Miracle-dz/UniFAR-FTUs huggingface dataset:
Population Pharmacokinetics of Propofol: A Multicenter Study

Background: Target-controlled infusion is an increasingly common type of administration for propofol. This method requires accurate knowledge of pharmacokinetics, including the effects of age and weight. The authors performed a multicenter population analysis to quantitate the effects of covariates. Methods: The authors analyzed 4,112 samples of 270 individuals (150 men, 120 women, aged 2–88 yr, weighing 12–100 kg). Population pharmacokinetic modeling was performed using NONMEM (NONMEM Project Group, University of California, San Francisco, CA). Inter- and intraindividual variability was estimated for clearances and volumes. The effects of age, weight, type of administration and sampling site were investigated. Results: The pharmacokinetics of propofol were best described by a three-compartment model. Weight was found to be a significant covariate for elimination clearance, the two intercompartmental clearances, and the volumes of the central compartment, the shallow peripheral compartment, and the deep peripheral compartment; power functions with exponents smaller than 1 yielded the best results. The estimates of these parameters for a 70-kg adult were 1.44 l/min, 2.25 l/min, 0.92 l/min, 9.3 l, 44.2 l, and 266 l, respectively. For patients older than 60 yr the elimination clearance decreased linearly. The volume of the central compartment decreased with age. For children, all parameters were increased when normalized to body weight. Venous data showed a decreased elimination clearance; bolus data were characterized by increases in the volumes of the central and shallow peripheral compartments and in the rapid distribution clearance (Cl2) and a decrease in the slow distribution clearance (Cl3). Conclusions: Pharmacokinetics of propofol can be well described by a three-compartment model. Inclusion of age and weight as covariates significantly improved the model. Adjusting pharmacokinetics to the individual patient should improve the precision of target-controlled infusion and may help to broaden the field of application for target-controlled infusion systems.
Hydrogenase activity in aged, nonviable Desulfovibrio vulgaris cultures and its significance in anaerobic biocorrosion

Batch cultures of Desulfovibrio vulgaris stored at 32 degrees C for 10 months have been found to retain 50% of the hydrogenase activity of a 1-day culture. The hydrogenase found in old cultures needs reducing conditions for its activation. Viable cell counts are negative after 6 months, showing that the hydrogenase activity does not depend on the presence of viable cells. These observations are of importance in the understanding of anaerobic biocorrosion of metals caused by depolarization phenomena.
KEN-Box-dependent Degradation of the Bub1 Spindle Checkpoint Kinase by the Anaphase-promoting Complex/Cyclosome*

The spindle checkpoint is a cell cycle surveillance mechanism that ensures the fidelity of chromosome segregation during mitosis and meiosis. Bub1 is a protein serine-threonine kinase that plays multiple roles in chromosome segregation and the spindle checkpoint. In response to misaligned chromosomes, Bub1 directly inhibits the ubiquitin ligase activity of the anaphase-promoting complex or cyclosome (APC/C) by phosphorylating its activator Cdc20. The protein level and the kinase activity of Bub1 are regulated during the cell cycle; they peak in mitosis and are low in G1/S phase. Here we show that Bub1 is degraded during mitotic exit and that degradation of Bub1 is mediated by APC/C in complex with its activator Cdh1 (APC/CCdh1). Overexpression of Cdh1 reduces the protein levels of ectopically expressed Bub1, whereas depletion of Cdh1 by RNA interference increases the level of the endogenous Bub1 protein. Bub1 is ubiquitinated by immunopurified APC/CCdh1 in vitro. We further identify two KEN-box motifs on Bub1 that are required for its degradation in vivo and ubiquitination in vitro. A Bub1 mutant protein with both KEN-boxes mutated is stable in cells but fails to elicit a cell cycle phenotype, indicating that degradation of Bub1 by APC/CCdh1 is not required for mitotic exit. Nevertheless, our study clearly demonstrates that Bub1, an APC/C inhibitor, is also an APC/C substrate. The antagonistic relationship between Bub1 and APC/C may help to prevent the premature accumulation of Bub1 during G1.
Syk Is Required for Monocyte/Macrophage Chemotaxis to CX3CL1 (Fractalkine)1

