bluuebunny/crossref_metadata_2025 huggingface dataset:
Chronic Airway Diseases in Adult Life and Childhood Infections
Authors: Ekici Mehmet , Ekici Aydanur , Akin Ahmet , Altinkaya Volkan , Bulcun Emel
Published: May 2007

Background: Respiratory disorders in childhood may predispose to pulmonary disease in late adult life. Objectives: The aim of this study was to evaluate the relationship between their effects in adult life and the characteristics of the respiratory system in childhood. Methods: A total of 10,224 parents and grandparents of students from 14 randomly selected primary schools in the city center were asked to answer questionnaires given to their children. 9,853 of 10,224 persons (the overall response rate was 96.3%) were eligible for analysis. In the questionnaire subjects were asked about respiratory system-related symptoms and characteristics. Results: Chronic cough [14.3 vs. 4.7%, OR 3.4 (2.6–4.4), p < 0.001], chronic bronchitis [35.3 vs. 11.8%, OR 4.0 (3.4–4.8), p < 0.001] and asthma [34.2 vs. 5.1%, OR 9.6 (8.0–11.5), p < 0.001] in the childhood respiratory infection group were more common than in the control group. Childhood respiratory infections were associated with an increased risk of asthma (OR 5.6, p < 0.001), chronic bronchitis (OR 2.3, p < 0.001) and chronic cough (OR 1.5, p < 0.001), after adjusting for possible confounding factors. In addition, the presence of dampness or visible mould, wall-to-wall carpets, pets at home and parents’ smoking during childhood were associated with an increased risk of frequent childhood respiratory infections. Conclusion: These results indicated that frequentrespiratory infections during childhood might play an important role in the occurrence of chronic airway diseases in adult life. The removing of risk factors for frequent childhood respiratory infections may reduce the subsequent risk of chronic airway disease in late adult life.
Tegaserod Inhibits the Serotonin Transporter SERT
Authors: Ismair Manfred G. , Kullak-Ublick Gerd A. , Blakely Randy D. , Fried Michael , Vavricka Stephan R.
Published: May 2007

Background: Tegaserod is a novel drug for the treatment of constipation-predominant irritable bowel syndrome. Tegaserod is thought to exert its prokinetic effect as a selective partial agonist of serotonin receptor type 4 (5-HT4) receptors located in the enteric nervous system. It is unknown, however, whether tegaserod interacts with the human serotonin reuptake transporter (hSERT) and the uptake transporters for dopamine (hDAT) and norepinephrine (hNET). Therefore, the aim of the present study was to investigate whether tegaserod inhibits SERT-, DAT-, and NET-mediated transport. Methods: Tegaserod inhibition of SERT-mediated [3H]5-HT and NET- and DAT-mediated [3H]dopamine uptake was measured in human embryonic kidney (HEK) 293 cells stably expressing hSERT, hDAT, and hNET in comparison with untransfected control HEK293-FT cells. Results: Tegaserod inhibited SERT-, DAT-, and NET-mediated transport with IC50-values of 11.7, 20.7, and 3.2 µmol/l, respectively, while 100 µmol/l estrone-3-sulfate or taurocholic acid, used as negative controls, failed to inhibit hSERT-mediated transport. Using Dixon plot analysis, inhibition kinetics yielded a non-competitive type of inhibition with an apparent inhibition konstant (Ki) of 3.1 µmol/l for SERT-mediated 5-HT transport. Conclusion: In the present study we propose an additional mechanism of action for tegaserod as a serotonin uptake inhibitor. By inhibiting SERT and increasing local 5-HT concentrations in the gut wall, tegaserod might exert its prokinetic action via a synergism between 5-HT4 agonism and low-affinity SERT inhibition.
Progress in the Magnetically Controlled Stereotactic Thrombosis of Intracranial Aneurysms
Authors: Alksne J.F.
Published: May 2007

Although our experience to date indicates that stereotactic thrombosis of intracranial aneurysms with a magnetic probe is a safe and effective procedure for patients with aneurysms of the anterior communicating artery which are less than 1 cm in diameter, additional improvements have been made to increase the safety of the procedure. It has been demonstrated that monitoring the pressure within the injection needle will insure that the needle is within the aneurysm before any iron is injected. Increasing the size of the magnetic probe and inserting coiled iron wire into the aneurysm will enhance the thrombosis of large aneurysms. Studies are still in progress on better methods for monitoring the progression of aneurysm thrombosis. One of the major advantages of the magnetic technique is that the aneurysmal fundus is punctured at the opposite pole from the aneurysmal neck. This may account for the absence of vasospasm seen in our cases as compared to the significant vasospasm reported with the electric thrombosis technique. The modifications described herein have not altered this principle.
Alleviation of Pain by Hypothalamic Stimulation in the Monkey
Authors: Black P. , Cianci S.N. , Markowitz R.S.
Published: May 2007

This study is concerned with stimulation of various subcortical loci as a means of attenuating the aversive properties of concurrent painful stimuli applied peripherally. The medial forebrain bundle (situated in lateral hypothalamus) of the monkey was found to yield consistent self-stimulation behavior. Stimulation of this positively reinforcing locus during delivery of painful shock to the ankle resulted in an attenuation by approximately one-third of the pain response. Other loci tested in limbic system produced little or no diminution in pain. Although the mechanism of this phenomenon is not clear, it is suggested that human trials may be warranted if further animal studies confirm the present observation.
Extensive Cephalic and Oral Pain Relieved by Midbrain Tractotomy
Authors: Nashold Jr. B.S.
Published: May 2007

