bluuebunny/crossref_metadata_2025_split huggingface dataset:
Acute Alcohol Intoxication‐Induced Microvascular Leakage
Authors: Doggett Travis M. , Breslin Jerome W. 
Published: September 2014

BackgroundAlcohol intoxication can increase inflammation and worsen injury, yet the mechanisms involved are not clear. We investigated whether acute alcohol intoxication increases microvascular permeability and investigated potential signaling mechanisms in endothelial cells that may be involved.MethodsConscious rats received a 2.5 g/kg alcohol bolus via gastric catheters to produce acute intoxication. Microvascular leakage of intravenously administered fluorescein isothiocyanate (FITC)‐conjugated albumin (FITC‐albumin) from the mesenteric microcirculation was assessed by intravital microscopy. Endothelial‐specific mechanisms were studied using cultured endothelial cell monolayers. Transendothelial electrical resistance (TER) served as an index of barrier function, before and after treatment with alcohol or its metabolite acetaldehyde. Pharmacologic agents were used to test the roles of alcohol metabolism, oxidative stress, p38 mitogen‐activated protein kinase (MAPK), myosin light‐chain kinase (MLCK), rho kinase (ROCK), and exchange protein activated by cAMP (Epac). VE‐cadherin localization was investigated to assess junctional integrity. Rac1 and RhoA activation was assessed by ELISA assays.ResultsAlcohol significantly increased FITC‐albumin extravasation from the mesenteric microcirculation. Alcohol also significantly decreased TER and disrupted VE‐cadherin organization at junctions. Acetaldehyde significantly decreased TER, but inhibition of alcohol dehydrogenase or application of a superoxide dismutase mimetic failed to prevent alcohol‐induced decreases in TER. Inhibition of p38 MAPK, but not MLCK or ROCK, significantly attenuated the alcohol‐induced barrier dysfunction. Alcohol rapidly decreased GTP‐bound Rac1 but not RhoA during the drop in TER. Activation of Epac increased TER, but did not prevent alcohol from decreasing TER. However, activation of Epac after initiation of alcohol‐induced barrier dysfunction quickly resolved TER to baseline levels.ConclusionsOur results suggest that alcohol intoxication increases microvascular permeability to plasma proteins. The data also suggest the endothelial‐specific mechanism involves the p38 MAPK, Rac1, and reorganization of VE‐cadherin at junctions. Last, activation of Epac can quickly resolve alcohol‐induced endothelial barrier dysfunction.
Do investors misprice components of net periodic pension cost?
Authors: Shin Yong‐Chul , Yu Kun 
Published: September 2014

AbstractWe examine whether and how investors misprice the components of net periodic pension cost under SFAS No. 87 and 158. We find that investors appear to have difficulty in understanding the transitory feature of other net periodic pension cost (PPOPCC) and thus overestimate its persistence, which in turn leads to the mispricing of PPOPCC in the pre‐158 period. We also find that SFAS No. 158 appears to reduce the mispricing of PPOPCC, suggesting a positive effect of SFAS No. 158 on investors' valuation of pension items in the income statement. Additional analysis suggests that investors also overestimate the persistence of, and thus misprice, pension‐related cash flows and accruals in the pre‐158 period and that SFAS No. 158 reduces the mispricing of pension‐related cash flows and accruals.
Low IL‐8 is associated with anxiety in suicidal patients: genetic variation and decreased protein levels
Authors: Janelidze S. , Suchankova P. , Ekman A. , Erhardt S. , Sellgren C. , Samuelsson M. , Westrin A. , Minthon L. , Hansson O. , Träskman‐Bendz L. , Brundin L. 
Published: September 2014

ObjectiveRecent studies indicate that inflammation may play a role in the pathophysiology of suicidality. Interleukin‐8 (IL‐8) is a chemokine that in addition to its function in the immune system also exert neuroprotective properties. The involvement of this chemokine in neuropsychiatric conditions is incompletely known.MethodWe measured plasma and cerebrospinal fluid (CSF) IL‐8, as well as the genotype frequency of a single nucleotide polymorphism (‐251A/T, rs4073) in the promoter region of the IL8 gene, in suicide attempters (n = 206) and healthy controls (n = 578).ResultsPlasma and CSF levels of IL‐8 were significantly lower in suicide attempters with anxiety than in healthy controls. IL‐8 in both plasma and CSF correlated negatively with symptoms of anxiety. Compared with the population‐based cohort, the IL‐8‐251T allele was more prevalent among female suicide attempters. Furthermore, suicide attempters carrying this allele showed more severe anxiety. This correlative study warrants further mechanistic studies on the effects of IL‐8 in the central nervous system.ConclusionWe suggest that IL‐8 might be involved in the biological mechanisms mediating resilience to anxiety. Thus, our findings highlight the chemokine IL‐8 as a potential target for future development of anti‐anxiety treatments and suicide prevention.
Association between Plasminogen Activator Inhibitor‐1 Gene Polymorphisms and Recurrent Pregnancy Loss: A Systematic Review and Meta‐Analysis
Authors: Chen Hui , Nie Shuping , Lu Ming 
Published: September 2014

