐dECMscaffold could be a successful novel candidate scaffold for cartilage tissue engineering.
Adenomatous polyposis coli (APC) membrane recruitment 3, a member of the APC membrane recruitment family of APC‐binding proteins, is a positive regulator of Wnt–β‐catenin signalling
Authors: Brauburger Katharina , Akyildiz Senem , Ruppert Jan G. , Graeb Michael , Bernkopf Dominic B. , Hadjihannas Michel V. , Behrens Jürgen
Published: November 2013

The adenomatous polyposis coli (APC) membrane recruitment (Amer) family proteins Amer1/Wilms tumour gene on the X chromosome and Amer2 are binding partners of the APC tumour suppressor protein, and act as negative regulators in the Wnt signalling cascade. So far, nothing has been known about the third member of the family, Amer3. Here we show that Amer3 binds to the armadillo repeat domain of APC, similarly to Amer1 and Amer2. Amer3 also binds to the Wnt pathway regulator conductin/axin2. Furthermore, we identified Amer1 as binding partner of Amer3. Whereas Amer1 and Amer2 are linked to the plasma membrane by an N‐terminal membrane localization domain, Amer3 lacks this domain. Amer3 localizes to the cytoplasm and nucleus of epithelial cells, and this is dependent on specific nuclear import and export sequences. Functionally, exogenous Amer3 enhances the expression of a β‐catenin/T‐cell factor‐dependent reporter gene, and knockdown of endogenous Amer3 reduces Wnt target gene expression in colorectal cancer cells. Thus, Amer3 acts as an activator of Wnt signalling, in contrast to Amer1 and Amer2, which are inhibitors, suggesting a nonredundant role of Amer proteins in the regulation of this pathway. Our data, together with those of previous studies, provide a comprehensive picture of similarities and differences within the Amer protein family.

Structured digital abstract

AMER3 physically interacts with APC by two hybrid (1, 2).

AMER3 physically interacts with APC by anti tag coimmunoprecipitation (1, 2, 3).

APC physically interacts with AMER3 by anti bait coimmunoprecipitation (View interaction).

AMER3 physically interacts with APC, AMER1 and Conductin by anti bait coimmunoprecipitation (View interaction).

AMER3 physically interacts with AMER1 by anti tag coimmunoprecipitation (1, 2).

AMER3 and APC colocalize by fluorescence microscopy (View interaction).

Conductin physically interacts with AMER3 by anti tag coimmunoprecipitation (View interaction).

APC physically interacts with AMER2 by anti tag coimmunoprecipitation (View interaction).

Conductin physically interacts with AMER3 by anti tag coimmunoprecipitation (1, 2).

AMER1 and AMER3 colocalize by fluorescence microscopy (View interaction).

APC physically interacts with AMER1 by anti tag coimmunoprecipitation (View interaction).
Measuring global oral proficiency in SLA research: A new elicited imitation test of L2 Chinese
Authors: Wu Shu‐Ling , Ortega Lourdes
Published: November 2013

This article describes a new Chinese Elicited Imitation Test (EIT) and reports on a study that investigated the degree to which it functions as a tool that can be used in second language acquisition research to gauge global second language (L2) oral proficiency. Eighty L2 Chinese learners, sampled from two university curricular levels so as to represent high and low linguistic abilities and including both heritage and foreign language learners, participated in the study by completing the EIT as well as an oral narrative task and a background questionnaire. The results suggest that the new Chinese EIT can help measure overall oral linguistic proficiency in L2 Chinese for a variety of research purposes.
Primary and rescue immune tolerance induction in children and adults: a multicentre international study with a VWF‐containing plasma‐derived FVIII concentrate
Authors: Oldenburg J. , Jiménez‐Yuste V. , Peiró‐Jordán R. , Aledort L. M. , Santagostino E.
Published: November 2013