CX3CL1 (fractalkine), the only member of the δ subclass of chemokines, is a known chemotactic factor for monocytes/macrophages as well as NK cells and T lymphocytes. In several pathologies, excessive production of CX3CL1 at specific sites leads primarily to monocyte/macrophage recruitment, which causes tissue and vascular damage. Despite their clinical relevance, the mechanisms underlying monocyte/macrophage chemotaxis to CX3CL1 remain poorly documented. The present report addresses this issue and identifies cell signaling crucial for this process. Using the murine monocyte/macrophage RAW cell line, we show that CX3CL1 treatment elicits a rapid and transient increase in F-actin and the formation of F-actin-enriched cell protrusions. CX3CL1 also triggers tyrosine phosphorylation of proteins localized in those protrusions. The protein tyrosine kinase Syk is activated upon CX3CL1 treatment, and reduction of Syk expression using RNA-mediated interference results in a specific and massive impairment of RAW cell migration to CX3CL1. Similar results are obtained using the Syk inhibitor, piceatannol. Cells with reduced Syk expression also exhibit a major defect in CX3CL1-induced cytoskeletal remodeling. These data suggest that in monocytes/macrophages, Syk is essential for proper reorganization of the actin cytoskeleton in response to CX3CL1 and is therefore required for cell chemotaxis to CX3CL1.
Effect of FR167653 on pancreatic ischemia-reperfusion injury in dogs.

BACKGROUND The role of inflammatory cytokines is still unclear in ischemia-reperfusion injury of the pancreas. We investigated the effect of FR167653 (FR), a newly developed compound that is a potent suppressor of interleukin (IL)-1beta and tumor necrosis factor (TNF)-alpha on ischemia-reperfusion injury of the isolated pancreatic tail in dogs. METHODS The tail of the pancreas was subjected to ischemia for 90 minutes. During occlusion of the vascular inflow, the head of the pancreas was removed. A control group (n = 14) and an FR treatment group (n = 11) were evaluated for survival rate, tissue blood flow, arterial oxygen pressure (Pao(2)), serum amylase and lipase levels, glucose and insulin, liver enzymes, creatinine, IL-1beta mRNA in the peripheral blood, and histopathology. RESULTS Six of the 14 control animals and 2 of the 11 FR-treated animals died. The FR treatment group showed lower amylase (P=.037) and lipase (P =.030) levels, lower IL-1beta mRNA expression (P =.033), and less pancreatic tissue damage (P =.041) than did the control group, but there was no remarkable change in endocrine function (P =.422). Pao(2) during the acute phase in the FR treatment group was maintained (P=.009), but pulmonary tissue was damaged. Results of biochemical and histologic examinations of the liver and kidneys were unremarkable. CONCLUSIONS FR ameliorates ischemia-reperfusion injury of the pancreas and reduces the production of inflammatory cytokines that may contribute to secondary damage to distant organs.
Comparative performance of 11kV silicone rubber polymeric insulators under Rotating Wheel Dip Test

This paper presents an experimental study of silicone rubber polymeric insulators for 11kV systems using a Rotating Wheel Dip Test (RWDT) based on IEC 62730:2012. The primary aim of this study is to compare the aging performance of polymeric insulators under AC voltages. Different insulator designs are investigated. A conventional polymeric insulator design has been adopted and compared with insulators having a textured surface. Textured surfaces have been developed by Cardiff University to increase the creepage distance and improve tracking/erosion performance. The results of long term testing are obtained; during the test cycle, and both voltage and current traces were acquired continuously. A number of parameters were then calculated during the post processing stage. These parameters include peak values, accumulated absorbed energy, power consumption and power factor angle. Using these parameters allows direct comparison between different insulator designs. In particular, the magnitude and shape of leakage current and the accumulated absorbed energy on the insulator surface were examined to characterise each insulator. Furthermore, continuous monitoring of the shed surfaces and the insulator trunk using an IR camera were undertaken to evaluate the temperature distribution along the surface profile. In addition, hydrophobicity tests were performed before and after completion of the test to evaluate the degradation level of the insulator surface and its material.
CT study on morphometry of frontal sinus

