bluuebunny/crossref_metadata_2025_split huggingface dataset:
Intranasal Spray Medications for Maintenance Therapy of Allergic Rhinitis
Authors: Berger William E. , Meltzer Eli O. 
Published: July 2015

Background Intranasal sprays are recommended as targeted therapy for allergic rhinitis (AR) by providing direct delivery of medication to the nasal mucosa, reducing the potential for systemic adverse effects, decreasing burden of disease, and improving quality of life. Objective To review currently available intranasal sprays indicated for maintenance therapy of AR in the United States: intranasal antihistamines (INAH); intranasal corticosteroids (INCS); and MP-AzeFlu, a single formulation nasal spray of the INAH, azelastine hydrochloride, and the INCS, fluticasone propionate. Methods MEDLINE searches were conducted to identify placebo-controlled studies of commercially available prescription nasal sprays at U.S.-approved doses and indications, and published after an earlier systematic review of AR treatment. Inclusion criteria were ≥20 subjects; duration of ≥2 weeks for seasonal (or episodic) AR, ≥4 weeks for perennial (or persistent) AR, and reporting a total nasal symptom score as a primary or secondary outcome. Results Twenty studies met the inclusion criteria: 4 pediatric, 16 adult/adolescent. There were 4 perennial AR studies (381 children, 1607 adults) and 16 seasonal AR trials (3081 children, 6548 adults). In these studies, 2451 subjects (481 children, 1970 adults) received an INCS, 3001 (1116 children, 1885 adults) received an INAH, and 346 adult subjects received MP-AzeFlu. All active treatments were well tolerated and effective as measured by the reduction in nasal symptoms. Head-to-head comparisons were only available for MP-AzeFlu versus the individual active agent components. MP-AzeFlu provided significantly greater symptom relief than either azelastine or fluticasone propionate alone and with an onset starting at 30 minutes after the dose. Conclusion The most recent addition to intranasal sprays for the maintenance therapy of AR is MP-AzeFlu, a single formulation nasal spray of azelastine hydrochloride and fluticasone propionate in an advanced delivery system. Analysis of clinical data showed this to be the first new intranasal medication that provides greater clinical benefit than an INCS in treating AR.
Evaluation of multiple ancillary therapies used in combination with an antimicrobial in newly received high-risk calves treated for bovine respiratory disease1
Authors: Wilson B. K. , Step D. L. , Maxwell C. L. , Wagner J. J. , Richards C. J. , Krehbiel C. R. 
Published: July 2015

AbstractAncillary therapy (ANC) is commonly provided in conjunction with an antimicrobial when treating calves for suspected bovine respiratory disease (BRD) in an attempt to improve the response to a suspected BRD challenge. The first experiment evaluated the effects of 3 ANC in combination with an antimicrobial in high-risk calves treated for BRD during a 56-d receiving period. Newly received crossbred steers (n = 516; initial BW = 217 ± 20 kg) were monitored by trained personnel for clinical signs of BRD. Calves that met antimicrobial treatment criteria (n = 320) were then randomly assigned to experimental ANC treatment (80 steers/experimental ANC treatment): intravenous flunixin meglumine injection (NSAID), intranasal viral vaccination (VACC), intramuscular vitamin C injection (VITC), or no ANC (NOAC). Animal served as the experimental unit for all variables except DMI and G:F (pen served as the experimental unit for DMI and G:F). Within calves treated 3 times for BRD, those receiving NOAC had lower (P &lt; 0.01) clinical severity scores (severity scores ranged from 0 to 4 on the basis of observed clinical signs and severity) and heavier (P = 0.01) BW than those receiving NSAID, VACC, or VITC at the time of third treatment. Between the second and third BRD treatments, calves receiving NOAC had decreased (P &lt; 0.01) daily BW loss (−0.13 kg ADG) compared with those receiving NSAID, VACC, or VITC (−1.30, −1.90, and −1.41 kg ADG, respectively). There were no differences in rectal temperature, combined mortalities and removals, or overall performance among the experimental ANC treatments. Overall, morbidity and mortality attributed to BRD across treatments were 66.5% and 13.2%, respectively. After the receiving period, a subset of calves (n = 126) were allocated to finishing pens to evaluate the effects ANC administration on finishing performance, carcass characteristics, and lung scores at harvest. Ultrasound estimates, BW, and visual appraisal were used to target a common physiological end point for each pen of calves. There were no differences among the experimental ANC observed during the finishing period (P ≥ 0.11). In summary, the use of NSAID, VACC, and VITC do not appear to positively impact clinical health and could potentially be detrimental to performance during the receiving period in high-risk calves receiving antimicrobial treatment for suspected BRD.
Assessment of Patients with Takayasu Arteritis in Routine Practice with Indian Takayasu Clinical Activity Score
Authors: Alibaz-Oner Fatma , Aydin Sibel Z. , Akar Servet , Aksu Kenan , Kamali Sevil , Yucel Eftal , Karadag Omer , Ozer Huseyin , Kiraz Sedat , Onen Fatos , Inanc Murat , Keser Gokhan , Akkoc Nurullah , Direskeneli Haner 
Published: July 2015

