bluuebunny/crossref_metadata_2025_split huggingface dataset:
Association of dysmenorrhea with interstitial cystitis/bladder pain syndrome: a case–control study
Authors: Chung Shiu‐Dong , Liu Shih‐Ping , Lin Herng‐Ching , Kang Jiunn‐Horng 
Published: June 2014

AbstractObjectiveInterstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic disabling condition of the urological system. Many gynecological conditions are reported to be associated with IC/BPS. This study presents epidemiological evidence of a possible association between dysmenorrhea and IC/BPS, using population‐based data.DesignA case–control study.SettingTaiwan.SampleThe study sample was retrieved from Taiwan's Longitudinal Health Insurance Database 2000, i.e. 291 women aged 18–45 years with a diagnosis of IC/BPS between January 2000 and December 2010 (cases) and 873 randomly selected controls matched on age and index date of ambulatory care visit. We used logistic regression conditioned on age to calculate the odds ratio of cases having a prior diagnosis of dysmenorrhea relative to controls.ResultsPrior dysmenorrhea was found in 87 (29.9%) cases and in 163 (18.7%) of the controls. Conditional logistic regression showed a crude odds ratio of 1.86 (95% confidence interval 1.37–2.52, p < 0.001) for prior dysmenorrhea among cases vs. controls. The adjusted odds ratio was 1.59 (95% confidence interval 1.13–2.23, p = 0.007) after adjusting for medical co‐morbidities.ConclusionThis population‐based study found that there is an association between IC/BPS and prior dysmenorrhea.
Long‐term trends and outcomes of anterior vitrectomy in Western Australia
Authors: Clark Antony , Morlet Nigel , Ng Jonathon Q. , Preen David B. , Semmens James B. 
Published: June 2014

AbstractPurposeTo describe trends, risk factors and outcomes of anterior vitrectomy during cataract and intraocular lens (IOL) surgery.MethodsAll patients 16 years and older undergoing cataract and IOL surgery in Western Australia (WA) from January 1980 to December 2001 (n = 115 815) were included. Hospital administrative data were used to identify all cataract and IOL procedures and subsequent admissions for retinal detachment, IOL dislocation, endophthalmitis and pseudophakic corneal oedema. Data were validated with chart review and analysed to identify trends and risk factors for anterior vitrectomy and the risk of subsequent complications.ResultsIn total, 1390 (1.2%) anterior vitrectomies were performed. The rate increased with change in surgical technique. Significant risk factors for anterior vitrectomy were age <50 years (OR 1.31), male sex (OR 1.23), IOL procedure (OR 11.45) and operations in public hospitals (OR 1.99) or rural/remote (OR 1.40) areas. Anterior vitrectomy was strongly associated with increased risk of retinal detachment (RD) (RR 18.5), endophthalmitis (RR 3.6), IOL dislocation (RR 21.1) and pseudophakic corneal oedema (RR 17.3). Retinal detachments and IOL dislocations occur earlier after anterior vitrectomy.ConclusionAnterior vitrectomy rates have remained stable since the introduction of phacoemulsification. Anterior vitrectomy is a major risk factor for serious complications compared with uncomplicated surgery, particularly RD and IOL dislocation. We identified an increasing trend in anterior vitrectomy being performed during extracapsular and IOL surgery.
Aspirin influences megakaryocytic gene expression leading to up‐regulation of multidrug resistance protein‐4 in human platelets
Authors: Massimi Isabella , Guerriero Raffaella , Lotti Lavinia Vittoria , Lulli Valentina , Borgognone Alessandra , Romani Federico , Barillà Francesco , Gaudio Carlo , Gabbianelli Marco , Frati Luigi , Pulcinelli Fabio M. 
Published: June 2014

