bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of Ritonavir‐Boosted Danoprevir, a Potent Hepatitis C Virus Protease Inhibitor, on the Pharmacokinetics of Methadone in Healthy Subjects Undergoing Methadone Maintenance Therapy
Authors: Moreira Sebastian A. , Morcos Peter N. , Navarro Mercidita T. , Bech Nuria , Smith Patrick F. , Brennan Barbara J. 
Published: August 2013

Study ObjectiveTo investigate the steady‐state pharmacokinetics of methadone when coadministered with ritonavir‐boosted danoprevir (DNVr).DesignOpen‐label, two‐period, single‐sequence pharmacokinetic study.SettingTwo U.S. research centers.PatientsEighteen methadone‐maintained healthy adults.Measurements and Main ResultsIn Period 1 (Day −1), subjects received their daily methadone maintenance therapy (MMT). In Period 2 (Days 1–10), subjects received MMT plus DNVr 100/100 mg twice/day. Pharmacokinetic parameters for the total concentrations of (R)‐ and (S)‐methadone on Days −1 and 10 were determined using noncompartmental methods. Unbound (R)‐ and (S)‐methadone concentrations at 3 hours postdose were also assessed on Days −1 and 10. Geometric mean ratios (GMRs) and 90% confidence intervals (CIs) were used to compare steady‐state (R)‐ and (S)‐methadone pharmacokinetics when MMT was administered with or without DNVr. Methadone withdrawal was assessed using the Subjective Opiate Withdrawal Scale. Compared with MMT alone, methadone AUCtau and Cmax GMR (90% CI) following coadministration with DNVr were 1.02 (0.91–1.15) and 1.01 (0.90–1.13) for (R)‐methadone, and 1.01 (0.90–1.13) and 0.99 (0.89–1.10) for (S)‐methadone, respectively. Unbound (R‐ and (S)‐methadone concentrations were comparable with or without DNVr. No instances of methadone withdrawal were reported. MMT in combination with DNVr was well tolerated.ConclusionCoadministration of DNVr with MMT resulted in no significant pharmacokinetic interactions or signs of methadone withdrawal. No dosage adjustment is needed for MMT when coadministered with DNVr.
In vivo and in vitro metabolism of the synthetic cannabinoid JWH‐200
Authors: De Brabanter Nik , Esposito Simone , Tudela Eva , Lootens Leen , Meuleman Philip , Leroux‐Roels Geert , Deventer Koen , Eenoo Peter Van 
Published: August 2013

RATIONALEThe synthetic cannabinoid JWH‐200 (1‐[2‐(4‐morpholinyl)ethyl]‐3‐(1‐naphthoyl)‐indole) appeared on the market around 2009. In order to identify markers for misuse of this compound and allow for the development of adequate routine methods, the metabolism of this compound was investigated using two models.METHODSIn vitro and in vivo (both with and without enzymatic hydrolysis) samples were purified by solid‐phase extraction and analyzed using liquid chromatography. Electrospray ionization high‐resolution Orbitrap mass spectrometry was used for the identification of the metabolites. To confirm the results in vivo, triple‐quadrupole mass spectrometry was employedRESULTSIn the in vitro model, using human liver microsomes, 22 metabolites were detected which could be divided into 11 metabolite classes. By using the chimeric mouse model with humanized liver, most of these metabolites were confirmed in vivo. It was found that all metabolites are excreted in urine as conjugates, mostly as glucuronides with varying conjugation rates.CONCLUSIONSThe metabolite formed by consecutive morpholine cleavage and oxidation of the remaining side chain to a carboxylic group was detected in the highest amounts with the longest detection time. Therefore, it is the best candidate metabolite to detect JWH‐200 abuse in urine. Copyright © 2013 John Wiley & Sons, Ltd.
A Square Peg in a Round Hole? Challenges with DALY‐based “Burden of Disease” Calculations in Surgery and a Call for Alternative Metrics
Authors: Gosselin Richard , Ozgediz Doruk , Poenaru Dan 
Published: August 2013

