bluuebunny/crossref_metadata_2025 huggingface dataset:
Acute endurance exercise increases plasma membrane fatty acid transport proteins in rat and human skeletal muscle
Authors: Bradley Nicolette S. , Snook Laelie A. , Jain Swati S. , Heigenhauser George J. F. , Bonen Arend , Spriet Lawrence L.
Published: October 2011

Fatty acid transport proteins are present on the plasma membrane and are involved in the uptake of long-chain fatty acids into skeletal muscle. The present study determined whether acute endurance exercise increased the plasma membrane content of fatty acid transport proteins in rat and human skeletal muscle and whether the increase was accompanied by an increase in long-chain fatty acid transport in rat skeletal muscle. Sixteen subjects cycled for 120 min at ∼60 ± 2% V̇o2peak. Two skeletal muscle biopsies were taken at rest and again following cycling. In a parallel study, eight Sprague-Dawley rats ran for 120 min at 20 m/min, whereas eight rats acted as nonrunning controls. Giant sarcolemmal vesicles were prepared, and protein content of FAT/CD36 and FABPpm was measured in human and rat vesicles and whole muscle homogenate. Palmitate uptake was measured in the rat vesicles. In human muscle, plasma membrane FAT/CD36 and FABPpm protein contents increased 75 and 20%, respectively, following 120 min of exercise. In rat muscle, plasma membrane FAT/CD36 and FABPpm increased 20 and 30%, respectively, and correlated with a 30% increase in palmitate transport following 120 min of running. These data suggest that the translocation of FAT/CD36 and FABPpm to the plasma membrane in rat skeletal muscle is related to the increase in fatty acid transport and oxidation that occurs with endurance running. This study is also the first to demonstrate that endurance cycling induces an increase in plasma membrane FAT/CD36 and FABPpm content in human skeletal muscle, which is predicted to increase fatty acid transport.
Hirsutism, virilism, polycystic ovarian disease, and the steroid-gonadotropin-feedback system: a career retrospective
Authors: Mahesh Virendra B.
Published: October 2011

This career retrospective describes how the initial work on the mechanism of hormone action provided the tools for the study of hirsutism, virilism, and polycystic ovarian disease. After excessive ovarian and or adrenal androgen secretion in polycystic ovarian disease had been established, the question whether the disease was genetic or acquired, methods to manage hirsutism and methods for the induction of ovulation were addressed. Recognizing that steroid gonadotropin feedback was an important regulatory factor, initial studies were done on the secretion of LH and FSH in the ovulatory cycle. This was followed by the study of basic mechanisms of steroid-gonadotropin feedback system, using castration and steroid replacement and the events surrounding the natural onset of puberty. Studies in ovariectomized rats showed that progesterone was a pivotal enhancer of estrogen-induced gonadotropin release, thus accounting for the preovulatory gonadotropin surge. The effects of progesterone were manifested by depletion of the occupied estrogen receptors of the anterior pituitary, release of hypothalamic LHRH, and inhibition of enzymes that degrade LHRH. Progesterone also promoted the synthesis of FSH in the pituitary. The 3α,5α-reduced metabolite of progesterone brought about selective LH release and acted using the GABAAreceptor system. The 5α-reduced metabolite of progesterone brought about selective FSH release; the ability of progesterone to bring about FSH release was dependent on its 5α-reduction. The GnRH neuron does not have steroid receptors; the steroid effect was shown to be mediated through the excitatory amino acid glutamate, which in turn stimulated nitric oxide. These observations led to the replacement of the long-accepted belief that ovarian steroids acted directly on the GnRH neuron by the novel concept that the steroid feedback effect was exerted at the glutamatergic neuron, which in turn regulated the GnRH neuron. The neuroprotective effects of estrogens on brain neurons are of considerable interest.
Defining the differential sensitivity to norepinephrine and angiotensin II in the ovine uterine vasculature
Authors: Rosenfeld Charles R. , DeSpain Kevin , Liu Xiao-tie
Published: October 2011

The intact ovine uterine vascular bed (UVB) is sensitive to α-agonists and refractory to angiotensin II (ANG II) during pregnancy; the converse occurs in the systemic circulation. The mechanism(s) responsible for these differences in uterine sensitivity are unclear and may reflect predominance of nonconstricting AT2 receptors (AT2R) in uterine vascular smooth muscle (UVSM). The contribution of the placental vasculature also is unclear. Third generation and precaruncular/placental arteries from nonpregnant ( n = 16) and term pregnant ( n = 23) sheep were used to study contraction responses to KCl, norepinephrine (NE), and ANG II (with/without ATR specific inhibitors) and determine UVSM ATR subtype expression and contractile protein content. KCl and NE increased third generation and precaruncular/placental UVSM contractions in a dose- and pregnancy-dependent manner ( P ≤ 0.001). ANG II only elicited modest contractions in third generation pregnant UVSM ( P = 0.04) and none in precaruncular/placental UVSM. Moreover, compared with KCl and NE, ANG II contractions were diminished ≥ 5-fold. Whereas KCl and ANG II contracted third generation>>precaruncular/placental UVSM, NE-induced contractions were similar throughout the UVB. However, each agonist increased third generation contractions ≥ 2-fold at term, paralleling increased actin/myosin and cellular protein content ( P ≤ 0.01). UVSM AT1R and AT2R expression was similar throughout the UVB and unchanged during pregnancy ( P > 0.1). AT1R inhibition blocked ANG II-mediated contractions; AT2R blockade, however, did not enhance contractions. AT2R predominate throughout the UVB of nonpregnant and pregnant sheep, contributing to an inherent refractoriness to ANG II. In contrast, NE elicits enhanced contractility throughout the ovine UVB that exceeds ANG II and increases further at term pregnancy.
Does a pitch center exist in auditory cortex?
Authors: Bendor Daniel
Published: November 2011