AimThe aim of the study was to investigate whether human megakaryocytic cells have an adaptive response to aspirin treatment, leading to an enhancement of multidrug resistance protein‐4 (MRP4) expression in circulating platelets responsible for a reduced aspirin action. We recently found that platelet MRP4 overexpression has a role in reducing aspirin action in patients after by‐pass surgery. Aspirin enhances MRP4‐mRNA levels in rat liver and drug administration transcriptionally regulates MRP4 gene expression through peroxisome proliferator‐activated receptor‐α (PPARα).MethodsThe effects induced by aspirin or PPARα agonist (WY14643) on MRP4 modulation were evaluated in vitro in a human megakaryoblastic DAMI cell line, in megakaryocytes (MKs) and in platelets obtained from human haematopoietic progenitor cell (HPC) cultures, and in vivo platelets obtained from aspirin treated healthy volunteers (HV).ResultsIn DAMI cells, aspirin and WY14643 treatment induced a significant increase in MRP4 and PPARα expression. In human MKs grown in the presence of either aspirin or WY14643, MRP4 and PPARα‐mRNA were higher than in control cultures and derived platelets showed an enhancement in MRP4 protein expression. The ability of aspirin to modulate MRP4 expression in MKs and to transfer it to platelets was also confirmed in vivo. In fact, we found the highest MRP4 mRNA and protein expression in platelets obtained from HV after 15 days' aspirin treatment.ConclusionsThe present study provides evidence, for the first time, that aspirin treatment affects the platelet protein pattern through MK genomic modulation. This work represents an innovative and attractive approach, useful both to identify patients less sensitive to aspirin and to improve pharmacological treatment in cardiovascular high‐risk patients.
Population pharmacokinetics of imipenem in critically ill patients with suspected ventilator‐associated pneumonia and evaluation of dosage regimens
Authors: Couffignal Camille , Pajot Olivier , Laouénan Cédric , Burdet Charles , Foucrier Arnaud , Wolff Michel , Armand‐Lefevre Laurence , Mentré France , Massias Laurent 
Published: June 2014

AimsSignificant alterations in the pharmacokinetics (PK) of antimicrobials have been reported in critically ill patients. We describe PK parameters of imipenem in intensive care unit (ICU) patients with suspected ventilator‐associated pneumonia and evaluate several dosage regimens.MethodsThis French multicentre, prospective, open‐label study was conducted in ICU patients with a presumptive diagnosis of ventilator‐associated pneumonia caused by Gram‐negative bacilli, who empirically received imipenem intravenously every 8 h. Plasma imipenem concentrations were measured during the fourth imipenem infusion using six samples (trough, 0.5, 1, 2, 5 and 8 h). Data were analysed with a population approach using the stochastic approximation expectation maximization algorithm in Monolix 4.2. A Monte Carlo simulation was performed to evaluate the following six dosage regimens: 500, 750 or 1000 mg with administration every 6 or 8 h. The pharmacodynamic target was defined as the probability of achieving a fractional time above the minimal inhibitory concentration (MIC) of >40%.ResultsFifty‐one patients were included in the PK analysis. Imipenem concentration data were best described by a two‐compartment model with three covariates (creatinine clearance, total bodyweight and serum albumin). Estimated clearance (between‐subject variability) was 13.2 l h−1 (38%) and estimated central volume 20.4 l (31%). At an MIC of 4 μg ml−1, the probability of achieving 40% fractional time > MIC was 91.8% for 0.5 h infusions of 750 mg every 6 h, 86.0% for 1000 mg every 8 h and 96.9% for 1000 mg every 6 h.ConclusionsThis population PK model accurately estimated imipenem concentrations in ICU patients. The simulation showed that for these patients, the best dosage regimen of imipenem is 750 mg every 6 h and not 1000 mg every 8 h.
Is there an antiandrogen withdrawal syndrome with enzalutamide?
Authors: Rodriguez‐Vida Alejo , Bianchini Diletta , Van Hemelrijck Mieke , Hughes Simon , Malik Zafar , Powles Thomas , Bahl Amit , Rudman Sarah , Payne Heather , de Bono Johann , Chowdhury Simon 
Published: June 2014

