bluuebunny/crossref_metadata_2025_split huggingface dataset:
Telaprevir: An NS3/4A Protease Inhibitor for the Treatment of Chronic Hepatitis C
Authors: Smith Lisa S , Nelson Michael , Naik Sagar , Woten Joanna 
Published: May 2011

Objective: To review the use of telaprevir for the treatment of chronic hepatitis C. Data Sources: Clinical studies were identified through MEDLINE (1966-January 2011), bibliographies of articles, clinicaltrials.gov, and fda.gov, using key words VX-950, telaprevir, and chronic hepatitis C. Study Selection and Data Extraction: Phase 1, 2, and 3 human and animal studies describing the pharmacology, pharmacokinetics, efficacy, and safety of telaprevir were identified. Additional articles were identified from the bibliographies of articles retrieved through MEDLINE. Data Synthesis: Telaprevir is an NS3/4A protease inhibitor under investigation for the treatment of chronic hepatitis C virus (HCV) with pegylated interferon and ribavirin. Telaprevir competes with viral peptide substrates for the active site of NS3 and inhibits NS3-NS4A protease activity. Telaprevir has activity against HCV genotype 1 infection in vitro and in vivo, but monotherapy results in rapid viral resistance. In 3 Phase 2 and 3 Phase 3 randomized placebo-controlled trials, 12 weeks of telaprevir, along with varying durations of ribavirin treatment, induced higher sustained virologic response (SVR) compared with ribavirin alone. SVR was approximately 70% in treatment-naïve patients, 50-60% for patients in whom SVR had not occurred with prior ribavirin treatment, and 40-45% of those who received ribavirin alone. There was a high incidence of maculopapular rash (52% in 1 trial) and anemia (27% in 1 trial) in telaprevir-treated patients. The average dropout rate in Phase 3 trials as a result of adverse effects was 13%. Conclusions: Twelve weeks of telaprevir with concomitant ribavirin treatment increases SVR for treatment-naïve and non-naïve patients with genotype 1 chronic HCV compared to 48 weeks of ribavirin treatment. Telaprevir may shorten the length of ribavirin therapy for some patients with extended rapid viral response, but viral mutations, adverse effects, and a high dropout rate may reduce the SVR seen in clinical practice.
Diabetes and Cardiovascular Disease Interventions by Community Pharmacists: A Systematic Review
Authors: Evans Charity D , Watson Erin , Eurich Dean T , Taylor Jeff G , Yakiwchuk Erin M , Shevchuk Yvonne M , Remillard Alfred , Blackburn David 
Published: May 2011

Objective: To systematically review and assess the quality of studies evaluating community pharmacist interventions for preventing or managing diabetes or cardiovascular disease (CVD) and/or their major risk factors. Data Sources: A comprehensive literature search was performed using MEDLINE (1950-February 2011), EMBASE (1980-February 2011), International Pharmaceutical Abstracts (1970-February 2011), Cumulative Index to Nursing and Allied Health Literature (1982-June 2007), and Cochrane Central Register of Controlled Trials (1898-February 2011). Search terms included: community pharmacy(ies), community pharmacist(s), cardiovascular, diabetes, and intervention. The grey literature was searched using the ProQuest Dissertations and Theses, Theses Canada, and OAlster databases. Study Selection and Data Extraction: Articles published in English or French with all study designs were considered for the review. Studies were included if they contained interventions designed to reduce the incidence, risk, or mortality of CVD or diabetes; affect clinical indicators of CVD or diabetes mellitus (including hypertension, dyslipidemia, or hemoglobin A1c); and/or improve adherence to treatment strategies. Only studies involving interventions carried out primarily by pharmacists in community pharmacy settings were included. Study quality was assessed using a checklist validated for both randomized and nonrandomized studies. Data Synthesis: A total of 4142 studies were initially identified, with 40 meeting our inclusion criteria. Eleven studies were randomized controlled trials, 4 were cluster randomized trials, and 2 studies had randomized before-after designs. The remaining studies were controlled before-after (n = 2), cohort (n = 4), and uncontrolled before-after (n = 17) designs. Interventions focused on diabetes (n = 12), hypertension (n = 9), medication adherence (n = 9), lipids (n = 5), evidence-based medication initiation or optimization (n = 3), risk factor prediction scores (n = 1), and body mass index (n = 1). All studies contained interventions focused at the patient level and the majority of studies (34/40) involved interventions directed at both the physician and patient. No specific intervention emerged as superior, and study quality was generally poor, making it difficult to determine the true effect of the interventions. Conclusions: Poor study quality, time-intensive interventions, and unproven clinical significance warrant the need for further high-quality studies of community pharmacist interventions for preventing or managing diabetes or CVD and/or their major risk factors.
Coiled coils as possible models of protein structure evolution
Authors: Gáspári Zoltán , Nyitray László 
Published: May 2011

