bluuebunny/crossref_metadata_2025 huggingface dataset:
Can abuse deterrent formulations make a difference? Expectation and speculation
Authors: Budman Simon H , Grimes Serrano Jill M , Butler Stephen F
Published: May 2009

It is critical that issues surrounding the abuse and misuse of prescription opioids be balanced with the need for these medications for the treatment of pain. One way to decrease the abuse of prescription opioid medications is to develop abuse deterrent formulations (or ADFs) that in some way prevent drug abusers from extracting out the active ingredient in order to employ alternate routes of administration, such as injection, snorting, and smoking. Several factors including the pharmacokinetic profile of the drug, the features of the drug formulation that make it attractive or unattractive for abuse, the type of drug abuser, the progression of one's addiction pathway, and one's social environment may all play a role in the abuse of prescription opioids and what methods are used to abuse these drugs. This paper will examine these factors in order to understand how they affect the abuse of prescription opioids and routes of administration, and how the development of ADFs may alter these patterns.
QLT0267, a small molecule inhibitor targeting integrin-linked kinase (ILK), and docetaxel can combine to produce synergistic interactions linked to enhanced cytotoxicity, reductions in P-AKT levels, altered F-actin architecture and improved treatment outcomes in an orthotopic breast cancer model
Authors: Kalra Jessica , Warburton Corinna , Fang Karen , Edwards Lincoln , Daynard Tim , Waterhouse Dawn , Dragowska Wieslawa , Sutherland Brent W , Dedhar Shoukat , Gelmon Karen , Bally Marcel
Published: May 2009

Introduction

Substantial preclinical evidence has indicated that inhibition of integrin linked-kinase (ILK) correlates with cytotoxic/cytostatic cellular effects, delayed tumor growth in animal models of cancer, and inhibition of angiogenesis. Widely anticipated to represent a very promising therapeutic target in several cancer indications, it is increasingly evident that optimal therapeutic benefits obtained using ILK targeting strategies will only be achieved in combination settings. The purpose of this study was to investigate the therapeutic potential of the ILK small molecule inhibitor, QLT0267 (267), alone or in combination with chemotherapies commonly used to treat breast cancer patients.

Methods

A single end-point metabolic assay was used as an initial screen for 267 interactions with selected chemotherapeutic agents. These in vitro assays were completed with seven breast cancer cell lines including several which over-expressed human epidermal growth factor receptor 2 (Her2). One agent, docetaxel (Dt), consistently produced synergistic interactions when combined with 267. Dt/267 interactions were further characterized by measuring therapeutic endpoints linked to phosphorylated protein kinase B (P-AKT) suppression, inhibition of vascular endothelial growth factor (VEGF) secretion and changes in cytoarchitecture. In vivo efficacy studies were completed in mice bearing orthotopic xenografts where tumor growth was assessed by bioluminescence and calliper methods.

Results

The combination of 267 and Dt resulted in increased cytotoxic activity, as determined using an assay of metabolic activity. Combinations of cisplatin, doxorubicin, vinorelbine, paclitaxel, and trastuzumab produced antagonistic interactions. Further endpoint analysis in cell lines with low Her2 levels revealed that the 267/Dt combinations resulted in: a three-fold decrease in concentration (dose) of 267 required to achieve 50% inhibition of P-AKT; and a dramatic disruption of normal filamentous-actin cellular architecture. In contrast to Her2-positive cell lines, three-fold higher concentrations of 267 were required to achieve 50% inhibition of P-AKT when the drug was used in combination with Dt. In vivo studies focusing on low Her2-expressing breast cancer cells (LCC6) implanted orthotopically demonstrated that treatment with 267/Dt engendered improved therapeutic effects when compared with mice treated with either agent alone.

Conclusions

The findings indicate that the 267/Dt drug combination confers increased (synergistic) therapeutic efficacy towards human breast cancer cells that express low levels of Her2.
Systemic analysis of the response of Aspergillus nigerto ambient pH
Authors: Andersen Mikael R , Lehmann Linda , Nielsen Jens
Published: May 2009

Background

The filamentous fungus Aspergillus niger is an exceptionally efficient producer of organic acids, which is one of the reasons for its relevance to industrial processes and commercial importance. While it is known that the mechanisms regulating this production are tied to the levels of ambient pH, the reasons and mechanisms for this are poorly understood.

Methods

To cast light on the connection between extracellular pH and acid production, we integrate results from two genome-based strategies: A novel method of genome-scale modeling of the response, and transcriptome analysis across three levels of pH.

Results

With genome scale modeling with an optimization for extracellular proton-production, it was possible to reproduce the preferred pH levels for citrate and oxalate. Transcriptome analysis and clustering expanded upon these results and allowed the identification of 162 clusters with distinct transcription patterns across the different pH-levels examined. New and previously described pH-dependent cis-acting promoter elements were identified. Combining transcriptome data with genomic coordinates identified four pH-regulated secondary metabolite gene clusters. Integration of regulatory profiles with functional genomics led to the identification of candidate genes for all steps of the pal/pacC pH signalling pathway.

Conclusions

The combination of genome-scale modeling with comparative genomics and transcriptome analysis has provided systems-wide insights into the evolution of highly efficient acidification as well as production process applicable knowledge on the transcriptional regulation of pH response in the industrially important A. niger. It has also made clear that filamentous fungi have evolved to employ several offensive strategies for out-competing rival organisms.
Differential regulation of HIF-1α isoforms in murine macrophages by TLR4 and adenosine A2A receptor agonists
Authors: Ramanathan Madhuri , Luo Wenting , Csóka Balázs , Haskó György , Lukashev Dmitry , Sitkovsky Michail V , Leibovich Samuel Joseph
Published: May 2009

Up-regulation of adenosine A2A receptors (A2ARs) and the HIF-1αl. 1 isoform plays an important role in the switch of macrophages from an inflammatory (M1) to an angiogenic (M2-like) phenotype.

