bluuebunny/crossref_metadata_2025 huggingface dataset:
Thirty-Day Mortality After Ischemic Stroke and Intracranial Hemorrhage in Patients With Atrial Fibrillation On and Off Anticoagulants
Authors: Fang Margaret C. , Go Alan S. , Chang Yuchiao , Borowsky Leila H. , Pomernacki Niela K. , Udaltsova Natalia , Singer Daniel E.
Published: April 2012

Background and Purpose—

Prescribing warfarin for atrial fibrillation depends in large part on the expected reduction in ischemic stroke risk versus the expected increased risk of intracranial hemorrhage (ICH). However, the anticoagulation decision also depends on the relative severity of such events. We assessed the impact of anticoagulation on 30-day mortality from ischemic stroke versus ICH in a large community-based cohort of patients with atrial fibrillation.

Methods—

We followed 13 559 patients with atrial fibrillation enrolled in an integrated healthcare delivery system for a median 6 years. Incident ischemic strokes and ICHs were identified from computerized databases and validated through medical record review. The association of warfarin and international normalized ratio at presentation with 30-day mortality was modeled using multivariable logistic regression adjusting for clinical factors.

Results—

We identified 1025 incident ischemic strokes and 299 ICHs during follow-up. Compared with no antithrombotic therapy, warfarin was associated with reduced Rankin score and lower 30-day mortality from ischemic stroke (adjusted OR, 0.64; 95% CI, 0.45–0.91) but a higher mortality from ICH (OR, 1.62; 95% CI, 0.88–2.98). Therapeutic international normalized ratios (2–3) were associated with an especially low ischemic stroke mortality (OR, 0.38; 95% CI, 0.20–0.70), whereas international normalized ratios >3 increased the odds of dying of ICH by 2.66-fold (95% CI, 1.21–5.86).

Conclusions—

Warfarin reduces 30-day mortality from ischemic stroke but increases ICH-related mortality. Both effects on event severity as well as on event rates need to be incorporated into rational decision-making about anticoagulants for atrial fibrillation.
Association Between Changes in Lipid Profiles and Progression of Symptomatic Intracranial Atherosclerotic Stenosis
Authors: Kim Dong-Eog , Kim Jeong-Yeon , Jeong Sang-Wuk , Cho Yong-Jin , Park Jong-Moo , Lee Ju-Hun , Kang Dong-Wha , Yu Kyung-Ho , Bae Hee-Joon , Hong Keun-Sik , Koo Ja-Seong , Lee Seung-Hoon , Lee Byung-Chul , Han Moon-Ku , Rha Joung-Ho , Lee Yong-Seok , Kim Gyeong-Moon , Chae Seok-Lae , Kim Jong S. , Kwon Sun U.
Published: April 2012

Background and Purpose—

Predictors of progression of intracranial atherosclerotic stenosis have not been clearly identified. We investigated whether poststroke changes in lipid profiles would affect the prognosis of symptomatic intracranial atherosclerotic stenosis.

Methods—

This is a substudy of Trial of cilOstazol in Symptomatic intracranial Stenosis 2 (TOSS-2). From 10 centers we enrolled 230 subjects with acute symptomatic stenosis in the M1 segment of the middle cerebral artery or basilar artery. At baseline and 7 months after stroke, subjects underwent MR angiogram and assessment of cardiovascular risk factors including lipoprotein levels. Progression of intracranial atherosclerotic stenosis was determined by comparing stenosis on the baseline and follow-up MR angiograms.

Results—

Cilostazol treatment was more frequently seen in the nonprogression group (109 of 198 [55.1%]) than in the progression group (11 of 32 [34.4%]). At 7 months after stroke when compared with baseline, low-density lipoprotein cholesterol and total cholesterol levels decreased in both groups. However, only nonprogressors showed increase in high-density lipoprotein cholesterol levels between baseline and follow-up. Changes in apolipoprotein B/apolipoprotein A-I levels were not different between the groups, although apolipoprotein B/A-I at 7 months was higher in progressors than in nonprogressors. Remnant lipoprotein cholesterol levels decreased in nonprogressors, whereas they did not change in progressors. In multivariable analyses, after adjusting for cilostazol treatment and remnant lipoprotein cholesterol reduction or apolipoprotein B/A-I at 7 months, high-density lipoprotein cholesterol elevation remained as a significant predictor for the nonprogression.

Conclusions—

This is the first prospective multicenter study to demonstrate that high-density lipoprotein cholesterol elevation, along with remnant lipoprotein cholesterol reduction and low apolipoprotein B/A-I, is associated with prevention of angiographic progression of symptomatic intracranial atherosclerotic stenosis.