ObjectiveTo examine prostate‐specific antigen (PSA) levels after enzalutamide discontinuation to assess whether an antiandrogen withdrawal syndrome (AAWS) exists with enzalutamide.MethodsWe retrospectively identified 30 consecutive patients with metastatic prostate cancer who were treated with enzalutamide after docetaxel. Post‐discontinuation PSA results were available for all patients and were determined at 2‐weekly intervals until starting further anticancer systemic therapy. PSA withdrawal response was defined as a PSA decline by ≥50% from the last on‐treatment PSA, with a confirmed decrease ≥3 weeks later. Patient characteristics were evaluated in relation to the AAWS using univariate logistic regression analysis.ResultsThe median (range) patient age was 70.5 (56–86) years and the median (range) follow‐up was 9.0 (0.5–16) months. The most common metastatic sites were the bone (86.7%) and lymph nodes (66.7%). Most patients (70%) had previously received abiraterone and 12 patients (40%) had also received cabazitaxel. The median (range) treatment duration with enzalutamide was 3.68 (1.12–21.39) months. PSA levels after enzalutamide withdrawal were monitored for a median (range) time of 35 (10–120) days. Only one patient (3.3%) had a confirmed PSA response ≥50% after enzalutamide discontinuation. One patient (3.3%) had a confirmed PSA response of between 30 and 50% and another patient (3.3%) had an unconfirmed PSA response of between 30 and 50%. The median overall survival was 15.5 months (95% CI 8.1–24.7). None of the factors analysed in the univariate analysis were significant predictors of PSA decline after enzalutamide discontinuation.ConclusionsThis retrospective study provides the first evidence that enzalutamide may have an AAWS in a minority of patients with metastatic castration‐resistant prostate cancer. Further studies are needed to confirm the existence of an enzalutamide AAWS and to assess its relevance in prostate cancer management.
BU08073 a buprenorphine analogue with partial agonist activity at μ‐receptors in vitro but long‐lasting opioid antagonist activity in vivo in mice
Authors: Khroyan T V , Wu J , Polgar W E , Cami‐Kobeci G , Fotaki N , Husbands S M , Toll L 
Published: June 2014

Background and PurposeBuprenorphine is a potent analgesic with high affinity at μ, δ and κ and moderate affinity at nociceptin opioid (NOP) receptors. Nevertheless, NOP receptor activation modulates the in vivo activity of buprenorphine. Structure activity studies were conducted to design buprenorphine analogues with high affinity at each of these receptors and to characterize them in in vitro and in vivo assays.Experimental ApproachCompounds were tested for binding affinity and functional activity using [35S]GTPγS binding at each receptor and a whole‐cell fluorescent assay at μ receptors. BU08073 was evaluated for antinociceptive agonist and antagonist activity and for its effects on anxiety in mice.Key ResultsBU08073 bound with high affinity to all opioid receptors. It had virtually no efficacy at δ, κ and NOP receptors, whereas at μ receptors, BU08073 has similar efficacy as buprenorphine in both functional assays. Alone, BU08073 has anxiogenic activity and produces very little antinociception. However, BU08073 blocks morphine and U50,488‐mediated antinociception. This blockade was not evident at 1 h post‐treatment, but is present at 6 h and remains for up to 3–6 days.Conclusions and ImplicationsThese studies provide structural requirements for synthesis of ‘universal’ opioid ligands. BU08073 had high affinity for all the opioid receptors, with moderate efficacy at μ receptors and reduced efficacy at NOP receptors, a profile suggesting potential analgesic activity. However, in vivo, BU08073 had long‐lasting antagonist activity, indicating that its pharmacokinetics determined both the time course of its effects and what receptor‐mediated effects were observed.Linked ArticlesThis article is part of a themed section on Opioids: New Pathways to Functional Selectivity. To view the other articles in this section visit http://dx.doi.org/10.1111/bph.2015.172.issue-2
Reforming election dates in Canada: Towards an explanatory framework
Authors: Alcantara Christopher , Roy Jason 
Published: June 2014