Adenosine A2AR and TLR agonists synergize to induce an “angiogenic switch” in macrophages, down-regulating TNF-α and up-regulating VEGF expression. This switch involves transcriptional regulation of VEGF by HIF-1, transcriptional induction of HIF-1α by LPS (TLR4 agonist), and A2AR-dependent post-transcriptional regulation of HIF-1α stability. Murine HIF-1α is expressed as two mRNA isoforms: HIF-1αI.1 and -I.2, which contain alternative first exons and promoters. HIF-1αI.2 is expressed ubiquitously, and HIF-1αI.1 is tissue-specific. We investigated the regulation of these isoforms in macrophages by TLR4 and A2AR agonists. HIF-1αI.1 is induced strongly compared with HIF-1αI.2 upon costimulation with LPS and A2AR agonists (NECA or CGS21680). In unstimulated cells, the I.1 isoform constituted ∼4% of HIF-1α transcripts; in LPS and NECA- or CGS21680-treated macrophages, this level was ∼15%, indicating a substantial contribution of HIF-1αI.1 to total HIF-1α expression. The promoters of both isoforms were induced by LPS but not enhanced further by NECA, suggesting A2AR-mediated post-transcriptional regulation. LPS/NECA-induced expression of HIF-1αI.1 was down-regulated by Bay 11-7085 (NF-κB inhibitor) and ZM241385 (A2AR antagonist). Although VEGF and IL-10 expression by HIF-1αI.1−/− macrophages was equivalent to that of wild-type macrophages, TNF-α, MIP-1α, IL-6, IL-12p40, and IL-1β expression was significantly greater, suggesting a role for HIF-1αI.1 in modulating expression of these cytokines. A2AR expression in unstimulated macrophages was low but was induced rapidly by LPS in a NF-κB-dependent manner. LPS-induced expression of A2ARs and HIF-1α and A2AR-dependent HIF-1α mRNA and protein stabilization provide mechanisms for the synergistic effects of LPS and A2AR agonists on macrophage VEGF expression.
Human defensins activate monocyte-derived dendritic cells, promote the production of proinflammatory cytokines, and up-regulate the surface expression of CD91
Authors: Presicce Pietro , Giannelli Stefania , Taddeo Adriano , Villa Maria Luisa , Della Bella Silvia
Published: May 2009

Immunostimulatory properties of defensins on DC promote maturation and proinflammatory response.

Defensins are endogenous defense peptides with well-defined antimicrobial activity against a broad spectrum of pathogens including bacteria, fungi, viruses, and parasites. Several lines of evidence suggest that defensins might also contribute to the regulation of host innate and adaptive immunity, but their immunomodulatory functions are still poorly understood. Herein, we studied the impact of human defensins on multiple functions of DCs, which are a central player in all immune responses, bridging innate and adaptive immunity. We challenged DCs differentiated in vitro from human moDCs with HNP-1 α-defensin or HBD-1. HNP-1 and HBD-1 were chemotactic for moDCs. Both defensins promoted the activation and maturation of moDCs, as assessed by up-regulation of surface expression of the costimulatory molecules CD80, CD86, and CD40, the maturation marker CD83, and HLA-DR. HNP-1 and HBD-1 also enhanced the production of the proinflammatory cytokines TNF-α, IL-6, and IL-12p70 but did not affect the production of the regulatory cytokine IL-10. According to these stimulatory effects, HNP-1 and HBD-1 increased the allostimulatory activity of moDCs significantly. Finally, HNP-1 and HBD-1 promoted the up-regulation of CD91 on the DC surface. CD91 is a scavenger receptor involved in the recognition of multiple ligands including defensins, thus suggesting that defensins may amplify their own effects through the activation of an autocrine loop. Taken together, our observations may provide new insight into the immunomodulatory properties of human defensins and may aid the exploration of new therapeutic strategies to potentiate antimicrobial and antitumor immunity.
Delayed-onset post-traumatic stress disorder among war veterans in primary care clinics
Authors: Frueh B. Christopher , Grubaugh Anouk L. , Yeager Derik E. , Magruder Kathryn M.
Published: May 2009

Background

Only limited empirical data support the existence of delayed-onset post-traumatic stress disorder (PTSD).

Aims

To expand our understanding of delayed-onset PTSD prevalence and phenomenology.

Method

A cross-sectional, epidemiological design (n = 747) incorporating structured interviews to obtain relevant information for analyses in a multisite study of military veterans.

Results

A small percentage of veterans with identified current PTSD (8.3%, 7/84), current subthreshold PTSD (6.9%, 2/29), and lifetime PTSD only (5.4%, 2/37) met criteria for delayed onset with PTSD symptoms initiating more than 6 months after the index trauma. Altogether only 0.4% (3/747) of the entire sample had current PTSD with delayed-onset symptoms developing more than 1 year after trauma exposure, and no PTSD symptom onset was reported more than 6 years posttrauma.