The aim of this study was to determine the prevalence and morphological characteristics of the frontal sinus in an adult population. This study was conducted retrospectively on paranasal CT scans in the axial and coronal planes of 300 cases (123 male and 177 female). The mean age was 40.74 ± 13.34 (range 20–83). Measurements of the width, height and anteroposterior length for each sinus and total width were obtained from CT scans. Measurements were compared statistically with relation to side and sex. The cases were divided into subgroups according to age for each sex and each measurement parameter was also compared among the subgroups. All measurements tended to be larger on the left side and were significantly larger in males than females. There was a significant difference in the anteroposterior lengths of right and left sides in both males and females and height for males and width for females. In both sexes, the highest values of measurements were usually observed at the 31–40 age group and there was a tendency to decrease with aging. The larger diameters of the left frontal sinus imply that it may be more possibly violated during surgical interventions. Morphometric features differed significantly in the two sexes at different ages and comparison with previous studies presented great regional variability. The size of the frontal sinus was seen to be related to age and sex. The knowledge provided in the present study is useful for some surgical procedures and widens the anthropometric knowledge of humanity. Clin. Anat. 21:287–293, 2008. © 2008 Wiley‐Liss, Inc.
Randomized trial of a self-administered decision aid for colorectal cancer screening

Objective Previous studies have not assessed whether evidence-based information about the outcomes of colorectal cancer screening increases informed choice among people from a range of socioeconomic backgrounds nor have they assessed whether this can be administered away from a health-care provider. Methods Randomized controlled trial in six primary care locations. Three hundred and fourteen people aged 50–74 years received a self-administered decision aid (DA) booklet about outcomes of biennial faecal occult blood testing (FOBT) screening or government consumer guidelines (G). Results Significantly more DA recipients (20.9%) were ‘informed’ compared with G recipients (5.8%) (P = 0.0001, OR 4.32; 95% CI 2.49 to 7.52); the DA did not affect values clarity (61.9% clear after DA versus 59.1% after G) nor screening decisions overall (87.3% would screen after DA versus 90.5% after G). Test uptake at one month was uniformly low (5.2% DA versus 6.6% G); mostly due to being ‘too busy’. DA recipients were more likely to make decisions ‘integrating’ knowledge with values (10.4% DA versus 1.5% G). Decisions not to screen were equally uncommon in both groups but more likely to be uninformed in G (P = 0.03). More DA recipients from all education levels were ‘informed’ (P = 0.02), particularly in lower education (50.0% DA versus 17.8% G) and university-educated groups (79.4% DA versus 32.1% G). Conclusion Detailed absolute risk and benefit information about FOBT screening can be effectively used at home by people to increase informed choice. The DA was effective in people with lower education levels. Trial Registration Unique Protocol ID 211705 ClinicalTrials.gov ID NCT 00148226.
CT Angiography in Stent-Graft Sizing: Impact of Using Inner vs. Outer Wall Measurements of Aortic Neck Diameters

Purpose To assess the impact of using inner wall vs. outer wall measurements on stent-graft sizing for endovascular repair of abdominal aortic aneurysm (AAA). Methods Preoperative static and electrocardiographically-gated 64-slice computed tomographic angiography (CTA) datasets were acquired on 40 consecutive AAA patients (29 men; mean age 78.9±6 years, range 75–89). On static images, the aortic neck diameters were manually measured twice by 2 readers at 3 clinically relevant levels (supra-, juxta-, and infrarenal). The measurements were obtained from intima-to-intima (inner wall) and from adventitia-to-adventitia (outer wall). Dynamically reconstructed scans were also reviewed in each phase of the cardiac cycle to identify inner and outer minimum/maximum diameters. Using inner and outer wall measurements performed on static images, readers selected the size of a stent-graft that required inner neck diameter measurements and then one that required outer wall diameters. To calculate the relative oversizing, each selected stent-graft size was compared to that obtained using dynamic measurements. Oversizing <4% or >30% was considered inadequate. Results Mean variations for the inner and outer wall diameters of 9.75%±4.01% and 8.66%±3.71%, respectively, were recorded on static CTAs; the absolute changes in diameters were 1.82±0.63 mm and 1.91±0.64 mm, respectively. No statistically significant differences were found relative to aortic pulsatility at the 3 levels in the neck for the inner or outer wall diameters. Significant variability was seen between inner (mean 20.8±3.4 mm) vs. outer (mean 23.7±4.3 mm; p<0.05) wall diameters. Stent-graft sizes significantly changed on the basis of the measurement method and device; for example, using the outer diameter to size a stent-graft that requires an inner diameter reference changed 36% of the selected stent-graft sizes, with ∼20% being excessively oversized. Conversely, using the inner diameter to size an outer-diameter–based stent-graft resulted in nearly 40% of the sizes being altered. Based on dynamic measurements, the changes were more dramatic: the oversizing was considered excessive in up to 90% of patients if the measurement method did not match the stent-graft's stipulated reference. Conclusions These data suggest that stent-graft sizing should follow the manufacturer's recommendations for using inner or outer diameter references based on dynamic patterns (mean value between diastolic and systolic diameters suggested).
Thigh Muscle Injuries in Youth Soccer