Pitch perception is an important component of hearing, allowing us to appreciate melodies and harmonies as well as recognize prosodic cues in speech. Multiple studies over the last decade have suggested that pitch is represented by a pitch-processing center in auditory cortex. However, recent data (Barker D, Plack CJ, Hall DA. Cereb Cortex. In press; Hall DA, Plack CJ. Cereb Cortex 19: 576–585, 2009) now challenge these previous claims of a human “pitch center.”
In VivoandIn VitroStudy of a Polylactide-Fiber-Reinforcedβ-Tricalcium Phosphate Composite Cage in an Ovine Anterior Cervical Intercorporal Fusion Model
Authors: Frantzén Janek , Pälli Aliisa , Kotilainen Esa , Heino Harri , Mannerström Bettina , Huhtala Heini , Kuokkanen Hannu , Sándor George K. , Leino Kari , Röyttä Matias , Parkkola Riitta , Suuronen Riitta , Miettinen Susanna , Aro Hannu T. , Haimi Suvi
Published: October 2011

A poly-70L/30DL-lactide (PLA70)–β-tricalcium phosphate (β-TCP) composite implant reinforced by continuous PLA-96L/4D-lactide (PLA96) fibers was designed forin vivospinal fusion. The pilot study was performed with four sheep, using titanium cage implants as controls. The composite implants failed to direct bone growth as desired, whereas the bone contact and the proper integration were evident with controls 6 months after implantation. Therefore, the PLA70/β-TCP composite matrix material was further analyzed in thein vitroexperiment by human and ovine adipose stem cells (hASCs and oASCs). The composites proved to be biocompatible as confirmed by live/dead assay. The proliferation rate of oASCs was higher than that of hASCs at all times during the 28 d culture period. Furthermore, the composites had only a minor osteogenic effect on oASCs, whereas the hASC osteogenesis on PLA70/β-TCP composites was evident. In conclusion, the composite implant material can be applied with hASCs for tissue engineering but not be evaluatedin vivowith sheep.
Gold Nanoparticles: Promising Nanomaterials for the Diagnosis of Cancer and HIV/AIDS
Authors: Kumar Anil , Mazinder Boruah Bhargavi , Liang Xing-Jie
Published: October 2011

Gold nanoparticles (AuNPs) are currently playing a significant role for human welfare in the field of clinical diagnosis as well as several biomedical applications. More and more research shows thatAuNPs-based technologies are becoming promising approaches in cancer research and AIDS treatment. In this paper, we have focused mainly on the exploitation of unique and characteristic properties ofAuNPs such as surface plasmon resonance (SPR), surface enhance Raman scattering (SERS), magnetic properties (MRI), and fluorescence behavior shown upon conjugation with biological and biocompatible ligands. These properties find wide prevalence in biodiagnostics like plasmon-based labeling and imaging, enzyme-linked immunosorbant assay (ELISA), and electrochemical-based methods that can pave the way for developing novel techniques towards diagnosis and therapy of cancer and human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS).
Feasibility of Batch Reactive Distillation with Equilibrium‐Limited Consecutive Reactions in Rectifier, Stripper, or Middle‐Vessel Column
Authors: Lukács T. , Stéger C. , Rév E. , Meyer M. , Lelkes Z.
Published: October 2011

A general overall feasibility methodology of batch reactive distillation of multireaction systems is developed to study all the possible configurations of batch reactive distillation. The general model equations are derived for multireaction system with any number of chemical equilibrium‐limited reactions and for any number of components. The present methodology is demonstrated with the detailed study of the transesterification of dimethyl carbonate in two reversible cascade reactions in batch reactive distillation process. Pure methanol is produced as distillate, and pure diethyl carbonate is produced at the bottom simultaneously in middle‐vessel column; in each section, continuous feeding of ethanol is necessary. The results of feasibility study are successfully validated by rigorous simulations.
Repetitive Complete Molar Pregnancy in a 54-Year-Old Patient in a Time Distance of Eighteen Years from the First Incident: Case Report and Mini Review
Authors: Oikonomidis Polychronis , Pergialiotis Basileios , Pitsouni Elina , Natsis Stavros , Lagkadas Antonios , Giannakopoulos Konstantinos
Published: October 2011

We report a case of complete hydatidiform mole in a 54-year-old patient referred to Gynecology department of General Hospital of Athens “Laiko”, with history of previous molar pregnancy at the age of thirty-six. Our purpose was to indicate the advanced maternal age beside the long recurrence distance of the disease, which was eighteen years after the first molar pregnancy. Our diagnostic approach was through measurement of serum beta-human chorionic gonadotropin (β-HCG) and pelvic ultrasound evaluation, and the chosen therapeutic approach was abdominal hysterectomy and bilateral salpingoophorectomy.
PDE-5 Inhibitors in Scleroderma Raynaud Phenomenon and Digital Ulcers: Current Status of Clinical Trials
Authors: Impens Ann J. , Phillips Kristine , Schiopu Elena
Published: November 2011