Most studies on immune tolerance induction (ITI) therapy in haemophilia A patients are focused on primary ITI in children. Here we report on the ITI outcome in a large retrospective cohort, including adults and patients with rescue ITI, treated with a pdFVIII/VWF concentrate. Retrospective data from haemophilic patients (FVIII< 2%) with inhibitors from 22 centres in Spain, Italy and Germany, who underwent primary or rescue ITI with pdFVIII/VWF concentrate, were collected. Complete success (CS), partial success (PS) and failure were defined based on the criteria of the consensus recommendations of the 2006 International ITI Workshop. A total of 41 cases of primary ITI (32 children and 9 adults) and 19 cases of rescue ITI (17 children and 2 adults) were evaluated. Success (CS+PS) rate of 87% was achieved in primary ITI and 74% in the higher risk profile of rescue ITI. Eight of nine (85%) patients with poorest prognosis (three or more of the known risk factors of poor response to ITI) achieved success (CS+PS). CS of 100% was observed in eight primary ITI patients with titre at start of ITI ≤2.5 BU and inhibitor peak ≤25 BU. The favourable response rates in primary and rescue ITI in children and in adult patients, even in the presence of poor prognostic factors, should be encouraged for broadening the indication of immune tolerance therapy in haemophilia A patients with inhibitors.
Social determinants and health‐related dimensions of quality of life in adult patients with haemophilia
Authors: Dolatkhah R. , Fakhari A. , Pezeshki M. Z. , Shabanlouei R. , Tavassoli N. , Gholchin M.
Published: November 2013

The availability of safe and effective factor replacement therapies, in persons with haemophilia (PWH), has in some countries answered the basic need for treatment of these patients. The findings suggest that adult patients who have always been on prophylaxis reported significantly better physical functioning, and thus better quality of life. This study is designed to evaluate the QoL in adult PWH, by focusing on social determinants of QoL and their relationship with health‐related dimensions, in Tabriz, Iran. The survey instrument was a self‐report 36 items questionnaire, ‘A36 Hemofilia – QoL’, which is a disease‐specific questionnaire for the assessment of the health‐related QoL in adults living with haemophilia. A total of 100 haemophilia A and B patients, aged over 17 years participated in this study within 1 year. QoL total score was 71.88 (±26.89 SD). Patients who treat in our Hemophilia Treatment Center, had better QoL score (P = 0.000), and education has a significant impact on the social aspects of QoL (P = 0.18). The QoL was very poor in urban area in contrast to patients who lived in the city (54.45 vs. 74.21 respectively). Single patients have a better QoL than married patients (76.56 vs. 68.50 respectively). Our results showed that low education and lack of awareness of the diseases among PWH lead to reduce of QoL and more disease complications. More and wider treatment and psychological care for improving quality of life of these patients are seriously recommended.
Peripheral blood T lymphocytes in systemic vasculitis: increased T cell receptor Vβ2 gene usage in microscopic polyarteritis
Authors: SIMPSON I J , SKINNER M A , GEURSEN A , PEAKE J S , ABBOTT W G , FRASER J D , LOCKWOOD C M , TAN P L J
Published: November 2013

Antigen recognition by T lymphocytes is mediated by cell surface receptors. T cell specificity depends on the variable, diversity and junctional (VDJ) regions of the α and β polypeptide chains of the T cell receptor (TCR). The expression of the variable region genes of the β chain (Vβ) has been analysed to study the involvement of peripheral blood T cells in systemic vasculitis. RNA was extracted from peripheral blood lymphocytes of 12 patients with microscopic polyarteritis, 10 with Wegener's granulomatosis, six with unclassified vasculitis, and 28 healthy age- and sex-matched individuals. Complementary DNA was made from RNA and amplified by the anchored polymerase chain reaction (PCR) using redundant oligonucleotide primers for the TCR Vβ genes. To determine if the dominant usage of a Vβ gene family reflected the presence of particular T cell clones, cDNA was amplified with primers for the specific Vβ gene family. The product was screened for sequence homogeneity by single-stranded conformational polymorphism (SSCP) and cloned to sequence the adjoining TCR (Dβ)Jβ region. A significant increase in the mean percentage expression of the Vβ 2.1 gene was seen in vasculitis patients (11·4+1·0% (mean + s.e.m.)) compared with controls (6·6 + 0·6%; P < 0·003). The most marked increase was seen in microscopic polyarteritis (13·9 + 1·7%; P < 0·0001). There were also increases in the expression of Vβ3, 13 and 14 in peripheral blood of vasculitis patients compared with controls. SSCP analysis of Vβ 2.1 amplified products indicated the presence of oligoclonal bands in a smaller proportion of patients (8/27) than controls (12/28). There was no strong evidence for the conservation of the TCR Vβ 2.1 junctional region sequence data from a sample group of three patients with oligoclonal bands. Thus, a subset of patients with systemic vasculitis, particularly those with microscopic polyarteritis, have increased TCR Vβ 2.1 gene expression in their peripheral blood T cell repertoire. As superantigens binding Vβ 2.1 are postulated to activate T cells with diverse CDR3 sequences, it is proposed that a superantigen is involved in the immunopathogenesis of vasculitis.
Glucocorticoid-mediated immunomodulation: hydrocortisone enhances immunosuppressive endogenous retroviral protein (p15E) expression in mouse immune cells
Authors: FIEGL M , STRASSER-WOZAK E , GELEY S , GSUR A , DRACH J , KOFLER R
Published: November 2013