Clinical Trial Registration Information—

URL:
http://www.clinicaltrials.gov
. Unique identifier: NCT00130039.
A Multilevel Memetic Algorithm for Large SAT-Encoded Problems
Authors: Bouhmala Noureddine
Published: April 2012

Many researchers have focused on the satisfiability problem and on many of its variants due to its applicability in many areas of artificial intelligence. This NP-complete problem refers to the task of finding a satisfying assignment that makes a Boolean expression evaluate to True. In this work, we introduce a memetic algorithm that makes use of the multilevel paradigm. The multilevel paradigm refers to the process of dividing large and difficult problems into smaller ones, which are hopefully much easier to solve, and then work backward toward the solution of the original problem, using a solution from a previous level as a starting solution at the next level. Results comparing the memetic with and without the multilevel paradigm are presented using problem instances drawn from real industrial hardware designs.
Lost in Translation: Climate Denial and the Return of the Political
Authors: Goeminne Gert
Published: April 2012

In this deliberately provocative commentary, I interrogate the relationship between two critical perspectives on the one-sided scientific framing of the climate issue: a constructivist interpretation of climate modeling on the one hand and the debate in political theory on the depoliticization of the public sphere on the other. I argue how they could be tied together in order to provide an enriched understanding of climate denial as a symptom rather than a cause of dysfunctional climate politics. It is my claim that in attempting to translate the universal validity of scientific knowledge into the contours of an inclusive, consensual negotiation model, the constitutive role of exclusion in the emergence of scientific objectivity is overlooked.
Ascending and Descending VPs in English
Authors: Janke Vikki , Neeleman Ad
Published: April 2012

We argue that English allows both rightward-descending VP shell structures and more traditional rightward-ascending VPs. The choice between these depends on case theory and economy. Case theory triggers VP shell formation whenever the verb is merged with a DP object after it has been merged with some other category. The reason is that VP shell formation allows verb and object to surface in adjacent positions, a prerequisite for case licensing in English. Economy has the effect that in all other circumstances, VP shell formation is blocked. Our argument is based on a range of intricate data, many of which involve the distribution of object-oriented floating quantifiers. We end with a discussion of the binding data that are often taken to support a uniformly descending structure—incorrectly, in our view.
The Italian Left Periphery: A View from Locality
Authors: Abels Klaus
Published: April 2012

In this article, I discuss the interaction of locality phenomena with the left periphery in Italian as elaborated in Rizzi 1997, 2001a, 2004b. It turns out that long-distance crossing possibilities fully predict the local orderings entailed by Rizzi’s left-peripheral template. In fact, both descriptive gains (in terms of topic positions) and explanatory gains (regarding the position and behavior of topics and of Rizzi’s (2001a) Int) can be made if local ordering is reduced to locality. This suggests that the left-peripheral template should be derived from some appropriate theory of locality and should not be taken as a theoretical primitive.
On the Relationship of Object Agreement and Accusative Case: Evidence from Amharic
Authors: Baker Mark C.
Published: April 2012

This article shows that accusative case and object agreement are not closely related in Amharic, a language in which both are morphologically overt. This suggests that it is wrong to generalize Chomsky’s claim that agreement and case are both manifestations of the same Agree relation from subjects to objects across the board. I show that object agreements in Amharic are the true manifestations of Agree (not pronominal clitics), whereas accusative case is assigned independently, to the lower of two nominals in the same domain. The relationship between case and agreement can thus vary parametrically.
On Raising out of Control
Authors: Ndayiragije Juvénal
Published: April 2012

Hornstein (1999) put forward two thought-provoking ideas that generated a stimulating debate on control: (a) A-movement out of CP complements of control verbs is a design feature of Universal Grammar as first suggested by Kuno (1976), and (b) obligatory control (OC) is an instance of A-movement. This article presents new evidence from Kirundi (Bantu) that supports (a) but defies (b), a paradox that is only apparent. Four sets of facts are discussed: antilocality in promise-constructions, control obviation in inverse OC constructions, passivization in transitive expletive OC constructions, and OC in long-distance inversion constructions. These facts are shown to challenge the movement account of OC while supporting (a) and the PRO-based account.
“I’m Ambivalent about It”
Authors: Hill Andrea , Arford Tammi , Lubitow Amy , Smollin Leandra M.
Published: April 2012

The increasing ubiquity of PowerPoint in the university classroom raises complex questions about pedagogy and the creation of dynamic and effective learning environments. Though much of the sociological teaching literature has focused on engagement and active learning, very little of this work has addressed the presence of PowerPoint in sociology classrooms. Teaching sociology requires discussion, critical thinking, and debate—characteristics many critics argue are at odds with PowerPoint’s unique presentation style. Utilizing survey data from faculty and students at a private university, this research explores PowerPoint usage and the many ways it influences the learning environment of the sociology classroom.
The David and Goliath Principle
Authors: Jeffries Carla H. , Hornsey Matthew J. , Sutton Robbie M. , Douglas Karen M. , Bain Paul G.
Published: April 2012

