bluuebunny/crossref_metadata_2025 huggingface dataset:
Re‐stocking practices and illegal fishing in northern Chile (SE Pacific coast): a study case
Authors: Ortiz Marco , Levins Richard
Published: March 2011

We constructed eco‐social models with different levels of complexity in order to represent the activities that fishermen operating under two different regimes, Chilean Territorial Use Rights in Fisheries (TURFs) and Open Access Areas (OAAs). We used Levins's loop analysis as a theoretical framework for assessing the local stability or sustainability of the models and management strategies represented by the scenarios. Our results suggest that the current harvest dynamics (scenario 1 of all models) cannot be locally stable or sustainable unless they meet the following conditions: (1) the abundance of Concholepas concholepas adults fluctuates close to its carrying capacity (K); and (2) the demand (market) presents some type of control (i.e. taxes). Likewise, simultaneous re‐stocking of C. concholepas adults and juveniles in TURFs seems to be sustainable only if the demand is controlled, thus, under current conditions it is not recommended as a management strategy. Alternatively, the simultaneously exploiting C. concholepas and re‐stocking juveniles can lead to stability, but again if the demand is controlled. The sustainability of illegal fishing of C. concholepas from OAAs (for re‐stocking into TURFs and for the local market) is not reached independent of the self‐dynamics of demand and the abundance of wild meta‐populations. Moreover, habitat destruction caused during the search for C. concholepas individuals in OAAs causes instability in the system and, therefore, educational efforts should be aimed at the fishermen as a way to avoid these practices. Given the results obtained, we find it difficult to consider TURFs – as a whole – to be a conservationist administrative measure. On the contrary, we believe that, as currently practiced, TURFs better resemble a simple program of C. concholepas mariculture, in which case they are comparable to traditional intensive agriculture, which is itself far from conservationist. The approach developed here is proposed as a general strategy for examining the consequences of natural changes and human interventions in marine coastal ecosystems.
Abundance trumps quality: bi‐trophic performance and parasitism risk fail to explain host use in the fall webworm
Authors: Mason Peri A. , Wilkes Steven R. , Lill John T. , Singer Michael S.
Published: March 2011

Factors including host abundance, quality, and the degree to which hosts provide enemy‐free space (EFS) may drive host plant choice by phytophagous insects. Herbivores may also experience fitness tradeoffs among hosts, promoting polyphagy. The fall webworm Hyphantria cunea is a dietary generalist that feeds on a broad array of trees across its geographic range. Here, we investigate the drivers of host tree use by the fall webworm in Connecticut (CT) and Maryland (MD). Neither caterpillar performance nor EFS was associated with the frequency with which host trees were used, and no tradeoff between host quality and EFS was identified. Vegetation surveys adjacent to host trees showed that at both localities, host use was non‐random with respect to tree species, and that the main predictor of use among suitable host trees was host tree abundance. This suggests that webworms are under selection to reduce search time for oviposition sites. Although we did not detect a tradeoff between host plant quality and availability in MD, we did identify that tradeoff in CT. This disparity amid otherwise similar patterns of host use between CT and MD may be explained by the relative rarity of high quality hosts in CT compared to MD. Our results illustrate that geographic mosaics in patterns of host use may arise in the absence of local adaptation if host use is based upon availability rather than host plant attributes.
Retinyl retinoate, a novel hybrid vitamin derivative, improves photoaged skin: a double‐blind, randomized‐controlled trial
Authors: Kim H. , Koh J. , Baek J. , Seo Y. , Kim B. , Kim J. , Lee J. , Ryoo H. , Jung H.
Published: March 2011

Background: All‐trans‐retinoic acid (RA) and all‐trans‐retinol (ROL) are not widely used as anti‐wrinkle agents due to their irritancy and photo‐stability, respectively. Therefore, the safety and photo‐stability in the development of RA or ROL derivatives have been an important issue.

Aim: To identify the efficacy of retinyl retinoate as an anti‐aging agent of cosmetics in treating females over 30 years old with periorbital wrinkles.

Methods: The clinical study was a prospective, double‐blind, randomized, and controlled study with a total of 11 Korean women. At every 4 weeks, the effectiveness was assessed with a global photodamage score, photographs, and image analysis using replicas and visiometers. The dermal distance and intensity was also evaluated using Dermascan C.

Results: A statistically significant improvement in facial wrinkles (P<0.05) in eleven volunteers was observed in a clinical trial. The successive application of 0.06% retinyl retinoate cream for 3 months showed decreased depth and area of wrinkles in comparison with 0.075% retinol cream. The visual wrinkle improvement and the maximum roughness improvement rate (R2) for retinyl retinoate cream were 22% higher than that of retinol cream after 12 weeks. A statistically significant increase was observed after 8 and 4 weeks for dermal distance and dermal intensity, respectively (P<0.05).

Conclusions: Retinyl retinoate had characteristic features of new anti‐aging agents, and effectively improved facial wrinkle conditions.
Soft Tissue Attachment to Titanium Implants Coated with Growth Factors
Authors: Bates Christopher , Marino Victor , Fazzalari Nicola L. , Bartold P. Mark
Published: March 2011

Background: Enhancing the connective tissue seal around dental implants may be an important factor in implant survival.

Purpose: The objective of the study was to investigate the effect of implant surface modification with either platelet‐derived growth factor (PDGF) or enamel matrix derivative (EMD) on connective tissue attachment to titanium implants.