To define glucocorticoid (GC)-regulated genes contributing to the anti-inflammatory and immunosuppressive effects of GC, previous work from our laboratory revealed up-regulation of transcripts from endogenous type B mouse mammary tumour virus (Mtv) and type C murine leukaemia virus (Emv) loci by high dose GC treatment of P388D1 macrophage-like cells. This study demonstrates enhancement of expression from Mtv and Emv loci in P388D1 cells by more physiological hydrocortisone concentrations (1 μM), and shows direct transcriptional mode of regulation by blocking GC-mediated signal transduction at different levels. Furthermore, we found up-regulation of Emv mRNA steady-state levels in murine lymphoid lineage cells (T-like EL4 and BW5147 cells; B-like X63 cells) upon GC treatment. The Emv transcripts shown by us to be GC-up-regulated encode for the transmembrane envelope protein TM/p15E which is highly conserved in several retroviruses. TM/p15E and the p15E-like products found in humans exert immunosuppressive effects in different test systems. Thus, our findings raise the possibility that immunomodulation by GC might be mediated in part by enhanced expression of p15E(-like) products.
A field study of the role of nurses in advocating for safe practice in hospitals
Authors: Choi Sandy Pin‐pin , Cheung Kin , Pang Samantha Mei‐che
Published: November 2013

Aim

To explicate nurses' role and the underlying processes involved in advocating for safe practice in hospitals.

Background

Nurses' role as patient advocates in safeguarding patients' interests and well‐being is constantly upheld. As previous studies have fallen short in delineating the processes of how and in what conditions the patient advocate role is operationalized, this study was conducted to fill the evidence gap through examining nurses' advocacy role and practices in real clinical contexts.

Design

A field study approach that involved multiple methods of data collection was adopted.

Methods

This study was conducted from February 2010–March 2011 in four medical units in two public hospitals in Hong Kong. Empirical data were generated from weekly field observations, review of relevant documents and individual semi‐structured interviews with 28 nurses and were then analysed through a comparative analysis process.

Results

Nurses play an integral role in ensuring safe practice in hospitals through mitigating risk arising from sudden changes in patients' health conditions and the hospitalization process and correcting near‐misses for co‐workers to prevent harm. The modelling of expert nurses and team‐based learning emerged as essential factors facilitating the development of nurses' advocacy role and practices. The state of ‘limited advocacy’, as characterized by the adoption of disempowering and coercive measures to ensure patient safety, clearly indicates a need to re‐examine the concept of advocacy in contemporary health care.