Conclusions

Retrospective reports of veterans reveal that delayed-onset PTSD (current, subthreshold or lifetime) is extremely rare 1 year post-trauma, and there was no evidence of PTSD symptom onset 6 or more years after trauma exposure.
Naltrexone implants after in-patient treatment for opioid dependence: randomised controlled trial
Authors: Kun⊘e Nikolaj , Lobmaier Philipp , Vederhus John Kåre , Hjerkinn Bj⊘rg , Hegstad Solfrid , Gossop Michael , Kristensen Øistein , Waal Helge
Published: May 2009

Background

Naltrexone has considerable potential in helping to prevent relapse in heroin dependency. A longer-lasting formulation for naltrexone treatment is desirable to further reduce non-adherence and relapse during treatment of opiate dependence.

Aims

To evaluate the safety and effectiveness of a 6-month naltrexone implant in reducing opioid use after in-patient treatment.

Method

A group of 56 abstinence-oriented patients who completed in-patient treatment for opioid dependence were randomly and openly assigned to receive either a 6-month naltrexone implant or their usual aftercare. Drug use and other outcomes were assessed at 6-month follow-up.

Results

Patients receiving naltrexone had on average 45 days less heroin use and 60 days less opioid use than controls in the 180-day period (bothP<0.05). Blood tests showed naltrexone levels above 1 ng/ml for the duration of 6 months. Two patients died, neither of whom had received an implant.

Conclusions

Naltrexone implant treatment safely and significantly reduces opioid use in a motivated population of patients.
Is hypochondriasis an anxiety disorder?
Authors: Olatunji Bunmi O. , Deacon Brett J. , Abramowitz Jonathan S.
Published: May 2009

Although hypochondriasis is currently classified as a somatoform
disorder, the underlying cognitive processes may be more consistent with
an anxiety disorder. This observation has important implications for
treatment and subsequent revisions of the diagnostic classification of
hypochondriasis.
The dangers of inflation: memories of trauma and post-traumatic stress disorder
Authors: Greenberg Neil , Wessely Simon
Published: May 2009

People who suffer from post-traumatic stress disorder (PTSD) are likely to find that their quality of life is substantially impaired. However, unlike other diagnoses, in order for clinicians to make a diagnosis of PTSD people have to be able to accurately recall the details of a traumatic incident. Yet recent evidence suggests that recall of such incidents is often unreliable. Clinicians should therefore exercise caution to avoid making inaccurate diagnoses.
Chondrocyte-Specific Modulation of Cyp27b1 Expression Supports a Role for Local Synthesis of 1,25-Dihydroxyvitamin D3 in Growth Plate Development
Authors: Naja Roy Pascal , Dardenne Olivier , Arabian Alice , St. Arnaud René
Published: May 2009

The Cyp27b1 enzyme (25-hydroxyvitamin D-1α-hydroxylase) that converts 25-hydroxyvitamin D into the active metabolite, 1,25-dihydroxyvitamin D3 [1,25(OH)2D3], is expressed in kidney but also in other cell types such as chondrocytes. This suggests that local production of 1,25(OH)2D3 could play an important role in the differentiation of these cells. To test this hypothesis, we engineered mutant mice that do not express the Cyp27b1 gene in chondrocytes. Inactivation of both alleles of the Cyp27b1 gene led to decreased RANKL expression and reduced osteoclastogenesis, increased width of the hypertrophic zone of the growth plate at embryonic d 15.5, increased bone volume in neonatal long bones, and increased expression of the chondrocytic differentiation markers Indian Hedgehog and PTH/PTHrP receptor. The expression of the angiogenic marker VEGF was decreased, accompanied by decreased platelet/endothelial cell adhesion molecule-1 staining in the neonatal growth plate, suggesting a delay in vascularization. In parallel, we engineered strains of mice overexpressing a Cyp27b1 transgene in chondrocytes by coupling the Cyp27b1 cDNA to the collagen α1(II) promoter. The transgenic mice showed a mirror image phenotype when compared with the tissue-specific inactivation, i.e. a reduction in the width of the hypertrophic zone of the embryonic growth plate, decreased bone volume in neonatal long bones, and inverse expression patterns of chondrocytic differentiation markers. These results support an intracrine role of 1,25(OH)2D3 in endochondral ossification and chondrocyte development in vivo.
Estradiol-17β Inhibits Gonadotropin-Releasing Hormone-Induced Ca2+ in Gonadotropes to Regulate Negative Feedback on Luteinizing Hormone Release
Authors: Iqbal Javed , Latchoumanin Olivier , Sari Ika P. , Lang Richard J. , Coleman Harold A. , Parkington Helena C. , Clarke Iain J.
Published: May 2009

In pituitary gonadotropes, estrogens have biphasic actions to cause an initial negative feedback followed by a positive feedback on LH secretion, but the mechanisms involved are not clearly understood. To investigate the feedback effects of estrogen, we used mixed ovine pituitary cell cultures (48–72 h), which were treated with 10−9m estradiol-17β (E2) or vehicle followed by a pulse of 10−9m GnRH. Medium was collected for LH assay and cells extracted to determine activation of MAPK (phosphorylated ERK-1/2). E2 treatment for 5 min reduced GnRH-induced LH release and caused phosphorylation of ERK-1/2. E2 alone also caused phosphorylation of ERK-1/2, similar to the response evoked by GnRH alone. GnRH increased cytoplasmic intracellular free calcium concentration ([Ca2+]i) and this was abolished by 2 min pretreatment with E2 or E-bovine serum albumen conjugate. Blockade of Ca2+ channels with nifedipine had no effect on the initial peak of GnRH-induced increase in [Ca2+]i but reduced its duration by 27 ± 6%. Depletion of intracellular Ca2+ stores with thapsigargin prevented GnRH-induced increase in [Ca2+]i. Thapsigargin (10−7m) or nifedipine (10−5m) pretreatment (15 min) of cells lowered GnRH-induced LH secretion by 30 ± 6 and 50% ± 4%, respectively. We conclude that inhibition of the GnRH-induced increase in [Ca2+]i in gonadotropes by E2 is a likely mechanism for the negative feedback effect of E2 on LH secretion involving a rapid nongenomic effect of E2. Activation of the MAPK pathway by E2 may be the mechanism for the time-delayed positive feedback effect on LH secretion at the level of the gonadotrope.
Rapid acceleration in dogs: ground forces and body posture dynamics
Authors: Walter Rebecca M. , Carrier David R.
Published: May 2009