Materials and Methods: Eighteen implants (Branemark® Mk III Groovy NP (3.3 mmØ × 10 mm, Nobel Biocare) were implanted subcutaneously into 12 rats. Six implants each were coated with either PDGF or EMD immediately prior to implantation and six implants were left uncoated. Implants were retrieved at 4 and 8 weeks and assessed histologically to compare the soft tissue adaptation to the implant surfaces.

Results: Ingrowth by soft connective tissue into the threads of all implants was noted at 4 and 8 weeks. Coating with growth factors did not alter the orientation of fibroblasts and collagen fibers. The depth of connective tissue penetration into the implant grooves was significantly greater for the implants coated with PDGF at 4 weeks. The thickness of the connective tissue in growth was significantly less for the implants coated with PDGF at 8 weeks.

Conclusion: Coating of the implant surface with rhPDGF‐BB or EMD can increase the speed and quantity of soft tissue healing around the implant surface.
Prosthetic Rehabilitation, Implant Survival and Quality of Life 2 to 5 Years after Resection of Oral Tumors
Authors: Katsoulis Joannis , Fierz Janine , IIzuka Takeyuki , Mericske‐Stern Regina
Published: March 2011

Background: After oral tumor resection, structural and functional rehabilitation by means of dental prostheses is complex, and positive treatment outcome is not always predictable.

Purpose: The objective of the study was to report on oral rehabilitation and quality of life 2–5 years after resection of malignant oral tumors.

Materials and Methods: Data of 46 patients (57 ± 7 years) who underwent oral tumor surgery were available. More than 50% of tumors were classified T3 or T4. Open oro‐nasal defects resulted in 12 patients and full mandibulary block resections in 23 patients. Comprehensive planning, implant placement, and prosthetic rehabilitation followed an interdisciplinary protocol. Analysis comprised tumor location, type of prostheses, implant survival, and quality of life.

Results: Because of advanced tumor status, resections resulted in marked alteration of the oral anatomy requiring complex treatment procedures. Prosthetic rehabilitation comprised fixed and removable prostheses, with 104 implants placed in 28 patients (60%). Early implant loss was high (13%) and cumulative survival rate of loaded implants was <90% after 5 years. Prosthetic plans had to be modified because of side effects of tumor therapy, complications with implants and tumor recurrence. The majority of patients rated quality of life favorable, but some experienced impaired swallowing, dry mouth, limited mouth opening, appearance, and soreness.

Conclusions: Some local effects of tumor therapy could not be significantly improved by prosthetic rehabilitation leading to functional and emotional disability. Many patients had passed away or felt too ill to fill the questionnaires. This case series confirms the complex anatomic alterations after tumor resection and the need for individual treatment approaches especially regarding prosthesis design. In spite of disease‐related local and general restrictions, most patients gave a positive assessment of quality of life.
Cross-Sectional Survey of Sexual Dysfunction and Quality of Life Among Older People in Indonesia
Authors: Santosa Ailiana , Őhman Ann , Högberg Ulf , Stenlund Hans , Hakimi Mohammad , Ng Nawi
Published: March 2011

Introduction

The burden of sexual dysfunction among older people in many low- and middle-income countries is not well known. Understanding sexual dysfunction among older people and its impact on quality of life is essential in the design of appropriate health promotion programs.

Aims

To assess levels of sexual function and their association with quality of life while controlling for different sociodemographic determinants and chronic diseases among men and women over 50 years of age in rural Indonesia.

Methods

A cross-sectional study was conducted in the Purworejo District, Central Java, Indonesia in 2007. The study involved 14,958 men and women over 50 years old. The association between sexual dysfunction and quality of life after controlling for potential confounders (e.g., sociodemographic determinants and self-reported chronic diseases) was analyzed by multivariable logistic regression.

Main Outcome Measures

Self-reported quality of life.

Results

Older men more commonly reported sexual activity, and sexual problems were more common among older women. The majority of older men and women reported their quality of life as good. Lack of sexual activity, dissatisfaction in sexual life, and presence of sexual problems were associated with poor self-reported quality of life in older men after adjustment for age, marital status, education, and history of chronic diseases. A presence of sexual problems was the only factor associated with poor self-reported quality of life in women. Being in a marital relationship might buffer the effect of sexual problems on quality of life in men and women.

Conclusion

Sexual dysfunction is associated with poor quality of life among older people in a rural Javanese setting. Therefore, promotion of sexual health should be an integral part of physical and mental health campaigns in older populations.
Impacting Factors for Recovery of Erectile Function Within 1 Year Following Robotic-Assisted Laparoscopic Radical Prostatectomy
Authors: Ko Woo Jin , Truesdale Matthew D. , Hruby Gregory W. , Landman Jaime , Badani Ketan K.
Published: March 2011

Introduction

Neurovascular bundle preservation generally results in good postoperative sexual function after radical prostatectomy. However, erectile function (EF) after radical prostatectomy is still a significant concern. The same surgical technique often results in different EF outcomes.

Aim

We evaluated factors that correlate with recovery of EF within 1 year after robotic-assisted laparoscopic radical prostatectomy (RALP).

Methods

From January 2008 to May 2009, 145 consecutive patients underwent RALP by one surgeon. Patients were followed postoperatively at 3-month intervals and assessed for EF recovery, defined as an erection sufficient for penetrative intercourse with satisfaction. Baseline demographics, medical comorbidities, degree of nerve sparing, and perioperative and postoperative variables were recorded. Univariate and multivariate analyses were used to determine factors associated with EF recovery.