Conclusion

The findings contribute to a more complete understanding of nurses' advocacy role and practices, which have a significant bearing on patient safety.
Long‐Term High‐Resolution Radar Rainfall Fields for Urban Hydrology
Authors: Wright Daniel B. , Smith James A. , Villarini Gabriele , Baeck Mary Lynn
Published: November 2013

Accurate records of high‐resolution rainfall fields are essential in urban hydrology, and are lacking in many areas. We develop a high‐resolution (15 min, 1 km2) radar rainfall data set for Charlotte, North Carolina during the 2001‐2010 period using the Hydro‐NEXRAD system with radar reflectivity from the National Weather Service Weather Surveillance Radar 1988 Doppler weather radar located in Greer, South Carolina. A dense network of 71 rain gages is used for estimating and correcting radar rainfall biases. Radar rainfall estimates with daily mean field bias (MFB) correction accurately capture the spatial and temporal structure of extreme rainfall, but bias correction at finer timescales can improve cold‐season and tropical cyclone rainfall estimates. Approximately 25 rain gages are sufficient to estimate daily MFB over an area of at least 2,500 km2, suggesting that robust bias correction is feasible in many urban areas. Conditional (rain‐rate dependent) bias can be removed, but at the expense of other performance criteria such as mean square error. Hydro‐NEXRAD radar rainfall estimates are also compared with the coarser resolution (hourly, 16 km2) Stage IV operational rainfall product. Stage IV is adequate for flood water balance studies but is insufficient for applications such as urban flood modeling, in which the temporal and spatial scales of relevant hydrologic processes are short. We recommend the increased use of high‐resolution radar rainfall fields in urban hydrology.
Telocytes in Crohn's disease
Authors: Milia Anna Franca , Ruffo Martina , Manetti Mirko , Rosa Irene , Conte Dalila , Fazi Marilena , Messerini Luca , Ibba‐Manneschi Lidia
Published: November 2013

Crohn's disease (CD) is a relapsing chronic inflammatory disorder that may involve all the gastrointestinal tract with a prevalence of terminal ileum. Intestinal lesions have a characteristic discontinuous and segmental distribution and may affect all layers of the gut wall. Telocytes (TC), a peculiar type of stromal cells, have been recently identified in a variety of tissues and organs, including gastrointestinal tract of humans and mammals. Several roles have been proposed for TC, including mechanical support, spatial relationships with different cell types, intercellular signalling and modulation of intestinal motility. The aim of our study was to investigate the presence and distribution of TC in disease‐affected and ‐unaffected ileal specimens from CD patients compared with controls. TC were identified by CD34/PDGFRα immunohistochemistry. In affected CD specimens TC disappeared, particularly where fibrosis and architectural derangement of the intestinal wall were observed. In the thickened muscularis mucosae and submucosa, few TC entrapped in the fibrotic extracellular matrix were found. A discontinuous network of TC was present around smooth muscle bundles, ganglia and enteric strands in the altered muscularis propria. At the myenteric plexus, the loss of TC network was paralleled by the loss of interstitial cells of Cajal network. In the unaffected CD specimens, TC were preserved in their distribution. Our results suggest that in CD the loss of TC might have important pathophysiological implications contributing to the architectural derangement of the intestinal wall and gut dysmotility. Further functional studies are necessary to better clarify the role of TC loss in CD pathophysiology.
Nutritional factors (nutritional aspects) in biliary disorders: Bile acid and lipid metabolism in gallstone diseases and pancreaticobiliary maljunction
Authors: Tazuma Susumu , Kanno Keishi , Sugiyama Akiko , Kishikawa Nobusuke
Published: November 2013

Nutritional factors play a key role in the pathogenesis of biliary diseases such as gallstones and pancreaticobiliary maljunction. Gallstones are primarily classified into cholesterol stone and pigment stone according to the major composition. Cholesterol gallstone formation is very likely based upon supersaturated bile formation, and pigment stones are formed in bile rich in bilirubin. Thus, defects of hepatic metabolism of lipids and organic anions lead to biliary stones. Here, the recent understanding of cholesterol gallstone pathogenesis is elaborated. On the other hand, there is another important link of biliary lipid degradation to serious biliary disease, namely pancreaticobiliary maljunction. Lysophosphatidylcholine (lysoPC), a derivative of phosphatidylcholine hydrolysis by phospholipase A2, is a highly abundant bioactive lipid mediator present in circulation as well as in bile. Increases in bile of lysoPC and phospholipase A2 have been reported in pancreaticobiliary maljunction and considered to be the major risk factor for biliary tract cancers. Further, oxidized fatty acids have been established as a potent ligand for G2A, a member of G protein‐coupled receptor family that mediates a diverse array of biological processes including cell growth and apoptosis. Thus, both of lysoPC and free fatty acids are supposed to play an important role through G2A in biliary inflammation and carcinogenesis of pancreaticobiliary maljunction. Taken together, nutritional factors, especially lipid compounds, are seemingly crucial in the pathogenesis of biliary diseases, and such a causal relationship is reviewed by mainly authors’ previous publications.
Treatment of non‐alcoholic fatty liver disease
Authors: Takei Yoshiyuki
Published: November 2013