Systemic sclerosis- (SSc-) related vasculopathy, as manifested by Raynaud's Phenomenon (RP) and digital ulcers (DUs), is associated with significant impairment of the quality of life and morbidity. The current vasoactive approach for SSc-RP, although employing vasodilators, is entirely off-label. PDE-5 inhibitors improve peripheral circulation, are well tolerated, and are widely used for various forms of constrictive vasculopathies. This class of medications has become one of the first lines of treatment of SSc-RP and SSc-DUs among rheumatologists that routinely treat SSc patients. Due to the lack of robust randomized clinical trials of PDE-5 inhibitors in SSc-RP/DUs, the PDE-5 inhibitors have not been FDA approved for these particular indications, which constitutes a significant barrier to prescribing this category of drugs. This paper reviews the current state of evidence-based knowledge in SSc-related vasculopathy and the use of PDE-5 inhibitors.
Joint Behaviour of Semirecursive Kernel Estimators of the Location and of the Size of the Mode of a Probability Density Function
Authors: Mokkadem Abdelkader , Pelletier Mariane , Thiam Baba
Published: October 2011

Let θ and μ denote the location and the size of the mode of a probability density. We study the joint convergence rates of semirecursive kernel estimators of θ and μ. We show how the estimation of the size of the mode allows measuring the relevance of the estimation of its location. We also enlighten that, beyond their computational advantage on nonrecursive estimators, the semirecursive estimators are preferable to use for the construction of confidence regions.
Is There a Regulatory Role of Immunoglobulins on Tissue Forming Cells Relevant in Chronic Inflammatory Lung Diseases?
Authors: Roth Michael
Published: November 2011

Epithelial cells, fibroblasts and smooth muscle cells together form and give structure to the airway wall. These three tissue forming cell types are structure giving elements and participate in the immune response to inhaled particles including allergens and dust. All three cell types actively contribute to the pathogenesis of chronic inflammatory lung diseases such as asthma and chronic obstructive pulmonary disease (COPD). Tissue forming cells respond directly to allergens through activated immunoglobulins which then bind to their corresponding cell surface receptors. It was only recently reported that allergens and particles traffic through epithelial cells without modification and bind to the immunoglobulin receptors on the surface of sub-epithelial mesenchymal cells. In consequence, these cells secrete pro-inflammatory cytokines, thereby extending the local inflammation. Furthermore, activation of the immunoglobulin receptors can induce proliferation and tissue remodeling of the tissue forming cells. New studies using anti-IgE antibody therapy indicate that the inhibition of immunoglobulins reduces the response of tissue forming cells. The unmeasured questions are: (i) why do tissue forming cells express immunoglobulin receptors and (ii) do tissue forming cells process immunoglobulin receptor bound particles? The focus of this review is to provide an overview of the expression and function of various immunoglobulin receptors.
A Note on Parabolic Liouville Theorems and Blow‐Up Rates for a Higher‐Order Semilinear Parabolic System
Authors: Cai Guocai , Pan Hongjing , Xing Ruixiang
Published: November 2011

We improve some results of Pan and Xing (2008) and extend the exponent range in Liouville‐type theorems for some parabolic systems of inequalities with the time variable on ℝ. As an immediate application of the parabolic Liouville‐type theorems, the range of the exponent in blow‐up rates for the corresponding systems is also improved.
An Unusual Cause of Anaemia of Chronic Disease: Lisinopril-Induced Chronic Inflammatory State
Authors: Eyre Toby , Van-Hamel-Parsons Victoria , Wang Lai Mun , Hughes Kathryn A. , Littlewood Timothy J.
Published: October 2011

We report the case of a patient with severe systemic symptoms (weight loss, malaise, and anorexia), eosinophilic oesophagitis, and raised inflammatory markers coinciding with the use of lisinopril. The onset of symptoms occurred after the administration of lisinopril and resolved shortly after cessation of the medication. Despite thorough investigation, no other cause of the systemic inflammation and anaemia of chronic disease was found. “Drug rash with eosinophilia and systemic symptoms” (DRESSs) syndrome describes a potentially serious multiorgan inflammatory response to certain classes of drugs; this includes the use of ACE inhibitors. Although this patient did not meet strict criteria for DRESSs, the subacute inflammatory syndrome with eosinophilic organ infiltration bears similar features. ACE inhibitors should be considered in the differential diagnosis in patients with nonspecific systemic inflammation and anaemia of chronic disease where no other cause is found.
The Coexistence of an Intrasellar Adenoma, Lymphocytic Hypophysitis, and Primary Pituitary Lymphoma in a Patient with Acromegaly
Authors: Martinez Jose Hernan , Davila Martinez Mariel , Mercado de Gorgola Marcos , Montalvo Luis F. , Tome Jaime E.
Published: October 2011