Because the ability to accelerate rapidly is crucial to the survival and reproductive fitness of most terrestrial animals, it is important to understand how the biomechanics of rapid acceleration differs from that of steady-state locomotion. Here we compare rapid acceleration with high-speed galloping in dogs to investigate the ways in which body and limb posture and ground forces are altered to produce effective acceleration. Seven dogs were videotaped at 250 Hz as they performed `maximum effort' accelerations,starting in a standing position on a force plate and one and two strides before it. These dogs began accelerations by rapidly flexing their ankles and knees as they dropped into a crouch. The crouched posture was maintained in the first accelerating stride such that the ankle and knee were significantly more flexed than during steady high-speed galloping. The hindlimb was also significantly more retracted over the first stance period than during high-speed galloping. Ground forces differed from steady-state locomotion in that rapidly accelerating dogs supported only 43% of their body weight with the forelimbs, compared with 56–64% in steady-state locomotion. The hindlimbs applied greater peak accelerating forces than the forelimbs, but the forelimbs contributed significantly to the dogs' acceleration by producing 43%of the total propulsive impulse. Kinematically, rapid acceleration differs from steady-state galloping in that the limbs are more flexed and more retracted, while the back undergoes greater pitching movement. Ground reaction forces also differ significantly from steady-state galloping in that almost no decelerating forces are applied while propulsive force impulses are three to six times greater.
Plasmatocyte-spreading peptide (PSP) plays a central role in insect cellular immune defenses against bacterial infection
Authors: Eleftherianos I. , Xu M. , Yadi H. , ffrench-Constant R. H. , Reynolds S. E.
Published: May 2009

Insect hemocytes (blood cells) are a central part of the insect's cellular response to bacterial pathogens, and these specialist cells can both recognize and engulf bacteria. During this process, hemocytes undergo poorly characterized changes in adhesiveness. Previously, a peptide termed plasmatocyte-spreading peptide (PSP), which induces the adhesion and spreading of plasmatocytes on foreign surfaces, has been identified in lepidopteran insects. Here, we investigate the function of this peptide in the moth Manduca sexta using RNA interference (RNAi) to prevent expression of the precursor protein proPSP. We show that infection with the insect-specific bacterial pathogen Photorhabdus luminescens and non-pathogenic Escherichia coli induces proPSP mRNA transcription in the insect fat body but not in hemocytes; subsequently, proPSP protein can be detected in cell-free hemolymph. We used RNAi to silence this upregulation of proPSP and found that the knock-down insects succumbed faster to infection with P. luminescens, but not E. coli. RNAi-treated insects infected with E. coli showed a reduction in the number of circulating hemocytes and higher bacterial growth in hemolymph as well as a reduction in overall cellular immune function compared with infected controls. Interestingly,RNAi-mediated depletion of proPSP adversely affected the formation of melanotic nodules but had no additional effect on other cellular responses when insects were infected with P. luminescens, indicating that this pathogen employs mechanisms that suppress key cellular immune functions in M. sexta. Our results provide evidence for the central role of PSP in M. sexta cellular defenses against bacterial infections.
The involvement of H+-ATPase and carbonic anhydrase in intestinal HCO3– secretion in seawater-acclimated rainbow trout
Authors: Grosell M. , Genz J. , Taylor J. R. , Perry S. F. , Gilmour K. M.
Published: May 2009

Pyloric caeca and anterior intestine epithelia from seawater-acclimated rainbow trout exhibit different electrophysiological parameters with lower transepithelial potential and higher epithelial conductance in the pyloric caeca than the anterior intestine. Both pyloric caeca and the anterior intestine secrete HCO3– at high rates in the absence of serosal HCO3–/CO2,demonstrating that endogenous CO2 is the principal source of HCO3– under resting control conditions. Apical,bafilomycin-sensitive, H+ extrusion occurs in the anterior intestine and probably acts to control luminal osmotic pressure while enhancing apical anion exchange; both processes with implications for water absorption. Cytosolic carbonic anhydrase (CAc) activity facilitates CO2 hydration to fuel apical anion exchange while membrane-associated, luminal CA activity probably facilitates the conversion of HCO3– to CO2. The significance of membrane-bound, luminal CA may be in part to reduce HCO3– gradients across the apical membrane to further enhance anion exchange and thus Cl– absorption and to facilitate the substantial CaCO3 precipitation occurring in the lumen of marine teleosts. In this way, membrane-bound, luminal CA thus promotes the absorption of osmolytes and reduction on luminal osmotic pressure, both of which will serve to enhance osmotic gradients to promote intestinal water absorption.
Seasonal changes in thermoregulatory responses to hypoxia in the Eastern chipmunk (Tamias striatus)
Authors: Levesque Danielle L. , Tattersall Glenn J.
Published: May 2009