Treatment of non‐alcoholic fatty liver disease involves not only the management of the liver disease itself but the associated metabolic risk factors as well. However, no single treatment has been shown to be universally efficacious. Effective treatment regimens directed at both decreasing insulin resistance as well as the processes of necroinflammation have been investigated and include lifestyle intervention, surgical treatment, and pharmacotherapy. Lifestyle modification, weight loss, and physical activity represent the cornerstone of treatment. Given the important role of insulin resistance in the pathophysiology of non‐alcoholic steatohepatitis, thiazolidinediones are used to improve insulin resistance. Ongoing large multicenter studies will provide information about long‐term efficacy and safety of pioglitazone in patients with non‐alcoholic steatohepatitis. Many other medications have shown promising results in the investigations using animal models and in preliminary pilot studies. Because the sample sizes of these studies were relatively small and the durations were short, further validation is required.
Role of the gut microbiota in human nutrition and metabolism
Authors: Ramakrishna Balakrishnan S
Published: November 2013

The human gastrointestinal tract harbors trillions of bacteria, most of which are commensal and have adapted over time to the milieu of the human colon. Their many metabolic interactions with each other, and with the human host, influence human nutrition and metabolism in diverse ways. Our understanding of these influences has come through breakthroughs in the molecular profiling of the phylogeny and the metabolic capacities of the microbiota. The gut microbiota produce a variety of nutrients including short‐chain fatty acids, B vitamins, and vitamin K. Because of their ability to interact with receptors on epithelial cells and subepithelial cells, the microbiota also release a number of cellular factors that influence human metabolism. Thus, they have potential roles in the pathogenesis of metabolic syndrome, diabetes, non‐alcoholic fatty liver disease, and cognition, which extend well beyond their traditional contribution to nutrition. This review explores the roles of the gut microbiota in human nutrition and metabolism, and the putative mechanisms underlying these effects.
The effect of simvastatin on systemic inflammation and endothelial dysfunction induced by periodontitis
Authors: Machado W. M. , Prestes A. P. , Costa T. P. , Mendes R. T. , Olchanheski L. R. , Sordi R. , Otuki M. F. , Fávero G. M. , Vellosa J. C. R. , Santos F. A. , Fernandes D.
Published: November 2013

Background and Objective

It has been demonstrated that periodontitis induces systemic inflammation, which may impair endothelial function leading to increased cardiovascular risk. The aim of this study was to evaluate the effect of simvastatin on systemic inflammatory markers and endothelial dysfunction induced by periodontitis.

Material and Methods

Wistar rats were subjected to ligature‐induced experimental periodontitis. Eight days after the procedure, the ligature and sham groups were randomly assigned to receive simvastatin or vehicle once a day until the 14th day, when the effects of acetylcholine and sodium nitroprusside on blood pressure were evaluated. Blood samples were collected and evaluated for plasma interleukin‐6C, ‐reactive protein and lipids. The maxilla and mandible were removed for bone loss analysis.

Results

Simvastatin treatment reduced systemic inflammation and endothelial dysfunction induced by periodontitis. Furthermore, simvastatin improved the blood lipid profile and reduced alveolar bone loss.

Conclusion

Simvastatin treatment, in addition to the improvement on serum lipid profile, may reduce other predictors of cardiovascular events associated with periodontitis.
The Efficacy and Safety of Ospemifene in Treating Dyspareunia Associated with Postmenopausal Vulvar and Vaginal Atrophy: A Systematic Review and Meta-Analysis
Authors: Cui Yuanshan , Zong Huantao , Yan Huilei , Li Nan , Zhang Yong
Published: November 2013

Introduction

Ospemifene, a novel selective estrogen receptor modulator, has been developed for the treatment of vulvovaginal atrophy and dyspareunia in postmenopausal women.

