bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Systematic Review Assessing the Economic Impact of Sildenafil Citrate (Viagra®) in the Treatment of Erectile Dysfunction
Authors: Martin Amber L. , Huelin Rachel , Wilson David , Foster Talia S. , Mould Joaquin F. 
Published: January 2013

ABSTRACT

Introduction
Sildenafil was the first oral phosphodiesterase type 5 (PDE5) inhibitor introduced as primary therapy for erectile dysfunction (ED). In the 7 years following its market launch, sildenafil was prescribed by more than 750,000 physicians to more than 23 million men worldwide. To date, few studies have evaluated the economic impact of sildenafil in treating ED.

Aim
To evaluate the cost-effectiveness and impact of sildenafil on health care costs for patients with ED in multiple countries.

Main Outcomes Measures
Economic outcomes including cost, cost-effectiveness, cost of illness, cost consequence, resource use, productivity, work loss, and willingness to pay (WTP) were investigated.

Methods
Using keywords related to economic outcomes and sildenafil, we systematically searched literature published between July 2001 and July 2011 using MEDLINE and EMBASE. Included articles pertained to costs, WTP, and economic evaluations.

Results
In the last 10 years, 12 studies assessed economic outcomes associated with sildenafil for ED. Most studies were conducted in the United States and the United Kingdom, with one study identified in Canada and one from Mexico. Six studies evaluated cost of illness, cost consequence, or cost of care, and four studies evaluated WTP or drug pricing by country in the United States and the United Kingdom. In the United States and the United Kingdom, costs to health care systems have increased with demand for treatment. Cost analyses suggested that sildenafil would lower direct costs compared with other PDE5 inhibitors. US and UK studies found that patients exhibited WTP for sildenafil. The two cost-effectiveness models we identified examined ED sub-groups, those with spinal cord injury and those with diabetes or hypertension. These models indicated favorable cost-effectiveness profiles for sildenafil compared with other active-treatment options in both Mexico and Canada.

Conclusions
The relative value of sildenafil vs. surgically implanted prosthetic devices and other PDE5 inhibitors, is underscored by patients' WTP, and cost-effectiveness in ED patients with comorbidities.
Weight Loss by Multidisciplinary Intervention Improves Endothelial and Sexual Function in Obese Fertile Women
Authors: Aversa Antonio , Bruzziches Roberto , Francomano Davide , Greco Emanuela A. , Violi Francesco , Lenzi Andrea , Donini Lorenzo M. 
Published: January 2013

ABSTRACT

Introduction
Weight loss in sexually active women improves their quality of life. At present, no studies have investigated whether weight loss may affect female sexual function in severe obese women.

Aim
The aim of this study was to investigate the effects of different programs of weight loss on female sexual dysfunction complaints and on endothelial function in premenopausal obese females.

Methods
Forty-four out of overall 80 obese fertile women (age 18–49 years; mean 36 years) were enrolled because of sexual complaints at Female Sexual Function Index-6 (FSFI-6 score ≤19). Patients were then allocated to different treatments of 8 weeks duration each: an intensive residential program with hypocaloric diet plus controlled physical exercise along with lifestyle modifications at a specialized clinic (Group A, N = 23) and a non-intensive outpatient clinic program consisting of hypocaloric diet and physical exercise at home (Group B, N = 21). Afterward, overall patients were allocated to an extended 8-week follow-up period consisting of outpatient clinic controlled diet plus physical exercise at home.

Main Outcome Measures
Primary end points were modifications of FSFI-6 scores and endothelial function as measured by reactive hyperemia (RHI) with EndoPat-2000. Secondary end points were modifications in body composition as measured by dual-energy X-ray absorptiometry (DEXA).

Results
After 16 weeks, FSFI-6 score and the frequency of sexual activity were significantly higher in Group A compared with Group B (P &lt; 0.01), and significant improvements in arousal, lubrication, and satisfaction sub-domain scores were also found (P &lt; 0.01). Group A showed improvements in RHI (P &lt; 0.01) and marked improvement in homeostasis model assessment of insulin resistance (P &lt; 0.001), anthropometric parameters as weight (P &lt; 0.01), body mass index (P &lt; 0.01), fat mass (P &lt; 0.0001), and percentage of fat mass (P &lt; 0.005) compared with Group B. A relationship between peak insulin (P &lt; 0.0001) and RHI (P &lt; 0.001) vs. FSFI-6 scores was found, respectively.