The concomitant presence of three histopathologically different entities in the pituitary gland is a rare occurrence. Most publications identify at least two distinct pathologies, mainly, a pituitary adenoma coexisting with a second intrasellar lesion. We present a case of a 71-year-old female referred for evaluation and treatment of acromegaly. Questioning revealed she was experiencing facial palsy, visual disturbances, and syncopal spells for several weeks. When laboratory evaluation showed elevated somatomedin (IGF-I) levels and an oral glucose tolerance test failed to demonstrate any suppression of her growth hormone (GH) values, an MRI of the pituitary revealed a sellar mass. A presumptive diagnosis of pituitary adenoma was established. The patient underwent transsphenoidal resection of the sellar mass, which proved to be a large B-cell lymphoma (Stage I-E) associated with areas of adenoma and lymphocytic hypophysitis.
Leukocyte Adhesion Molecules in Diabetic Retinopathy
Authors: Noda Kousuke , Nakao Shintaro , Ishida Susumu , Ishibashi Tatsuro
Published: November 2011

Diabetes is a systemic disease that causes a number of metabolic and physiologic abnormalities. One of the major microvascular complications of diabetes is diabetic retinopathy (DR), a leading cause of blindness in people over age 50. The mechanisms underlying the development of DR are not fully understood; however, extensive studies have recently implicated chronic, low-grade inflammation in the pathophysiology of DR. During inflammation leukocytes undergo sequential adhesive interactions with endothelial cells to migrate into the inflamed tissues, a process known as the “leukocyte recruitment cascade” which is orchestrated by precise adhesion molecule expression on the cell surface of leukocytes and the endothelium. This paper summarizes the recent clinical and preclinical works on the roles of leukocyte adhesion molecules in DR.
Immunomonitoring Results of a Phase II/III Study of Malignant Ascites Patients Treated with the Trifunctional Antibody Catumaxomab (Anti-EpCAM × Anti-CD3)
Authors: Jäger Michael , Schoberth Alexandra , Ruf Peter , Hess Juergen , Hennig Michael , Schmalfeldt Barbara , Wimberger Pauline , Ströhlein Michael , Theissen Bettina , Heiss Markus M. , Lindhofer Horst
Published: November 2011

Patients with malignant ascites secondary to primary carcinomas benefit from intraperitoneal therapy with the trifunctional antibody catumaxomab (anti-EpCAM × anti-CD3). Here, we report the analysis of peritoneal fluid samples from 258 patients with malignant ascites randomized to catumaxomab or control groups to investigate the molecular effects of catumaxomab treatment. In the catumaxomab group, tumor cell numbers and peritoneal levels of VEGF decreased, whereas the activation status of CD4+ and CD8+ T-cell populations increased more than two-fold after treatment. Notably, CD133+/EpCAM+ cancer stem cells vanished from the catumaxomab samples but not from the control samples. In vitro investigations indicated that catumaxomab eliminated tumor cells in a manner associated with release of proinflammatory Th1 cytokines. Together, our findings show that catumaxomab therapy activates peritoneal T cells and eliminates EpCAM+ tumor cells, establishing a molecular and cellular basis to understand in vivo efficacy within the immunosuppressed malignant ascites tissue microenvironment. Cancer Res; 72(1); 24–32. ©2011 AACR.
Reduced Expression of the Androgen Receptor by Third Generation of Antisense Shows Antitumor Activity in Models of Prostate Cancer
Authors: Zhang Yixian , Castaneda Stephen , Dumble Melissa , Wang Maoliang , Mileski Mary , Qu Zhengxing , Kim Steven , Shi Victoria , Kraft Patricia , Gao Ying , Pak Jenny , Sapra Puja , Bandaru Raj , Zhao Hong , Vessella Robert L. , Horak Ivan D. , Greenberger Lee M.
Published: October 2011

The androgen receptor (AR) is a member of a unique class of transcription factors because it contains a ligand-binding domain that, when activated, results in nuclear translocation and the transcriptional activation of genes associated with prostate cancer development. Although androgen deprivation therapies are effective initially for the treatment of prostate cancer, the disease eventually relapses and progresses to castration-resistant prostate cancer (CRPC). Nonetheless, the AR still plays a critical role because late-stage investigational agents that deplete testosterone (abiraterone) or block ligand binding (MDV3100) can still control tumor growth in patients with CRPC. These findings indicate that downmodulation of AR expression may provide a complementary strategy for treating CRPC. In this article, we describe a novel, locked, nucleic acid–based antisense oligonucleotide, designated EZN-4176. When administered as a single agent, EZN-4176 specifically downmodulated AR mRNA and protein, and this was coordinated with inhibition of the growth of both androgen-sensitive and CRPC tumors in vitro as well as in animal models. The effect was specific because no effect on growth was observed with a control antisense oligonucleotide that does not recognize AR mRNA, nor on tumors derived from the PC3, AR-negative, tumor cell line. In addition, EZN-4176 reduced AR luciferase reporter activity in a CRPC model derived from C4-2b cells that were implanted intratibially, indicating that the molecule may control prostate cancer that has metastasized to the bone. These data, together with the continued dependency of CRPC on the AR signaling pathway, justify the ongoing phase I evaluation of EZN-4176 in patients with CRPC. Mol Cancer Ther; 10(12); 2309–19. ©2011 AACR.
Therapeutic Potential of AZD1480 for the Treatment of Human Glioblastoma
Authors: McFarland Braden C. , Ma Jing-Yuan , Langford Catherine P. , Gillespie G. Yancey , Yu Hao , Zheng Ying , Nozell Susan E. , Huszar Dennis , Benveniste Etty N.
Published: October 2011