AbstractCoiled coils are formed by two or more α-helices wrapped around one another. This structural motif often guides di-, tri- or multimerization of proteins involved in diverse biological processes such as membrane fusion, signal transduction and the organization of the cytoskeleton. Although coiled coil motifs seem conceptually simple and their existence was proposed in the early 1950s, the high variability of the motif makes coiled coil prediction from sequence a difficult task. They might be confused with intrinsically disordered sequences and even more with a recently described structural motif, the charged single α-helix. By contrast, the versatility of coiled coil structures renders them an ideal candidate for protein (re)design and many novel variants have been successfully created to date. In this paper, we review coiled coils in the light of protein evolution by putting our present understanding of the motif and its variants in the context of structural interconversions. We argue that coiled coils are ideal subjects for studies of subtle and large-scale structural changes because of their well-characterized and versatile nature.
Effect of apolipoprotein E polymorphism on statin-induced decreases in plasma lipids and cardiovascular events
Authors: Hubacek Jaroslav A. , Vrablik Michal 
Published: May 2011

AbstractHypercholesterolemia or dyslipidemia is an independent risk factor for cardiovascular disease and statins (inhibitors of a key enzyme of cholesterol synthesis, 3-hydroxymethyl glutaryl coenzyme A reductase) are the drugs of choice for decreasing plasma cholesterol. It has been estimated that genetic factors can explain 40%–60% of final cholesterol concentrations and approximately 70% of the efficacy of statin treatment. The gene most often analyzed in the context of statin efficacy is the gene for apolipoprotein E (APOE). This review summarizes evidence of the association between variations in theAPOEgene locus and the response of plasma lipids to statin therapy. Although the results are not consistent, carriers of theAPOE4allele seems to be less responsive to statins than carriers ofAPOE2andAPOE3alleles. This effect is partially context-dependent (gene-gender interactions; gene-nutrition and gene-smoking interactions have not yet been studied) and the absolute differences vary between different population groups.
Approaching Parents to Take Part in a Cleft Gene Bank: A Qualitative Pilot Study
Authors: Williams Lucy , Dures Emma , Waylen Andrea , Ireland Tony , Rumsey Nichola , Sandy Jonathan 
Published: May 2011

Objective A gene bank, comprising genetic material and environmental and family history data, is being established in the United Kingdom to improve the understanding of the etiology of orofacial clefting (OFC). This study aimed to identify factors that might contribute to participation in a cleft gene bank and what issues need to be considered in approaching parents to be included. Design A qualitative approach was adopted, using focus groups and interviews. Transcripts of audio recordings were analyzed using inductive thematic analysis. Participants A UK cleft center invited 100 families of children born with OFC to participate. Inclusion criteria included any parent of a child aged between 6 months and 16 years willing to take part. Sixteen parents participated. Results Participants were generally motivated to take part in a cleft gene bank because they value the discovery of new knowledge of the etiology of OFC. They wanted reassurance about the purpose and integrity of the project. Many conveyed shock at the diagnosis of cleft and offered mixed accounts of experiences with health care professionals. They suggested an individualized approach from a trustworthy and sensitive professional when being invited to join the gene bank, avoiding difficult times associated with new-baby challenges and issues related to the cleft. Conclusions This pilot study indicates that parents of children born with OFC would be supportive of developing a cleft gene bank, but sensitive issues need to be considered.
Antiretroviral Prophylaxis and the Risk of Cleft Lip and Palate: Preliminary Signal Detection in the Food and Drug Administration's Adverse Events Reporting System Database
Authors: Cartsos Vassiliki M. , Palaska Pinelopi Kleio , Zavras Athanasios I. 
Published: May 2011