Two studies documented the “David and Goliath” rule—the tendency for people to perceive criticism of “David” groups (groups with low power and status) as less normatively permissible than criticism of “Goliath” groups (groups with high power and status). The authors confirmed the existence of the David and Goliath rule across Western and Chinese cultures (Study 1). However, the rule was endorsed more strongly in Western than in Chinese cultures, an effect mediated by cultural differences in power distance. Study 2 identified the psychological underpinnings of this rule in an Australian sample. Lower social dominance orientation (SDO) was associated with greater endorsement of the rule, an effect mediated through the differential attribution of stereotypes. Specifically, those low in SDO were more likely to attribute traits of warmth and incompetence to David versus Goliath groups, a pattern of stereotypes that was related to the protection of David groups from criticism.
The Effect of a Computerized Prescribing and Calculating System on Hypo‐ and Hyperglycemias and on Prescribing Time Efficiency in Neonatal Intensive Care Patients
Authors: Maat Barbara , Rademaker Carin M. A. , Oostveen Marloes I. , Krediet Tannette G. , Egberts Toine C. G. , Bollen Casper W.
Published: April 2012

Background: Prescribing glucose requires complex calculations because glucose is present in parenteral and enteral nutrition and drug vehicles, making it error prone and contributing to the burden of prescribing errors. Objective: Evaluation of the impact of a computerized physician order entry (CPOE) system with clinical decision support (CDS) for glucose control in neonatal intensive care patients (NICU) focusing on hypo‐ and hyperglycemic episodes and prescribing time efficiency. Methods: An interrupted time‐series design to examine the effect of CPOE on hypo‐ and hyperglycemias and a crossover simulation study to examine the influence of CPOE on prescribing time efficiency. NICU patients at risk for glucose imbalance hospitalized at the University Medical Center Utrecht during 2001–2007 were selected. The risks of hypo‐ and hyperglycemias were expressed as incidences per 100 patient days in consecutive 3‐month intervals during 3 years before and after CPOE implementation. To assess prescribing time efficiency, time needed to calculate glucose intake with and without CPOE was measured. Results: No significant difference was found between pre‐ and post‐CPOE mean incidences of hypo‐ and hyperglycemias per 100 hospital days of neonates at risk in every 3‐month period (hypoglycemias, 4.0 [95% confidence interval, 3.2–4.8] pre‐CPOE and 3.1 [2.7–3.5] post‐CPOE, P = .88; hyperglycemias, 6.0 [4.3–7.7] pre‐CPOE and 5.0 [3.7–6.3] post‐CPOE, P = .75). CPOE led to a significant time reduction of 16% (1.3 [0.3–2.3] minutes) for simple and 60% (8.6 [5.1–12.1] minutes) for complex calculations. Conclusions: CPOE including a special CDS tool preserved accuracy for calculation and control of glucose intake and increased prescribing time efficiency.
Determination of mercury, cadmium and lead in human milk in Iran
Authors: Goudarzi MA , Parsaei P , Nayebpour F , Rahimi E
Published: April 2012

Breast milk contains both essential and nonessential trace elements. Mercury, cadmium and lead are nonessential, potentially toxic heavy metals with hematotoxic, neurotoxic and nephrotoxic properties even at very low concentrations. The objectives of this study were to determine the concentrations of mercury, cadmium and lead in the breast milk of healthy lactating women who were living in Isfahan, Iran. Concentrations of mercury, cadmium and lead were determined by graphite furnace atomic absorption spectrometry in 37 milk samples from healthy lactating women collected on first to sixth postpartum week. Accuracy of the analysis was checked by various methods including the use of reference material. The mean ± SD of the concentrations of mercury, cadmium and lead in human milk were 0.92 ± 0.54 μg/L (range 0.0–2.07 μg/L), 1.92 ± 1.04 μg/L (range 0.45–5.87 μg/L) and 7.11 ± 3.96 μg/L (range 3.06–19.47 μg/L), respectively. The results of this study showed that the concentrations of mercury, lead and cadmium in the milk samples from lactating women in Isfahan were high, which makes a major public health hazard for the inhabitants, especially neonatal and children, of the industrial locations. The results of the present study indicate a need for establishing safe intake values of heavy metals in human milk.
Gender and ethnic differences in occupational positions and earnings among nurses and engineers in Norway: identical educational choices, unequal outcomes
Authors: Karlsen Hilde
Published: April 2012

Research shows that men who pursue an education in a female-traditional occupation are more likely to be employed outside their occupation, in management positions and in better paid positions than their female colleagues. It is not clear whether this holds for men with an immigrant background and whether differences in employment positions and earnings between men of different ethnic origins are more or less pronounced in female-traditional occupations than in male-traditional professions. This article compares individuals educated in nursing and engineering (i.e. archetypical examples of female- and male-traditional professions, respectively). Results show that findings based on men with a majority ethnic background cannot be generalized to male immigrants. Differences in the likelihood of being employed outside professional nursing and engineering are pronounced between native-born Norwegian men and men with a non-western immigrant background. Nursing seems, however, to offer greater career prospects for ethnic minorities than does engineering.
Women’s equality in the Scandinavian academy: a distant dream?
Authors: Seierstad Cathrine , Healy Geraldine
Published: April 2012