Background: Participation in soccer at younger ages with attendant risk of muscle injury is increasing. Purpose: To delineate patterns of thigh muscle injury and predictors of recovery in male youth soccer academy players. Study Design: Cohort study (prognosis); Level of evidence, 2. Methods: Forty-one English Premiership soccer academy squads (all male, aged 8-16 years) over a 5-year period comprising 12 306 player seasons were studied prospectively for pattern, mechanism, and outcome after thigh muscle injury. Event analysis was used to identify independent predictors of slow recovery. Results: A total of 1288 injuries were recorded representing an incidence (mean [SD]) of 0.42 (0.24) per thousand hours of training with a mean annual incidence of 0.52. Midfield players received the most injuries, followed by defense and attack positions. The quadriceps muscle group was most likely to be injured. There were 345 reinjuries (27%). Median time off for a primary injury was 13 days (interquartile range, 7-22 days) and 12 days (7-21 days) following a reinjury. Risk of such injury increased as the game progressed toward the end of the first half period (P = .028), and this risk persisted throughout the entire second half. There were 2 peaks of incidence (January and September). The percentage of the total for hamstring, adductor, and quadriceps injuries did not significantly change with player age. However, the proportion of injuries that were severe increased with age of player (t = 3.72, P = .010). Poor prognostic factors for recovery were hamstring injuries (z = 2.182, P = .029), contact injury (z = −3.137, P = .002), and older age (z = −2.2298, P = .022). Conclusion: The risk for prolonged recovery from thigh muscle injury was found to increase with age of the player and contact mechanism. The risk of injury increased toward the end of the first half, and this risk persisted throughout the second half. Delayed recovery was significantly associated with a hamstring muscle injury, first injury, and contact mechanism. This study, for the first time, allows identification of youth male soccer players at high-risk for prolonged symptoms after thigh muscle injury.
Dental Awareness among Parents and Oral Health of Paediatric Cancer Patients Receiving Chemotherapy.

INTRODUCTION Dental care is often overlooked by the parents of children receiving treatment for cancer including chemotherapy who are in a phase of severe immunosuppression. AIM (i) To study dental attitudes of parents of children receiving chemotherapy towards importance of dental care. (ii) To evaluate oral hygiene status and compare it with healthy controls. MATERIALS AND METHODS A questionnaire assessing the awareness towards dental care was given to the parents of 47 paediatric patients suffering from cancer receiving chemotherapy and to parents of 47 paediatric patients reporting to outpatient Department of Pedodontics at SGT Dental College. Oral examination was also carried out for both the groups and DMFT/dmft, plaque and gingival index were noted. RESULTS Parents had a varying opinion regarding dental health of their child. The caries status of children in the control group was greater than children in the study group. The mean plaque index of children in the control group (1.40) was greater than children in the study group (1.34) which was statistically significant according to Mann-Whitney U test. The gingival health of children in the study group was better than children in the control group which was also not statistically significant. CONCLUSION This study highlights need for a periodic referral of the child cancer patients to the paediatric dental clinic in hospitals for the timely dental care.
Treatment of Uremic Pruritus: A Systematic Review.