AbstractIntroductionIn recent years, surgical providers and advocates have engaged in a growing effort to establish metrics to estimate capacity for surgical services as well the burden of surgical diseases in resource‐limited settings. The burden of disease (BoD) studies have established the disability‐adjusted life year (DALY) as the primary metric to measure both disability and premature mortality. Nonetheless, DALY‐based approaches present methodological challenges, some of which are unique to surgical conditions, not fully addressed through the multiple iterations of the BoD studies, including the most recent study.Methods and ResultsThis paper examines these challenges in detail, including issues around age‐weighting and discounting, and estimates of disability‐weights for specific conditions. Surgical burden measurements of specific conditions, or through the assessment of hospital wards as platforms for service delivery, still have unresolved methodological hurdles. The 2010 BoD study addresses some of these issues, but many questions still remain. Other methods estimating surgical prevalence, backlogs in treatment, and disability incurred by delays in care may provide more practical approaches to disease burden that can be useful tools for clinicians and health advocates.ConclusionsThese approaches warrant further exploration in LMICs and these debates require active engagement by surgical providers and advocates globally.
Treatment of Large Acetabular Defects: A Surgical Technique Utilizing Impaction Grafting into a Metallic Mesh
Authors: Buckup Johannes , Salinas Emiliano Alvarez , Valle Alejandro Gonzalez Della , Boettner Friedrich 
Published: August 2013

Background Revision total hip arthroplasty in cases with severe acetabular bone loss is challenging. In the presence of combined cavitary and segmental defects without superior acetabular coverage, reconstructions with a structural acetabular allograft protected by a cage or a custom-made triflange cage have been the treatment of choice. The current paper describes an impaction grafting into a mesh for uncontained defects in revision total hip arthroplasty. Description of Technique After restoring containment with a mesh fixed with small fragment screws, defects were restored using impaction grafting combined with a cemented all-polyethylene cup. Patients and Methods Fourteen consecutive acetabular impaction graftings were performed by two surgeons. All patients had a type 3B defect according to the Paprosky classification. Results No re-revisions or radiographic failure was detected in the early follow-up period. Conclusion Impaction grafting into a mesh is an interesting treatment option to restore bone in combined cavitary and segmental defects.
Characterization of Enzymatically Interesterified Canola Oil and Fully‐Hydrogenated Canola Oil Blends Under Supercritical CO2
Authors: Jenab Ehsan , Temelli Feral 
Published: August 2013

AbstractBlends of canola oil and fully‐hydrogenated canola oil (FHCO) containing 10, 30, and 50 wt% FHCO were interesterified enzymatically using Lipozyme TL IM (6 % of initial substrates, w/v) under supercritical CO2 at 10 MPa and 65 °C for 2 h. Changes in polymorphic behavior and crystal morphology of non‐interesterified initial blends (NIB) and purified enzymatically interesterified products (PEIP) were studied using X‐ray diffraction spectroscopy (XRD) and polarized light microscopy. As well, the effects of blend ratio and enzymatic interesterification on rheological behavior were investigated. XRD analysis demonstrated the predominance of α form in FHCO while blending it with canola oil induced the formation of β form after crystallizing the samples at 24 and 5 °C for 12 h. Enzymatic interesterification caused the appearance of β′ forms and dramatically changed crystal morphology. The PEIP samples contained fewer crystal particles compared to NIB, but the crystals were more symmetrical. The elastic modulus (solid‐like behavior) (G′) was lower in NIB with 30 wt% FHCO compared to the one with 50 wt% FHCO. Enzymatic interesterification also had a strong effect on G′ of the samples as it decreased after interesterification. The results of this study will help the development of conversion technologies under supercritical conditions in order to formulate more healthy fats having appropriate functional properties to address the industrial demand for the production of margarine and pastry shortenings.
Turbulent transport of a high-Schmidt-number scalar near an air–water interface
Authors: Variano Evan A. , Cowen Edwin A. 
Published: August 2013

AbstractWe measure solute transport near a turbulent air–water interface at which there is zero mean shear. The interface is stirred by high-Reynolds-number homogeneous isotropic turbulence generated far below the surface, and solute transport into the water is driven by an imposed concentration gradient. The air–water interface is held at a constant concentration much higher than that in the bulk of the water by maintaining pure${\mathrm{CO} }_{2} $gas above a water tank that has been initially purged of dissolved${\mathrm{CO} }_{2} $. We measure velocity and concentration fluctuations below the air–water interface, from the viscous sublayer to the middle of the ‘source region’ where the effects of the surface are first felt. Our laboratory measurement technique uses quantitative imaging to collect simultaneous concentration and velocity fields, which are measured at a resolution that reveals the dynamics in the turbulent inertial subrange. Two-point statistics reveal the spatial structure of velocity and concentration fluctuations, and are examined as a function of depth beneath the air–water interface. There is a clear dominance of large scales at all depths for all quantities, but the relative importance of scales changes markedly with proximity to the interface. Quadrant analysis of the turbulent scalar flux shows a four-way balance of flux components far from the interface, which near the interface evolves into a two-way balance between motions that are raising and lowering parcels of low-concentration fluid.
Turbulent spots in a channel: large-scale flow and self-sustainability
Authors: Lemoult Grégoire , Aider Jean-Luc , Wesfreid José Eduardo 
Published: August 2013