Mammalian heterotherms are known to be more tolerant of low oxygen levels than homeotherms. However, heterotherms demonstrate extreme seasonality in daily heterothermy and torpor expression. Because hypoxia depresses body temperature (Tb) and metabolism in mammals, it was of interest to see if seasonal comparisons of normothermic animals of a species capable of hibernation produce changes in their responses to hypoxia that would reflect a seasonal change in hypoxia tolerance. The species studied, the Eastern chipmunk (Tamias striatus, Linnaeus 1758), is known to enter into torpor exclusively in the winter. To test for seasonal differences in the metabolic and thermoregulatory responses to hypoxia (9.9 kPa), flow-through respirometry was used to compare oxygen consumption, minimum thermal conductance and Tb under fixed ambient temperature(Ta) conditions whereas a thermal gradient was used to assess selected Ta and Tb in response to hypoxia, in both summer- and winter-acclimated animals. No differences were observed between seasons in resting metabolism or thermal conductance in normoxic, normothermic animals. Providing the animals with a choice of Ta in hypoxia attenuated the hypoxic drop in Tb in both seasons, suggesting that the reported fall in Tb in hypoxia is not fully manifested in the behavioural pathways responsible for thermoregulation in chipmunks. Instead, Tb in hypoxia tends to be more variable and dependent on both Ta and season. Although Tbdropped in hypoxia in both seasons, the decrease was less in the winter with no corresponding decrease in metabolism, indicating that winter chipmunks are more tolerant to hypoxia than summer animals.
Optimale Steuerung eines dynamischen Schmelzcarbonat-Brennstoffzellen-ModellsOptimal Control of a Molten Carbonate Fuel Cell Model
Authors: Chudej Kurt , Pesch Hans Josef , Sternberg Kati
Published: May 2009

In diesem Artikel werden Ergebnisse der optimalen Steuerung eines Schmelzcarbonat- Brennstoffzellensystems unter Lastwechseln präsentiert. Den umfangreichen Berechnungen liegt ein detailliertes, validiertes mathematisches Modell zugrunde, das die zeitliche und örtliche Dynamik der Gasströme, deren elektro-chemische Reaktionen und die in der Zelle herrschenden Temperaturen und elektrischen Spannungen beschreibt. Das mathematische Modell besteht aus einem hochdimensionalen, nichtlinearen partiell differential-algebraischen Gleichungssystem mit einer parabolischen Gleichung für die Wärmeleitung im Elektrolyten der Zelle sowie hyperbolischen Transportgleichungen für den reaktiven Gastransport. Die Potentialfelder werden in jedem Ortspunkt durch ein differential-algebraisches Gleichungssystem beschrieben. Darüber hinaus gehen in die rechten Seiten der Differentialgleichungen Integralterme ein. Der Gasstrom zwischen Anode und Kathode wird über einen katalytischen Nachbrenner und eine Mischkammer geführt, sodass die Verknüpfung von Anode zu Kathode durch ein differential- algebraisches Gleichungssystem beschrieben wird. Die Einlassbedingungen am Anodeneingang und am Lufteinlass bieten die Möglichkeit der Steuerung der Brennstoffzelle. Damit sind numerische Simulationen und extrem zeitaufwändige optimale Steuerungen, z. B. eines Lastwechsels möglich, die den Brennstoffzellenstapel optimal von einem stationären Zustand in einen anderen überführen. Die numerischen Resultate belegen die Leistungsfähigkeit moderner Methoden der Optimalen Steuerung. Hier kommt eine Methode zum Tragen, bei der alle Gleichungen erst diskretisiert, dann optimiert werden.
Action Research in Public Schools: Is it Research? Should it Be Reviewed?
Authors: Sigler Ellen
Published: May 2009

Teachers conduct in-class action research to solve classroom problems. Cases of K-12 classroom action research were examined to determine which of them require ethics review. A variety of action research projects were collected and transformed into fictitious examples that could be systematically examined to answer these questions pertinent to whether ethics review is required. The resulting analysis suggested that much classroom action research is a local curriculum development activity, which solves important problems but does not require ethics review for various reasons. If it is human research, as defined in the U.S. Common Rule, and is funded by an agency covered by the Common Rule, or if it is not funded but is human research conducted within an institution that has agreed to review all human research, ethics review is legally required unless the intervention is normal educational practice. However, since some action research may trigger other legal requirements, such as the U.S. Family Educational Rights and Privacy Act of 1979 (FERPA), it may be desirable to have some form of school-based review, but typically not human subjects ethics review.
Education and Ethnic Identity Formation among Children of Latin American and Caribbean Immigrants
Authors: Feliciano Cynthia
Published: May 2009

While some scholars argue that ethnic identities influence educational achievement, few studies have examined whether education influences ethnic identity formation. This study uses a longitudinal survey to examine changes in ethnic identities from adolescence to adulthood among children of Latin American and Caribbean immigrants and how educational attainments, and other life experiences, relate to those changes. Contrary to assimilation frameworks suggesting that incorporation into mainstream higher education institutions should lead to greater identification as American or with U.S.-created racial/panethnic categories, such as Latino or black, these findings show that the most educated adult respondents identified with both their countries of origin and the United States, regardless of how they identified as adolescents. This study suggests that educational institutions are important contexts in which racial and ethnic identities are formed.
Family Socioeconomic Status, Parental Involvement, and College Major Choices—Gender, Race/Ethnic, and Nativity Patterns
Authors: Ma Yingyi
Published: May 2009

College major choice is a much-neglected yet highly significant topic in sociological research. This article focuses on family socioeconomic status (SES) and parental involvement to examine potential family influences on patterned college major choice by gender, race/ethnicity, and nativity. Using data from the National Education Longitudinal Study 1988–1994 (NELS: 88–94), this study confirms old gender patterns and finds new racial/ethnic patterns in college major choice. Lower SES children are found to favor more lucrative college majors. Family SES is found to have differential effects on men and women and for racial/ethnic minorities and whites. Parental involvement in children's domain-specific education exerts significant effects on children's college major choice. These together suggest important theoretical and policy implications.
Effects of Hawthorn on the Progression of Heart Failure in a Rat Model of Aortic Constriction
Authors: Hwang Hyun Seok , Boluyt Marvin O. , Converso Kimber , Russell Mark W. , Bleske Barry E.
Published: May 2009

Study Objective. To determine the effects of hawthorn (Crataegus oxycantha) on left ventricular remodeling and function in pressure overload‐induced heart failure in an animal model.