Objective.To assess the Indian Takayasu Clinical Activity Score (ITAS2010) in followup of Takayasu arteritis (TA).Methods.ITAS2010 forms were filled in prospectively (n = 144). Clinical activity was assessed with physician’s global assessment (PGA) and criteria defined by Kerr,et al.Results.ITAS2010 was significantly higher in patients with active disease. Total agreement between ITAS2010 and PGA was 66.4%, and between ITAS2010 and Kerr,et alwas 82.8%. During followup, 14 of 15 patients showing vascular progression with imaging were categorized as having inactive disease according to ITAS2010.Conclusion.ITAS2010 was discriminatory for activity during the followup, but the agreement between PGA and ITAS2010 was moderate. Future work should include the incorporation of advanced vascular imaging and demonstration of ITAS2010 as a scalable measure and not simply a dichotomous measure of activity/flare versus remission.
An Internet-based Controlled Trial Aimed to Improve Osteoporosis Prevention among Chronic Glucocorticoid Users
Authors: Warriner Amy H. , Outman Ryan C. , Allison Jeroan J. , Curtis Jeffrey R. , Markward Nathan J. , Redden David T. , Safford Monika M. , Stanek Eric J. , Steinkellner Amy R. , Saag Kenneth G. 
Published: July 2015

Objective.To address the low prevention and treatment rates for those at risk of glucocorticoid-induced osteoporosis (GIOP), we evaluated the influence of a direct-to-patient, Internet-based educational video intervention using “storytelling” on rates of antiosteoporosis medication use among chronic glucocorticoid users who were members of an online pharmacy refill service.Methods.We identified members who refilled ≥ 5 mg/day of prednisone (or equivalent) for 90 contiguous days and had no GIOP therapy for ≥ 12 months. Using patient stories, we developed an online video addressing risk factors and treatment options, and delivered it to members refilling a glucocorticoid prescription. The intervention consisted of two 45-day “Video ON” periods, during which the video automatically appeared at the time of refill, and two 45-day “Video OFF” periods, during which there was no video. Members could also “self-initiate” watching the video by going to the video link. We used an interrupted time series design to evaluate the effectiveness of this intervention on GIOP prescription therapies over 6 months.Results.Among 3017 members (64.8%) exposed to the intervention, 59% had measurable video viewing time, of which 3% “self-initiated” the video. The GIOP prescription rate in the “Video ON” group was 2.9% versus 2.7% for the “Video OFF” group. There was a nonsignificant trend toward greater GIOP prescription in members who self-initiated the video versus automated viewing (5.7% vs 2.9%, p = 0.1).Conclusion.Among adults at high risk of GIOP, prescription rates were not significantly affected by an online educational video presented at the time of glucocorticoid refill. ClinicalTrials.gov Identifier: NCT01378689.
Differential Tissue-Specific Function of Adora2b in Cardioprotection
Authors: Seo Seong-wook , Koeppen Michael , Bonney Stephanie , Gobel Merit , Thayer Molly , Harter Patrick N. , Ravid Katya , Eltzschig Holger K. , Mittelbronn Michel , Walker Lori , Eckle Tobias 
Published: July 2015