AbstractUsing a large-time-resolved particle image velocimetry field of view, a developing turbulent spot is followed in space and time in a rectangular channel flow for more than 100 advective time units. We show that the flow can be decomposed into a large-scale motion consisting of an asymmetric quadrupole centred on the spot and a small-scale part consisting of streamwise streaks. From the temporal evolution of the energy of the streamwise and spanwise velocity perturbations, it is suggested that a self-sustaining process can occur in a turbulent spot above a given Reynolds number.
Screening and assessment instruments for use in Indigenous-specific alcohol and drug treatment rehabilitation
Authors: Stephens Anne , Bohanna India , Graham Deborah , Clough Alan R. 
Published: August 2013

Objective: The study's aim was to review instruments suitable for assessing Australian Indigenous clients’ treatment needs, and changes in wellbeing while receiving treatment for substance misuse at a culturally competent residential setting in north Queensland, Australia.Method: Searches of electronic databases, previously published reviews and websites was conducted. Instruments were selected according to their use in alcohol and drug treatment, developed for and/or validated with Australian Indigenous populations and applicability to measuring wellbeing.Findings: Forty instruments were identified and their characteristics summarised according to five descriptive categories: (1) evidence of psychometric utility and previous use in alcohol and drug treatment settings, (2) developed for, used with, and/or validated specifically for Australian Indigenous populations, (3) a flexible administrative method of self-report and/or interview, (4) an administration time of less than 20 minutes and (5) freely accessible in the public domain.Conclusions: Few instruments were found to have been validated specifically for use with Australian Indigenous people for use in drug and alcohol treatment. In order to measure wellbeing change and effective treatment, it may be possible to appropriately modify mainstream instruments, however, validation and sensitivity assessment of instruments for use with Australian Aboriginal and Torres Strait Islander people, is urgently required.
Designing and developing a literature-derived, population-based dietary inflammatory index
Authors: Shivappa Nitin , Steck Susan E , Hurley Thomas G , Hussey James R , Hébert James R 
Published: August 2013

AbstractObjectiveTo design and develop a literature-derived, population-based dietary inflammatory index (DII) to compare diverse populations on the inflammatory potential of their diets.DesignPeer-reviewed primary research articles published through December 2010 on the effect of diet on inflammation were screened for possible inclusion in the DII scoring algorithm. Qualifying articles were scored according to whether each dietary parameter increased (+1), decreased (−1) or had no (0) effect on six inflammatory biomarkers: IL-1β, IL-4, IL-6, IL-10, TNF-α and C-reactive protein.SettingThe Dietary Inflammatory Index Development Study was conducted in the Cancer Prevention and Control Program of the University of South Carolina in Columbia, SC, USA from 2011 to 2012.ResultsA total of ≈6500 articles published through December 2010 on the effect of dietary parameters on the six inflammatory markers were screened for inclusion in the DII scoring algorithm. Eleven food consumption data sets from countries around the world were identified that allowed individuals’ intakes to be expressed relative to the range of intakes of the forty-five food parameters observed across these diverse populations. Qualifying articles (n 1943) were read and scored based on the forty-five pro- and anti-inflammatory food parameters identified in the search. When fit to this composite global database, the DII score of the maximally pro-inflammatory diet was +7·98, the maximally anti-inflammatory DII score was −8·87 and the median was +0·23.ConclusionsThe DII reflects both a robust literature base and standardization of individual intakes to global referent values. The success of this first-of-a-kind attempt at relating intakes of inflammation-modulating foods relative to global norms sets the stage for use of the DII in a wide variety of epidemiological and clinical studies.
Mediterranean diet adherence rates in Sicily, southern Italy
Authors: Grosso Giuseppe , Marventano Stefano , Giorgianni Gabriele , Raciti Teodoro , Galvano Fabio , Mistretta Antonio 
Published: August 2013