While Scandinavian countries are deemed the most equal in the world, vertical sex segregation remains resilient in the Scandinavian academy. This article investigates women’s equality in universities in three Scandinavian countries, Denmark, Norway and Sweden, countries where women’s share of professorships is below the EU average. It explores the perception of Swedish, Danish and Norwegian women academics with respect to sex equality, hiring and discrimination. In doing so, it exposes the resilience of inequality regimes in Scandinavian universities and thereby questions the reality of sex equality in countries deemed the ‘most equal’. However, the article also finds that Norwegian respondents were less likely to report discrimination and it reflects on the reasons for differences between the Scandinavian countries.
New technique for determining the critical loads of a thin coating on a tool–steel substrate by considering the initiation of cracks in the coating
Authors: Feng Jiling , Qin Yi , Raghavan Rejin , Michler Johann , Almandoz Eluxka , Fuentes Gonzalo G
Published: April 2012

In this article, a mathematical algorithm is derived to accurately determine the critical load of indentation for the initiation of cracks on the surface of a hard coating on a soft substrate, based on the measurement of the diameter of circumferential cracks in micro-indentation impressions. The critical load required for the initiation of the first crack predicted using this technique is shown to be in good agreement with experimental results, indicating the feasibility of the technique proposed. The rationality of the approach proposed was further explored by investigating the fracture mechanism of the surface in a multilayer-coated surface using a finite element model, which was developed with the parameterised modelling approach, in combination with the cohesive-zone model.
A local adaptive differential quadrature method for solving multi-dimensional heat transport equation at the microscale
Authors: Wu Jiun-Yu , Wang Hui-Ching , Char Ming-I , Tai Bo-Chen
Published: April 2012

In this article, we employed the local adaptive differential quadrature method to solve multi-dimensional heat transport equation at the microscale. The local adaptive differential quadrature method was employed to tackle the boundary conditions by using both localized interpolation basis functions and exterior grid points. We found that accurate numerical solution can be obtained by using a small number of gird points for boundary treatments. The governing equation of heat transport was employed to describe the thermal behavior of microstructures, which was of vital importance in microtechnology applications. Four examples showed the effectiveness and accuracy of our algorism in providing excellent estimates of unknown temperature from the given data. We found that the proposed scheme is applicable to the heat transport equation at the microscale.
Effects of asymmetry and learning on phonotaxis in a robot based on the lizard auditory system
Authors: Zhang Lei , Hallam John , Christensen-Dalsgaard Jakob
Published: April 2012

Lizards have strong directional hearing across a broad band of frequencies. The directionality can be attributed to the acoustical properties of the ear, especially the strong acoustical coupling of the two eardrums. The peripheral auditory system of the lizard has previously been modeled in bilaterally symmetric form and several types of bilaterally asymmetric models have also been considered. Both in simulation by software and experiment with a mobile robot, the symmetric model shows a strong phonotaxis while asymmetric models show frequency-dependent direction errors determined by the type and magnitude of their intrinsic bias. To attain effective directional hearing, the bias in the peripheral system should be compensated. In this article, with the peripheral models, we design a decision model and a behavior model, a virtual robot, to simulate the auditory system of the lizard in software. The decision model is trained using three alternative training algorithms, which are evaluated and compared using experimental testing. The results demonstrate that the trained decision model is able to compensate for the frequency-dependent direction errors generated by the asymmetric peripheral models. With both symmetric and asymmetric peripheral models, the robot shows consistent and effective phonotaxis.
Inequities Compounded
Authors: SmithBattle Lee , Leonard Victoria
Published: April 2012

Teen mothers as a cohort are disproportionately disadvantaged before pregnancy and are assumed to be further disadvantaged by an early pregnancy. A growing number of studies report that teen mothers and their children are disadvantaged slightly, if at all, by young maternal age. These studies highlight the social determinants of early childbearing but do not reveal the social contexts that shape the transition into adulthood for teen mothers’ offspring. This report addresses this gap by presenting two cases from a longitudinal study that investigated how family members’ lives unfold in the context of race, class, family practices, and communities. By the sixth wave, two of the mothers’ first-born children had become teen parents. Both cases showcase the diverse outcomes and cumulative impact of social advantage and disadvantage on the transition into young adulthood. Implications are described in relation to what is known about social inequities in the transition into adulthood.
The Geography of Drug Market Activities and Child Maltreatment
Authors: Freisthler Bridget , Kepple Nancy J. , Holmes Megan R.
Published: April 2012

This study examines how drug market activities place children at risk of maltreatment over space and time. Data were collected for 95 Census tracts in Sacramento, California, over 7 years and were analyzed using Bayesian space–time models. Referrals for child maltreatment investigations were less likely to occur in places where current drug market activity was present. However, past-year local and spatially lagged drugs sales were positively related to referrals. After the investigative phase, Census tracts with more drug sales had higher numbers of substantiations, and those with more possessions also had more entries into foster care. The temporal delay between drug sales and child maltreatment referrals may indicate that the surveillance systems designed to protect children may not be responsive to changing neighborhood conditions or be indicative of the time it takes for the detrimental effects of the drug use to appear.
Doubts, dilemmas and decisions: towards ethical research on gender and schooling in South Africa
Authors: Morrell Robert , Epstein Debbie , Moletsane Relehobile
Published: April 2012