Main Outcome Measures

Postoperative sexual outcomes were attained prospectively via our erectile state questionnaire.

Results

Complete follow-up EF data were available on 89 men. Within 1-year follow-up, 56 men (62.9%) recovered EF and 33 men (37.1%) did not. In univariate logistic regression analysis, race (black), diabetes mellitus, hyperlipidemia, and clinical T2 carcinoma of the prostate were associated with diminished EF. Higher-preoperative Sexual Health Inventory for Men score and incremental nerve sparing (enhanced lateral prostatic fascia sparing) were associated with higher odds of recovering potency. In multivariate analysis, hyperlipidemia was primary comorbidity associated with diminished EF, and bilateral nerve sparing with a minimum unilateral-enhanced status was the impacting factor for EF recovery within 1 year after surgery.

Conclusions

Bilateral nerve preservation with a minimum unilateral-enhanced status is associated with improved recovery of EF, and hyperlipidemia is a significant negative predictive factor of postoperative EF recovery within 1 year following RALP. Therefore, it is important to control hyperlipidemia as well as to use the proper surgical technique in maximizing EF recovery within 1 year after radical prostatectomy.
Cardiovascular Mortality in Men with Erectile Dysfunction: Increased Risk But Not Inevitable
Authors: Chew Kew-Kim , Gibson Nicholas , Sanfilippo Frank , Stuckey Bronwyn , Bremner Alexandra
Published: March 2011

Introduction

It is unclear whether men with erectile dysfunction (ED) ultimately die of cardiovascular (CV) causes.

Aim

This study examined the causes of death in men with ED and their risk of CV death.

Methods

Based on statutory death registrations and hospital morbidity data, the risk of CV death in men with ED in a linked-data study was assessed against the CV mortality risk in a reference male population.

Main Outcome Measures

Deaths from CV causes as proportions of all deaths. Age-specific rate, mortality rate ratio (MRR), standardized mortality rate ratio (SMRR), and adjusted hazard ratio (HR).

Results

CV mortality was 4.0%. Compared with the reference population, the risk of CV death was higher in men with ED (SMRR 2.2; 95% confidence interval [CI] 1.6, 3.0). Risk of CV mortality was higher in men with CV disease prior to ED (adjusted HR 1.7; 95% CI 1.1, 2.6) or with history of hospital admissions for CV events (adjusted HR 2.2; 95% CI 1.3, 3.8), compared with those without the respective history. MRR was significantly increased in the 40–69 years age group (MRR 4.1; 95% CI 3.2, 5.2). The median time interval between manifestation of ED and CV death was 10.0 years. A greater proportion of deaths from oncological than from CV causes (25.0% vs. 10.8%) occurred within the first 5 years of the manifestation of ED.

Conclusions

Although the risk of CV mortality is greater in men with ED, almost as many men die of oncological as of CV causes, with a higher proportion of oncological deaths occurring sooner subsequent to the first manifestation of ED.
Asthma and Risk of Erectile Dysfunction—A Nationwide Population-Based Study
Authors: Chou Kun-Ta , Huang Chin-Chou , Chen Yuh-Min , Perng Diang-Wang , Chao Heng-Sheng , Chan Wan-Leong , Leu Hsin-Bang
Published: March 2011

Introduction

The increased prevalence of erectile dysfunction (ED) has been reported in patients with chronic obstructive pulmonary disease, and sustained systemic inflammation seems to play a central role in this linkage. Asthma is also a chronic inflammatory airway disorder, eliciting a low-grade systemic inflammation; however, the influence of asthma on ED has not been investigated.

Aim

Our study strived to explore the relationship of asthma and the subsequent development of ED using a nationwide, population-based database.

Methods

From 2000 to 2007, we identified newly diagnosed asthma cases involving male patients 18–55 years old. A control cohort without asthma, which was matched for age and comorbidities, was selected for comparison.

Main Outcome Measures

The two cohorts were followed up, and we observed the occurrence of ED by registry of ED diagnosis in the database.

Results

Of the 17,302 sampled patients (3,466 asthma patients vs. 13,836 control), 114 (0.66%) experienced ED during a mean follow-up period of 4.56 years, including 34 (0.98% of the asthma patients) from the asthma cohort and 80 (0.58%) from the control group. Subjects with asthma experienced a 1.909-fold (95% confidence interval [CI], 1.276–2.856; P =0.002) increase in incident ED, which was independent of age, the number of clinical visits for urologist, and other comorbidities. Kaplan–Meier analysis also revealed the tendency of asthma patients for ED development (log rank test, P =0.002). The risk of ED was higher in cases with more frequent clinical visits for asthma (asthma patients with clinical visits with >24 times/year vs. <12 times/year: hazard ratio [HR]: 4.154 [95% CI:1.392–12.396], P =0.011; clinical visits with 12–24 times/year vs. <12 times/year HR: 3.534 [95% CI:1.245–10.032], P =0.018).