Aberrant activation of the Janus kinase (JAK)/signal transducer and activator of transcription (STAT) pathway has been implicated in glioblastoma (GBM) progression. To develop a therapeutic strategy to inhibit STAT-3 signaling, we have evaluated the effects of AZD1480, a pharmacologic inhibitor of JAK1 and JAK2. In this study, the in vitro efficacy of AZD1480 was tested in human and murine glioma cell lines. AZD1480 treatment effectively blocks constitutive and stimulus-induced JAK1, JAK2, and STAT-3 phosphorylation in both human and murine glioma cells, and leads to a decrease in cell proliferation and induction of apoptosis. Furthermore, we used human xenograft GBM samples as models for the study of JAK/STAT-3 signaling in vivo, because human GBM samples propagated as xenografts in nude mice retain both the hallmark genetic alterations and the invasive phenotype seen in vivo. In these xenograft tumors, JAK2 and STAT-3 are constitutively active, but levels vary among tumors, which is consistent with the heterogeneity of GBMs. AZD1480 inhibits constitutive and stimulus-induced phosphorylation of JAK2 and STAT-3 in these GBM xenograft tumors in vitro, downstream gene expression, and inhibits cell proliferation. Furthermore, AZD1480 suppresses STAT-3 activation in the glioma-initiating cell population in GBM tumors. In vivo, AZD1480 inhibits the growth of subcutaneous tumors and increases survival of mice bearing intracranial GBM tumors by inhibiting STAT-3 activity, indicating that pharmacologic inhibition of the JAK/STAT-3 pathway by AZD1480 should be considered for study in the treatment of patients with GBM tumors. Mol Cancer Ther; 10(12); 2384–93. ©2011 AACR.
Randomized, Double-Blind, Placebo-Controlled Trial of Polyphenon E in Prostate Cancer Patients before Prostatectomy: Evaluation of Potential Chemopreventive Activities
Authors: Nguyen Mike M. , Ahmann Frederick R. , Nagle Raymond B. , Hsu Chiu-Hsieh , Tangrea Joseph A. , Parnes Howard L. , Sokoloff Mitchell H. , Gretzer Matthew B. , Chow H-H. Sherry
Published: November 2011

Compelling preclinical and pilot clinical data support the role of green tea polyphenols in prostate cancer prevention. We conducted a randomized, double-blind, placebo-controlled trial of polyphenon E (enriched green tea polyphenol extract) in men with prostate cancer scheduled to undergo radical prostatectomy. The study aimed to determine the bioavailability of green tea polyphenols in prostate tissue and to measure its effects on systemic and tissue biomarkers of prostate cancer carcinogenesis. Participants received either polyphenon E (containing 800 mg epigallocatechin gallate) or placebo daily for 3 to 6 weeks before surgery. Following the intervention, green tea polyphenol levels in the prostatectomy tissue were low to undetectable. Polyphenon E intervention resulted in favorable but not statistically significant changes in serum prostate-specific antigen, serum insulin-like growth factor axis, and oxidative DNA damage in blood leukocytes. Tissue biomarkers of cell proliferation, apoptosis, and angiogenesis in the prostatectomy tissue did not differ between the treatment arms. The proportion of subjects who had a decrease in Gleason score between biopsy and surgical specimens was greater in those on polyphenon E but was not statistically significant. The study's findings of low bioavailability and/or bioaccumulation of green tea polyphenols in prostate tissue and statistically insignificant changes in systemic and tissue biomarkers from 3 to 6 weeks of administration suggests that prostate cancer preventive activity of green tea polyphenols, if occurring, may be through indirect means and/or that the activity may need to be evaluated with longer intervention durations, repeated dosing, or in patients at earlier stages of the disease. Cancer Prev Res; 5(2); 290–8. ©2011 AACR.
Crosstalk between Smad and Mitogen-Activated Protein Kinases for the Regulation of Apoptosis in Cyclosporine A- Induced Renal Tubular Injury
Authors: Iwayama Hideyuki , Sakamoto Tatsuo , Nawa Akihiro , Ueda Norishi
Published: October 2011

Background/Aims: It remains elusive whether there is a crosstalk between Smad and mitogen-activated protein kinases (MAPKs) and whether it regulates cyclosporine A (CyA)-induced apoptosis in renal proximal tubular cells (RPTCs). Methods: The effect of CyA on nuclear translocation of Smad2/3 and MAPKs (measured by Western blotting or immunofluorescence) and apoptosis (determined by Hoechst 33258 staining) was examined in HK-2 cells. Results: CyA induced apoptosis at 24 h and nuclear translocation of phosphorylated (p)-Smad2/3 at 3 h, which was continued till 24 h. CyA enhanced the expression of p-ERK at 1 h, which was continued till 24 h, and of p-p38MAPK at 1–6 h, which returned to control level at 12 h. CyA did not affect JNK. An inhibitor of ERK, PD98059, prevented CyA-induced nuclear translocation of Smad2/3 and apoptosis. An inhibitor of p38MAPK, SB202190, deteriorated CyA-induced nuclear translocation of p-Smad2/3. Epidermal growth factor (EGF) activated ERK and p38MAPK but not JNK. EGF-induced activation of MAPKs ameliorated CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Inhibition of p38MAPK but not of ERK abolished the protective effect of EGF on CyA-induced nuclear translocation of p-Smad2/3 and apoptosis. Conclusion: Crosstalk between R-Smad and p38MAPK/ERK, but not JNK differentially regulates apoptosis in CyA-induced RPTC injury.
On the Height of the Warm Core in Tropical Cyclones
Authors: Stern Daniel P. , Nolan David S.
Published: November 2011