Unilateral dorsomedial midbrain tractotomy was employed to relieve extensive pain from the head, neck, and oropharynx. Pains originating within the oral cavity and ear subsided. Reflex coughing spasms and trismus associated with the pain stopped. Ocular and motor dysfunctions cleared in most of our patients; these two postoperative symptoms still remain the most serious complications in this operation.
Type A Eagerness-Energy Across Developmental Periods Predicts Adulthood Carotid Intima-Media Thickness
Authors: Keltikangas-Järvinen Liisa , Hintsa Taina , Kivimäki Mika , Puttonen Sampsa , Juonala Markus , Viikari Jorma S.A. , Raitakari Olli T.
Published: May 2007

Objective—

We examined the Type A behavior across developmental periods as a predictor of adult carotid artery intima-media thickness (IMT).

Methods and Results—

In this prospective cohort study of 408 men and 606 women, socioeconomic background and biological risk factors of participants were assessed at baseline at age 6 to 18 years of age, Type A behavior (Hunter-Wolf A-B Rating Scale) at the 6-, 9-, and 21-year follow-ups (subjects being 12 to 24, 15 to 27, and 27 to 39 years, respectively), and carotid IMT, adulthood socioeconomic situation, and biological risk factors at the 21-year follow-up when participants were at age 27 to 39 years of age. In men, the eagerness-energy component of Type A behavior, measured at any time point, was associated with thicker carotid IMT (
P
<0.008,
P
<0.04,
P
<0.03, and
P
<0.02 for the first, second, and third assessment, and for the average score, respectively), and this association was independent of early and adult risk factors. In women, the hard-driving component at baseline (
P
<0.04) but not later was independently related to thinner carotid IMT. The other components of Type A behavior (impatience-aggression and leadership) were not associated with IMT.

Conclusions—

Eagerness-energy component of Type A behavior over different developmental transitions seems to be a robust predictor of IMT in men.
El estudio de la discapacidad física desde la Psicología Social
Authors: Ruiz Josefa , Moya Miguel
Published: May 2007

En este trabajo se ha realizado un recorrido histórico de la investigación psicosocial sobre la discapacidad, resumiendo los trabajos sobre discapacidad física publicados en diferentes revistas de carácter marcadamente psicosocial, tanto en lengua inglesa como española. Las principales líneas de investigación o temáticas de dichos trabajos hacen referencia a: a) naturaleza de la estigmatización de las personas con discapacidad, b) naturaleza de la interacción entre personas con y sin discapacidad c) estrategias de afrontamiento del estigma por parte de las personas con discapacidad, y, finalmente d) estrategias de intervención social que eliminan o reducen la imagen negativa de la persona con discapacidad y su estigma.
Sueños y realidades del movimiento antiglobalización
Authors: Pastor Juan , Ovejero Anastasio
Published: May 2007

En primer lugar, nos acercaremos a los movimientos sociales desde la perspectiva de la psicología social. A continuación propondremos el movimiento antiglobalización como un ejemplo de movimiento social. Por último, reflexionaremos acerca de lo que persiguen y lo que acaban por conseguir estos movimientos sociales.
Midiendo contagio emocional: adaptación de la escala de Doherty
Authors: Gouveia Valdiney V. , Gouveia Rildésia S. V. , Guerra Valeschka M. , Santos Walberto S. , de Medeiros Emerson-Diógenes
Published: May 2007

El objetivo de este estudio fue adaptar la Escala de Contagio Emocional al contexto español. Específicamente, se intentó conocer su estructura factorial y fiabilidad, comprobar la adecuación de los modelos uni y multifactorials, y verificar si las puntuaciones en el contagio emocional varian según el género de los sujetos. Participaron 323 personas, la mayoría mujeres (66.6%) y estudiantes universitarias (55%), con un promedio de edad de 26.7 años. Los sujetos cumplimentaron la Escala de Contagio Emocional, además de cinco preguntas demográficas. El análisis de componentes principales sugirió una estructura unifactorial de contagio emocional. Sin embargo, cuando los modelos uni y multifactoriales fueron comparados, éstos últimos se mostraron más adecuados. Las mujeres tuvieron puntuaciones más altas en el contagio emocional que los varones, con independencia del factor tratado. De este estudio se concluye que la Escala de Contagio Emocional presenta parámetros psicométricos satisfactorios, coherentes con los observados por Doherty.
Persistence of High Health Care Expenditures among Children in Medicaid
Authors: Shenkman Elizabeth , Knapp Caprice , Sappington David , Vogel Bruce , Schatz Des
Published: May 2007

Cross-sectional studies show that a small percentage of children consume a large portion of the health care dollar. However, little is known about the persistence of high health care expenditures among children enrolled in Medicaid health maintenance organizations (HMOs) or in primary care case management (PCCM) programs. This study found substantial expenditure persistence during a 3-year period. Among Temporary Aid to Needy Families (TANF) children in HMOs in the top 10 percent of the expenditure distribution in 2003, 34 percent remained in the top 10 percent in 2004, and 23 percent remained in the top 10 percent in 2005. Similar patterns were observed for TANF children in the PCCM. Expenditure persistence varied based on the enrollees' enabling and need characteristics, providing opportunities to identify children with high health care expenditures who may benefit from care coordination.
Determinants of Implementation Effectiveness
Authors: Helfrich Christian D. , Weiner Bryan J. , McKinney Martha M. , Minasian Lori
Published: May 2007