AbstractObjectiveTo assess adherence to the Mediterranean diet and nutrient intakes in a population of Sicily, southern Italy and to evaluate possible determinants, particularly socio-cultural and lifestyle factors.DesignCross-sectional.SettingUrban and rural areas of eastern Sicily.SubjectsBetween May 2009 and December 2010, 3090 adults were randomly recruited through the collaboration of fourteen general practitioners. Adherence to the Mediterranean diet was measured by the MedDietScore. Nutrient intakes were assessed through the 24 h recall of the previous day's dietary intake.ResultsRural participants were barely more adherent to the Mediterranean diet than their urban counterparts (mean scores were 27·8 and 27·2, respectively, P = 0·037). The MedDietScore was correlated with intakes of MUFA, fibre and vitamin C, as well as with consumption of non-refined cereals, vegetables, fruit, meat, dairy products, alcohol and nuts. Regression analysis revealed that older and more educated people were more likely to be in the highest tertile of MedDietScore (OR = 1.90; 95 % CI 1·39, 2·59 and OR = 1·29; 95 % CI 1·05, 1·58, respectively). A significant difference in quantity (moderate) and quality (red wine and beer) of alcohol was found according to adherence to the Mediterranean diet. Finally, more active participants were 1·5 times more likely to form part of the high-adherence group.ConclusionsA slow but concrete moving away from traditional patterns has been observed in younger people and low educated people. Public health interventions should focus on these target populations in order to improve the quality of their diet.
Nondestructive Characterization and Enzyme Cleaning of Painted Surfaces: Assessment from the Macro to Nano Level
Authors: Pereira Catarina , Busani Tito , Branco Luis C. , Joosten Ineke , Sandu Irina Crina Anca 
Published: August 2013

AbstractThis work establishes a multiscale and multitechnique nondestructive approach as valid methodology for monitoring surface properties and evaluating the effectiveness of enzymatic removal of varnishes from paintings/polychrome artefacts.Mock-up samples (documented reconstructions of oil, tempera, and gilded layers on canvas and wooden supports) were covered with different proteinaceous varnishes (egg white, animal and fish glue, casein) and then characterized before and after the removal of these coatings with enzyme-based solutions. The varnish was cleaned in several steps (two dry swabs and two wet swabs) with a clearance step for removing the residues from proteinaceous varnish or from enzyme solution.Microscopy [stereomicroscopy (SM), optical microscopy (OM), atomic force microscopy (AFM), and scanning electron microscopy (SEM)] and colorimetric (CIEL*a*b* system) techniques were used for characterization of the reconstruction surfaces at different scales (macro-scale by SM and OM; micro-scale by SEM and nano-scale by AFM). These techniques were also used to monitor the cleaning treatment.Although results presented in this work were obtained for the specific treatment of enzyme removal, the methodology could be extended to other types of materials and cleaning. Further experiments on real works of art are needed for a complete validation of the methodology.
The relationship between body image, age, and distress in women facing breast cancer surgery
Authors: Miller Sarah J. , Schnur Julie B. , Weinberger-Litman Sarah L. , Montgomery Guy H. 
Published: August 2013

AbstractObjectives:Research suggests that the strength of the relationship between body image and emotional distress decreases with age. Past research has focused on expected aging-related body changes, and has not yet examined unexpected body changes (e.g., breast cancer surgery). The present post-hoc study assessed relationships between age, body image, and emotional distress in women facing breast cancer surgery.Methods:Older (≥65 years, n = 40) and younger (<65 years, n = 40) women were matched on race/ethnicity, marital status, and surgery type. Within one week prior to surgery, participants completed measures of demographics, aspects of body image, and emotional distress (general and surgery-specific).Results:Results indicated that: (1) body image did not differ by age (p > 0.999); (2) older women reported less pre-surgical emotional distress than younger women (p's < 0.01); and, (3) age moderated the relationship between body image and emotional distress (p's < 0.06).Significance of results:The results suggest that younger women, particularly those with poor body image, are at an increased risk for pre-surgical emotional distress. These women may benefit from pre-surgical interventions designed to improve body image or to reduce pre-surgical emotional distress.
LRRFIP2 negatively regulates NLRP3 inflammasome activation in macrophages by promoting Flightless-I-mediated caspase-1 inhibition
Authors: Jin Jing , Yu Qian , Han Chaofeng , Hu Xiang , Xu Sheng , Wang Qingqing , Wang Jianli , Li Nan , Cao Xuetao 
Published: August 2013