Conclusions

Asthma may be an independent risk factor for ED, and risk of ED probably increases in accordance with asthma severity.
SWEETNESS EQUIVALENCE OF DIFFERENT SWEETENERS IN STRAWBERRY‐FLAVORED YOGURT
Authors: REIS RONIELLI C. , MINIM VALÉRIA P.R. , BOLINI HELENA M.A. , DIAS BEATRIZ R.P. , MINIM LUIS A. , CERESINO ELAINE B.
Published: March 2011

To successfully substitute sucrose for sweeteners, further studies must be carried out based on previous knowledge of sweetener concentration to determine the equivalent sweetness of such compounds. In this work, sweetness equivalence of strawberry‐flavored yogurt with different sweeteners and/or their combinations (aspartame, acesulfame‐K, cyclamate, saccharin, stevia and sucralose) and yogurt sweetened with 11.5% w/w sucrose was measured using the sensory magnitude estimation method. The sweetness concentrations equivalent to strawberry yogurt sweetened with 11.5% w/w sucrose in the tested sweeteners were 0.072% w/w for aspartame, 0.042% w/w for aspartame/acesulfame‐K (2:1), 0.064% w/w for cyclamate/saccharin, 0.043% w/w for cyclamate/saccharin (2:1)/stevia (1.8:1) and 0.30% w/w for sucralose. These results can promote the use of different sweetener combinations in strawberry‐flavored yogurt, specially acesulfame‐K and stevia, once they produce more pleasing in this product.

PRACTICAL APPLICATIONS

This study provides some useful information, since there is no data in the literature about sweetness equivalence of sweeteners in yogurt, but only in simpler matrices such as pure water, juices, coffee and teas. The use of stevia blend presented several advantages such as increased sweetening power, demonstrating the potential of this natural sweetener. The magnitude estimation method has been successful in this study, being an important tool for development of new low‐calorie products. It may be noted that when evaluating different types of food using the same kinds of sweeteners, these promote distinct characteristics and that reflect directly on the sensory quality of the final product. Thus, such studies generate important information for the food industries working with dietetic food.
coral Software: QSAR for Anticancer Agents
Authors: Benfenati Emilio , Toropov Andrey A. , Toropova Alla P. , Manganaro Alberto , Gonella Diaza Rodolfo
Published: March 2011

CORrelations And Logic (coral at http://www.insilico.eu/coral) is freeware aimed at establishing a quantitative structure – property/activity relationships (QSPR/QSAR). Simplified molecular input line entry system (SMILES) is used to represent the molecular structure. In fact, symbols in SMILES nomenclatures are indicators of the presence of defined molecular fragments. By means of the calculation with Monte Carlo optimization of the so called correlation weights (contributions) for the above‐mentioned molecular fragments, one can define optimal SMILES‐based descriptors, which are correlated with an endpoint for the training set. The predictability of these descriptors for an external validation set can be estimated. A collection of SMILES‐based models of anticancer activity of 1,4‐dihydro‐4‐oxo‐1‐(2‐thiazolyl)‐1,8‐naphthyridines for different splits into training and validation set which are calculated with the coral are examined and discussed. Good performance has been obtained for three splits: the r2 ranged between 0.778 and 0.829 for the sub‐training set, between 0.828 and 0.933 for the calibration set, and between 0.807 and 0.931 for the validation set.
Influence of electrochemical polishing on the mechanical behaviour of nickel‐titanium rotary files
Authors: da Silva Marcio A. C. , Ponciano Gomes José Antônio da C. , Ormiga Fabiola
Published: March 2011

The purpose of this study was to evaluate the influence of electrochemical polishing on the cyclic fatigue, cutting efficiency and surface topography of Miltex nickel‐titanium rotary files. A group of files were submitted to electrochemical polishing. New files and polished files were tested for flexural fatigue and for cutting efficiency. Scanning electron microscopy observations of all files were carried out to compare the surface morphologies of polished and new files. The t‐test was used to compare the groups for cutting efficiency. Scanning electron microscopy analysis indicated that the polishing resulted in more regular surfaces in relation to the new files. Electropolished files attained a significantly higher number of cycles to fracture than new unpolished files. No statistical difference exists between the groups in relation to the cutting efficiency (t‐test, P < 0.05). The polished files keep their integrity for a significantly higher number of cycles to fracture than the new files, without compromising cutting efficiency.
HYDROCARBONS IN THE MIDDLE MIOCENE JERIBE FORMATION, DYALA REGION, NE IRAQ
Authors: Al‐Ameri T.K. , Zumberge J. , Markarian Z.M.
Published: March 2011

The Lower Miocene Jeribe Formation in northern and NE Iraq is composed principally of dolomitic limestones with typical porosity in the range of 10–24% and mean permeability of 30 mD. The formation serves as a reservoir for oil and gas at the East Baghdad field, gas at Mansuriya, Khashim Ahmar, Pulkhana and Chia Surkh fields, and oil at Injana, Gillabat, Qumar and Jambur. A regional seal is provided by the anhydrites of the Lower Fars (Fat'ha) Formation.

For this study, oil samples from the Jeribe Formation at Jambur oilfield, Oligocene Baba Formation at Baba Dome (Kirkuk field) and Late Cretaceous Tanuma and Khasib Formations at East Baghdad field were analysed in order to investigate their genetic relationships. Graphical presentation of the analytical results (including plots of pristane/nC17 versus phytane/nCl8, triangular plots of steranes, tricyclic terpane scatter plots, and graphs of pristanelphytane versus carbon isotope ratio) indicated that the oils belong to a single oil family and are derived from kerogen Types II and III. The oils have undergone minor biodegradation and are of high maturity. They were derived from marine organic matter deposited with carbonate‐rich source rocks in suboxic‐anoxic settings.