AbstractSince 2001, ten governments in Canada have passed fixed election date legislation. The typical assumption in the literature is that governments did so as a way to address public concerns about the undemocratic nature of calling and timing elections. This argument, however, does not explain the timing (that is, when the legislation was passed by each jurisdiction) of this policy change. We approach this puzzle deductively by applying the theoretical insights of multiple streams theory to the Canadian experiences. Our findings suggest that although all three streams were important, the political stream is crucial for explaining the timing of the legislation.
The temptation of provincial criminal law
Authors: Baker Dennis 
Published: June 2014

AbstractUnder s.91 (27) of the BNA Act, 1867, the Federal Parliament has the exclusive authority to legislate “criminal law.” This has not stopped the provinces from passing “quasi‐criminal” laws that are difficult to distinguish from criminal law. Recent legislation regarding “public fighting” and civil remedies for criminal acts suggest there are few legal obstacles to enacting provincial criminal law. This article identifies such provincial criminal laws, explains how the modern doctrines of federalism might invite and allow for their enactment, and discusses impacts on criminal justice policy and administration. It highlights the discretion afforded the Crown and police in charging individuals under the federal Criminal Code or similar provincial laws (or municipal by‐laws). While provincial or local laws may allow for more efficient law enforcement, they do so at the expense of the procedural guarantees associated with the criminal law.
Structural Basis for Low‐Affinity Binding of Non‐R2 Carboxylate‐Substituted Tricyclic Quinoline Analogs to CK2α: Comparative Molecular Dynamics Simulation Studies
Authors: Zhou Yue , Li Xitao , Zhang Na , Zhong Rugang 
Published: June 2014

Protein kinase CK2 is a novel potential target for cancer treatment. The tricyclic quinoline compound CX‐4945 (R2 = COOH) is the first bioavailable CK2 inhibitor used in human clinical trials for advanced solid tumors. CX‐4945 analogs with non‐R2 carboxylate function were demonstrated to be approximately 5000‐fold less potent than compound 12 (R2 = COOH) in vitro. Molecular docking and molecular dynamics simulations were employed to elucidate the structural mechanisms through which the R2 non‐ionizable and R3 carboxylic acid substituents influence binding affinity. Results show that the structure of CK2α and the orientation of ligands changed to different degrees in non‐R2 carboxylate function systems. The inappropriate electrostatic interactions between the non‐R2 carboxylate group and the positive region lead to improper protein–ligand recognition, which is followed by the reorientation of tricyclic skeletons. For CK2α, the affected positions are distributed over the glycine‐rich loop (G‐loop), C‐loop, and the β4/β5 loop. The allosteric mechanisms between the deviated ligands and the changed regions are proposed. Detailed energy calculation and residue‐based energy decomposition indicate the energetic influences on the contributions of the critical residues. These results are in accordance with one another and could provide rational clues to the design of more potent CK2 inhibitors.
Expression of cytokines, chemokines and other effector molecules in two prototypic autoinflammatory skin diseases, pyoderma gangrenosum and Sweet's syndrome
Authors: Marzano A V , Fanoni D , Antiga E , Quaglino P , Caproni M , Crosti C , Meroni P L , Cugno M 
Published: June 2014