Human plasminogen activator inhibitor‐1 (PAI‐1) is closely related to embryonic development and pregnancy success. The association between PAI‐1 gene polymorphisms (PAI‐1‐844G/A and PAI‐1‐675G/A) and the risk of recurrent pregnancy loss (RPL) is controversial. Therefore, we perform this review to clarify the association between PAI‐1 gene polymorphisms and RPL risk. We performed a systematic search for studies that described the effect of PAI‐1 polymorphisms on RPL risk. The odds ratios (ORs) with corresponding 95% confidence intervals (CIs) were considered under recessive genetic models. Furthermore, we conducted a subgroup analysis based on the studies' geographic regions of origin. Data were analyzed using Stata 11.2 software. Eighteen studies were included, and a high degree of statistical heterogeneity existed among the studies. In this study, we found a significant association between the PAI‐1‐675G/A polymorphism and the risk of RPL under the recessive model (OR = 1.70, 95% CI = 1.21–2.38). However, no significant association between the PAI‐1‐844G/A polymorphism and RPL was noted. PAI‐1‐675G/A (4G/5G) polymorphisms play a potential role in RPL. The screening of PAI‐1 (4G/5G) gene mutations should be included during an RPL diagnostic workup, and patients should be treated using anticoagulant therapy during pregnancy if necessary.
Adenosine A1 receptor‐dependent and independent pathways in modulating renal vascular responses to angiotensin II
Authors: Gao X. , Peleli M. , Zollbrecht C. , Patzak A. , Persson A. E. G. , Carlström M. 
Published: September 2014

AbstractAimRenal afferent arterioles are the effector site for autoregulation of glomerular perfusion and filtration. There is synergistic interaction between angiotensin II (ANG II) and adenosine (Ado) in regulating arteriolar contraction; however, the mechanisms are not clear. In this context, this study investigated the contribution of A1 receptor‐dependent and independent signalling mechanisms.MethodsIsolated perfused afferent arterioles from transgenic mice (A1+/+ and A1−/−) were used for vascular reactivity studies. Cultured vascular smooth muscle cells (VSMC) were used for phosphorylation studies of signalling proteins that induce arteriolar contraction.ResultsMaximal arteriolar contraction to ANG II was attenuated in A1−/− (22%) compared with A1+/+ (40%). Simultaneous incubation with low‐dose ado (10−8 mol L−1) enhanced ANG II‐induced contraction in A1+/+ (58%), but also in A1−/− (42%). An ado transporter inhibitor (NBTI) abolished this synergistic effect in A1−/−, but not in wild‐type mice. Incubation with Ado + ANG II increased p38 phosphorylation in aortic VSMC from both genotypes, but treatment with NBTI only blocked phosphorylation in A1−/−. Combination of ANG II + Ado also increased MLC phosphorylation in A1+/+ but not significantly in A1−/−, and NBTI had no effects. In agreement, Ado + ANG II‐induced phosphorylation of p38 and MLC in rat pre‐glomerular VSMC was not affected by NBTI. However, during pharmacological inhibition of the A1 receptor simultaneous treatment with NBTI reduced phosphorylation of both p38 and MLC to control levels.ConclusionInteraction between ANG II and Ado in VSMC normally involves A1 receptor signalling, but this can be compensated by receptor independent actions that phosphorylate p38 MAPK and MLC.
Effects of Cucurbitacin E, a Tetracyclic Triterpene Compound from Cucurbitaceae, on the Pharmacokinetics and Pharmacodynamics of Warfarin in Rats
Authors: Ding Tonggui , Zhang Yuanjin , Chen Ang , Tang Yu , Liu Mingyao , Wang Xin 
Published: September 2014