The warm-core structure of tropical cyclones is examined in idealized simulations using the Weather Research and Forecasting (WRF) Model. The maximum perturbation temperature in a control simulation occurs in the midtroposphere (5–6 km), in contrast to the upper-tropospheric (>10 km) warm core that is widely believed to be typical. This conventional view is reassessed and found to be largely based on three case studies, and it is argued that the “typical” warm-core structure is actually not well known. In the control simulation, the height of the warm core is nearly constant over a wide range of intensities. From additional simulations in which either the size of the initial vortex or the microphysics parameterization is varied, it is shown that the warm core is generally found at 4–8 km. A secondary maximum often develops near 13–14 km but is almost always weaker than the primary warm core. It is demonstrated that microwave remote sensing instruments are of insufficient resolution to detect this midlevel warm core, and the conclusions of some studies that have utilized these instruments may not be reliable. Using simple arguments based on thermal wind balance, it is shown that the height of the warm core is not necessarily related to either the height where the vertical shear of the tangential winds is maximized or the height where the radial temperature gradient is maximized. In particular, changes in the height of the warm core need not imply changes in either the intensity of the storm or in the manner in which the winds in the eyewall decay with height.
Nutrition Screening Tools
Authors: Skipper Annalynn , Ferguson Maree , Thompson Kyle , Castellanos Victoria H. , Porcari Judy
Published: November 2011

In response to questions about tools for nutrition screening, an evidence analysis project was developed to identify the most valid and reliable nutrition screening tools for use in acute care and hospital‐based ambulatory care settings. An oversight group defined nutrition screening and literature search criteria. A trained analyst conducted structured searches of the literature for studies of nutrition screening tools according to predetermined criteria. Eleven nutrition screening tools designed to detect undernutrition in patients in acute care and hospital‐based ambulatory care were identified. Trained analysts evaluated articles for quality using criteria specified by the American Dietetic Association's Evidence Analysis Library. Members of the oversight group assigned quality grades to the tools based on the quality of the supporting evidence, including reliability and validity data. One tool, the NRS‐2002, received a grade I, and 4 tools—the Simple Two‐Part Tool, the Mini‐Nutritional Assessment–Short Form (MNA‐SF), the Malnutrition Screening Tool (MST), and Malnutrition Universal Screening Tool (MUST)—received a grade II. The MST was the only tool shown to be both valid and reliable for identifying undernutrition in the settings studied. Thus, validated nutrition screening tools that are simple and easy to use are available for application in acute care and hospital‐based ambulatory care settings.
The use of observational scales to monitor symptom control and depth of sedation in patients requiring palliative sedation: A systematic review
Authors: Brinkkemper Tijn , van Norel Arjanne M , Szadek Karolina M , Loer Stephan A , Zuurmond Wouter WA , Perez Roberto SGM
Published: November 2011

Background:

Palliative sedation is the intentional lowering of consciousness of a patient in the last phase of life to relieve suffering from refractory symptoms such as pain, delirium and dyspnoea.

Aim:

In this systematic review, we evaluated the use of monitoring scales to assess the degree of control of refractory symptoms and/or the depth of the sedation.

Design:

A database search of PubMed and Embase was performed up to January 2010 using the search terms ‘palliative sedation’ OR ‘terminal sedation’.

Data sources:

Retro- and prospective studies as well as reviews and guidelines containing information about monitoring of palliative sedation, written in the English, German or Dutch language were included.

Results:

The search yielded 264 articles of which 30 were considered relevant. Most studies focused on monitoring refractory symptoms (pain, fatigue or delirium) or the level of awareness to control the level of sedation. Four prospective and one retrospective study used scales validated in other settings: the Numeric Pain Rating Scale, the Visual Analogue Scale, the Memorial Delirium Assessment Scale, the Communication Capacity Scale and Agitation Distress Scale. Only the Community Capacity Scale was partially validated for use in a palliative sedation setting. One guideline described the use of a scale validated in another setting.

Conclusions:

A minority of studies reported the use of observational scales to monitor the effect of palliative sedation. Future studies should be focused on establishing proper instruments, most adequate frequency and timing of assessment, and interdisciplinary evaluation of sedation depth and symptom control for palliative sedation.
American Academy of Pediatrics Section on Breastfeeding
Authors: Szucs Kinga A.
Published: November 2011

The Section on Breastfeeding is one of 50 sections of the American Academy of Pediatrics. In this Physicians’ Focus, we describe the mission, vision, and activities of the Section on Breastfeeding and the benefits it provides to patients, health care professionals, and the general public. We also highlight opportunities to participate in the section.
Determinants of Voter Participation in Neighborhood Council Elections
Authors: Houston Douglas , Ong Paul M.
Published: November 2011