Abstract
The adenosine A2b receptor (Adora2b) has been implicated in cardioprotection from myocardial ischemia. As such, Adora2b was found to be critical in ischemic preconditioning (IP) or ischemia/reperfusion (IR) injury of the heart. Whereas Adora2b is present on various cells types, the tissue-specific role of Adora2b in cardioprotection is still unknown. To study the tissue-specific role of Adora2b signaling on inflammatory cells, endothelia, or myocytes during myocardial ischemia in vivo, we intercrossed floxed Adora2b mice with Lyz2-Cre+, VE-cadherin-Cre+, or myosin-Cre+ transgenic mice, respectively. Mice were exposed to 60 min of myocardial ischemia with or without IP (four times for 5 min) followed by 120 min of reperfusion. Cardioprotection by IP was abolished in Adora2bf/f-VE-cadherin-Cre+ or Adora2bf/f-myosin-Cre+, indicating that Adora2b signaling on endothelia or myocytes mediates IP. In contrast, primarily Adora2b signaling on inflammatory cells was necessary to provide cardioprotection in IR injury, indicated by significantly larger infarcts and higher troponin levels in Adora2bf/f-Lyz2-Cre+ mice only. Cytokine profiling of IR injury in Adora2bf/f-Lyz2-Cre+ mice pointed toward polymorphonuclear neutrophils (PMNs). Analysis of PMNs from Adora2bf/f-Lyz2-Cre+ confirmed PMNs as one source of identified tissue cytokines. Finally, adoptive transfer of Adora2b−/− PMNs revealed a critical role of Adora2b on PMNs in cardioprotection from IR injury. Adora2b signaling mediates different types of cardioprotection in a tissue-specific manner. These findings have implications for the use of Adora2b agonists in the treatment or prevention of myocardial injury by ischemia.
Prenatal Allospecific NK Cell Tolerance Hinges on Instructive Allorecognition through the Activating Receptor during Development
Authors: Alhajjat Amir M. , Strong Beverly S. , Lee Amanda E. , Turner Lucas E. , Wadhwani Ram K. , Ortaldo John R. , Heusel Jonathan W. , Shaaban Aimen F. 
Published: July 2015

Abstract
Little is known about how the prenatal interaction between NK cells and alloantigens shapes the developing NK cell repertoire toward tolerance or immunity. Specifically, the effect on NK cell education arising from developmental corecognition of alloantigens by activating and inhibitory receptors with shared specificity is uncharacterized. Using a murine prenatal transplantation model, we examined the manner in which this seemingly conflicting input affects NK cell licensing and repertoire formation in mixed hematopoietic chimeras. We found that prenatal NK cell tolerance arose from the elimination of phenotypically hostile NK cells that express an allospecific activating receptor without coexpressing any allospecific inhibitory receptors. Importantly, the checkpoint for the system appeared to occur centrally within the bone marrow during the final stage of NK cell maturation and hinged on the instructive recognition of allogeneic ligand by the activating receptor rather than through the inhibitory receptor as classically proposed. Residual nondeleted hostile NK cells expressing only the activating receptor exhibited an immature, anergic phenotype, but retained the capacity to upregulate inhibitory receptor expression in peripheral sites. However, the potential for this adaptive change to occur was lost in developmentally mature chimeras. Collectively, these findings illuminate the intrinsic process in which developmental allorecognition through the activating receptor regulates the emergence of durable NK cell tolerance and establishes a new paradigm to fundamentally guide future investigations of prenatal NK cell–allospecific education.
BTB-ZF Protein Znf131 Regulates Cell Growth of Developing and Mature T Cells
Authors: Iguchi Tomohiro , Aoki Kazuhisa , Ikawa Tomokatsu , Taoka Masato , Taya Choji , Yoshitani Hiroshi , Toma-Hirano Makiko , Koiwai Osamu , Isobe Toshiaki , Kawamoto Hiroshi , Masai Hisao , Miyatake Shoichiro 
Published: July 2015

Abstract
Many members of the BTB-ZF family have been shown to play important roles in lymphocyte development and function. The role of zinc finger Znf131 (also known as Zbtb35) in T cell lineage was elucidated through the production of mice with floxed allele to disrupt at different stages of development. In this article, we present that Znf131 is critical for T cell development during double-negative to double-positive stage, with which significant cell expansion triggered by the pre-TCR signal is coupled. In mature T cells, Znf131 is required for the activation of effector genes, as well as robust proliferation induced upon TCR signal. One of the cyclin-dependent kinase inhibitors, p21Cip1 encoded by cdkn1a gene, is one of the targets of Znf131. The regulation of T cell proliferation by Znf131 is in part attributed to its suppression on the expression of p21Cip1.
Violence Against Women: What’s Law Got to Do With It? A Reflection on Gang Rape in India
Authors: Sharma Richa , Bazilli Susan 
Published: July 2015