This article discusses the tension between ‘do no harm’ on the one hand and the integrity of the research process and its intended goals on the other. We discuss a set of choices confronted in the process of researching gender and sexuality in the context of HIV in South African schools. One dilemma was what to do with information that suggested that an adjunct member of the research team was undermining the gender equality goals of the project and possibly contravening school rules, national law and the professional teacher’s code. We explore how we confronted the dilemma of balancing ethical and consent requirements with the reality of interactions and culturally embedded responsibilities and moral considerations.
Going Global
Authors: Khubchandani Jagdish , Simmons Rob
Published: April 2012

Global health promotion is now becoming an integral part of foreign policy of many countries. Health Promotion Practice has always kept pace with changes in the field of health education and promotion. The Society for Public Health Education Board of Trustees and the Editorial Board of Health Promotion Practice are pleased to announce the launch of a new department, “Global Health Promotion.” This introductory commentary for the new Global Health Promotion Department of Health Promotion Practice defines global health and the new challenges for health education and health promotion. The “ecology” of global health promotion is presented as a framework to initiate dialog and discussion. Global health domains and competencies are discussed as future directions. In this commentary, we also present our vision and mission for the department as we strive for linkages between research, practice, policy, and population health promotion through cross-cultural collaboration. A call for general and departmental submissions—in the form of original research papers, case studies, symposium reports, interviews, and other forms of interprofessional communication—is included to bridge research and practice in global health promotion.
Examining the “Exchange” in Leader–Member Exchange
Authors: Sherman Kimberly E. , Kennedy Deanna M. , Woodard Melissa S. , McComb Sara A.
Published: April 2012

Leader–member exchange (LMX) ratings from 375 supervisor–subordinate pairs were used to examine employee outcomes within the context of leader and member agreement/disagreement on the quality of their exchange relationship. The outcomes of interest included members’ turnover intentions and actual turnover within the 6 months following the initial survey. Results indicate that outcomes varied across the different dyadic relationships. Furthermore, the LMX variable (i.e., the leader’s rating, member’s rating, or both) that was significantly related to intent to turnover and actual turnover when both LMX variables were added to the model simultaneously was contingent on the nature of the LMX relationship being examined.
Predicting Team Performance in a Dynamic Environment
Authors: Walker Alexander D. , Muth Eric R. , Switzer Fred S. , Rosopa Patrick J.
Published: April 2012

Teams that operate in complex and dynamic environments must maintain a certain level of cognitive readiness among team members to ensure high levels of performance in response to potentially uncertain and time sensitive situations. In the current study, the authors sought to identify a physiological measure that could help predict team performance during a complex and dynamic task. Specifically, they examined whether measuring team members’ autonomic nervous system activity could predict subsequent performance on a dynamic process control task. Thirty-four teams of two (35 males, 33 females) completed a processing plant simulation during four varying levels of individual and team difficulty. Sympathetic and parasympathetic nervous system activity was measured throughout the task with an electrocardiogram and an impedance cardiogram and was combined to create a measure of team autonomic activity. Regression analyses showed that team autonomic activity accounted for 10% of the variance in team performance scores. In conclusion, the current study showed that team performance can be predicted from team autonomic activity, which supports the argument that a team’s physiological state could serve as an indicator of cognitive readiness.
How Emotions Are Shaped by Bodily States
Authors: Critchley Hugo D. , Nagai Yoko
Published: April 2012

The state of the body is central to guiding motivational behaviours. Here we discuss how afferent information from face and viscera influence the processing and communication of emotional states. We highlight (a) the fine-grained impact that facial muscular and patterned visceral responses exert on emotional appraisal and communicative signals; (b) short-term changes in visceral state that bias brain responses to emotive stimuli; (c) the commonality of brain pathways and substrates mediating short- and long-term bodily effects on emotional processes; (d) how topographically distinct representations of different bodily states are coupled to reported feelings associated with subtypes of disgust; and (e) how pupil signals contribute to affective exchange. Integrating these observations enriches our understanding of emotional processes and psychopathology.
Emotion and the Unreal Self: Depersonalization Disorder and De-Affectualization
Authors: Medford Nick
Published: April 2012

Depersonalization disorder (DPD) is a psychiatric condition in which there is a pervasive change in the quality of subjective experience, in the absence of psychosis. The core complaint is a persistent and disturbing feeling that experience of oneself and the world has become empty, lifeless, and not fully real. A greatly reduced emotional responsivity, or “de-affectualization,” is frequently described. This article examines the phenomenology and neurobiology of DPD with a particular emphasis on the emotional aspects. It is argued that the study of DPD may provide valuable insights into the relationship between emotion, experience, and identity.
Chronic constipation: new diagnostic and treatment approaches
Authors: Lacy Brian E. , Levenick John M. , Crowell Michael
Published: April 2012