A range of biomarker ratios and parameters including a C28/ C29 sterane ratio of 0.9, an oleanane index of 0.2 and low tricyclic terpane values indicate a Late Jurassic or Early Cretaceous age for the source rocks, and this age is consistent with palynomorph analyses. Potential source rocks are present in the Upper Jurassic – Lower Cretaceous Chia Gara Formation and the Middle Jurassic Sargelu Formation at the Jambur, Pulkhana, Qumar and Mansuriya fields; minor source rock intervals occur in the Balambo and Sarmord Formations. Hydrocarbon generation and expulsion from the Chia Gara Formation was indicated by pyrolysate organic matter, palynofacies type (A), and the maturity of Gleichenidites spores.

Oil migration from the Chia Gara Formation source rocks (and minor oil migration from the Sargelu Formation) into the Jeribe Formation reservoirs took place along steeply‐dipping faults which are observed on seismic sections and which cut through the Upper Jurassic Gotnia Anhydrite seal. Migration is confirmed by the presence of asphalt residues in the Upper Cretaceous Shiranish Formation and by a high migration index (Rock Eval SI / TOC) in the Chia Gara Formation. These processes and elements together form a Jurassic/Cretaceous – Tertiary petroleum system whose top‐seal is the Lower Fars (Fat'ha) Formation anhydrite.
CONDENSATES IN THE PY30‐I STRUCTURE, PANYU UPLIFT, PEARL RIVER MOUTH BASIN, SOUTH CHINA SEA: EVIDENCE FOR HYDROTHERMAL ACTIVITY ASSOCIATED WITH PETROLEUM MIGRATION AND ACCUMULATION
Authors: Guo Xiaowen , He Sheng , Liu Keyu , Cao Feng , Shi Hesheng , Zhu Junzhang
Published: March 2011

Condensates are present in the PY30–1 structure in the Panyu Uplift, Pearl River Mouth Basin. Biomarkers and compound‐specific stable carbon isotope ratios of three condensate and two source rock samples indicate that the condensates were generated by lacustrine mudstones and coals in the Oligocene Enping Formation with a minor contribution from mudstones in the Eocene Wenchang Formation. Elevated vitrinite reflectance values, high smectite‐illite transformation ratios, and elevated fluid inclusion homogenization temperatures (about 100®C higher than normal borehole temperatures) point to the influence of hydrothermal fluids at the PY30–1 structure. Hydrocarbon migration was found to have occurred at the same time as hydrothermal activity.

Modelling of formation pressure evolution in the Wenchang and Enping Formation source rocks in the Baiyun Depression, adjacent to the south of the Panyu Uplift, suggest that there were three episodes of overpressure release at approximately 40–37 Ma, 33–31 Ma and 16–10 Ma. Overpressure release was probably induced by uplift and erosion during the Zhuqiong, Nanhai and Dongsha phases of tectonic deformation, respectively. The third episode of overpressure release coincided with the main phase of hydrocarbon migration.

The accumulation of condensates at the PY30–1 structure probably followed hydrocarbon expulsion from source rocks as a result of overpressure release in the adjacent Baiyun Depression. Vertical migration into overlying reservoir rocks occurred through faults associated with a fluid diapir which is present at the core of the PY30‐I structure. The faults are pathways along which petroleum can migrate up to shallow reservoirs.
Innovation in coronary artery disease and heart failure: clinical benefits of pure heart rate reduction with ivabradine
Authors: Canet Emmanuel , Lerebours Guy , Vilaine Jean‐Paul
Published: March 2011

The link between elevated heart rate and cardiovascular events is established in healthy individuals and in patients with cardiovascular disease. The new agent, ivabradine, specifically and selectively inhibits the If current, with the sole action of heart rate reduction, with no impact on any other cardiac parameters. The benefits of “pure” heart rate reduction with ivabradine have been the focus of one of the largest clinical development programs ever performed, involving >20,000 individuals. Ivabradine has anti‐ischemic and antianginal efficacy in monotherapy, as well as in combination with other antianginals, such as beta‐blockers, and is safe and well tolerated. Two major morbidity–mortality trials, BEAUTIFUL and SHIFT, showed that heart rate reduction with ivabradine dramatically improves prognosis in patients with coronary artery disease and left ventricular dysfunction, symptomatic angina, or chronic heart failure. The development of ivabradine represents a clear innovation in the management of cardiovascular disease.
Advances in the diagnosis of respiratory tract infections: role of the Luminex xTAG respiratory viral panel
Authors: Krunic Nancy , Merante Frank , Yaghoubian Sevana , Himsworth David , Janeczko Richard
Published: March 2011

Clinical laboratories providing an etiological diagnosis of respiratory tract infections (RTI) have increasingly relied on nucleic acid amplification tests. Polymerase chain reaction‐based methods are becoming more standardized, and several have undergone the scrutiny of regulatory agencies mandated to assess the risks and benefits of implementing pathogen‐detection assays into diagnostic algorithms. Respiratory viruses lead to both upper and lower RTI and are implicated in exacerbations of chronic pulmonary conditions. Viruses from different taxonomic families present with overlapping clinical signs and symptoms, necessitating an accurate laboratory diagnosis. The clinical utility of diagnostic algorithms incorporating tests for respiratory viruses will depend on the breadth of pathogen coverage and the time to reliable and actionable results. This review covers strategies for detecting a panel of respiratory viruses employed over the last decade that have enabled an etiological diagnosis of RTI in a cost‐effective manner.
The discovery and development of rivaroxaban
Authors: Misselwitz Frank , Berkowitz Scott D. , Perzborn Elisabeth
Published: March 2011