Many innovations in the health sector are complex, requiring coordinated use by multiple organizational members to achieve benefits. Often, complex innovations are adopted with great anticipation only to fail during implementation. The health services literature provides limited conceptual guidance to researchers and practitioners about implementation of complex innovations. In the present study, we adapt an organizational framework of innovation implementation developed and validated in a manufacturing setting and explore the extent to which it aptly characterizes implementation in health sector organizations. Through comparative case studies of four cancer clinical research networks, we illustrate how this conceptual framework captures key determinants of the implementation of new programs in cancer prevention and control (CP/C) research and helps explain observed differences in implementation effectiveness. Key determinants include management support and innovation-values fit, which contribute to an organizational “climate” for implementation. We explore the implications for researchers and managers.
Physician Attitudes toward Pay-for-Quality Programs
Authors: Young Gary J. , Meterko Mark , White Bert , Bokhour Barbara G. , Sautter Karen M. , Berlowitz Dan , Burgess James F.
Published: May 2007

Pay-for-quality (P4Q) initiatives are becoming an increasingly popular mechanism for improving quality performance and reducing health care costs in the United States. Because these programs often target primary care physicians, it is important to understand how these physicians perceive and respond to P4Q to design successful programs going forward. This study reports results of a survey regarding attitudes toward P4Q among physicians participating in such programs in Massachusetts and California. Findings indicate physicians have generally positive attitudes toward the concept of P4Q, but are ambivalent about certain features of these programs as currently designed and implemented.
JAM-A mediates neutrophil transmigration in a stimulus-specific manner in vivo: evidence for sequential roles for JAM-A and PECAM-1 in neutrophil transmigration
Authors: Woodfin Abigail , Reichel Christoph Andreas , Khandoga Andrej , Corada Monica , Voisin Mathieu-Benoit , Scheiermann Christoph , Haskard Dorian O. , Dejana Elisabetta , Krombach Fritz , Nourshargh Sussan
Published: May 2007

Junctional adhesion molecule-A (JAM-A) is a transmembrane protein expressed at tight junctions of endothelial and epithelial cells and on the surface of platelets and leukocytes. The role of JAM-A in leukocyte transmigration in vivo was directly investigated by intravital microscopy using both a JAM-A–neutralizing monoclonal antibody (mAb) (BV-11) and JAM-A–deficient (knockout [KO]) mice. Leukocyte transmigration (but not adhesion) through mouse cremasteric venules as stimulated by interleukin 1β (IL-1β) or ischemia/reperfusion (I/R) injury was significantly reduced in wild-type mice treated with BV-11 and in JAM-A KO animals. In contrast, JAM-A blockade/genetic deletion had no effect on responses elicited by leukotriene B4 (LTB4) or platelet-activating factor (PAF). Furthermore, using a leukocyte transfer method and mice deficient in endothelial-cell JAM-A, evidence was obtained for the involvement of endothelial-cell JAM-A in leukocyte transmigration mediated by IL-1β. Investigation of the functional relationship between JAM-A and PECAM-1 (CD31) determined that dual blockade/deletion of these proteins does not lead to an inhibitory effect greater than that seen with blockade/deletion of either molecule alone. The latter appeared to be due to the fact that JAM-A and PECAM-1 can act sequentially to mediate leukocyte migration through venular walls in vivo.
Effect of induction agent on vasopressor and steroid use, and outcome in patients with septic shock
Authors: Ray David Charles , McKeown Dermot William
Published: May 2007

Introduction

In seriously ill patients, etomidate gives cardiovascular stability at induction of anaesthesia, but there is concern over possible adrenal suppression. Etomidate could reduce steroid synthesis and increase the need for vasopressor and steroid therapy. The outcome could be worse than in patients given other induction agents.

Methods

We reviewed 159 septic shock patients admitted to our intensive care unit (ICU) over a 40-month period to study the association between induction agent and clinical outcome, including vasopressor, inotrope, and steroid therapy. From our records, we retrieved induction agent use; vasopressor administration at induction; vasopressor, inotrope, and steroid administration in the ICU; and hospital outcome.

Results

Hospital mortality was 65%. The numbers of patients given an induction agent were 74, etomidate; 25, propofol; 26, thiopental; 18, other agent; and 16, no agent. Vasopressor, inotrope, or steroid administration and outcome were not related to the induction agent chosen. Corticosteroid therapy given to patients who received etomidate did not affect outcome. Vasopressor therapy was required less frequently and in smaller doses when etomidate was used to induce anaesthesia. We found no evidence that either clinical outcome or therapy was affected when etomidate was used. Etomidate caused less cardiovascular depression than other induction agents in patients with septic shock.

Conclusion

Etomidate use for critically ill patients should consider all of these issues and not simply the possibility of adrenal suppression, which may not be important when steroid supplements are used.
C-Reactive Protein before and after Weight Loss in Overweight Women with and without Polycystic Ovary Syndrome
Authors: Moran Lisa J. , Noakes Manny , Clifton Peter M. , Wittert Gary A. , Belobrajdic Damien P. , Norman Robert J.
Published: May 2007

Background: Polycystic ovary syndrome (PCOS) is associated with reproductive and metabolic abnormalities. It is unknown whether overweight women with and without PCOS achieve similar benefits from weight loss for cardiovascular risk factors.

Method: Overweight body mass index-matched women with (n = 15) and without (n = 17) PCOS (weight, 95.3 ± 17.6 kg; body mass index, 35.6 ± 5.3 kg/m2, mean ± sd) followed an 8-wk weight loss regime.