Aim

We carried out a systematic review and meta-analysis to assess the efficacy and safety of the drug for treating dyspareunia associated with postmenopausal vulvar and vaginal atrophy.

Methods

A literature review was performed to identify all published randomized double-blind, placebo-controlled trials of ospemifene for the treatment of vulvovaginal atrophy and dyspareunia. The search included the following databases: MEDLINE, EMBASE, and the Cochrane Controlled Trials Register. The reference lists of the retrieved studies were also investigated. A systematic review and meta-analysis was conducted.

Main Outcome Measures

Six publications involving a total of 1,772 patients were used in the analysis, including three randomized controlled trials (RCTs) that were short-term (12 weeks) comparisons of ospemifene with placebo and three RCTs that were long-term (1 year) comparisons of ospemifene with placebo.

Results

For the comparison of short-term ospemifene with placebo, parabasal cells (the standardized mean difference [SMD] = −37.5, 95% confidence interval [CI] = −41.83 to −33.17, P < 0.00001), superficial cells (SMD = 9.24, 95% CI = 7.70 to 10.79, P < 0.00001), vaginal PH (SMD = −0.89, 95% CI = −0.98 to −0.80, P = 0.00001), and dyspareunia (SMD = −0.37, 95% CI = −0.43 to −0.30, P = 0.00001) indicated that ospemifene was more effective than the placebo. For the comparison of long-term ospemifene with placebo, endometrial thickness (SMD = 0.90, 95% CI = 0.58 to 1.23, P = 0.00001), treatment emergent adverse event, discontinuations due to adverse event, and serious adverse event indicated that ospemifene was generally safe.

Conclusions

This meta-analysis indicates that ospemifene to be an effective and safe treatment for dyspareunia associated with postmenopausal vulvar and vaginal atrophy.
Determinants of Sexual Activity in Four Birth Cohorts of Swedish 70-year-olds Examined 1971–2001
Authors: Beckman Nils , Waern Margda , Östling Svante , Sundh Valter , Skoog Ingmar
Published: November 2013

Introduction

Knowledge about determinants of sexual activity in older adults in the general population is limited. Human senescence has been delayed by a decade, and people are reaching old age in better health.

Aim

The aim of this study was to investigate determinants of sexual activity in four birth cohorts of non-demented 70-year-olds examined in 1971–1977 and 1992–2001.

Main Outcome Measure

The main outcome measure was sexual activity (defined as intercourse) during the past year.

Methods

The study is based on cross-sectional data from four population samples of 70-year-olds from Gothenburg, Sweden (N = 1,407) systematically sampled from the Swedish population register.

Results

In the time periods 1971–1972 and 2000–2001, sexual activity among men increased from 47% to 66%, and in women from 12% to 34%. Sexual activity was related to positive attitude toward sexuality, sexual debut before age 20, having a very happy relationship, having a physically and mentally healthy partner, self-reported good global health, interviewer-rated good mental health, being married/cohabiting, satisfaction with sleep, and drinking alcohol more than three times a week. Having an older partner, diabetes mellitus, coronary heart disease, higher physical health-sum score, and depression were related to less sexual activity. Interaction effects for birth cohort, with stronger positive associations in 1971–1972, were found for positive attitude toward sexuality, strong desire at age 20–30, premarital sexuality, having a younger partner, self-reported good global health, interviewer-rated good global mental health, overweight, and satisfaction with sleep. Having an older partner and depression showed stronger negative associations in the 1970s. Physical health-sum score showed a stronger negative association in 1992–2001.

Conclusions

We found that determinants of sexual activity in older people are numerous and varied, and change over time. It is thus important that health professionals and others take a holistic approach when dealing with sexual problems in older adults. Sexual aging should be part of health care and medical education. Clinicians should be trained to ask older patients about sexual concerns.