SummaryPyoderma gangrenosum (PG) and Sweet's syndrome (SS) are two inflammatory skin diseases presenting with painful ulcers and erythematous plaques, respectively; both disorders have a debilitating clinical behaviour and PG is potentially life-threatening. Recently, PG and SS have been included among the autoinflammatory diseases, which are characterized by recurrent episodes of sterile inflammation, without circulating autoantibodies and autoreactive T cells. However, an autoinflammatory pattern clearly supporting this inclusion has never been demonstrated. We studied 16 patients with PG, six with SS and six controls, evaluating, using a sandwich-based protein antibody array method, the expression profile of inflammatory effector molecules in PG, SS and normal skin. The expressions of interleukin (IL)-1 beta and its receptor I were significantly higher in PG (P = 0·0001 for both) and SS (P = 0·004–0·040) than in controls. In PG, chemokines such as IL-8 (P = 0·0001), chemokine (C-X-C motif) ligand (CXCL) 1/2/3 (P = 0·002), CXCL 16 (P = 0·003) and regulated upon activation normal T cell expressed and secreted (RANTES) (P = 0·005) were over-expressed. In SS, IL-8 (P = 0·018), CXCL 1/2/3 (P = 0·006) and CXCL 16 (P = 0·036) but not RANTES were over-expressed, suggesting that chemokine-mediated signals are lower than in PG. Fas/Fas ligand and CD40/CD40 ligand systems were over-expressed in PG (P = 0·0001 for Fas, P = 0·009 for Fas ligand, P = 0·012 for CD40, P = 0·0001 for CD40 ligand), contributing to tissue damage and inflammation, while their role seems to be less significant in SS. Over-expression of cytokines/chemokines and molecules amplifying the inflammatory network supports the view that PG and SS are autoinflammatory diseases. The differences in expression profile of inflammatory effectors between these two disorders may explain the stronger local aggressiveness in PG than SS.
Thyroid-associated orbitopathy is linked to gastrointestinal autoimmunity
Authors: Ponto K A , Schuppan D , Zwiener I , Binder H , Mirshahi A , Diana T , Pitz S , Pfeiffer N , Kahaly G J 
Published: June 2014

Summary
Common autoimmune disorders tend to co-exist in the same subjects and cluster in families. The objective of this study was to determine the prevalence of autoimmune co-morbidity in patients with autoimmune thyroid disease (AITD) with and without thyroid-associated orbitopathy (TAO). This was a cross-sectional study conducted at an academic tertiary referral centre. Of 1310 patients with AITD [n = 777 or 59% with Graves' disease (GD) and n = 533, 41% with Hashimoto's thyroiditis (HT)] followed at a specialized joint thyroid–eye out-patient clinic, 176 (13·4%) had an adult type of the autoimmune polyglandular syndrome, 129 (9·8%) type 1 diabetes, 111 (8·5%) coeliac disease, 60 (4·6%) type A autoimmune gastritis, 57 (4·4%) vitiligo and 25 (1·9%) Addison's disease. Coeliac disease and autoimmune gastritis were associated positively with GD [odds ratio (OR) = 2·18; P = 0·002 and OR = 6·52; P &lt; 0·001], whereas type 1 diabetes, Addison's disease, autoimmune primary hypogonadism, alopecia areata, rheumatoid arthritis and Sjögren's syndrome were ‘protective’ for GD and thus linked to HT, OR = 0·49 (P &lt; 0·001), 0·06 (P &lt; 0·001), 0·25 (P &lt; 0·001), 0·50 (P = 0·090) and 0·32 (P = 0·003), respectively. Of 610 (46·6%) AITD patients with TAO, 584 (95·7%) and 26 (4·3%) had GD and HT, respectively (P &lt; 0·001). TAO was most prevalent in GD patients with coeliac disease (94%, OR = 1·87, P &lt; 0·001). Multivariate analysis showed high OR for coeliac disease and autoimmune gastritis (3·4 and 4·03, both P &lt; 0·001) pertaining to the association with TAO while type 1 diabetes, Addison's disease and alopecia areata were protective for TAO. In patients with TAO, coeliac disease is the most prevalent co-morbid autoimmune condition and rates are increased compared to GD patients without TAO.
The Effect of Platelet Proteins Released in Response to Titanium Implant Surfaces on Macrophage Pro‐Inflammatory Cytokine Gene Expression
Authors: Alfarsi Mohammed A. , Hamlet Stephen M. , Ivanovski Saso 
Published: June 2014