Neighborhood governance has emerged as an important arena for voluntary civic engagement, but little is known about how election participation varies across neighborhoods. We examined the election participation of 88 Los Angeles neighborhood councils (NCs) and found much of the variation can be explained by neighborhood demographic and socioeconomic characteristics. Consistent with the voting participation literature, NCs with a higher percentage of Hispanic or poor residents had lower participation. Contrary to expectations, NCs with a higher percentage of Asian/Pacific Islander residents or lower educational attainment had higher participation. Interestingly, the presence of nonresidential NC stakeholders, such as business owners, workers, and nonprofit organizations, was not significantly related to participation after controlling for other factors.
The effect of geometric features on multi-axial fatigue behaviour of aluminothermic rail welds
Authors: Salehi Iman , Mutton Peter , Kapoor Ajay
Published: November 2011

Aluminothermic rail welds typically exhibit a variable and often inferior performance when compared with flash butt welds. Fatigue failure as a result of surface defects or harsh geometric features in the presence of high axle loads and tractive forces gives rise to the so-called straight break and horizontal split web fractures. In this study, the reduction of fatigue performance due to geometric irregularities is investigated using a multi-axial high cycle fatigue criterion based on the critical plane concept. A thermo-structural finite element model of a track containing an aluminothermic weld is linked with a developed computer code to perform fatigue crack initiation analysis. Two geometrically different aluminothermic welds, one of which is widely used in Australian heavy haul railways, are investigated in terms of fatigue probability, to facilitate a better insight into the effect of weld collar shape and geometry at the edge of the weld collar on fatigue behaviour. The results confirm that the amount of fatigue damage is critically dependent on the geometric features of the collar edge, especially at the underhead radius which undergoes severe fatigue loading under some operational conditions.
Film-Induced Heritage Site Conservation
Authors: Pan Steve , Ryan Chris
Published: November 2011

It has been contended that a link exists between films and the creation of tourist locations. A film can have an unintended consequence that leads to community actions and subsequent policy initiatives that are supportive of conservation of potential tourism cultural assets. This article analyses the processes by which one such film created a heightened awareness of the heritage values of a location setting in Hong Kong that led to changes in public policy. This case study highlights media’s role in shaping and changing public opinion. It examines through framing analysis the way in which public debate changed, thereby highlighting the way in which conservation activists and other stakeholders played out competing roles and the manner in which they sought to influence media coverage of the site. The article also points out the need to establish a set of consistent standards of conserving heritage sites rather than relying on a film to be the “savior.”
The Impact of Other Customers on Customer Experiences
Authors: Miao Li , Mattila Anna S.
Published: November 2011

Managing customer experiences is critical to the success of hospitality businesses in today’s economic climate and competitive environment. A better understanding of the impact of other customers on customer experiences is needed, as sharing the service environment with other customers is often an inherent part of the experience. To that end, this research examines the impact of other customers on customer experiences from a psychological distance perspective. The results from two experimental studies provide strong empirical evidence for the effect of psychological distance from other customers on a host of customer responses, such as spontaneous emotional responses, symbolic emotional responses, emotion-regulation strategies, and encounter satisfaction. Additionally, this research examines how other-customer-elicited responses jointly affect the overall customer experience.
A mixed-methods investigation to explore how women living in disadvantaged areas might be supported to improve their diets
Authors: Lawrence Wendy , Keyte Jeanette , Tinati Tannaze , Haslam Cheryl , Baird Janis , Margetts Barrie , Swift Judy , Cooper Cyrus , Barker Mary
Published: November 2011

Mixed-methods explored the potential for using Sure Start Children’s Centres (SSCCs) to deliver an intervention to improve the diets of disadvantaged women and their children. In an ‘expert’ discussion, SSCC staff described gaining women’s trust, meeting needs and bringing about change as key to engaging women successfully. Structured observations in SSCCs showed they host activities in an environment conducive to building relationships and meeting women’s needs. However, staff often missed opportunities to support women to make dietary changes. These data suggest that an intervention to help staff make the most of these opportunities would have the best chance of success.
‘Breaking the fourth wall’: 3D virtual worlds as tools for knowledge repatriation in archaeology
Authors: Dawson Peter , Levy Richard , Lyons Natasha
Published: November 2011

Interactive 3-dimensional worlds and computer modeling can be used to excite interest in archaeology among indigenous groups such as the Inuit of the North American Arctic and Greenland. Using two case studies – a recently completed exhibition for the Virtual Museum of Canada on Thule Inuit whalebone houses and an interactive virtual world structured around the Siglit-Inuvialuit sod house – we explore how digital replicas might be used in the repatriation of traditional knowledge. This idea is examined through theexperiences of nine Inuit Elders who explored our digital reconstructions of Thule and Siglit-Inuvialuit dwellings in 3D. Discussions with the Elders suggest that the generic sense of ‘presence’ generated by 3D viewing enhanced their feelings of connectedness to their past. This would imply that virtual reality and 3D technology might be useful in establishing new discourses in archaeological interpretation, as well as assisting in the exploration, construction, and maintenance of cultural identities through knowledge repatriation.
Anger as a Hidden Motivator
Authors: Veling Harm , Ruys Kirsten I. , Aarts Henk
Published: November 2011