Results: All subjects had similar reductions in weight (3.9 ± 3.6 kg, 3.8%, vs. 4.5 ± 4.1 kg, 4.7%, respectively, for PCOS and non-PCOS), waist circumference, fat mass, triglycerides, free testosterone, and fasting and postprandial insulin. At baseline, C-reactive protein (CRP) between groups was not significantly different (5.5 ± 3.1 mg/liter for PCOS vs. 4.9 ± 3.0 mg/liter for non-PCOS). There was a significant interaction between PCOS status and CRP (P = 0.016) such that CRP decreased with weight loss for non-PCOS women (−1.2 ± 1.8 mg/liter; P = 0.025) but not for PCOS women. For all women, the change in CRP correlated with the change in weight (r = 0.560; P = 0.003), fat mass (r = 0.477; P = 0.016), and postprandial insulin (r = 0.402; P = 0.046). Adiponectin, IL-6, and TNF-α were not significantly different between groups before or after weight loss. Only subjects with baseline CRP levels below the median (4.52 mg/liter) showed increases in adiponectin (0.98 ± 1.3 μg/liter) (P = 0.015) and greater reductions in triglycerides (P = 0.001) with weight loss.

Conclusion: A 4–5% weight loss improved lipid, glucose, and insulin profiles in women with and without PCOS. This degree of weight loss was not effective in lowering CRP concentrations in PCOS women, suggesting that greater weight loss is required in this group to achieve equivalent cardiovascular benefit to non-PCOS women.
An Increased Incidence of Overt Hypothyroidism after Iodine Fortification of Salt in Denmark: A Prospective Population Study
Authors: Bülow Pedersen Inge , Laurberg Peter , Knudsen Nils , Jørgensen Torben , Perrild Hans , Ovesen Lars , Rasmussen Lone Banke
Published: May 2007

Context: Iodine fortification (IF) of salt was introduced in Denmark in 1998. Little is known about the effect of a minor increase in iodine intake on the incidence of hypothyroidism. We prospectively identified all new cases of overt hypothyroidism in two areas of Denmark before and for the first 7 yr after IF had been introduced.

Methods: A computer-based register was used to identify continuously all new cases of overt hypothyroidism in two subcohorts with previous moderate and mild iodine deficiency (ID), respectively (Aalborg, n = 310,124, urinary iodine = 45 μg/liter; and Copenhagen, n = 225,707, urinary iodine = 61 μg/liter). Data were obtained 1) before IF (1997–1998), 2) during voluntary IF (1999–2000), 3) during early (2001–2002) and 4) during late (2003–2005) period with mandatory IF.

Results: The overall incidence rate of hypothyroidism increased during the study period: baseline, 38.3/100,000·yr; voluntary IF, 43.7 (not significant vs. baseline); early mandatory IF, 48.7 [vs. baseline, rate ratio (RR) = 1.27; 95% confidence interval (CI) = 1.10–1.47]; and late mandatory IF, 47.2 (vs. baseline, RR = 1.23; 95% CI = 1.07–1.42). There was a geographic difference because hypothyroidism increased only in the area with previous moderate ID: Aalborg, late mandatory IF vs. baseline, 40.3/29.7 (RR = 1.11; 95% CI = 1.11–1.66); Copenhagen, 56.7/51.6 (RR = 1.10; 95% CI = 0.90–1.34). The increase occurred in young and middle-aged adults.

Conclusion: Even a cautious iodization of salt was accompanied by a moderate increase in the incidence rate of overt hypothyroidism. This occurred primarily in young and middle-aged subjects with previous moderate ID.
“The Future Is Entirely Fabulous”: The Baroque Genealogy of Latin America's Modernity
Authors: Kaup Monika
Published: May 2007

Monika Kaup is associate professor of English and adjunct associate professor of comparative literature at the University of Washington. She is author of Rewriting North American Borders in Chicano and Chicana Narrative. She is working on two new book projects: Baroque New Worlds: Representation, Transculturation, Counterconquest, edited with Lois Parkinson Zamora (forthcoming), and American Neobaroques: Twentieth-Century Cycles of Rearticulation.
The FERM protein Epb4.1l5 is required for organization of the neural plate and for the epithelial-mesenchymal transition at the primitive streak of the mouse embryo
Authors: Lee Jeffrey D. , Silva-Gagliardi Nancy F. , Tepass Ulrich , McGlade C. Jane , Anderson Kathryn V.
Published: May 2007

During early mouse development, a single-layered epithelium is transformed into the three germ layers that are the basis of the embryonic body plan. Here we describe an ENU-induced mutation, limulus (lulu), which disrupts gastrulation and the organization of all three embryonic germ layers. Positional cloning and analysis of additional alleles show that luluis a null allele of the FERM-domain gene erythrocyte protein band 4.1-like 5(Epb4.1l5). During gastrulation, some cells in lulu mutants are trapped in the primitive streak at an intermediate stage of the epithelial-mesenchymal transition; as a result, the embryos have very little paraxial mesoderm. Epithelial layers of the later lulu embryo are also disrupted: definitive endoderm is specified but does not form a gut tube,and the neural plate is broad and forms ectopic folds rather than closing to make the neural tube. In contrast to zebrafish and Drosophila, in which orthologs of Epb4.1l5 control the apical localization and activity of Crumbs proteins, mouse Crumbs proteins are localized normally to the apical surface of the lulu mutant epiblast and neural plate. However, the defects in both the lulu primitive streak and neural plate are associated with disruption of the normal organization of the actin cytoskeleton. We propose that mouse Lulu (Epb4.1l5) helps anchor the actin-myosin contractile machinery to the membrane to allow the dynamic rearrangements of epithelia that mediate embryonic morphogenesis.
Ena/VASP function in retinal axons is required for terminal arborization but not pathway navigation
Authors: Dwivedy Asha , Gertler Frank B. , Miller Jeffrey , Holt Christine E. , Lebrand Cecile
Published: May 2007