The brutal gang rape of a physiotherapy student in India in December 2012 drew the world’s attention to the problem of sexual violence against women in the country. Protests and mass public reaction towards the case pressurized the government to respond to the crisis by changing the laws on sexual violence. However, these new laws have not led to a decrease in VAW. Is this the result of the failure of the rule of law? Or does it highlight the limitations of law in absence of social change? This paper addresses the need for using law as a key tool in addressing violence against women in India. It recognizes that unless we address the structural and root causes of violence against women, our analysis will be limited. It is important to bridge the creation of new laws, with an analysis that speaks to the role of hypermasculinity, neoliberalism and culture in VAW. If unaddressed, what may result instead are quick fixes, symbolized by passing laws that act as token gestures, rather than leading to transformative action.
The Effect of Using Web-Cam Chat on the Undergraduate EFL Students’ Pragmatic Competence
Authors: Bataineh Ahmad Mousa , Hussein Nadhim Obaid 
Published: July 2015

<p>This study aimed to investigate the effect of using web-cam chat on developing of the pragmatic aspects of language by college-level English as foreign language (EFL) learners in Jordan. A quantitative approach was applied to determine first, whether the use of web-cam chats had a positive effect on EFL learners’ pragmatic competence. Second, the effect of presenting pragmatic through two delivery systems face-to-face, in-class activities and computer-mediated communication (CMC) via web-cam chats i.e. Facebook and Skype was investigated in this study. The sample of the study consisted of thirty-two undergraduate students who made up two intact classes in a "Conversation Skills course, which call Penguin Functional English by Peter Watcyn-J0nes .Code N 1302109” at AL al-Bayt University in Jordan, during the second semester of the academic year 2013/2014. The students were interviewed in order to know their actual levels in the pragmatic aspects of English before starting the experiment. The sample was divided into two groups; the control group (15 students) was taught the course content using the regular communicative method through which students received instructor-led lessons from the textbook, while group two, the experimental (17 students) was taught using web-cam chat. After conducting the activities, a post test was administered. Scores were tabulated and prepared for statistical analysis. The results showed that web-cam chat had a positive impact on the EFL learners’ pragmatic competence. Learners who studied via web-cam chat performed better on the pragmatic aspects of English post-test than those who did not. The findings also indicated that technology can be a valuable tool for delivering pragmatic instruction. Moreover, the findings of the study revealed that students acquired the speaking and listening skills in web-cam chat more efficiently and effectively than in the regular communicative method.</p>
Responsabilidade social: contra ou a favor?
Authors: Garcia Joana Coeli Ribeiro , Raimundo Jorge , Ferreira Josivan De Oliveira , Fernandes Tatiana Falcão de Souza 
Published: July 2015

<p><strong>Introdução</strong>: Discute a responsabilidade social (RS) sob a ótica empresarial enfatizando as diferenças que surgem a partir da teoria neoliberal sobre a responsabilidade social empresarial (RSE) e da possibilidade de ações de melhoria da sociedade como um todo. A filantropia é considerada como o início de toda ação de RS.</p><p><strong>Objetivo:</strong> Compreender os conceitos de responsabilidade social a fim de estabelecer paralelos sobre o que as empresas desenvolvem, ampliando a percepção do que as organizações praticam atualmente.</p><p><strong>Metodologia</strong>: O artigo é desenvolvido a partir de uma metodologia com abordagem bibliográfica de natureza teórica.</p><p><strong>Resultados</strong>: A partir das diferenças existentes entre filantropia e RS é possível compreender esta última, ultrapassando expectativas econômicas. A ação ética na RS significa que as organizações devem aplicá-la em sua política de gestão e na cultura, incorporando-a às atividades sociais que beneficiam o ser humano.</p><p><strong>Conclusão</strong>: Numa visão pragmática e realista, conclui-se que a RSE na atuação gerencial das organizações repercute favoravelmente na sociedade, quando desenvolvida de forma contínua e com seu pleno sentido para a sustentabilidade social e ambiental do planeta, além de contribuir para a construção de uma sociedade cidadã por meio da ética e da melhoria das condições de vida de todos.</p>
Differentiation of Odontoblast-Like Cells From Mouse Induced Pluripotent Stem Cells by Pax9 and Bmp4 Transfection
Authors: Seki Daisuke , Takeshita Nobuo , Oyanagi Toshihito , Sasaki Shutaro , Takano Ikuko , Hasegawa Masakazu , Takano-Yamamoto Teruko 
Published: July 2015