Conclusions
A multidisciplinary approach to female obesity appears to be superior to conventional outpatient clinic to produce weight loss and to improve several aspects of sexual dysfunction in obese women. Such changes might be related to persistent improvements in endothelial function and in insulin resistance.
A Phase 2a Multicenter, Double-Blind, Placebo-Controlled, Crossover Trial to Investigate the Efficacy, Safety, and Toleration of CP-866,087 (a High-Affinity Mu-Opioid Receptor Antagonist) in Premenopausal Women Diagnosed with Female Sexual Arousal Disorder (FSAD)
Authors: Orri Miguel , Abraham Lucy , Giraldi Annamaria 
Published: January 2013

ABSTRACT

Introduction
Female sexual arousal disorder (FSAD) is a condition that can affect women of all ages and have a significant negative impact on emotional well-being.

Aims
The aim of this study is to prospectively evaluate the effects of CP-866,087, a selective mu-opioid receptor antagonist, in premenopausal women with FSAD.

Methods
The study included 51 women (20–45 years of age) with FSAD. All women received placebo and two of three planned doses of CP-866,087 (1, 3, and 10 mg) for 6 weeks in each of three double-blind treatment periods. Efficacy was determined through a series of measures to assess sexual functioning, sexual activity, sexual distress, and perceived meaningful benefit as a result of treatment. In addition, a semi-structured exit interview was conducted at the end of the fourth treatment period or withdrawal to provide a more in-depth, qualitative description of the participants' symptoms, response to treatment, and treatment satisfaction to augment the quantitative assessments.

Main Outcome Measures
The within-subject differences from placebo in the change from baseline were compared across a range of measures of sexual function. Summary statistics and 90% confidence intervals were calculated. A qualitative analysis of the exit interview was conducted based on grounded theory methods.

Results
Although improvements were seen with CP-866,087 in the key efficacy end points, there was no clinical treatment benefit over placebo. The exit interview analysis suggested that being part of the study and taking positive action to search for a solution to the women's sexual disorder may have been a significant factor in the behavioral changes that were seen, as opposed to the drug treatment itself.

Conclusions
Discerning the potential benefit of pharmacotherapy in a heterogeneous condition such as FSAD is challenging. Participation in a clinical trial combined with a commitment to actively engage in sexual activity may in itself create an environment that is conducive to symptom improvement.
Termite mounds as browsing hotspots: an exception to the rule
Authors: O'Connor T.G. 
Published: January 2013

AbstractIn African savannas, termite mounds usually serve as browsing hotspots for mammals because of their soil fertility. Van der Plas et al., in this issue, describe that browsers avoid the unpalatable, evergreen tree species on mounds of Macrotermes natalensis in a mesic savanna, preferring mainly leguminous species with high leaf N and P concentrations in the matrix. This exception is probably a consequence of the fertile soils of the study area, and highlights the importance of environmental context for assessing ecological interactions.
Survey of Chinese Historical Syntax Part I: Pre‐Archaic and Archaic Chinese
Authors: Aldridge Edith 
Published: January 2013

AbstractThis is the first of two articles presenting a brief overview of Chinese historical syntax from the Pre‐Archaic period to Middle Chinese. The phenomena under examination in the two papers are primarily aspects of pre‐medieval grammar which differ markedly from modern Chinese varieties, specifically fronting of object NPs to preverbal position, the asymmetry between subject and object relative clause formation, and the encoding of argument structure alternations like active and passive. I relate each of these characteristics to morphological distinctions on nouns, verbs, or pronouns, which are either overtly represented in the logographic writing system in Archaic Chinese or have been reconstructed for (Pre‐)Archaic Chinese. In the second part of this series, I discuss the changes in the Archaic Chinese grammatical features and correlate these innovations with the loss of the (Pre‐)Archaic Chinese morphology. The main goal of these articles is to highlight a common denominator, i.e. the morphology, which enables a systemic view of pre‐medieval Chinese and the changes which have resulted in the striking differences observed in Middle Chinese and beyond.
Stepwise colonization of the Andes by Ruddy Ducks and the evolution of novel β‐globin variants
Authors: Muñoz‐Fuentes V. , Cortázar‐Chinarro M. , Lozano‐Jaramillo M. , McCracken K. G. 
Published: January 2013