Design. Randomized, parallel, dose‐ranging animal study.

Setting. University research facility.

Animals. Seventy‐four male Sprague‐Dawley rats; 44 were included in the final analysis.

Intervention. Rats underwent a sham operation or aortic constriction. Rats subjected to the sham operation were treated with vehicle (10% agar‐agar), and those subjected to aortic constriction were treated with vehicle or hawthorn (C. oxycantha special extract WS 1442) 1.3, 13, or 130 mg/kg for 5 months.

Measurements and Main Results. Rats and their hearts were weighed, and echocardiographic measurements were performed at baseline and at 2, 3, 4, and 5 months after aortic constriction. Protein expression for markers of fibrosis and for atrial natriuretic factor was also measured. Aortic constriction increased the left ventricular:body weight ratio by 53% in vehicle‐treated rats; Hawthorn treatment did not significantly affect the aortic constriction‐induced increase in this ratio. Left ventricular volumes and dimensions at systole and diastole significantly increased 5 months after aortic constriction compared with baseline in rats given vehicle (> 20% increase, p<0.05) but not in those given hawthorn 130 mg/kg (< 10% increase). After aortic constriction, the velocity of circumferential shortening significantly decreased in the vehicle group but not in the medium‐ or high‐dose groups. In the aortic constriction‐vehicle group, the induced increases in messenger RNA expression for atrial natriuretic factor (∼1000%) and fibronectin (∼80%) were significantly attenuated by highdose hawthorn treatment by approximately 80% and 50%, respectively.

Conclusion. Hawthorn treatment exhibited modest beneficial effects on cardiac remodeling and function during long‐term, pressure overload‐induced heart failure in rats.
Comparison of the Modification of Diet in Renal Disease and Cockcroft‐Gault Equations for Dosing Antimicrobials
Authors: Hermsen Elizabeth D. , Maiefski Ms. Melissa , Florescu Marius C. , Qiu Fang , Rupp Mark E.
Published: May 2009

Study Objectives. To determine the concordance between the Modification of Diet in Renal Disease (MDRD) and Cockcroft‐Gault equations for glomerular filtration rate (GFR) estimation, the impact of using each equation on antimicrobial dosing, the difference in estimated GFR in patients with acute kidney disease (AKD) versus chronic kidney disease (CKD), and the correlation between the MDRD, Cockcroft‐Gault equation, and expert medical opinion for estimating GFR in patients with AKD.

Design. Retrospective cohort study.

Setting. A 689‐bed academic medical center.

Patients. A total of 372 adults hospitalized with either AKD or CKD between January 1, 2007, and May 31, 2007, and who received at least one antimicrobial drug; patients with stage 1 or 2 CKD or those receiving dialysis were excluded.

Measurements and Main Results. Data were collected from electronic medical records on patient characteristics, laboratory values, antimicrobial drugs requiring dosage adjustment due to renal dysfunction, and estimated GFRs provided by the laboratory (MDRD estimation). In addition, estimated GFRs were calculated using the Cockcroft‐Gault equation. For patients with AKD, a third GFR was estimated by a nephrologist. For all patients, the MDRD GFR was significantly higher than the Cockcroft‐Gault GFR (p<0.001). Level of concordance for the need for dosage adjustment based on the two equations was moderate (κ coefficient 0.57, 95% confidence interval 0.5‐0.63); 99.1% of patients with discordant dose recommendations would receive a higher dose if the MDRD GFR was used. In the AKD versus CKD groups, mean MDRD GFR was significantly higher than the Cockcroft‐Gault GFR in both groups (p<0.0001), but the difference was significantly greater in the CKD group (p<0.0001). In patients with AKD, the GFR estimated by expert opinion was greater than that estimated by the Cockcroft‐Gault equation (p=0.04), but was similar to the MDRD equation (p=0.07).

Conclusion. The estimated GFR obtained with the MDRD equation was consistently higher than that from the Cockcroft‐Gault equation in patients with AKD or CKD. In patients with AKD, the MDRD GFR more closely correlated with expert opinion than the Cockcroft‐Gault, suggesting that the MDRD method may be applicable to this patient population. Moderate concordance between the two equations for the need for antimicrobial dosage adjustment due to renal dysfunction was found, but the specific dosage change was different for approximately 40% of patients, with 99% receiving higher doses when the MDRD GFR is used. These dosing differences may be significant, depending on drug safety profile, type of infection, and causative pathogen.
Transcriptional activation of zebrafish cyp11a1 promoter is dependent on the nuclear receptor Ff1b
Authors: Quek Sue Ing , Chan Woon Khiong
Published: May 2009