Objective Antiretroviral prophylaxis has been found to be effective in preventing vertical HIV transmission to the offspring of infected mothers. Because medicine and the art of public health require benefits to outweigh any plausible risks, our study aimed to explore and quantify preliminary associations between antiretroviral medications and clefting. Methods We analyzed 5 years of available data from the Food and Drug Administration's Adverse Events Reporting System (Medwatch program) and calculated reporting odds ratios (RORs) and their associated 95% confidence intervals (CIs). Results The medications with the highest effects were efavirenz with an ROR of 196 (95% CI, 86 to 447), lamivudine with an ROR of 60.2 (95% CI, 14.25 to 148), the combination abacavir sulfate/lamivudine/zidovudine with an ROR of 59.3, and nelfinavir with and ROR of 50.5, followed by nevirapine, lopinavir/ritonavir, and lamivudine/zidovudine. Conclusion Given the multifactorial etiology of cleft lip and palate, further studies are needed to assess the relative safety of antiretroviral prophylaxis and the specific conditions or potential synergies that might lead to the development of this defect.
Measuring Clinical Change in Routine Mental Health Care: Differences Between First Time and Longer Term Service Users
Authors: Parabiaghi Alberto , Rapisarda Filippo , D'Avanzo Barbara , Erlicher Arcadio , Lora Antonio , Barbato Angelo 
Published: May 2011

Objective: The aims were to assess the feasibility of routinely collecting outcome data in everyday mental health services across Italy and to evaluate clinical change in a cohort of patients stratified by illness duration. Method: A prevalence sample of patients attending nine Italian community mental health services (CMHS) was assessed over one year with the Health of the Nation Outcome Scales (HoNOS). The patients were classified on the basis of the duration of their contact with services. Clinical outcome was evaluated taking into account parameters of reliable and clinically significant change (RCSC). Predictors of change included clinical and socio-demographic characteristics at first assessment and six month reliable improvement. Results: 2059 patients were evaluated with only 3% attrition at follow up; 22% of first time and about 7% of longer term users achieved reliable improvement at one year. First contacts had a better outcome than longer term users and significant differences were seen at both group and individual level. Reliable improvement at six months was the best predictor of clinical improvement at one year for the whole cohort. Conclusion: The study demonstrated the feasibility of routine outcome assessment and gave an expected and realistic picture of the one-year outcome of a representative sample of patients attending a group of Italian CMHS. RCSC showed potential utility as a means of communicating with clinicians and decision makers.
‘It used to be about the kids’: Nutrition Reform and the Montreal Protestant School Board
Authors: Povitz Lana 
Published: May 2011

Abstract: The nutrition programs that developed in Montreal Protestant schools during the 1970s attest to a deepening awareness of child and adolescent welfare. The combination of grassroots activism and government support that brought about these initiatives took place in the context of post–Quiet Revolution Quebec, when Montrealers were grappling with the role that the newly activist state should play in social life. At the same time, school nutrition reform was part of a broader ongoing renegotiation of state responsibility. Both in Canada and the United States, governments were steadily assuming a mantle of responsibility for expanded liberal rights.
The YMDD and rtA194T Mutations Result in Decreased Replication Capacity in Wild-Type HBV as well as in HBV with Precore and Basal Core Promoter Mutations
Authors: Zhu Yuao , Curtis Maria , Borroto-Esoda Katyna 
Published: May 2011

Background: A recent study indicated that addition of the hepatitis B e antigen (HBeAg) precore (PC) or basal core promoter (BCP) mutations to wild-type HBV offset the reduced replication of the HBV polymerase rtA194T ±rtL180M+rtM204V mutations. rtA194T was reportedly associated with tenofovir resistance. We investigated these findings in genotype D HBV, where both PC and BCP naturally occur in vivo. Methods: A plasmid containing a wild-type 1.3 genome length genotype D HBV laboratory strain was used as a parent for PC, BCP, rtA194T ±rtL180M+rtM204V, rtL180M+rtM204V and rtM204I mutants. Viral replication was evaluated by Southern blot analysis of intracellular HBV core DNA following transient transfection of HepG2 cells. Drug susceptibility was evaluated by quantitative PCR of intracellular HBV DNA. Results: PC and BCP mutations each increased HBV DNA replication by approximately 200% over wild-type. rtA194T reduced replication by <40%, whereas rtL180M+rtM204V, rtL180M+rtA194T+rtM204V or rtM204I each reduced by >75% from their respective wild-type, PC or BCP genome backbone ( P<0.05). The enhanced replication by PC or BCP offset the reduction by rtA194T; however, the other reverse transcriptase (RT) mutations in PC or BCP backbones remained signifcantly lower than wild-type ( P<0.05). Regardless of the backbone, rtA194T ±rtL180M+rtM204V remained susceptible to tenofovir in vitro. rtA194T alone remained susceptible to lamivudine, while rtL180M+rtM204V and rtL180M+rtA194T+rtM204V were resistant. Conclusions: PC or BCP mutations increased HBV DNA replication, offset the decreased replication by rtA194T alone, but they did not fully rescue the impaired replication conferred by other RT mutations as compared with wild-type. rtA194T ±rtL180M+rtM204V did not confer tenofovir resistance.
Tonometry in Keratoconic Eyes before and after Riboflavin/UVA Corneal Collagen Crosslinking Using Three Different Tonometers
Authors: Gkika Maria G. , Labiris Georgios , Kozobolis Vassilios P. 
Published: May 2011