AbstractAndean uplift played a key role in Neotropical bird diversification, yet past dispersal and genetic adaptation to high‐altitude environments remain little understood. Here we use multilocus population genetics to study population history and historical demographic processes in the ruddy duck (Oxyura jamaicensis), a stiff‐tailed diving duck comprising three subspecies distributed from Canada to Tierra del Fuego and inhabiting wetlands from sea level to 4500 m in the Andes. We sequenced the mitochondrial DNA, four autosomal introns and three haemoglobin genes (αA, αD, βA) and used isolation‐with‐migration (IM) models to study gene flow between North America and South America, and between the tropical and southern Andes. Our analyses indicated that ruddy ducks dispersed first from North America to the tropical Andes, then from the tropical Andes to the southern Andes. While no nonsynonymous substitutions were found in either α globin gene, three amino acid substitutions were observed in the βA globin. Based on phylogenetic reconstruction and power analysis, the first βA substitution, found in all Andean individuals, was acquired when ruddy ducks dispersed from low altitude in North America to high altitude in the tropical Andes, whereas the two additional substitutions occurred more recently, when ruddy ducks dispersed from high altitude in the tropical Andes to low altitude in the southern Andes. This stepwise colonization pattern accompanied by polarized βA globin amino acid replacements suggest that ruddy ducks first acclimatized or adapted to the Andean highlands and then again to the lowlands. In addition, ruddy ducks colonized the Andean highlands via a less common route as compared to other waterbird species that colonized the Andes northwards from the southern cone of South America.
Hydrogen peroxide‐regulated genes in the Medicago truncatula–Sinorhizobium meliloti symbiosis
Authors: Andrio Emilie , Marino Daniel , Marmeys Anthony , de Segonzac Marion Dunoyer , Damiani Isabelle , Genre Andrea , Huguet Stéphanie , Frendo Pierre , Puppo Alain , Pauly Nicolas 
Published: January 2013

Summary

Reactive oxygen species (ROS), particularly hydrogen peroxide (H2O2), play an important role in signalling in various cellular processes. The involvement of H2O2 in the Medicago truncatula–Sinorhizobium meliloti symbiotic interaction raises questions about its effect on gene expression.

A transcriptome analysis was performed on inoculated roots of M. truncatula in which ROS production was inhibited with diphenylene iodonium (DPI). In total, 301 genes potentially regulated by ROS content were identified 2 d after inoculation. These genes included MtSpk1, which encodes a putative protein kinase and is induced by exogenous H2O2 treatment.

MtSpk1 gene expression was also induced by nodulation factor treatment. MtSpk1 transcription was observed in infected root hair cells, nodule primordia and the infection zone of mature nodules. Analysis with a fluorescent protein probe specific for H2O2 showed that MtSpk1 expression and H2O2 were similarly distributed in the nodule infection zone. Finally, the establishment of symbiosis was impaired by MtSpk1 downregulation with an artificial micro‐RNA.

Several genes regulated by H2O2 during the establishment of rhizobial symbiosis were identified. The involvement of MtSpk1 in the establishment of the symbiosis is proposed.
Current options for management of biliary atresia
Authors: Gallo Amy , Esquivel Carlos O. 
Published: January 2013

AbstractIt is encouraging that we are improving the technical aspects of treatment modalities for biliary atresia. However, it is clear that more needs to be done to best develop new treatment plans while applying the modalities we have (porto‐enterostomy or liver transplantation or both) in a way that will afford the best survival and quality‐of‐life. This review article will discuss a number of points that are vital to improving care and illustrates the need to further scrutinize treatment decisions.
The Middle‐class in the German Welfare State: Beneficial Involvement at Stake?
Authors: Mau Steffen , Sachweh Patrick 
Published: January 2013