The cytochrome P450scc (cholesterol side-chain cleavage enzyme) encoded by CYP11A1 catalyzes the first step in steroidogenesis by converting cholesterol to pregnenolone, and thus, controls the synthesis rate of steroid hormones. In mammals, steroidogenic factor 1 (SF1) has been implicated in the cAMP-mediated transcriptional activation of CYP11A1 promoter. In zebrafish, Ff1b has been established as the homolog of SF1. To assess the dependency of cyp11a1 expression on Ff1b, the putative promoter of zebrafish cyp11a1, spanning 1.7 kb, was isolated and bioinformatic analysis revealed two conserved FF1 response elements (FREs) that potentially bind Ff1b. Transfection studies in cell lines of different lineages confirmed that this promoter fragment contained the necessary regulatory elements required for its basal transcription. Truncation and mutagenesis studies performed in Y1 adrenocortical cells revealed that only the proximal FRE was essential for transcriptional activation. Electrophoretic mobility shift assay, however, indicated that Ff1b bound to both FREs, while their in vivo occupancy was confirmed using a chromatin immunoprecipitation assay. Lastly, the cyp11a1 promoter was able to direct EGFP expression specifically to the interrenal gland and genital ridge when transiently expressed in microinjected zebrafish embryos, and the promoter activity is potentiated by ff1b overexpression as measured from luciferase reporter activity in zebrafish embryos.
Clinical and Histological Comparison of Extraction Socket Healing Following the Use of Autologous Platelet-Rich Fibrin Matrix (PRFM) to Ridge Preservation Procedures Employing Demineralized Freeze Dried Bone Allograft Material and Membrane
Authors: Simon B.I , Zatcoff A.L , Kong J.J.W , O’Connell S.M
Published: May 2009

Background:

The healing potential of platelet growth factors has generated interest in using Platelet-Rich Plasma (PRP) in ridge preservation procedures. A canine study was performed to determine if extraction sites treated with platelet-rich fibrin matrix (PRFM) exhibit enhanced healing compared to sites treated with non-viable materials.

Methods:

Four dog’s extraction sockets were treated individually with PRFM, PRFM and membrane, Demineralized Freeze-Dried Bone Allograft (DFDBA) and membrane, PRFM and DFDBA, and untreated control. Treatment sequencing permitted clinical and histologic evaluation of healing at 10 days, 2, 3, 6 and 12 weeks.

Results:

Healing was more rapid in the PRFM and PRFM and membrane sites. By 3 weeks those sockets had osseous fill. Sites containing DFDBA had little new bone at 6 weeks. By 12 weeks those sockets had osseous fill but DFDBA particles were still noted in coronal areas.

Conclusions:

PRFM alone may be the best graft for ridge preservation procedures. Advantages: faster healing, and elimination of disadvantages involved in using barrier membranes.
RNA Detection and Subtype C Assessment of HIV-1 in Infants with Diarrhea in Ethiopia
Authors: Ayele Workenesh , Assefa Tsehai , Lulseged Sileshi , Tegbaru Belete , Berhanu Hiwot , Tamene Wegene , Ahmedin Zenit , Tensai Birzaf W , Tafesse Mengistu , Goudsmit Jaap , Berkhout Ben , Paxton William A , deBaar Michel P , Messele Tsehaynesh , Pollakis Georgios
Published: May 2009

In the absence of chemoprophylaxis, HIV-1 transmission occurs in 13-42% of infants born to HIV-1 positive mothers. All exposed infants acquire maternal HIV-1 antibodies that persist for up to 15 months, thereby hampering diagnosis. In resource limited settings, clinical symptoms are the indices of established infection against validated laboratorybased markers. Here we enrolled 1200 children hospitalized for diarrheal and other illnesses. 20-25% of those tested, aged 15 months or younger, were found to be HIV-1-seropositive. Where sufficient plasma was available, HIV-1 RNA detection was performed using a subtype-insensitive assay, with 71.1% of seropositive infants presenting with diarrhea showing positive. From sub-typing analysis, we identified that viruses of the C’ sub-cluster were predominated amongst infants. Although this study may overestimate the HIV-1 frequency through testing symptomatic infants, diarrhea can be seen as a useful marker indicating HIV-1 infection in infants less than 15 months old.
The relationship among achievement motivation, psychological contract and work attitudes
Authors: Lee Hung-Wen , Liu Ching-Hsiang
Published: May 2009

Recently the business environment has changed greatly. Banks must increase operational efficiency and service quality to build competitive advantages. The priority for upgrading service quality is to improve employees' work attitude. Staff of banks were selected as subjects to explore
the influences of achievement motivation, psychological contracts, and work attitudes. Results were: 1) Achievement motivation significantly influences psychological contract. 2) Psychological contract significantly influences work attitude. 3) Achievement motivation significantly influences
work attitude. 4) Achievement motivation significantly influences work attitude through psychological contracts. It is recommended that when managers select staff, they should consider individuals with more achievement motivation, and who are willing to fulfill psychological contracts since
they have a better work attitude.
Predictors of academic success in first semester baccalaureate nursing students
Authors: Peterson Virginia M.
Published: May 2009

Recently the number of students graduating from nursing programs has been insufficient to replace nurses leaving the workforce. The attrition rate for students entering baccalaureate nursing education programs is approximately 30%, with most (82.3%), leaving in their first semester
of study (Morgan, 2001). Schools of nursing need to establish ways to decrease student attrition from programs. This study was an attempt to determine whether self-esteem, self-efficacy, and environmental variables are predictors of student attrition in first-semester baccalaureate nursing
students, using a descriptive correlational design to explore the relationship between these variables in a non-probability convenience sample of 66 first semester baccalaureate nursing students. No statistically significant relationship between self-esteem, self-efficacy, or environmental
variables and student attrition was revealed.
Long-term Follow-up of Craniofacial Alterations in Juvenile Idiopathic Arthritis
Authors: Twilt Marinka , Schulten Alcuin J. M. , Prahl-Andersen Birte , van Suijlekom-Smit Lisette W. A.
Published: May 2009

Objective: To investigate changes in the craniofacial skeleton in relation to the changes in condylar alterations that occur during long-term follow-up in patients with juvenile idiopathic arthritis.