AbstractBackground and PurposePlatelets are one of the earliest cell types to interact with surgically inserted titanium implants. This in vitro study investigated the effect of titanium surface‐induced platelet releasate on macrophage cytokine gene expression.Materials and MethodsTo mimic the in vivo temporal sequence of platelet arrival and protein production at the implant surface and the subsequent effect of these proteins on mediators of the immune response, the levels of platelet attachment and activation in response to culture on smooth polished, sandblasted and acid‐etched (SLA), and hydrophilic‐modifiedSLA(modSLA) titanium surfaces were first determined by microscopy and protein assay. The subsequent effect of the platelet‐released proteins on humanTHP‐1 macrophage cytokine gene expression was determined by polymerase chain reaction array after 1 and 3 days of macrophage culture on the titanium surfaces in platelet‐releasate conditioned media.ResultsPlatelet attachment was surface dependent with decreased attachment observed on the hydrophilic (modSLA) surface. The platelet releasate, when considered independently of the surface effect, elicited an overall pro‐inflammatory response in macrophage cytokine gene expression, that is, the expression of typical pro‐inflammatory cytokine genes such asTNF,IL1a,IL1b, andCCL1was significantly up‐regulated whereas the expression of anti‐inflammatory cytokine genes such asIL10,CxCL12, andCxCL13was significantly down‐regulated. However, following platelet exposure to different surface modifications, the platelet releasate significantly attenuated the macrophage pro‐inflammatory response to microrough (SLA) titanium and hastened an anti‐inflammatory response to hydrophilic (modSLA) titanium.ConclusionsTheses results demonstrate that titanium surface topography and chemistry are able to influence the proteomic profile released by platelets, which can subsequently influence macrophage pro‐inflammatory cytokine expression. This immunomodulation may be an important mechanism via which titanium surface modification influences osseointegration.
Relationship between pulse pressure variation and echocardiographic indices of left ventricular filling pressure in critically ill patients
Authors: Cameli Matteo , Bigio Elisa , Lisi Matteo , Righini Francesca M. , Galderisi Maurizio , Franchi Federico , Scolletta Sabino , Mondillo Sergio 
Published: June 2014

SummaryBackgroundPulse pressure variation (PPV) is a dynamic index of fluid responsiveness. This parameter helps clinicians in improving haemodynamic status while avoiding potential fluid overload. Echocardiographic indices, such as E/E' ratio and left atrial (LA) strain by speckle tracking echocardiography (STE), are used to estimate left ventricular (LV) filling pressures. This study aimed at exploring the relationship between PPV and echocardiographic indices of LV filling pressures in critically ill patients.MethodsTwenty‐two patients (mean age of 50·9 ± 21·6, male/female = 15/7) admitted to intensive care unit, and requiring mechanical ventilation and invasive arterial pressure monitoring, were studied. In all patients, two independent operators assessed simultaneously PPV, using a pulse contour method, mean E/E' ratio and peak atrial longitudinal strain (PALS) by means of STE. PALS values were obtained by averaging LA segments measured in the 4‐chamber and 2‐chamber views (global PALS).ResultsA significant negative correlation was found between mean E/E' ratio and PPV (R2 = −0·76; P<0·001). A positive correlation between global PALS and PPV was found (R2 = 0·80, P<0·001). Mean global PALS of 26·2% demonstrated excellent accuracy (Area Under Roc Curve = 0·86, P<0·001), and good sensitivity (92%) and specificity (86%) in predicting a PPV >15%.ConclusionIn a group of mechanically ventilated patients PPV, derived from pulse contour analysis, and echocardiographic preload parameters were well correlated. Global PALS by STE provided better estimation of PPV than mean E/E' ratio. PALS seems a potential alternative to PPV in assessing fluid responsiveness in critically ill patients.