The Enabled/vasodilator-stimulated phosphoprotein (Ena/VASP) family of proteins is required for filopodia formation in growth cones and plays a crucial role in guidance cue-induced remodeling of the actin cytoskeleton. In vivo studies with pharmacological inhibitors of actin polymerization have previously provided evidence for the view that filopodia are needed for growth cone navigation in the developing visual pathway. Here we have re-examined this issue using an alternative strategy to generate growth cones without filopodia in vivo by artificially targeting Xena/XVASP (Xenopushomologs of Ena/VASP) proteins to mitochondria in retinal ganglion cells(RGCs). We used the specific binding of the EVH1 domain of the Ena/VASP family of proteins with the ligand motif FP4 to sequester the protein at the mitochondria surface. RGCs with reduced function of Xena/XVASP proteins extended fewer axons out of the eye and possessed dynamic lamellipodial growth cones missing filopodia that advanced slowly in the optic tract. Surprisingly,despite lacking filopodia, the axons navigated along the optic pathway without obvious guidance errors, indicating that the Xena/XVASP family of proteins and filopodial protrusions are non-essential for pathfinding in retinal axons. However, depletion of Xena/XVASP proteins severely impaired the ability of growth cones to form branches within the optic tectum, suggesting that this protein family, and probably filopodia, plays a key role in establishing terminal arborizations.
DrosophilaNemo antagonizes BMP signaling by phosphorylation of Mad and inhibition of its nuclear accumulation
Authors: Zeng Yi Arial , Rahnama Maryam , Wang Simon , Sosu-Sedzorme Worlanyo , Verheyen Esther M.
Published: May 2007

Drosophila Nemo is the founding member of the Nemo-like kinase(Nlk) family of serine/threonine protein kinases that are involved in several Wnt signal transduction pathways. Here we report a novel function for Nemo in the inhibition of bone morphogenetic protein (BMP) signaling. Genetic interaction studies demonstrate that nemo can antagonize BMP signaling and can inhibit the expression of BMP target genes during wing development. Nemo can bind to and phosphorylate the BMP effector Mad. In cell culture, phosphorylation by Nemo blocks the nuclear accumulation of Mad by promoting export of Mad from the nucleus in a kinase-dependent manner. This is the first example of the inhibition of Drosophila BMP signaling by a MAPK and represents a novel mechanism of Smad inhibition through the phosphorylation of a conserved serine residue within the MH1 domain of Mad.
Bacteroides fragilis toxin stimulates intestinal epithelial cell shedding and γ-secretase-dependent E-cadherin cleavage
Authors: Wu Shaoguang , Rhee Ki-Jong , Zhang Ming , Franco Augusto , Sears Cynthia L.
Published: May 2007

Enterotoxigenic Bacteroides fragilis – organisms that live in the colon – secrete a metalloprotease toxin, B. fragilis toxin. This toxin binds to a specific intestinal epithelial cell receptor and stimulates cell proliferation, which is dependent, in part, on E-cadherin degradation and β-catenin–T-cell-factor nuclear signaling. γ-Secretase (or presenilin-1) is an intramembrane cleaving protease and is a positive regulator of E-cadherin cleavage and a negative regulator of β-catenin signaling. Here we examine the mechanistic details of toxin-initiated E-cadherin cleavage. B. fragilis toxin stimulated shedding of cell membrane proteins, including the 80 kDa E-cadherin ectodomain. Shedding of this domain required biologically active toxin and was not mediated by MMP-7, ADAM10 or ADAM17. Inhibition of γ-secretase blocked toxin-induced proteolysis of the 33 kDa intracellular E-cadherin domain causing cell membrane retention of a distinct β-catenin pool without diminishing toxin-induced cell proliferation. Unexpectedly, γ-secretase positively regulated basal cell proliferation dependent on the β-catenin–T-cell-factor complex. We conclude that toxin induces step-wise cleavage of E-cadherin, which is dependent on toxin metalloprotease and γ-secretase. Our results suggest that differentially regulated β-catenin pools associate with the E-cadherin–γ-secretase adherens junction complex; one pool regulated by γ-secretase is important to intestinal epithelial cell homeostasis.
Complementary and Alternative Medicine Use Among Hispanics in the United States
Authors: Ortiz Blanca I , Shields Kelly M , Clauson Kevin A , Clay Patrick G
Published: May 2007

OBJECTIVE:

To review the use of complementary and alternative medicine (CAM) in Hispanics in the US and highlight the modalities most likely to be unfamiliar to healthcare practitioners.

DATA SOURCES:

A search of the literature published in English and a subsequent bibliographic search were conducted using MEDLINE, International Pharmaceutical Abstracts, EMBASE, Cumulative Index of Nursing and Allied Health Literature, and Manual Alternative and Natural Therapy Index System (1980– March 2007). Primary search terms included, but were not limited to, Hispanic, Latino, complementary and alternative medicine, and dietary supplements. Studies that assessed or evaluated the use of CAM in the Hispanic population were reviewed. Articles that included both Hispanics and non-Hispanics were also included.