AbstractThe NLRP3 inflammasome is the most characterized inflammasome activated by cellular infection or stress, which is responsible for the maturation of proinflammatory cytokines IL-1β and IL-18. The precise molecular mechanism for negative regulation of NLRP3 inflammasome activation needs to be further defined. Here we identify leucine-rich repeat Fli-I-interacting protein 2 (LRRFIP2) as an NLRP3-associated protein and an inhibitor for NLRP3 inflammasome activation. LRRFIP2 binds to NLRP3 via its N terminus upon NLRP3 inflammasome activation, and also interacts with Flightless-I, a pseudosubstrate of caspase-1, via its Coil motif. Knockdown of Flightless-I significantly promotes NLRP3 inflammasome activation. LRRFIP2 enhances the interaction between Flightless-I and caspase-1, facilitating the inhibitory effect of Flightless-I on caspase-1 activation. Furthermore, silencing of Flightless-I abrogates the inhibitory effect of LRRFIP2 on NLRP3 inflammasome. These data demonstrate that LRRFIP2 inhibits NLRP3 inflammasome activation by recruiting the caspase-1 inhibitor Flightless-I, thus outlining a new mechanism for negative regulation of NLRP3 inflammasome.
Assessment of Maraviroc Exposure–Response Relationship at 48 Weeks in Treatment‐Experienced HIV‐1–Infected Patients in the MOTIVATE Studies
Authors: Jacqmin P , Wade JR , Weatherley B , Snoeck E , Marshall S , McFadyen L 
Published: August 2013

Efficacy exposure–response relationships of the CCR5 antagonist maraviroc were evaluated across two phase III clinical trials. This post‐hoc analysis used 48‐week efficacy data from 841 treatment‐experienced patients infected with CCR5‐tropic human immunodeficiency virus type 1 (HIV‐1), identified by the enhanced sensitivity Trofile assay. Probability of treatment success (viral RNA <50 copies/ml) was modeled using generalized additive logistic regression, testing exposure, clinical, and virologic variables. Prognostic factors for treatment success (in decreasing order of Akaike information criterion (AIC) change) were: maraviroc treatment, high‐weighted overall susceptibility to background treatment, absence of an undetectable maraviroc concentration, high baseline CD4 count (BCD4), low viral load (VL), race (other than black), absence of non‐R5 baseline tropism (BTRP), and absence of fosamprenavir (FPV). No concentration–response relationship was found with treatment (maraviroc vs. placebo) and presence/absence of undetectable maraviroc concentration (adherence marker) in the model. The maraviroc doses studied (300 or 150 mg with potent CYP3A4 inhibitors once (q.d.)/twice daily (b.i.d.)) deliver concentrations near the top of the concentration–response curve.CPT: Pharmacometrics & Systems Pharmacology (2013) 2, e64; doi:10.1038/psp.2013.42; published online 14 August 2013
Identification of protein phosphatase 1 as a regulator of the LRRK2 phosphorylation cycle
Authors: Lobbestael Evy , Zhao Jing , Rudenko Iakov N. , Beylina Aleksandra , Gao Fangye , Wetter Justin , Beullens Monique , Bollen Mathieu , Cookson Mark R. , Baekelandt Veerle , Nichols R. Jeremy , Taymans Jean-Marc 
Published: August 2013

A cluster of phosphorylation sites in LRRK2 (leucine-rich repeat kinase 2), including Ser910, Ser935, Ser955 and Ser973, is important for PD (Parkinson's disease) pathogenesis as several PD-linked LRRK2 mutants are dephosphorylated at these sites. LRRK2 is also dephosphorylated in cells after pharmacological inhibition of its kinase activity, which is currently proposed as a strategy for disease-modifying PD therapy. Despite this importance of LRRK2 dephosphorylation in mutant LRRK2 pathological mechanism(s) and in LRRK2′s response to inhibition, the mechanism by which this occurs is unknown. Therefore we aimed to identify the phosphatase for LRRK2. Using a panel of recombinant phosphatases, we found that PP1 (protein phosphatase 1) efficiently dephosphorylates LRRK2 in vitro. PP1 activity on LRRK2 dephosphorylation was confirmed in cells using PP1 inhibition to reverse LRRK2 dephosphorylation induced by the potent LRRK2 kinase inhibitor LRRK2-IN1 as well as in R1441G mutant LRRK2. We also found that PP1 and LRRK2 can form a complex in cells. Furthermore, we observed that PP1 inhibition modulates LRRK2′s cellular phenotype by reducing skein-like LRRK2-positive structures associated with dephosphorylation. In conclusion, the present study reveals PP1 as the physiological LRRK2 phosphatase, responsible for LRRK2 dephosphorylation observed in PD mutant LRRK2 and after LRRK2 kinase inhibition.