AbstractThe working‐class is typically regarded as the driving force of welfare state development. Yet, some argue that the middle‐classes' beneficial involvement in the welfare state is crucial for its financial sustainability and popular legitimacy. Against this backdrop, we investigate how recent welfare state reforms in Germany which affect the status of the middle‐class are viewed and discussed by this group. Germany is a particularly interesting case because its welfare state is seen to be centred on the desires of the middle‐class, especially through its focus on status maintenance and horizontal redistribution over the life‐course. However, the move from status maintenance to minimum income support in unemployment provision and the strengthening of private old age provision challenge this assumption. Thus, we ask how the German middle‐class views the emerging abandonment of the principle of status maintenance and the shift from collective to individual responsibility. Based on qualitative material from focus groups, we find that individual responsibility is generally supported, but that the state is still assigned responsibility for providing basic levels of social security. Furthermore, for those groups seen as less capable of acting individually responsible (e.g. the poor or long‐term unemployed) the ‘inducement’ of – or assistance for – individually responsible behaviour by the state is demanded. Overall, while the principle of ‘individual responsibility’ seems to find some resonance among the middle‐class members interviewed, they still try to balance individual and collective responsibility.
Worrisome Trend of New Multiple Mechanisms of Linezolid Resistance in Staphylococcal Clones Diffused in Italy
Authors: Campanile Floriana , Mongelli Gino , Bongiorno Dafne , Adembri Chiara , Ballardini Milva , Falcone Marco , Menichetti Francesco , Repetto Antonella , Sabia Carla , Sartor Assunta , Scarparo Claudio , Tascini Carlo , Venditti Mario , Zoppi Federica , Stefani Stefania 
Published: January 2013

ABSTRACT

In order to assess the frequency of clinically relevant linezolid-resistant staphylococcal isolates, and the role of linezolid in maintaining and coselecting multiple resistance mechanisms (
cfr
, 23S rRNA, L3/L4 mutations), a prospective Italian study was performed from 2010 to 2011 to confirm the diffusion of three major multidrug-resistant clones (ST2, ST5, ST23).
Enterovirus 71 Infection Cleaves a Negative Regulator for Viral Internal Ribosomal Entry Site-Driven Translation
Authors: Chen Li-Lien , Kung Yu-An , Weng Kuo-Feng , Lin Jing-Yi , Horng Jim-Tong , Shih Shin-Ru 
Published: January 2013

ABSTRACT

Far-upstream element-binding protein 2 (FBP2) is an internal ribosomal entry site (IRES)
trans
-acting factor (ITAF) that negatively regulates enterovirus 71 (EV71) translation. This study shows that EV71 infection cleaved FBP2. Live EV71 and the EV71 replicon (but not UV-inactivated virus particles) induced FBP2 cleavage, suggesting that viral replication results in FBP2 cleavage. The results also showed that virus-induced proteasome, autophagy, and caspase activity co-contribute to EV71-induced FBP2 cleavage. Using FLAG-fused FBP2, we mapped the potential cleavage fragments of FBP2 in infected cells. We also found that FBP2 altered its function when its carboxyl terminus was cleaved. This study presents a mechanism for virus-induced cellular events to cleave a negative regulator for viral IRES-driven translation.
Prostate-Specific Antigen-Retargeted Recombinant Newcastle Disease Virus for Prostate Cancer Virotherapy
Authors: Shobana Raghunath , Samal Siba K. , Elankumaran Subbiah 
Published: January 2013

ABSTRACT

Oncolytic virus (OV) therapies of cancer are based on the use of replication-competent, tumor-selective viruses with limited toxicity. Newcastle disease virus (NDV), an avian paramyxovirus, is a promising OV and is inherently tumor selective and cytotoxic only to tumor cells. Replication is restricted in normal cells. Despite encouraging phase I/II clinical trials with NDV, further refinements for tumor-specific targeting are needed to enhance its therapeutic index. Systemically delivered NDV fails to reach solid tumors in therapeutic concentrations and also spreads poorly within the tumors due to barriers including complement, innate immunity, and the extracellular matrix. Overcoming these hurdles is paramount to realizing the exceptional oncolytic efficacy of NDV. We engineered the F protein of NDV and generated a recombinant NDV (rNDV) whose F protein is cleavable exclusively by prostate-specific antigen (PSA). The rNDV replicated efficiently and specifically in prostate cancer (CaP) cells and 3-dimensional prostaspheres but failed to replicate in the absence of PSA. Induction of intracellular PSA production by a synthetic androgen analog (R1881) enhanced fusogenicity in androgen-responsive CaP cells. Further, PSA-cleavable rNDV caused specific lysis of androgen-independent and androgen-responsive/nonresponsive CaP cells and prostaspheres, with a half-maximal effective concentration (EC
50
) ranging from a multiplicity of infection of 0.01 to 0.1. PSA-retargeted NDV efficiently lysed prostasphere tumor mimics, suggesting efficacy
in vivo
. Also, PSA-cleavable NDV failed to replicate in chicken embryos, indicating no pathogenicity for chickens. Prostate-specific antigen targeting is likely to enhance the therapeutic index of rNDV owing to tumor-restricted replication and enhanced fusogenicity.
In VitroModeling of Human Bocavirus 1 Infection of Polarized Primary Human Airway Epithelia
Authors: Deng Xuefeng , Yan Ziying , Luo Yong , Xu Jian , Cheng Fang , Li Yi , Engelhardt John F. , Qiu Jianming 
Published: January 2013