Chronic constipation is a highly prevalent disorder that affects approximately 15% of the US population. Chronic constipation refers to patients who have had symptoms for more than 6 months. In clinical practice, chronic constipation is often used interchangeably with the term functional constipation. This is best defined using the Rome III criteria, which involves an evaluation of stool frequency in addition to symptoms of straining, feelings of incomplete evacuation, and the need to use manual maneuvers to assist with stool evacuation. Symptoms can be burdensome, leading to a reduction in patients’ quality of life. As a national healthcare issue, chronic constipation is also important because it imposes a significant economic impact on the healthcare system. A number of treatment options are currently available, both over-the-counter and by prescription, although not all patients respond to these therapies. This review will focus on new medical treatment options for the management of chronic constipation, and the safety and efficacy of these agents will be reviewed. In addition, the efficacy of new diagnostic tests to evaluate colonic motility and anorectal function are described.
Histamine is a modulator of metamorphic competence in Strongylocentrotus purpuratus(Echinodermata: Echinoidea)
Authors: Sutherby Josh , Giardini Jamie-Lee , Nguyen Julia , Wessel Gary , Leguia Mariana , Heyland Andreas
Published: April 2012

Background

A metamorphic life-history is present in the majority of animal phyla. This developmental mode is particularly prominent among marine invertebrates with a bentho-planktonic life cycle, where a pelagic larval form transforms into a benthic adult. Metamorphic competence (the stage at which a larva is capable to undergo the metamorphic transformation and settlement) is an important adaptation both ecologically and physiologically. The competence period maintains the larval state until suitable settlement sites are encountered, at which point the larvae settle in response to settlement cues. The mechanistic basis for metamorphosis (the morphogenetic transition from a larva to a juvenile including settlement), i.e. the molecular and cellular processes underlying metamorphosis in marine invertebrate species, is poorly understood. Histamine (HA), a neurotransmitter used for various physiological and developmental functions among animals, has a critical role in sea urchin fertilization and in the induction of metamorphosis. Here we test the premise that HA functions as a developmental modulator of metamorphic competence in the sea urchin Strongylocentrotus purpuratus.

Results

Our results provide strong evidence that HA leads to the acquisition of metamorphic competence in S. purpuratus larvae. Pharmacological analysis of several HA receptor antagonists and an inhibitor of HA synthesis indicates a function of HA in metamorphic competence as well as programmed cell death (PCD) during arm retraction. Furthermore we identified an extensive network of histaminergic neurons in pre-metamorphic and metamorphically competent larvae. Analysis of this network throughout larval development indicates that the maturation of specific neuronal clusters correlates with the acquisition of metamorphic competence. Moreover, histamine receptor antagonist treatment leads to the induction of caspase mediated apoptosis in competent larvae.

Conclusions

We conclude that HA is a modulator of metamorphic competence in S. purpuratus development and hypothesize that HA may have played an important role in the evolution of settlement strategies in echinoids. Our findings provide novel insights into the evolution of HA signalling and its function in one of the most important and widespread life history transitions in the animal kingdom - metamorphosis.
Cooperative interactions in the West Nile virus mutant swarm
Authors: Ciota Alexander T , Ehrbar Dylan J , Van Slyke Greta A , Willsey Graham G , Kramer Laura D
Published: April 2012

Background

RNA viruses including arthropod-borne viruses (arboviruses) exist as highly genetically diverse mutant swarms within individual hosts. A more complete understanding of the phenotypic correlates of these diverse swarms is needed in order to equate RNA swarm breadth and composition to specific adaptive and evolutionary outcomes.

Results

Here, we determined clonal fitness landscapes of mosquito cell-adapted West Nile virus (WNV) and assessed how altering the capacity for interactions among variants affects mutant swarm dynamics and swarm fitness. Our results demonstrate that although there is significant mutational robustness in the WNV swarm, genetic diversity also corresponds to substantial phenotypic diversity in terms of relative fitness in vitro. In addition, our data demonstrate that increasing levels of co-infection can lead to widespread strain complementation, which acts to maintain high levels of phenotypic and genetic diversity and potentially slow selection for individual variants. Lastly, we show that cooperative interactions may lead to swarm fitness levels which exceed the relative fitness levels of any individual genotype.

Conclusions

These studies demonstrate the profound effects variant interactions can have on arbovirus evolution and adaptation, and provide a baseline by which to study the impact of this phenomenon in natural systems.
Copper compound induces autophagy and apoptosis of glioma cells by reactive oxygen species and jnk activation
Authors: Trejo-Solís Cristina , Jimenez-Farfan Dolores , Rodriguez-Enriquez Sara , Fernandez-Valverde Francisca , Cruz-Salgado Arturo , Ruiz-Azuara Lena , Sotelo Julio
Published: April 2012

Background

Glioblastoma multiforme (GBM) is the most aggressive of the primary brain tumors, with a grim prognosis despite intensive treatment. In the past decades, progress in research has not significantly increased overall survival rate.

Methods

The in vitro antineoplastic effect and mechanism of action of Casiopeina III-ia (Cas III-ia), a copper compound, on rat malignant glioma C6 cells was investigated.