STUDY SELECTION AND DATA EXTRACTION:

The literature search yielded 42 articles focused on the use of CAM by Hispanics. Survey was the most common method used in these studies, although some hybrid interviews were also conducted.

DATA SYNTHESIS:

Hispanics were identified homogenously in some studies and more correctly as a heterogeneous population in others. Some trials examined overall CAM use, whereas others looked at specific dietary supplements and herbs. Most reports found a higher than expected rate of CAM use in Hispanics (50–90%). A number of products potentially unfamiliar to healthcare practitioners, such as linden, sapodilla, and star anise, were reported as commonly used in several studies. Many studies were limited by the sample size or use of only one Hispanic subgroup.

CONCLUSIONS:

Hispanics use a wide range of CAM therapies, including several that may be unfamiliar to healthcare practitioners. Understanding the rationale, motivations, and history of Hispanics' use of CAM will enhance the cultural competence of healthcare professionals and help address these patients' medical needs.

TRASFONDO:

El uso de terapias de medicina complementaria y alternativa (CAM) es común entre los pacientes y se cree que la etnicidad influye en la frecuencia y extensión de su uso. Los pacientes de origen Hispano son una sub-población en rápido crecimiento. Con el fin de proveer efectivamente cuidado a este grupo de pacientes, es importante entender el papel de las terapias CAM en los tratamientos de esta población.
Providing Patient Care in Community Pharmacies: Practice and Research in Finland
Authors: Bell J Simon , Väänänen Minna , Ovaskainen Harri , Närhi Ulla , Airaksinen Marja S
Published: May 2007

OBJECTIVE:

To describe the provision of patient care in community pharmacies in Finland.

FINDINGS:

The network of 799 community pharmacies across Finland dispensed 42.1 million prescriptions in 2005. Medication counseling has been mandated by law since 1983 and only pharmacists are permitted to provide therapeutic advice in pharmacies. Measurable improvements in the rates of pharmacists' medication counseling have been observed since 2000. Long-term national pharmacy practice initiatives commenced with the World Health Organization EuroPharm Forum's Questions to Ask About Your Medicines campaign from 1993 to 1996. This was followed by the larger Customized Information for the Benefit of Community Pharmacy Patients project. Since the late 1990s, Finnish pharmacies have actively participated in ongoing national public health programs, initially in the areas of asthma and diabetes, and more recently in the treatment and prevention of heart disease. Automated dose dispensing and electronic prescribing are in the process of wider uptake and implementation. A nationwide multidisciplinary project to improve the use of drugs in older people has recently been announced and research in this area is underway.

DISCUSSION:

Research has focused on improving the quality of patient care as a strategic priority in community pharmacies. The development of community pharmacy services in Finland has been characterized by strong collaboration among the professional associations, university departments of social pharmacy, continuing education centers, and practicing pharmacists.

CONCLUSIONS:

Implementation of new patient care services has required long-term, systematic, and well coordinated actions at the local and national levels. Future services will seek to promote the quality use of medications and to ensure that rising costs do not limit uniform access to drugs by all Finnish residents.
Methylnaltrexone Mechanisms of Action and Effects on Opioid Bowel Dysfunction and Other Opioid Adverse Effects
Authors: Yuan Chun-Su
Published: May 2007

OBJECTIVE:

To review the mechanisms of action of methylnaltrexone and its effects on opioid bowel dysfunction, as well as its effects on other opioid-induced adverse effects (ADEs), and its potential roles in clinical practice.

DATA SOURCES:

A literature search using the MEDLINE and Cochrane Collaboration databases for articles published between 1966 and March 2007 was performed. Additional data sources were obtained from manual searches of recent journal articles, book chapters, and monographs. An updated literature search showed no additional publications.

STUDY SELECTION AND DATA EXTRACTION:

Abstracts and original preclinical and clinical research reports published in the English language were identified for review. Review articles, commentaries, and news reports of this compound were excluded. Literature related to opioids, opioid receptors, opioid antagonists, methylnaltrexone, opioid-induced bowel dysfunction, constipation, nausea, and vomiting was evaluated and selected based on consideration of the support shown for the proof of concept, mechanistic findings, and timeliness. Fifty-eight original articles from preclinical studies and clinical trials using methylnaltrexone were identified. Pharmacologic action, benefits, and ADEs of methylnaltrexone were reviewed, with a focus on its effects on bowel dysfunction after opioids. Emphases were placed on its receptor binding activities and therapeutically relevant sites of action (peripheral vs central), in which peripheral opioid receptors in the body contribute to physiological and drug-induced effects.

DATA SYNTHESIS:

Morphine and related opioids are associated with a number of limiting ADEs, including opioid-induced bowel dysfunction. Methylnaltrexone, a quaternary derivative of naltrexone, blocks peripheral effects of opioids while sparing central analgesic effects. It is currently under late-stage clinical investigation for the treatment of opioid-induced constipation in patients with advanced illness. Reported results showed the drug to be generally well-tolerated. The rapid reversal of constipation is very encouraging. Hastening postoperative discharge may also be possible.

CONCLUSIONS:

Methylnaltrexone has the potential to prevent or treat opioid-induced peripherally mediated ADEs on bowel dysfunction without interfering with central analgesia. The study of methylnaltrexone leads to a greater understanding of the mechanisms of action of opioid pharmacology.
Cognitive appraisals, distress and disability among persons in low vision rehabilitation
Authors: Dreer Laura E. , Elliott Timothy R. , Berry Jack , Fletcher Donald C. , Swanson Marsha , Christopher J. McNeal
Published: May 2007

ObjectiveExamined cognitive appraisals of interference and tolerance in the prediction of distress and self‐reported disability among persons presenting for low vision rehabilitation.