Abstract

The field of tooth regeneration has progressed in recent years, and human tooth regeneration could become viable in the future. Because induced pluripotent stem (iPS) cells can differentiate into odontogenic cells given appropriate conditions, iPS cells are a potential cell source for tooth regeneration. However, a definitive method to induce iPS cell-derived odontogenic cells has not been established. We describe a novel method of odontoblast differentiation from iPS cells using gene transfection. We generated mouse iPS cell-derived neural crest-like cells (iNCLCs), which exhibited neural crest markers. Next, we differentiated iNCLCs into odontoblast-like cells by transfection of Pax9 and Bmp4 expression plasmids. Exogenous Pax9 upregulated expression of Msx1 and dentin matrix protein 1 (Dmp1) in iNCLCs but not bone morphogenetic protein 4 (Bmp4) or dentin sialophosphoprotein (Dspp). Exogenous Bmp4 upregulated expression of Msx1, Dmp1, and Dspp in iNCLCs, but not Pax9. Moreover, cotransfection of Pax9 and Bmp4 plasmids in iNCLCs revealed a higher expression of Pax9 than when Pax9 plasmid was used alone. In contrast, exogenous Pax9 downregulated Bmp4 overexpression. Cotransfection of Pax9 and Bmp4 synergistically upregulated Dmp1 expression; however, Pax9 overexpression downregulated exogenous Bmp4-induced Dspp expression. Together, these findings suggest that an interaction between exogenous Pax9- and Bmp4-induced signaling modulated Dmp1 and Dspp expression. In conclusion, transfection of Pax9 and Bmp4 expression plasmids in iNCLCs induced gene expression associated with odontoblast differentiation, suggesting that iNCLCs differentiated into odontoblast-like cells. The iPS cell-derived odontoblast-like cells could be a useful cell source for tooth regeneration.

Significance
It has been reported that induced pluripotent stem (iPS) cells differentiate into odontogenic cells by administration of recombinant growth factors and coculture with odontogenic cells. Therefore, they can be potential cell sources for tooth regeneration. However, these previous methods still have problems, such as usage of other cell types, heterogeneity of differentiated cells, and tumorigenicity. In the present study, a novel method to differentiate iPS cells into odontoblast-like cells without tumorigenicity using gene transfection was established. It is an important advance in the establishment of efficient methods to generate homogeneous functional odontogenic cells derived from iPS cells.
Drug Transporter-Mediated Protection of Cancer Stem Cells From Ionophore Antibiotics
Authors: Boesch Maximilian , Zeimet Alain G. , Rumpold Holger , Gastl Guenther , Sopper Sieghart , Wolf Dominik 
Published: July 2015

Abstract

Ionophore antibiotics were reported to selectively kill cancer stem cells and to overcome multidrug resistance, but mechanistic studies of the significance of drug transporters for treatment with these compounds are lacking. We applied chemosensitivity testing of well-characterized human cancer cell lines to elaborate on whether drug transporters are involved in protection from the cytotoxic effects of the ionophore antibiotics salinomycin and nigericin. Our experiments demonstrated that ionophore antibiotics were ineffective against both stem-like ovarian cancer side population cells (expressing either ABCB1 or ABCG2) and K562/Dox-H1 cells, which constitute a genetically defined model system for ABCB1 expression. Considering that cancer stem cells often express high levels of drug transporters, we deduced from our results that ionophore antibiotics are less suited to cancer stem cell-targeted treatment than previously thought.

Significance
Ionophore antibiotics such as salinomycin have repeatedly been shown to target cancer stem and progenitor cells from various tumor entities. Meanwhile, cancer stem cell (CSC)-selective toxicity of ionophore antibiotics seems to be a commonly accepted concept that is about to encourage their clinical testing. This study provides data that challenge the concept of targeted elimination of CSC by ionophore antibiotics. Stem-like ovarian cancer side population (SP) cells expressing high levels of ABC drug transporters are shown to largely resist the cytotoxic effects of salinomycin and nigericin. Furthermore, using a small interfering RNA-based knockdown model specific for ABCB1, this study demonstrates that ABC drug transporters are indeed causally involved in mediating protection from ionophore antibiotics. Considering that it is a hallmark of CSCs to exhibit drug resistance conferred by ABC drug transporters, it must be deduced from these results that CSCs may also be protected from ionophore antibiotics by means of drug-transporter mediated efflux.