Purpose To evaluate the Goldmann applanation tonometer (GAT), the Pascal dynamic contour tonometer (PDCT), and the ocular response analyzer (ORA) tonometer in measuring intraocular pressure (IOP) in keratoconic eyes before and after riboflavin/ultraviolet A corneal collagen crosslinking (CXL), to assess agreement among devices and to analyze the impact of some ocular parameters on their measurements. Methods Fifty keratoconic eyes were included. Intraocular pressure was measured with GAT, PDCT, and ORA before and after CXL. Fifty nonkeratoconic eyes served as controls. Device agreements were calculated by Bland-Altman analysis. The effect of some ocular characteristics on IOP measurement differences between tonometers was determined. Results Between the 2 groups, there were statistically significant differences in all examined parameters. Preoperatively, in both groups a statistically significant difference was found in IOP measurements among devices (p<0.05). Bland-Altman analysis showed a bias among devices. On average, PDCT overread GAT and ORA. The IOP measurement differences were better predicted by corneal resistance factor. Postoperatively, in keratoconus eyes, there was no statistically significant difference in IOP measurements among the 3 tonometers (p>0.05). The IOP readings with all tonometers after treatment were higher than those obtained preoperatively; however, not to a statistically significant level, with the exception of PDCT and ORA readings at the first month postoperatively. Corneal resistance factor measurements have no significant change after CXL. Conclusions Pascal dynamic contour tonometer could provide more consistent and closer to the true IOP readings than GAT and ORA in healthy eyes with corneal thickness outside the 520-550 μm range, in keratoconus patients and after CXL. Corneal resistance factor was associated significantly with agreement among devices.
Three‐Dimensional Polymer Constructs Exhibiting a Tunable Negative Poisson's Ratio
Authors: Fozdar David Y. , Soman Pranav , Lee Jin Woo , Han Li‐Hsin , Chen Shaochen 
Published: May 2011

AbstractYoung's modulus and Poisson's ratio of a porous polymeric construct (scaffold) quantitatively describe how it supports and transmits external stresses to its surroundings. While Young's modulus is always non‐negative and highly tunable in magnitude, Poisson's ratio can, indeed, take on negative values despite the fact that it is non‐negative for virtually every naturally occurring and artificial material. In some applications, a construct having a tunable negative Poisson's ratio (an auxetic construct) may be more suitable for supporting the external forces imposed upon it by its environment. Here, three‐dimensional polyethylene glycol scaffolds with tunable negative Poisson's ratios are fabricated. Digital micromirror device projection printing (DMD‐PP) is used to print single‐layer constructs composed of cellular structures (pores) with special geometries, arrangements, and deformation mechanisms. The presence of the unit‐cellular structures tunes the magnitude and polarity (positive or negative) of Poisson's ratio. Multilayer constructs are fabricated with DMD‐PP by stacking the single‐layer constructs with alternating layers of vertical connecting posts. The Poisson's ratios of the single‐ and multilayer constructs are determined from strain experiments, which show (1) that the Poisson's ratios of the constructs are accurately predicted by analytical deformation models and (2) that no slipping occurrs between layers in the multilayer constructs and the addition of new layers does not affect Poisson's ratio.
Activation of Dioxygen by Cobaloxime and Nitric Oxide for Efficient TEMPO‐Catalyzed Oxidation of Alcohols
Authors: Jing Yuanyuan , Jiang Jun , Yan Bo , Lu Shuai , Jiao Jiemin , Xue Huazhen , Yang Guanyu , Zheng Gengxiu 
Published: May 2011