DesignCross‐sectional; correlational and path analyses.

MethodsOne‐hundred and thirteen patients (mean age, 71 years; 52 men and 61 women) presenting for low vision rehabilitation at a university‐based centre for low vision rehabilitation participated in an initial clinical vision examination and completed several questionnaires to evaluate cognitive appraisals, emotional distress and self‐reported disability.

ResultsPath analyses indicated that greater tolerance was associated with less interference imposed by vision loss. Greater tolerance was also associated with less emotional distress and symptom severity (visual acuity) was associated with self‐reported disability. Cognitive appraisals (tolerance and interference) indirectly influenced self‐reported disability through emotional distress.

ConclusionsThe data indicate that appraisals of personal ability to tolerate vision loss and the perceived interference of vision loss on goal‐directed behaviour and expected activities have greater influence on distress and are subsequently predictive of disability in comparison with objective symptoms (visual acuity). Implications for clinical interventions and further research are discussed.
Adhesion Is Prerequisite, But Alone Insufficient, to Elicit Stem Cell Pluripotency
Authors: Karpowicz Phillip , Inoue Tomoyuki , Runciman Sue , Deveale Brian , Seaberg Raewyn , Gertsenstein Marina , Byers Lois , Yamanaka Yojiro , Tondat Sandra , Slevin John , Hitoshi Seiji , Rossant Janet , van der Kooy Derek
Published: May 2007

Primitive mammalian neural stem cells (NSCs), arising during the earliest stages of embryogenesis, possess pluripotency in embryo chimera assays in contrast to definitive NSCs found in the adult. We hypothesized that adhesive differences determine the association of stem cells with embryonic cells in chimera assays and hence their ability to contribute to later tissues. We show that primitive NSCs and definitive NSCs possess adhesive differences, resulting from differential cadherin expression, that lead to a double dissociation in outcomes after introduction into the early- versus midgestation embryo. Primitive NSCs are able to sort with the cells of the inner cell mass and thus contribute to early embryogenesis, in contrast to definitive NSCs, which cannot. Conversely, primitive NSCs sort away from cells of the embryonic day 9.5 telencephalon and are unable to contribute to neural tissues at midembryogenesis, in contrast to definitive NSCs, which can. Overcoming these adhesive differences by E-cadherin overexpression allows some definitive NSCs to integrate into the inner cell mass but is insufficient to allow them to contribute to later development. These adhesive differences suggest an evolving compartmentalization in multipotent NSCs during development and serve to illustrate the importance of cell–cell association for revealing cellular contribution.
Heterosynaptic Scaling of Developing GABAergic Synapses: Dependence on Glutamatergic Input and Developmental Stage
Authors: Liu Yan , Zhang Li I. , Tao Huizhong W.
Published: May 2007

A proportionality or balance between coactivated excitatory and inhibitory inputs is often observed for individual cortical neurons and is proposed to be important for their functions. This feature of neural circuits may arise from coordinated modulation of excitatory and inhibitory synaptic inputs, a mechanism that remains unknown. Here,in vivowhole-cell recordings from tectal neurons of youngXenopustadpoles reveals activity-dependent bidirectional modifications of GABAergic inputs. At early developmental stages when GABAergic inputs dominate visually evoked responses, repetitive visual stimulation leads to long-term depression of GABAergic inputs. At later stages when convergent glutamatergic inputs are much stronger, long-term potentiation (LTP) of GABAergic inputs is induced. The polarity of GABAergic plasticity depends on the ratio between the magnitude of coactivated glutamatergic and GABAergic inputs (E/Iratio) to the tectal cell: LTP is induced only when theE/Iratio is above a threshold, and the level of LTP correlates linearly with the logarithm of theE/Iratio. The induction of LTP requires the activation of postsynaptic NMDA receptors, as well as presynaptic TrkB signaling likely through retrograde BDNF (brain-derived neurotrophic factor) and is achieved by overcoming a predominant depression process mediated by NMDA receptors on the presynaptic GABAergic neurons. Our results indicate that the strength of developing GABAergic synapses can be scaled in accordance to coactivated convergent glutamatergic input. This mechanism may contribute to the formation of functional neural circuits with correlated excitatory and inhibitory inputs.
Fast Vesicle Replenishment and Rapid Recovery from Desensitization at a Single Synaptic Release Site
Authors: Crowley John J. , Carter Adam G. , Regehr Wade G.
Published: May 2007

When the synaptic connection between two neurons consists of a small number of release sites, the ability to maintain transmission at high frequencies is limited by vesicle mobilization and by the response of postsynaptic receptors. These two properties were examined at single release sites between granule cells and stellate cells by triggering bursts of quantal events either with α-latrotoxin or with high-frequency trains of presynaptic activity. Bursts and evoked responses consisted of tens to hundreds of events with frequencies of up to hundreds per second. This indicates that single release sites can rapidly supply vesicles from a reserve pool to a release-ready pool. In addition, postsynaptic AMPA receptors recover from desensitization with a time constant of ∼5 ms. Thus, even for synapses composed of a single release site, granule cells can effectively activate stellate cells during sustained high-frequency transmission because of rapid vesicle mobilization and fast recovery of AMPA receptors from desensitization.
Functional Coupling between the Prefrontal Cortex and Dopamine Neurons in the Ventral Tegmental Area
Authors: Gao Ming , Liu Chang-Liang , Yang Shen , Jin Guo-Zhang , Bunney Benjamin S. , Shi Wei-Xing
Published: May 2007