Thromboembolic conditions present a considerable challenge to healthcare services because they are associated with substantial morbidity and mortality. The mainstays of prevention and treatment are anticoagulants and antiplatelet agents. Established anticoagulants have drawbacks that make their use difficult to manage and sustain. This has stimulated the search for new oral anticoagulants that are more convenient and yet still effective. This paper describes the development and future potential of rivaroxaban (Xarelto™; Bayer Schering Pharma AG, Berlin, Germany)—the first oral, direct Factor Xa inhibitor to be approved for clinical use in the prevention of venous thromboembolism in adult patients undergoing elective hip or knee replacement surgery.
Raltegravir: the first HIV‐1 integrase strand transfer inhibitor in the HIV armamentarium
Authors: Nguyen Bach‐Yen T. , Isaacs Robin D. , Teppler Hedy , Leavitt Randi Y. , Sklar Peter , Iwamoto Marian , Wenning Larissa A. , Miller Michael D. , Chen Joshua , Kemp Ramon , Xu Wei , Fromtling Robert A. , Vacca Joseph P. , Young Steven D. , Rowley Michael , Lower Michael W. , Gottesdiener Keith M. , Hazuda Daria J.
Published: March 2011

Raltegravir is the first integrase strand transfer inhibitor approved for the treatment of HIV‐1 infection. As the first agent in this new class of antiretroviral therapies, raltegravir has demonstrated safety and efficacy in treatment‐naive as well as heavily pretreated HIV‐infected patients failing therapy with multidrug‐resistant virus. Raltegravir has a favorable drug interaction profile that permits both administration to a wide, demographically diverse patient population and coadministration with many other therapeutic agents, including antiretroviral agents and supportive medications, without restrictions or dose adjustment. Data through 96 weeks of follow‐up in three phase III studies, protocol 021 (STARTMRK) in treatment‐naive patients, and protocols 018 (BENCHMRK‐1) and 019 (BENCHMRK‐2) in treatment‐experienced patients, demonstrated the potent and durable antiretroviral and immunologic effects and the favorable long‐term safety profile of raltegravir in both treatment‐naive and treatment‐experienced patients. Raltegravir represents an important addition to the current armamentarium for the treatment of HIV infection.
Novartis Malaria Initiative: best practice example of pharmaceutical industry's engagement in the fight against malaria
Authors: Lefèvre Gilbert , Marrast Anne Claire , Grueninger Heiner
Published: March 2011

Despite considerable advances in the treatment and prevention of malaria, Plasmodium falciparum is still a threat to millions of people across the world, particularly in sub‐Saharan Africa, with infants and young children bearing the greatest burden in terms of morbidity and mortality. Since 1999, the artemisinin‐based combination therapy artemether‐lumefantrine (AL; Coartem™) has been made available. A wealth of evidence supports consistently high efficacy of AL, and a favorable safety and tolerability profile has been demonstrated. The child‐friendly dispersible formulation of AL has proven to be as effective and well tolerated as the standard tablets, and will encourage ease of administration and improved adherence to the drug regimen. This article reviews the significant impact made by AL on the progress in malaria control and describes the way forward for the Novartis Malaria Initiative in leading the fight against malaria.
A review of the history, properties, and use of the immunomodulatory compound lenalidomide
Authors: Zeldis Jerome B. , Knight Robert , Hussein Mohamad , Chopra Rajesh , Muller George
Published: March 2011

Lenalidomide (REVLIMID™), an immunomodulatory compound targeting both cancer cells and their microenvironment, has substantial activity in several difficult‐to‐manage hematological malignancies. In previously treated multiple myeloma, lenalidomide produces high‐quality responses combined with sustained disease control. Recently, several randomized studies have demonstrated a clinical benefit of continuous lenalidomide treatment in newly diagnosed multiple myeloma. In many patients with refractory anemia associated with lower risk myelodysplastic syndromes and a 5q chromosome deletion, lenalidomide leads to transfusion independence, considerably improving quality of life. It has a manageable safety profile, and its oral formulation reduces the burden on patients. Several phase III trials are ongoing in other indications currently underserved by conventional therapy, such as chronic lymphocytic leukemia, non‐Hodgkin's lymphoma, and prostate cancer. Several early‐stage studies are exploring lenalidomide alone and in combination across different hematological malignancies, solid tumors, and immune‐related disorders.
Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis
Authors: Yin J. Kevin , Khandaker Gulam , Rashid Harunor , Heron Leon , Ridda Iman , Booy Robert
Published: March 2011

Please cite this paper as: Yin et al. (2011) Immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccine: systematic review and meta‐analysis. Influenza and Other Respiratory Viruses 5(5), 299–305.