BACKGROUND Uremic pruritus is a common and burdensome symptom afflicting patients with advanced chronic kidney disease (CKD) and has been declared a priority for CKD research by patients. The optimal treatments for uremic pruritus are not well defined. STUDY DESIGN Systematic review. SETTING & POPULATION Adult patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. SELECTION CRITERIA FOR STUDIES PubMed, CINAHL, Embase, International Pharmaceutical Abstracts, Scopus, Cochrane Library, and ClinicalTrials.gov from their inception to March 6, 2017, were systematically searched for randomized controlled trials (RCTs) of uremic pruritus treatments in patients with advanced CKD (stage ≥ 3) or receiving any form of dialysis. 2 reviewers extracted data independently. Risk of bias was assessed using the Cochrane Collaboration risk-of-bias tool. INTERVENTION Any intervention for the treatment of uremic pruritus was included. OUTCOMES A quantitative change in pruritus intensity on a visual analogue, verbal rating, or numerical rating scale. RESULTS 44 RCTs examining 39 different treatments were included in the review. These treatments included gabapentin, pregabalin, mast cell stabilizers, phototherapy, hemodialysis modifications, and multiple other systemic and topical treatments. The largest body of evidence was found for the effectiveness of gabapentin. Due to the limited number of trials for the other treatments included, we are unable to comment on their efficacy. Risk of bias in most studies was high. LIMITATIONS Heterogeneity in design, treatments, and outcome measures rendered comparisons difficult and precluded meta-analysis. CONCLUSIONS Despite the acknowledged importance of uremic pruritus to patients, with the exception of gabapentin, the current evidence for treatments is weak. Large, simple, rigorous, multiarm RCTs of promising therapies are urgently needed.
Platelet‐rich plasma activates tendon‐derived stem cells to promote regeneration of Achilles tendon rupture in rats

This study investigates whether platelet‐rich plasma (PRP) is an activator of tendon‐derived stem cells (TDSCs) to promote regeneration of Achilles tendon post‐rupture in rats. In the in vitro study, PRGF (activated PRP) significantly enhanced cell DNA synthesis, improved viability and promoted proliferation, while facilitating cell migration and the recruitment of TDSCs. In addition, TDSCs were mixed with collagen and PRP to form collagen–TDSC constructs (CTC) and PRP–collagen–TDSC constructs (PCTCs). After 3 weeks of culture in vitro, we found that most of the encapsulated TDSCs in the CTCs and PCTCs were still alive, while cells in the PCTCs showed a more aligned arrangement compared to the CTCs. In addition, the micro‐structure of PCTC showed more obvious fibre‐like tissues and formed a cyclic microvascular structure. The tenocyte‐related genes types I and III collagen, Tenascin‐C and Scleraxis of TDSCs in the PCTCs and CTCs were upregulated with time, and PCTCs showed more significance than CTCs (p < 0.05). After in vivo transplantation, the CTCs and PCTCs showed stimulatory effects on Achilles tendon healing. Moreover, the PCTCs improved the macroscopic appearance, histological morphology and biomechanical strength of ruptured Achilles tendon better than CTC. These results indicate that PRP can activate TDSCs to improve the quality of Achilles tendon rupture healing in the early stages. Copyright © 2015 John Wiley & Sons, Ltd.
Carbon-11-NNC 112: a radioligand for PET examination of striatal and neocortical D1-dopamine receptors.

UNLABELLED The aim of this work was to explore the potential of a selective D1-dopamine receptor antagonist as a new radioligand for PET examination of striatal and neocortical D1-dopamine receptors. METHODS The active (+)- and inactive (-)-enantiomers of [11C]NNC 112 were radiolabeled using the N-methylation approach and were examined by PET in cynomolgus monkeys and healthy men. Metabolite levels in plasma were measured by gradient high-performance liquid chromatography (HPLC). RESULTS N-methylation of the corresponding desmethyl precursors with [11C]methyl triflate gave high total radiochemical yield (50%-60%) and specific radioactivity (110 GBq/micromol). (+)-[11C]NNC 112 binding in cynomolgus monkeys was 5.77+/-0.31 and 2.36+/-0.14 times higher in the striatum and neocortex, respectively, than in the cerebellum at a transient equilibrium that appeared 40-50 min after injection. The binding of (+)-[11C]NNC 112 is stereoselective, because the brain distribution of the inactive (-)-enantiomer was on an equally low level for all brain regions. Displacement and pretreatment experiments using unlabeled SCH 23390 and ketanserin confirms that (+)-[11C]NNC 112 binds specifically and reversibly to D1-dopamine receptors. The radioactivity ratios of the striatum, frontal cortex and nucleus accumbens to the cerebellum were 3.8-4.0, 1.7-2.0 and 2.8-3.1, respectively, at a transient equilibrium that appeared 40-50 min after injection in four healthy human subjects. Linear graphical analysis gave distribution volume ratios of 3.9 and 1.5 in the putamen and frontal cortex, respectively. The fraction of the total radioactivity in human plasma representing unchanged (+)-[11C]NNC 112 was 85% at 5 min and 25% at 75 min after injection. CONCLUSION (+)-[11C]NNC 112 should be a useful PET radioligand for quantitative examination of not only striatal but neocortical D1-dopamine receptors in man.