ABSTRACTHuman bocavirus 1 (HBoV1) is an emerging human-pathogenic respiratory virus. We characterized two important features of HBoV1 infection in polarized primary human airway epithelia (HAE). Apical HBoV1 infection of HAE at a low multiplicity of infection causes disruption of the tight junction barrier, loss of cilia, and epithelial cell hypertrophy, which are hallmarks of the airway epithelial damage caused by HBoV1 infection. HBoV1 also infects HAE from the basolateral surface productively, although less efficiently, and this also leads to the characteristic airway epithelial damage.
Would they dope? Revisiting the Goldman dilemma
Authors: Connor James , Woolf Jules , Mazanov Jason 
Published: January 2013

Background/aimDiscussions of doping often report Goldman's sensational results that half of the elite athletes asked would take a drug that guaranteed sporting success which would also result in their death in 5 years’ time. There has never been any effort to assess the properties of the ‘Goldman dilemma’ or replicate the results in the post World Anti-Doping Agency context. This research evaluated the dilemma with contemporary elite athletes.MethodsParticipants at an elite-level track and field meet in North America were segregated into an interview or online response. After basic demographics, participants were presented with three variant ‘Goldman’ dilemmas counter-balanced for presentation order.ResultsOnly 2 out of 212 samples (119 men, 93 women, mean age 20.89) reported that they would take the Faustian bargain offered by the original Goldman dilemma. However, if there were no consequences to the (illegal) drug use, then 25/212 indicated that they would take the substance (no death condition). Legality also changes the acceptance rate to 13/212 even with death as a consequence. Regression modelling showed that no other variable was significant (gender, competitive level, type of sport) and there was no statistical difference between the interview and online collection method.ConclusionsGoldman's results do not match our sample. A subset of athletes is willing to dope and another subset is willing to sacrifice their life to achieve success, although to a much lesser degree than that observed by Goldman. A larger scale online survey is now viable to answer important questions such as variation across sports.
Developing a multidisciplinary approach within the ED towards domestic violence presentations
Authors: Basu Subhashis , Ratcliffe Giles 
Published: January 2013

AimTo improve the detection and quality of care of patients who attend the emergency department (ED) with confirmed or suspected domestic abuse (DA).DesignA quality improvement report on the design, implementation and evaluation of a specialised service and structured training programme to detect and manage DA presentations within an emergency medicine department.SettingThe study was set in the ED at the Northern General Hospital, Sheffield, UK.Key measures for improvementKey measures for improvement included introducing a service within the ED to help staff manage DA and coordinate responses; improve staff confidence in detecting DA; develop a structured and consistent process by which to manage DA presentations.Strategies for changeAn Independent Domestic Violence Advocate service was introduced into the department in July 2011 through a multiagency agreement. A structured training and education programme was delivered to ED staff. A ‘communications form’ was developed for DA risk assessment and case management. The process was reviewed quarterly.ResultsOne hundred and seventy-two referrals were made to the service (121 distinct clients) over a 12-month period. Staff reported greater confidence in detecting DA, and community partners highlighted the role the service had in improving DA detection and care quality within the city.ConclusionsStrong leadership and prioritising the issue within the department has facilitated the development of the process and contributed substantially to its success. Support from community partners has been invaluable in tailoring the service and education programme to the needs of staff and patients within the department.