The emergence of the 2009 H1N1 pandemic has highlighted the need to have immunogenicity and safety data on the new pandemic vaccines. There is already considerable heterogeneity in the types of vaccine available and of study performed around the world. A systematic review and meta‐analysis is needed to assess the immunogenicity and safety of pandemic influenza A (H1N1) 2009 vaccines. We searched Medline, EMBASE, the Cochrane Library and other online databases up to 1st October 2010 for studies in any language comparing different pandemic H1N1 vaccines, with or without placebo, in healthy populations aged at least 6 months. The primary outcome was seroprotection according to haemagglutination inhibition (HI). Safety outcomes were adverse events. Meta‐analysis was performed for the primary outcome. We identified 18 articles, 1 only on safety and 17 on immunogenicity, although 1 was a duplicate. We included 16 articles in the meta‐analysis, covering 17 921 subjects. Adequate seroprotection (≥70%) was almost invariably achieved in all age groups, and even after one dose and at low antigen content (except in children under 3 years receiving one dose of non‐adjuvanted vaccine). Non‐adjuvanted vaccine from international companies and adjuvanted vaccines containing oil in water emulsion (e.g. AS03, MF59), rather than aluminium, performed better. Two serious vaccination‐associated adverse events were reported, both of which resolved fully. No death or case of Guillain–Barré syndrome was reported. The pandemic influenza (H1N1) 2009 vaccine, with or without adjuvant, appears generally to be seroprotective after just one dose and safe among healthy populations aged ≥36 months; very young children (6–35 months) may need to receive two doses of non‐adjuvanted vaccine or one dose of AS03A/B‐adjuvanted product to achieve seroprotection.
Non‐Resolving Aspects of Acute Inflammation after Spinal Cord Injury (SCI): Indices and Resolution Plateau
Authors: Prüss Harald , Kopp Marcel A , Brommer Benedikt , Gatzemeier Nicole , Laginha Ines , Dirnagl Ulrich , Schwab Jan M
Published: March 2011

Inflammatory resolution is an active, highly regulated process already encoded at the onset of inflammation and required to prevent the transition into chronic inflammation associated with spreading of tissue injury and exacerbated scarring. We introduce objective, quantitative measurements [resolution indices (Ri) and resolution plateau (RP)] to characterize inflammatory resolution and to determine the persistence (“dwell time”) of differential leukocyte subpopulations at the lesion site after acute experimental spinal cord injury (SCI). The cell type‐specific resolution interval Ri (time between maximum cell numbers and the point when they are reduced to 50%) ranges from 1.2 days for neutrophils, 1.5 days for T lymphocytes, to 55 days for microglia/macrophages. As the resolution interval neglects exiting cell trafficking in the later period of resolution (49%–0% of lesional cells), we introduced the RP, a marker for the persisting, chronified leukocyte subsets, which are likely to participate in late degeneration and non‐resolving inflammation. Here, we identify the acute inflammatory response in central nervous system (CNS) lesions as partly non self‐limiting. Both extended resolution intervals (reduced leukocyte clearance) and elevated plateaus (permanent lesional cell numbers) provide quantitative measures to characterize residual, sustained inflammation and define cognate timeframes of impaired resolution after acute SCI.
Cisapride: What can we learn from the rise and fall of a prokinetic?
Authors: QUIGLEY Eamonn MM
Published: March 2011

Cisapride, the prototype serotonergic agent, evolved from a body of research that defined the key roles of serotonergic receptors in gastrointestinal motor and sensory function. Impressed by its in vitro properties and encouraged by clinical trial data, cisapride became the drug of choice for the treatment of a wide range of motility disorders and clinicians appeared impressed by its efficacy and comfortable with its side‐effect profile. Once serious cardiac events began to be reported in association with cisapride therapy, dark clouds rapidly gathered and soon enveloped the drug, leading to its widespread withdrawal from markets. What lessons can we learn from the story of cisapride? How can its brief but spectacular rise and equally sensational demise inform the development of new drugs which are so sorely needed in the management of motility and functional gastrointestinal disorders? This review explores the background to the development of cisapride, its history in clinical trials and the experience with adverse events and, in so doing, attempts to identify lessons for the future in the therapeutics of enteric neuromodulatory drugs.
Evaluation of three different hepatitis C virus typing methods for detection of mixed‐genotype infections
Authors: IDREES Muhammad , UR REHMAN Irshad , MANZOOR Sobia , AKBAR Haji , BUTT Sadia , AFZAL Samia , YOUSAF Muhammad Zubair , HUSSAIN Abrar
Published: March 2011

OBJECTIVE:  To evaluate the clinical applicability of an eligible assay for the true prevalence of hepatitis C virus (HCV) mixed‐genotype infections.

METHODS:  A newly developed HCV genotyping method targeting all six major HCV genotypes and 12 subtypes, restriction fragment length polymorphism (RFLP) and a serotyping assay were utilized for the detection of HCV mixed‐genotype infections using known HCV genotypes and unknown samples.

RESULTS:  In a defined mix of HCV genotypes, a genotype present at levels as low as 8.3% was detected by our newly developed assay, showing a threefold increase in sensitivity over that of direct deoxyribonucleic (DNA) sequencing. A comparative study of the accuracy among the three genotyping methods was carried out on samples obtained from 50 thalassemic patients who received multiple blood transfusions. The results showed that viruses in approximately 42% of the samples from this group were determined to be infected with mixed genotypes by our newly developed method. A serotyping assay and RFLP analysis, performed with poor results, could identify only 18% and 10% of mixed‐genotype infections, respectively.

CONCLUSION:  The newly developed assay may be the method of choice when detection of genotypes present at low levels in mixed‐genotype infections due to its higher level of sensitivity.
An experimental study of betadine irrigation for preventing infection during the natural orifice transluminal endoscopic surgery (NOTES) procedure
Authors: ZHENG Yong Zhi , WANG Dong , GU Jun Jun , ZHOU Miao Miao , Yu KONG Xiang , Xin DENG Shang , Ju SU Xiao , YIN Jie , GONG Yan Fang , WU Ren Pei , LI Zhao Shen
Published: March 2011

OBJECTIVE:  To study the effect and feasibility of using betadine irrigation of the gastrointestinal tract for preventing infection during the natural orifice transluminal endoscopic surgery (NOTES) procedure.