Materials and Methods: Temporomandibular joint (TMJ) involvement is defined as a condylar alteration that is observed on the orthopantomogram. Lateral cephalograms were used to determine linear and angular measurements.

Results: Seventy of 97 patients from the initial study cohort were included, with a mean follow-up of 68 months. The overall prevalence of condylar alterations and posterior rotation of the mandible decreased; however, the prevalence of retrognathia remained the same. Patients showed improvement in the degree of retrognathia and posterior rotation (40% ANB, 51% OP-SN, and 44% GO-GN-SN). Improvement in the degree of retrognathia was seen more often in patients with improved condylar alterations than in patients with persistent alterations and in those without alterations (50%, 33%, and 28%, respectively). The degree of posterior rotation improved almost equally in patients without TMJ involvement and in patients with improved condylar alterations (57% and 50% by OP-SN, and 67% and 38% GO-GN-SN, respectively) and did not improve in patients with stable persistent alterations.

Conclusion: Both condylar and craniofacial alterations can improve in patients with juvenile idiopathic arthritis.
Changes of Caspase-1 after the Application of Orthodontic Forces in the Periodontal Tissues of Rats
Authors: Yan Xiulin , Chen Jiang , Hao Yuquan , Wang Yan , Zhu Li
Published: May 2009

Objective: To investigate the changes of caspase-1 in orthodontic tooth movement and to determine whether the changes are phase-specific.

Materials and Methods: Eighty Wistar rats were included in this study. Sentalloy closed-coil springs were placed to induce a mesial traction force on the lower right first molar. The animals were killed after 1, 3, 7, and 14 days (n = 20 at each time point). The mandibles of 10 rats were sampled for histomorphometric analysis and immunohistochemical assay, and the periodontal tissues of 10 other rats were sampled for detecting caspase-1 mRNA and protein by real-time RT-PCR and by Western blotting, respectively.

Results: The inflammatory reaction was evident in paraffin sections with hematoxylin-eosin staining. The immunohistochemical assay showed that orthodontic forces significantly increased the number of caspase-1-positive cells in the periodontal ligament (PDL). Mechanical force triggered an increase of caspase-1 mRNA in periodontal tissues. The expression of caspase-1 mRNA increased from day 1, reached the peak on day 3, and then decreased. The results of Western blotting indicated that the levels of both procaspase-1 and P20 subunit significantly increased after the application of orthodontic forces, compared with those in controls (P < .05).

Conclusion: Caspase-1 level increases during orthodontic tooth movement and changes with different phases, which might play a significant role in orthodontic tooth movement.
Optimal Loading Conditions for Controlled Movement of Anterior Teeth in Sliding Mechanics
Authors: Tominaga Jun-ya , Tanaka Motohiro , Koga Yoshiyuki , Gonzales Carmen , Kobayashi Masaru , Yoshida Noriaki
Published: May 2009

Objective: To determine optimal loading conditions such as height of retraction force on the power arm and its position on the archwire in sliding mechanics.

Materials and Methods: A 3D finite element method (FEM) was used to simulate en masse anterior teeth retraction in sliding mechanics. The degree of labiolingual tipping of the maxillary central incisor was calculated when the retraction force was applied to different heights of a power arm set mesial or distal to the canine.

Results: When the power arm was placed mesial to the canine, at the level of 0 mm (bracket slot level), uncontrolled lingual crown tipping of the incisor was observed and the anterior segment of the archwire was deformed downward. At a power arm height of 5.5 mm, bodily movement was produced and the archwire was less deformed. When the power arm height exceeded 5.5 mm, the anterior segment of the archwire was raised upward and lingual root tipping occurred. When the power arm was placed distal to the canine, lingual crown tipping was observed up to a level of 11.2 mm.

Conclusions: Placement of the power arm of an archwire between the lateral incisor and canine enables orthodontists to maintain better control of the anterior teeth in sliding mechanics. Both the biomechanical principles associated with the tooth's center of resistance and the deformation of the archwire should be taken into consideration for predicting and planning orthodontic tooth movement.
Relationship between Occlusal Force and Mandibular Condyle Morphology
Authors: Kurusu Aya , Horiuchi Mariko , Soma Kunimichi
Published: May 2009

Objective: To clarify the relationship between occlusal force and mandibular condyle morphology using clinical data.

Materials and Methods: The subjects were 40 female patients with malocclusion. The mandibular condyle morphology was assessed by using limited cone-beam CT imaging. The maximum occlusal force was calculated by using pressure-sensitive films. Maxillofacial morphologies were analyzed by using data from lateral cephalograms.

Results: Correlation analysis showed that the occlusal force was correlated with the lateral and posterior radii of the condyles, and with the mandibular plane angle to the Frankfort horizontal plane (FH). Moreover, condylar length was significantly correlated with the occlusal plane angle to the FH, the mandibular plane angle to the FH, the ramus inclination, and the posterior facial height (S-Go). Low-occlusal-force patients tended to have smaller mandibular condyles. This size-related difference was more remarkable on the lateral and posterior side.

Conclusions: Occlusal force influences not only maxillofacial morphology but also mandibular condyle morphology.