Results

Cas III-ia significantly inhibited cell proliferation, inducing autophagy and apoptosis, which correlated with the formation of autophagic vacuoles, overexpression of LC3, Beclin 1, Atg 7, Bax and Bid proteins. A decrease was detected in the mitochondrial membrane potential and in the activity of caspase 3 and 8, together with the generation of intracellular reactive oxygen species (ROS) and increased activity of c-jun NH2-terminal kinase (JNK). The presence of 3-methyladenine (as selective autophagy inhibitor) increased the antineoplastic effect of Cas III-ia, while Z-VAD-FMK only showed partial protection from the antineoplastic effect induced by Cas III-ia, and ROS antioxidants (N-acetylcysteine) decreased apoptosis, autophagy and JNK activity. Moreover, the JNK –specific inhibitor SP600125 prevented Cas III-ia-induced cell death.

Conclusions

Our data suggest that Cas III-ia induces cell death by autophagy and apoptosis, in part due to the activation of ROS –dependent JNK signaling. These findings support further studies of Cas III-ia as candidate for treatment of human malignant glioma.
Artemether resistance in vitro is linked to mutations in PfATP6 that also interact with mutations in PfMDR1 in travellers returning with Plasmodium falciparum infections
Authors: Pillai Dylan R , Lau Rachel , Khairnar Krishna , Lepore Rosalba , Via Allegra , Staines Henry M , Krishna Sanjeev
Published: April 2012

Background

Monitoring resistance phenotypes forPlasmodium falciparum, usingin vitrogrowth assays, and relating findings to parasite genotype has proved particularly challenging for the study of resistance to artemisinins.

Methods

Plasmodium falciparumisolates cultured from 28 returning travellers diagnosed with malaria were assessed for sensitivity to artemisinin, artemether, dihydroartemisinin and artesunate and findings related to mutations inpfatp6andpfmdr1.

Results

Resistance to artemetherin vitrowas significantly associated with apfatp6haplotype encoding two amino acid substitutions (pfatp6A623E and S769N; (mean IC50(95% CI) values of 8.2 (5.7 – 10.7) for A623/S769versus623E/769 N 13.5 (9.8 – 17.3) nM with a mean increase of 65%; p = 0.012). Increased copy number ofpfmdr1was not itself associated with increased IC50values for artemether, but when interactions between thepfatp6haplotype and increased copy number ofpfmdr1were examined together, a highly significant association was noted with IC50values for artemether (mean IC50(95% CI) values of 8.7 (5.9 – 11.6)versus16.3 (10.7 – 21.8) nM with a mean increase of 87%; p = 0.0068). Previously described SNPs inpfmdr1are also associated with differences in sensitivity to some artemisinins.

Conclusions

These findings were further explored in molecular modelling experiments that suggest mutations inpfatp6are unlikely to affect differential binding of artemisinins at their proposed site, whereas there may be differences in such binding associated with mutations inpfmdr1. Implications for a hypothesis that artemisinin resistance may be exacerbated by interactions between PfATP6 and PfMDR1 and for epidemiological studies to monitor emerging resistance are discussed.
A rare giant gastrointestinal stromal tumor of the stomach traversing the upper abdomen: a case report and literature review
Authors: Zhou Lei , Liu Chang , Bai Ji-Gang , Wei Ji-Chao , Qu Kai , Tian Feng , Tai Ming-Hui , Wang Rui-Tao , Meng Fan-Di
Published: April 2012

We present the case of a 66-year-old woman with a huge gastrointestinal stromal tumor of the stomach that traversed her upper abdomen. The predominant abdominal sign was a huge, palpable mass, but there were no other distinctive findings in her physical examination or her routine blood workup, including biochemical markers. It was difficult to judge the origin of the mass upon imaging. Furthermore, radiological findings revealed that the mass had a complex relationship with many major blood vessels. An exploratory laparotomy revealed a huge tumor protruding from the anterior wall of the stomach fundus, on the lesser curvature of the stomach, measuring approximately 21 × 34 × 11 cm in diameter and weighing 5.5 kg. A complete resection was performed and the tumor was characterized on immunohistochemistry as a gastrointestinal stromal tumor of the stomach. Preoperative diagnosis of gastrointestinal stromal tumors can be difficult, and we hope that the presentation of this rare case and literature review will benefit other diagnosing clinicians having similar problems.
Proteolytic activation of proapoptotic kinase protein kinase Cδ by tumor necrosis factor α death receptor signaling in dopaminergic neurons during neuroinflammation
Authors: Gordon Richard , Anantharam Vellareddy , Kanthasamy Anumantha G , Kanthasamy Arthi
Published: April 2012

Background

The mechanisms of progressive dopaminergic neuronal loss in Parkinson’s disease (PD) remain poorly understood, largely due to the complex etiology and multifactorial nature of disease pathogenesis. Several lines of evidence from human studies and experimental models over the last decade have identified neuroinflammation as a potential pathophysiological mechanism contributing to disease progression. Tumor necrosis factor α (TNF) has recently emerged as the primary neuroinflammatory mediator that can elicit dopaminergic cell death in PD. However, the signaling pathways by which TNF mediates dopaminergic cell death have not been completely elucidated.

Methods

In this study we used a dopaminergic neuronal cell model and recombinant TNF to characterize intracellular signaling pathways activated during TNF-induced dopaminergic neurotoxicity. Etanercept and neutralizing antibodies to tumor necrosis factor receptor 1 (TNFR1) were used to block TNF signaling. We confirmed the results from our mechanistic studies in primary embryonic mesencephalic cultures and in vivo using the stereotaxic lipopolysaccharide (LPS) model of nigral dopaminergic degeneration.