AbstractThis study firstly investigated the effects of cucurbitacin E (CuE), a tetracyclic triterpene compound from Cucurbitaceae, on the pharmacokinetics (PK) and pharmacodynamics (PD) of warfarin, a model CYP2C probe substrate, in the rat. In PK studies, the concentration of warfarin in blood samples was determined by HPLC‐DAD, and the PK parameters were analysed using non‐compartmental methods. In PD studies, the prothrombin time (PT) in blood plasma at each sample point was measured via thromboplastin reagents. CuE treatment (50, 100 and 200 μg/kg, i.p.) decreased warfarin clearance (28–32%), increased the area under the curve (AUC0–∞; 55–62%) and prolonged plasma half‐life (t1/2; 58–72%). At the same time, the anticoagulation effect of warfarin (PTmax) was also significantly increased in the presence of CuE. These data demonstrated that CuE affected the PK and PD of warfarin, and these effects may be due to the inhibition of CYP2C activity by CuE. Hence, careful monitoring should be carried out during concomitant use of herbal products containing CuE with drugs that are metabolized by CYP2C enzymes.
Altered Frequency Distribution in the Electroencephalogram is Correlated to the Analgesic Effect of Remifentanil
Authors: Graversen Carina , Malver Lasse P. , Kurita Geana P. , Staahl Camilla , Christrup Lona L. , Sjøgren Per , Drewes Asbjørn M. 
Published: September 2014

AbstractOpioids alter resting state brain oscillations by multiple and complex factors, which are still to be elucidated. To increase our knowledge, multi‐channel electroencephalography (EEG) was subjected to multivariate pattern analysis (MVPA), to identify the most descriptive frequency bands and scalp locations altered by remifentanil in healthy volunteers. Sixty‐two channels of resting EEG followed by independent measures of pain scores to heat and bone pain were recorded in 21 healthy males before and during remifentanil infusion in a placebo‐controlled, double‐blind crossover study. EEG frequency distributions were extracted by a continuous wavelet transform and normalized into delta, theta, alpha, beta and gamma bands. Alterations relative to pre‐treatment responses were calculated for all channels and used as input to the MVPA. Compared to placebo, remifentanil increased the delta band and decreased the theta and alpha band oscillations as a mean over all channels (all p ≤ 0.007). The most discriminative channels in these frequency bands were F1 in delta (83.33%, p = 0.0023) and theta bands (95.24%, p < 0.0001), and C6 in the alpha band (80.95%, p = 0.0054). These alterations were correlated to individual changes in heat pain in the delta (p = 0.045), theta (p = 0.038) and alpha (p = 0.039) bands and to bone pain in the alpha band (p = 0.0092). Hence, MVPA of multi‐channel EEG was able to identify frequency bands and corresponding channels most sensitive to altered brain activity during remifentanil treatment. As the EEG alterations were correlated to the analgesic effect, the approach may prove to be a novel methodology for monitoring individual efficacy to opioids.
Group Variable Selection via Convex Log-Exp-Sum Penalty with Application to a Breast Cancer Survivor Study
Authors: Geng Zhigeng , Wang Sijian , Yu Menggang , Monahan Patrick O. , Champion Victoria , Wahba Grace 
Published: September 2014

SummaryIn many scientific and engineering applications, covariates are naturally grouped. When the group structures are available among covariates, people are usually interested in identifying both important groups and important variables within the selected groups. Among existing successful group variable selection methods, some methods fail to conduct the within group selection. Some methods are able to conduct both group and within group selection, but the corresponding objective functions are non-convex. Such a non-convexity may require extra numerical effort. In this article, we propose a novel Log-Exp-Sum(LES) penalty for group variable selection. The LES penalty is strictly convex. It can identify important groups as well as select important variables within the group. We develop an efficient group-level coordinate descent algorithm to fit the model. We also derive non-asymptotic error bounds and asymptotic group selection consistency for our method in the high-dimensional setting where the number of covariates can be much larger than the sample size. Numerical results demonstrate the good performance of our method in both variable selection and prediction. We applied the proposed method to an American Cancer Society breast cancer survivor dataset. The findings are clinically meaningful and may help design intervention programs to improve the qualify of life for breast cancer survivors.
Urinary tract infections during the first year after renal transplantation: one center's experience and a review of the literature
Authors: Gołębiewska Justyna E. , Dębska‐Ślizień Alicja , Rutkowski Bolesław 
Published: September 2014