The authors examined whether creating associations between products and anger, a negative but also approach-related emotion, motivates people to get or invest in these products when these products are considered attainable. Experiment 1 demonstrated that participants spontaneously spent more physical effort to get anger-related (compared to neutral) products they could attain as gifts. Experiment 2 showed that participants paid more money for anger-related (compared to neutral) products and thus perceived them as more valuable, regardless of whether the anger–product association was established consciously or unconsciously. Importantly, Experiment 2 also revealed that anger-related products were only perceived as more valuable when they were considered in terms of attainability. The authors conclude that anger can be a hidden motivator: Anger-related products that are perceived in terms of attainability act as rewards that motivate people to obtain these products.
A fitness assay for comparing RNAi effects across multiple C. elegans genotypes
Authors: Elvin Mark , Snoek Laurens B , Frejno Martin , Klemstein Ulrike , Kammenga Jan E , Poulin Gino B
Published: November 2011

Background

RNAi technology by feeding of E. coli containing dsRNA in C. elegans has significantly contributed to further our understanding of many different fields, including genetics, molecular biology, developmental biology and functional genomics. Most of this research has been carried out in a single genotype or genetic background. However, RNAi effects in one genotype do not reveal the allelic effects that segregate in natural populations and contribute to phenotypic variation.

Results

Here we present a method that allows for rapidly comparing RNAi effects among diverse genotypes at an improved high throughput rate. It is based on assessing the fitness of a population of worms by measuring the rate at which E. coli is consumed. Critically, we demonstrate the analytical power of this method by QTL mapping the loss of RNAi sensitivity (in the germline) in a recombinant inbred population derived from a cross between Bristol and a natural isolate from Hawaii. Hawaii has lost RNAi sensitivity in the germline. We found that polymorphisms in ppw-1 contribute to this loss of RNAi sensitivity, but that other loci are also likely to be important.

Conclusions

In summary, we have established a fast method that improves the throughput of RNAi in liquid, that generates quantitative data, that is easy to implement in most laboratories, and importantly that enables QTL mapping using RNAi.
Arcanolysin is a cholesterol-dependent cytolysin of the human pathogen Arcanobacterium haemolyticum
Authors: Jost B Helen , Lucas Erynn A , Billington Stephen J , Ratner Adam J , McGee David J
Published: October 2011

Background

Arcanobacterium haemolyticum is an emerging human pathogen that causes pharyngitis, wound infections, and a variety of occasional invasive diseases. Since its initial discovery in 1946, this Gram positive organism has been known to have hemolytic activity, yet no hemolysin has been previously reported. A. haemolyticum also displays variable hemolytic activity on laboratory blood agar that is dependent upon which species the blood is derived.

Results

Here we describe a cholesterol-dependent cytolysin (CDC) secreted by A. haemolyticum, designated arcanolysin (aln), which is present in all strains (n = 52) tested by DNA dot hybridization. Among the known CDCs, ALN is most closely related to pyolysin (PLO) from Trueperella (formerly Arcanobacterium) pyogenes. The aln probe, however, did not hybridize to DNA from T. pyogenes. The aln open reading frame has a lower mol %G+C (46.7%) than the rest of the A. haemolyticum genome (53.1%) and is flanked by two tRNA genes, consistent with probable acquisition by horizontal transfer. The ALN protein (~ 64 kDa) contains a predicted signal sequence, a putative PEST sequence, and a variant undecapeptide within domain 4, which is typically important for function of the toxins. The gene encoding ALN was cloned and expressed in Escherichia coli as a functional recombinant toxin. Recombinant ALN had hemolytic activity on erythrocytes and cytolytic activity on cultured cells from human, rabbit, pig and horse origins but was poorly active on ovine, bovine, murine, and canine cells. ALN was less sensitive to inhibition by free cholesterol than perfringolysin O, consistent with the presence of the variant undecapeptide.

Conclusions

ALN is a newly identified CDC with hemolytic activity and unique properties in the CDC family and may be a virulence determinant for A. haemolyticum.
Decrease of virulence for BALB/c mice produced by continuous subculturing of Nocardia brasiliensis
Authors: Almaguer-Chávez Janeth A , Welsh Oliverio , Lozano-Garza Hector G , Said-Fernández Salvador , Romero-Díaz Víktor J , Ocampo-Candiani Jorge , Vera-Cabrera Lucio
Published: October 2011

Background

Subculturing has been extensively used to attenuate human pathogens. In this work we studied the effect of continuous subculturing of Nocardia brasiliensis HUJEG-1 on virulence in a murine model.

Methods

Nocardia brasiliensis HUJEG-1 was subcultured up to 130 times on brain heart infusion over four years. BALB/c mice were inoculated in the right foot pad with the bacteria subcultured 0, 40, 80, 100 and 130 times (T0, T40, T80 T100 and T130). The induction of resistance was tested by using T130 to inoculate a group of mice followed by challenge with T0 12 weeks later. Biopsies were taken from the newly infected foot-pad and immunostained with antibodies against CD4, CD8 and CD14 in order to analyze the in situ immunological changes.

Results

When using T40, T80 T100 and T130 as inoculums we observed lesions in 10, 5, 0 and 0 percent of the animals, respectively, at the end of 12 weeks. In contrast, their controls produced mycetoma in 80, 80, 70 and 60% of the inoculated animals. When studying the protection of T130, we observed a partial resistance to the infection. Immunostaining revealed an intense CD4+ lymphocytic and macrophage infiltrate in healing lesions.

Conclusions

After 130 in vitro passages of N. brasiliensis HUJEG-1 a severe decrease in its virulence was observed. Immunization of BALB/c mice, with these attenuated cells, produced a state of partial resistance to infection with the non-subcultured isolate.