AbstractThe aerobic oxidation of alcohols to their corresponding carbonyl compounds could be efficiently accomplished by using the combination of cobalt nitrate, dimethylglyoxime and 2,2,6,6‐tetramethylpiperidine 1‐oxyl (TEMPO) as a novel catalytic system, and various alcohols including primary and secondary benzylic, allylic and aliphatic alcohols could be quantitatively converted to the corresponding aldehydes or ketones at 70 °C under 0.4 MPa dioxygen pressure in dichloromethane. During the oxidation, the in situ generated cobaloxime and nitric oxide (NO) were responsible for the activation of dioxygen, respectively, thereby, two concerted catalytic routes exist: cobaloxime‐activating‐dioxygen TEMPO‐catalyzed and NO‐activating‐dioxygen TEMPO‐catalyzed aerobic oxidation of alcohols.
Opposite effect of inflammation on subventricular zone versus hippocampal precursors in brain injury
Authors: Covey Matthew V. , Loporchio Dean , Buono Krista D. , Levison Steven W. 
Published: May 2011

AbstractObjective:Inflammation promotes epidermal wound healing but is considered detrimental to recovery from central nervous system injury. Sick infants have increased levels of cytokines in their cerebrospinal fluid that correlate with poor neurological outcome. In this study, we investigated the role of neuroinflammation and more specifically interleukin 6 (IL‐6) in the amplification of subventricular zone (SVZ) and subgranular zone (SGZ) neural precursors after neonatal brain injury.Methods:Neonatal hypoxia/ischemia (H/I) was induced in P6 rat pups, and IL‐6 was quantified with or without indomethacin administration. Neural precursor responses were evaluated by neurosphere assays as well as by stereological analyses. Studies were performed to determine how IL‐6 and leukemia‐inhibiting factor (LIF) affect SVZ cell expansion, proliferation, and self‐renewal.Results:Consistent with earlier studies, medially situated SVZ cells expanded after H/I. Contrary to our expectations, indomethacin significantly decreased both the initial reactive increase in these precursors and their ability to self‐renew. By contrast, indomethacin increased proliferation in the SGZ and lateral SVZ. Indomethacin diminished the accumulation of microglia/macrophages and IL‐6 production after H/I. In vitro IL‐6 enhanced neurosphere growth, self‐renewal, and tripotentiality and was more effective than LIF in promoting self‐renewal. Enhanced precursor self‐renewal also was obtained using prostaglandin E2, which is downstream of cyclooxygenase 2 and a target of indomethacin.Interpretation:These data implicate neuroinflammation and in particular IL‐6 as a positive effector of primitive neural precursor expansion after neonatal brain injury. These findings have important clinical implications, as indomethacin and other anti‐inflammatory agents are administered to premature infants for a variety of reasons. ANN NEUROL 2011;
A software support to initiate systems engineering students in service‐oriented computing
Authors: Mateos Cristian , Crasso Marco , Zunino Alejandro , Campo Marcelo 
Published: May 2011

ABSTRACTAn evolutionary process that is currently taking place in the software industry is the shift from developing applications from scratch to discovering and assembling services published in the Internet. This has given birth to a new computing paradigm called service‐oriented computing (SOC). We investigated whether simplifying and automating tasks inherent to SOC‐based development, while exploiting systems engineering students' experience in earlier paradigms, namely object orientation, reduce the cognitive effort needed to learn SOC. The study involved 38 undergraduate students plus 7 postgraduate students from 4 universities, which attended a course about SOC development models and technologies. Then, they were asked to develop a real‐life service‐oriented application using two alternatives, namely existing SOC libraries and a software support of our own named EasySOC. EasySOC promotes using common object‐oriented design patterns to structure service‐oriented applications, facilitates service discovery, and hides many technological details from users. The students were surveyed about their perception on both alternatives using a Likert‐based questionnaire. Results show that the students, who had no previous experience in service‐oriented notions before the experiment, perceived that EasySOC allows focusing on essential aspects of the paradigm while concealing accidental aspects, and provides adequate support and guidance to bridge the gap. © 2011 Wiley Periodicals, Inc. Comput Appl Eng Educ 22:252–265, 2014; View this article online at wileyonlinelibrary.com/journal/cae; DOI 10.1002/cae.20551