AbstractBackgroundThe aim of the study was to evaluate the incidence, clinical manifestations, microbiology, risk factors, and the influence of UTIs on renal graft function.MethodsWe analyzed clinical data, urine cultures performed within the first 12 months after RTx, and renal function within 24 months in consecutive patients undergoing RTx at Gdańsk Transplantation Centre between January 2007 and December 2009.ResultsWe studied data from 209 RTx recipients, 59.3% men, with a mean age of 46.4 ± 14 yr. We observed 322 UTI episodes in 111 patients, including asymptomatic bacteriuria (53%, n = 170), lower UTIs (25%, n = 82), upper UTIs (22%, n = 57), and 13 cases of urosepsis. Thirty‐eight percent of UTIs were diagnosed during the first post‐transplant month. The most frequently isolated uropathogen was Enterococcus faecium (36%, n = 44) and from the second month E. coli (58%, n = 114). Risk factors were female gender, induction use, history of recurrent UTIs before RTx, acute rejection (AR), CMV infection, vesico‐ureteral reflux or strictures at uretero‐vesical junction, and high comorbidity. Renal graft function measured by eGFR was significantly worse in patients suffering from UTIs from the baseline. However, the evolution of renal graft function did not differ significantly between patients with and without UTIs.ConclusionsLower renal graft function may promote UTIs or UTIs may not allow a complete recovery of graft function after transplantation.
Contribution of impaired renal function to cardiovascular risk prediction models in renal transplant recipients
Authors: Benguzzi Mowad , Mansell Holly , Hassan Abubakar , Elmoselhi Hamdi , Mainra Rahul , Shoker Ahmed 
Published: September 2014

AbstractBackgroundThe Framingham risk score (FRS) and cardiovascular risk calculator for renal transplant recipients (CRCRTR‐MACE) quantify cardiovascular risk in renal transplant recipients (RTR). In contrast to the FRS, the CRCRTR‐MACE includes serum creatinine as a variable in the risk prediction equation.ObjectiveTo determine the influence of impaired renal function on performances of the two equations.MethodsA chart review of 270 RTR transplanted from 1979 to 2012. High risk was defined at scores ≥20%. Standard statistical analyses included multivariate analysis (MVA), stepwise analysis, and odds ratio to estimate contributions of risk factors.ResultsMean transplant duration was 9.51 ± 6.65 yr. Mean eGFR was 59.19 ± 28.26 mL/min/1.73 m2. FRS and CRCRTR‐MACE scores of least 20% were present in 9.3% and 24.8%, respectively, while 7.2% and 11.2% of RTR with eGFR ≥60 mL/min/1.73 m2 were high risk, respectively. Mean age, blood pressure, TC:HDL ratio, smoking, and diabetes were evenly distributed in patients with varying eGFR. FRS scores remained similar at wide eGFR range (≤30 mL/min/1.73 m2–≥90 mL/min/1.73 m2), while CRCRTR‐MACE scores significantly increased as eGFR decreased.ConclusionsCRCRTR‐MACE identified more patients at high cardiovascular risk, even in those with more favorable renal function, suggesting a fundamental difference between the two calculators beyond renal function.
Randomized comparison of recovery time after use of remifentanil alone versus midazolam and meperidine for colonoscopy anesthesia
Authors: Hong Mi Jin , Sung In‐Kyung , Lee Sang Pyo , Cheon Bo‐Kyung , Kang Hyun , Kim Tae‐Yop 
Published: September 2014

Background and AimAlthough the combination of midazolam‐meperidine has been widely used as a sedation regimen for colonoscopy, its residual effect which is longer than the duration of a colonoscopy procedure can delay patient recovery and discharge. Remifentanil, an ultra‐short‐acting opioid, has a very brief duration of action. We hypothesized that using remifentanil alone for colonoscopy would provide shorter recovery time compared with the midazolam‐meperidine combination.MethodsTime to achieve Aldrete score = 10 was determined and compared in patients who were randomly allocated to receive remifentanil alone (group‐R, n = 27) or a midazolam‐meperidine combination (group‐MM, n = 27) for colonoscopy. Intergroup differences in sedation, recall analgesia, cardio‐respiratory profiles, and satisfaction of patient and endoscopist were also determined during and after colonoscopy.ResultsGroup‐R showed a significantly shorter recovery time than group‐MM (median [25–75%], 0 [0–10] vs 30 [15–30] min, P < 0.001). Group‐R showed significantly higher bispectral‐index values during colonoscopy (92 [85–96] vs 84 [80–87], P = 0.001); a higher incidence of recall of explanations given during and after colonoscopy (100 vs 48% and 96 vs 52%, both P < 0.001); and a lower distress score (visual analog scale 30/100 vs 37/100 mm, P = 0.002), than did group‐MM. Neither extent of pain, incidence of hemodynamic instability nor incidence of respiratory depression differed between the groups.ConclusionsRemifentanil for colonoscopy afforded faster recovery compared to midazolam‐meperidine combination. It also provided greater patient–endoscopist communication and satisfaction with comparable patient analgesia and cardiorespiratory profile during colonoscopy.
Acknowledging and allocating responsibility for clinical inertia in the management of Type 2 diabetes in primary care: a qualitative study
Authors: Zafar A. , Stone M. A. , Davies M. J. , Khunti K. 
Published: September 2014