Results

TNF signaling in dopaminergic neuronal cells triggered the activation of protein kinase Cδ (PKCδ), an isoform of the novel PKC family, by caspase-3 and caspase-8 dependent proteolytic cleavage. Both TNFR1 neutralizing antibodies and the soluble TNF receptor Etanercept blocked TNF-induced PKCδ proteolytic activation. Proteolytic activation of PKCδ was accompanied by translocation of the kinase to the nucleus. Notably, inhibition of PKCδ signaling by small interfering (si)RNA or overexpression of a PKCδ cleavage-resistant mutant protected against TNF-induced dopaminergic neuronal cell death. Further, primary dopaminergic neurons obtained from PKCδ knockout (−/−) mice were resistant to TNF toxicity. The proteolytic activation of PKCδ in the mouse substantia nigra in the neuroinflammatory LPS model was also observed.

Conclusions

Collectively, these results identify proteolytic activation of PKCδ proapoptotic signaling as a key downstream effector of dopaminergic cell death induced by TNF. These findings also provide a rationale for therapeutically targeting PKCδ to mitigate progressive dopaminergic degeneration resulting from chronic neuroinflammatory processes.
Aerobic endurance training versus relaxation training in patients with migraine (ARMIG): study protocol for a randomized controlled trial
Authors: Totzeck Andreas , Unverzagt Susanne , Bak Maja , Augst Pierre , Diener Hans-Christoph , Gaul Charly
Published: April 2012

Background

Migraine is one of the most frequent headache diseases and impairs patients’ quality of life. Up to now, many randomized studies reported efficacy of prophylactic therapy with medications such as beta-blockers or anti-epileptic drugs. Non-medical treatment, like aerobic endurance training, is considered to be an encouraging alternative in migraine prophylaxis. However, there is still a lack of prospective, high-quality randomized trials. We therefore designed a randomized controlled trial to evaluate the efficacy of aerobic endurance training versus relaxation training in patients with migraine (ARMIG).

Methods

This is a single-center, open-label, prospective, randomized trial. Sixty participants with migraine are randomly allocated to either endurance training or a relaxation group. After baseline headache diary documentation over at least 4 weeks, participants in the exercise group will start moderate aerobic endurance training under a sport therapist’s supervision at least 3 times a week over a 12-week period. The second group will perform Jacobson’s progressive muscle relaxation training guided by a trained relaxation therapist, also at least 3 times a week over a 12-week period. Both study arms will train in groups of up to 10 participants. More frequent individual training is possible. The follow-up period will be 12 weeks after the training period. The general state of health, possible state of anxiety or depression, impairments due to the headache disorder, pain-related disabilities, the headache-specific locus of control, and the motor fitness status are measured with standardized questionnaires.

Discussion

The study design is adequate to generate meaningful results. The trial will be helpful in gaining important data on exercise training for non-medical migraine prophylaxis.

Trial registration

The trial is registered at ClinicalTrials.gov: NCT01407861.
Three dimensional socket preservation: a technique for soft tissue augmentation along with socket grafting
Authors: Gholami Gholam Ali , Aghaloo Maryam , Ghanavati Farzin , Amid Reza , Kadkhodazadeh Mahdi
Published: April 2012

Background

A cursory review of the current socket preservation literatures well depicts the necessity of further esthetic considerations through the corrective procedures of the alveolar ridge upon and post extraction. A new technique has been described here is a rotational pedicle combined epithelialized and connective tissue graft (RPC graft) adjunct with immediate guided tissue regeneration (GBR) procedure.

Results

We reviewed this technique through a case report and discuss it’s benefit in compare to other socket preservation procedures.

Conclusion

The main advantages of RPC graft would be summarized as follows: stable primary closure during bone remodeling, saving or crating sufficient vestibular depth, making adequate keratinized gingiva on the buccal surface, and being esthetically pleasant.
Molecular evidence of Culex pipiens form molestus and hybrids pipiens/molestus in Morocco, North Africa
Authors: Amraoui Fadila , Tijane Mhamed , Sarih Mhammed , Failloux Anna-Bella
Published: April 2012

Background

Culex pipiens L. is the most widespread mosquito vector in temperate regions including North Africa. Cx. pipiens has two recognized forms or biotypes; pipiens and molestus are morphologically indistinguishable with distinct behavior and physiology that may influence their vectorial status. In our study, we prospected for the different forms of Cx. pipiens in Morocco.

Methods

Cx. pipiens larvae were collected in 9 sites throughout Morocco during summer 2010 and reared until imago stage. Cx. pipiens was identified using diagnostic primers designed for the flanking region of microsatellite CQ11.

Results

We established the presence of both forms of Cx. pipiens and their hybrids in Morocco.

Conclusions

Molecular identification provides the first evidence of the presence of Cx. pipiens form molestus in Morocco and hybrids between pipiens and molestus forms in North Africa. The epidemiological implications of our findings are discussed.