METHODS:  Twelve sows were used in this study. Four sows in the control group were lavaged with 500 mL saline. The eight sows in the experimental group were first lavaged with 500 mL saline and then irrigated with 200 mL betadine. A total of 5 mL of gastrointestinal (GI) tract fluid was collected before and after lavage, respectively, and 5 mL of peritoneal fluid was collected at the end of the NOTES procedure. A follow‐up endoscopic examination of the GI tract was performed 24 h after NOTES. The animals were killed and necropsied after 3 weeks.

RESULTS:  Irrigation with betadine of the GI tract significantly reduced the bacterial load of GI fluid. One sow died of diaphragmatic injury. No inflammation, ulcer or bleeding were observed in the experimental group by endoscopy after 24 h. More adhesions and abscesses were found in the control group than in the experimental group after 3 weeks. Only one case of adhesion was observed in the experimental group using the transcolonic approach.

CONCLUSIONS:  Betadine irrigation of the GI tract is effective and feasible for preventing infection during the NOTES procedure. Further studies are needed for assessing the effectiveness and safety of betadine irrigation in the clinical application of NOTES.
Controlled autolysis facilitates the polyhydroxyalkanoate recovery in Pseudomonas putida KT2440
Authors: Martínez Virginia , García Pedro , García José Luis , Prieto María Auxiliadora
Published: March 2011

The development of efficient recovery processes is essential to reduce the cost of polyhydroxyalkanoates (PHAs) production. In this work, a programmed self‐disruptive Pseudomonas putida BXHL strain, derived from the prototype medium‐chain‐length PHA producer bacterium P. putida KT2440, was constructed as a proof of concept for exploring the possibility to control and facilitate the release of PHA granules to the extracellular medium. The new autolytic cell disruption system is based on two simultaneous strategies: the coordinated action of two proteins from the pneumococcal bacteriophage EJ‐1, an endolysin (Ejl) and a holin (Ejh), and the mutation of the tolB gene, which exhibits alterations in outer membrane integrity that induce lysis hypersensitivity. The ejl and ejh coding genes were expressed under a XylS/Pm monocopy expression system inserted into the chromosome of the tolB mutant strain, in the presence of 3‐methylbenzoate as inducer molecule. Our results demonstrate that the intracellular presence of PHA granules confers resistance to cell envelope. Conditions to control the cell autolysis in P. putida BXHL in terms of optimal fermentation, PHA content and PHA recovery have been set up by exploring the sensitivity to detergents, chelating agents and wet biomass solubility in organic solvents such as ethyl acetate.
Membrane proteins of Pseudoalteromonas tunicata during the transition from planktonic to extracellular matrix‐adherent state
Authors: Hoke David E. , Zhang Kunkun , Egan Suhelen , Hatfaludi Tamas , Buckle Ashley M. , Adler Ben
Published: March 2011

Pseudoalteromonas tunicata is a marine bacterium that was originally isolated from the surface of the tunicate Ciona intestinalis. Since C. intestinalis expresses extracellular matrix (ECM) and P. tunicata has a gene encoding a functional ECM‐binding protein, we hypothesized that P. tunicata could adhere to this host via protein‐ECM interactions and as a result change its membrane proteome. An in vitro adhesion assay was developed to show that P. tunicata adheres strongly to ECM. To further study the adhesion biology of P. tunicata, two‐dimensional (2D) electrophoresis was used to explore the membrane‐associated sub‐proteome of P. tunicata during planktonic, adherent and non‐adherent states. More than 30 proteins were resolved using blue native (BN)/SDS 2D PAGE, many of which were identified by mass spectrometry. BN/SDS PAGE also allowed the identification of several novel protein complexes, which indicate structural and functional relationships for these proteins and related proteins in several other organisms. A proteomic change associated with adhesion was identified by comparison of 2D gels from the three model states. Collectively, these studies explore the membrane proteome of P. tunicata during the transition from planktonic to ECM‐adherent states.
Legionella spp. outdoors: colonization, communication and persistence
Authors: Hilbi Hubert , Hoffmann Christine , Harrison Christopher F.
Published: March 2011

Bacteria of the genus Legionella persist in a wide range of environmental habitats, including biofilms, protozoa and nematodes. Legionellaceae are ‘accidental’ human pathogens that upon inhalation cause a severe pneumonia termed ‘Legionnaires' disease’. The interactions of L. pneumophila with eukaryotic hosts are governed by the Icm/Dot type IV secretion system (T4SS) and more than 150 ‘effector proteins’, which subvert signal transduction pathways and promote the formation of the replication‐permissive ‘Legionella‐containing vacuole’. The Icm/Dot T4SS is essential to infect free‐living protozoa, such as the amoeba Dictyostelium discoideum, as well as the nematode Caenorhabditis elegans, or mammalian macrophages. To adapt to different niches, L. pneumophila not only responds to exogenous cues, but also to endogenous signals, such as the α‐hydroxyketone compound LAI‐1 (Legionella autoinducer‐1). The long‐term adaptation of Legionella spp. is based on extensive horizontal DNA transfer. In fact, Legionella spp. have acquired canonical ‘genomic islands’ of prokaryotic origin, but also a number of eukaryotic genes. Since many aspects of Legionella virulence against environmental predators and immune phagocytes are similar, an understanding of Legionella ecology provides valuable insights into the pathogenesis of legionellaceae for humans.