AbstractAimsFailure to intensify treatment in patients with Type 2 diabetes with suboptimal blood glucose control has been termed clinical inertia and has been shown to contribute to poorer patient outcomes. We aimed to identify and explore perceptions about clinical inertia from the perspective of primary healthcare providers.MethodsA qualitative study was conducted in Leicestershire and Northamptonshire, UK. Purposive sampling was based on healthcare providers working in primary care settings with ‘higher’ and ‘lower’ target achievement based on routine data. Twenty semi‐structured interviews were conducted, face‐to‐face or by telephone. Thematic analysis was informed by the constant comparative approach.ResultsAn important broad theme that emerged during the analysis was related to attribution and explanation of responsibility for clinical inertia. This included general willingness to accept a degree of responsibility for clinical inertia. In some cases, however, participants had inaccurate perceptions about levels of target achievement in their primary care centres, as indicated by routine data. Participants sought to lessen their own sense of accountability by highlighting patient‐level barriers such as comorbidities and human fallibility, and also system‐level barriers, particularly time constraints. Perceptions about ways of addressing the problem of clinical inertia were not seen as straightforward, further emphasizing a complex and cumulative pattern of barriers.ConclusionsIn order to understand and address the problem of clinical inertia, provider, patient‐ and system‐level barriers should be considered together rather than as separate issues. Acknowledgement of responsibility should be regarded positively as a motivator for change.
Time course and mechanisms of the anti‐hypertensive and renal effects of liraglutide treatment
Authors: von Scholten B. J. , Lajer M. , Goetze J. P. , Persson F. , Rossing P. 
Published: September 2014

AbstractAimsGlucagon‐like peptide–1 receptor agonist studies have revealed clinically significant reductions in systolic blood pressure (SBP). The aim was to investigate the time course of the anti‐hypertensive effect of liraglutide treatment and potential underlying mechanisms.MethodsWe used an open‐label, single‐centre trial; 31 participants with Type 2 diabetes and hypertension completed the study. All participants were treated with liraglutide escalated to a maximum dose of 1.8 mg/day for 7 weeks, followed by a 21–day washout period. The primary outcome was a change in 24–h SBP.ResultsTwenty‐four‐h SBP increased by 10 mmHg on day 3 (P = 0.008) and 7 mmHg on day 7 (P = 0.033, 0.6 mg/day). On day 29, (1.8 mg/day), 24–h SBP was 7 mmHg lower compared with baseline (P = 0.11). Following the treatment period (day 49) and after washout (day 70), 24–h BP was equivalent to baseline. In addition, extracellular volume (ECV) was reduced by 2.0 l [95% confidence interval (CI) = 1.0–3.1 l, P < 0.001] and midregional‐pro‐atrial natriuretic peptide (MR–proANP) was reduced by 20% (95% CI = 12–28%, P < 0.001). Also, urinary albumin excretion declined by 30% (95% CI = 12–44%, P = 0.003), GFR by 11 ml/min/1.73 m2 (95% CI = 7.2–14.4 ml/min/1.73 m2, P < 0.001) and fractional albumin excretion by 29% (95% CI = 3–48%, P = 0.032).ConclusionsLiraglutide treatment was associated with an initial increase in 24–h SBP, followed by a 7 mmHg reduction after escalation to 1.8 mg/day. This effect subsided after 4 weeks of maximum dose. Reductions in ECV and MR–proANP may explain the anti‐hypertensive potential. Liraglutide treatment was associated with reversible reductions in albuminuria and GFR, which has to be confirmed in randomized trials.
Feature selection for clustering categorical data with an embedded modelling approach
Authors: Silvestre Cláudia , Cardoso Margarida G. M. S. , Figueiredo Mário 
Published: September 2014

AbstractResearch on the problem of feature selection for clustering continues to develop. This is a challenging task, mainly due to the absence of class labels to guide the search for relevant features. Categorical feature selection for clustering has rarely been addressed in the literature, with most of the proposed approaches having focused on numerical data. In this work, we propose an approach to simultaneously cluster categorical data and select a subset of relevant features. Our approach is based on a modification of a finite mixture model (of multinomial distributions), where a set of latent variables indicate the relevance of each feature. To estimate the model parameters, we implement a variant of the expectation‐maximization algorithm that simultaneously selects the subset of relevant features, using a minimum message length criterion. The proposed approach compares favourably with two baseline methods: a filter based on an entropy measure and a wrapper based on mutual information. The results obtained on synthetic data illustrate the ability of the proposed expectation‐maximization method to recover ground truth. An application to real data, referred to official statistics, shows its usefulness.