Stimulation of the prefrontal cortex (PFC) has been shown to have an excitatory influence on dopamine (DA) neurons. We report here that, under nonstimulated conditions, the activity of DA neurons in the ventral tegmental area (VTA) also covaries, on a subsecond timescale, with the activity of PFC cells. Thus, in 67% of VTA DA neurons recorded in chloral hydrate-anesthetized rats, the firing of the cell displayed a slow oscillation (SO) that was highly coherent with the activity of PFC neurons. The SO was suppressed by transections immediately caudal to the PFC or by intra-PFC infusion of tetrodotoxin, suggesting that it depends on inputs derived from the PFC. Unexpectedly, the SO in most VTA DA neurons was reversed in phase relative to PFC cell activity, suggesting that at least part of PFC information is transferred to DA neurons indirectly through inhibitory relay neurons. These results, together with those reported previously, suggest that the PFC can act through multiple pathways to exert both excitatory and inhibitory influences on DA neurons. The observed functional coupling between DA and PFC neurons further suggests that these pathways not only allow a bidirectional control of DA neurons by the PFC, but also enable action potential-dependent DA release to be coordinated, on a subsecond timescale, with glutamate release from PFC terminals. Further understanding of this coordinated activity may provide important new insights into brain functions and disorders thought to involve both VTA DA and PFC neurons.
Emotionen der Skepsis
Authors: Hartmann Martin
Published: May 2007

Inwieweit kann die Rolle, die einzelne Emotionen wie Scham, Eifersucht oder Ekel in den Shakespeare-Deutungen Cavells spielen, für eine allgemeinere Theorie der Emotionen fruchtbar gemacht werden? Leitende Annahme ist, dass eine narrative Konstruktion einzelner Emotionen im Kontext eines Selbstverständnisses den ‘direkten Repräsentationalismus’ korrigieren kann, der viele gegenwärtige Emotionstheorien bestimmt. Es geht vor allem um den Nachweis, dass eine Einbettung des Emotionsphänomens in narrativ zu rekonstruierende Selbstverständnisse einhergeht mit einer Neubestimmung der Grundlage der Beurteilung einzelner Emotionen. Cavells Begriff der Anerkennung liefert erste Bausteine der ethischen Basis der Beurteilung dieser Emotionen.
Citizen-Consumers and Public Service Reform: At the Limits of Neoliberalism?
Authors: Clarke John
Published: May 2007

This article addresses the question: what is not neoliberal? It explores the problem of treating neoliberalism's universalising ambitions as having come true in practice and argues that this obscures both the uneven and partial impact of neoliberalism and the forms of political cultural work that are needed to make it come true. Focusing on one quintessential neoliberal development – the transformation of citizens into consumers – the article uses evidence from a recent study of public service reform in the United Kingdom to suggest that neoliberal subjects have not (yet) materialised in this specific context. It considers how New Labour and neoliberal discourses ‘tell the time’ of other social imaginaries, attempting to residualise them as leftovers from earlier ways of thinking.
Middle Turbinate Graft for Repair of Cerebral Spinal Fluid Leaks
Authors: Marks Steven C.
Published: May 2007

Endoscopic management of CSF leaks has been reported as highly successful by several authors. Various techniques are used for site preparation, graft selection, and graft stabilization. In this report the middle turbinate as a donor site for repair is described. Guidelines for harvest, preparation, and application are presented. The middle turbinate graft can be used as a free mucosal graft for linear cracks or small defects, as a composite bone/mucosal graft for moderate sized defects, or as a donor site for separate bone and mucosal grafts for large defects or encephaloceles when intracranial bone placement is desirable. Experience with 18 patients is presented with 100% initial graft take, and 17/18 (94%) with long term success. The middle turbinate is an excellent source of donor material for repair of almost any endoscopically repairable CSF leak.
A Potential Role for Nasal Obstruction in Development of Acute Sinusitis: An Infection Study in Rabbits
Authors: Gnoy Alex R. , Gannon Patrick J. , Ganjian Emil , Fliegelman Lawrence , Farber David , Silvers Adam , Lawson William
Published: May 2007

The sequence of events that predispose to the onset of sinusitis are usually attributed to pathophysiologic factors within the ostiomeatal complex. Ostial compromise or obstruction with reduced clearance of antral pathogens has been implicated as a major factor that contributes to early sinus disease. Recent work in this laboratory has indicated that other processes may also contribute to this cascade. Using an infectious model in rabbits, the role of nasal obstruction in early, acute sinusitis was studied. Unilateral nasal closure was followed by bilateral inoculation with 108 CFU of Streptococcus pneumoniae type 3. Antral gas composition was examined on days 1, 2, 3, 5, 7, and 14, and swabs obtained for culture. Representative rabbits underwent CT scans to evaluate changes in nasal and sinus mucosa. Results showed a significant increase in CO2 and a trend toward a decrease in O2 on the obstructed side. There was also a significant decrease in obstructed CO2 levels from postoperative days (POD) 1–14. Acute sinusitis was not observed in any animal; however, nasal obstruction gave rise to a dramatic prolongation of bacterial retention. On days 2–7 bacteria was consistently cultured from the obstructed side only. CT scans on POD 2 and POD 3 showed mucosal thickening in the sinus and infundibulum on the obstructed side, indicative of sinus pathology. These results indicate that nasal obstruction may be a key factor in the cascade of events that predispose to the onset of sinus disease.