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Execution of the Pharmacist-Driven Penicillin and Cephalosporin Sensitivity Review Instrument: An airplane pilot Analysis.
rade inflammation and/or body weight.

ClinicalTrials.gov NCT02417012 Graphical abstract.
ClinicalTrials.gov NCT02417012 Graphical abstract.
We studied for the first time the long-term effects of a combined physical activity and dietary intervention on insulin resistance and fasting plasma glucose in a general population of predominantly normal-weight children.

We carried out a 2year non-randomised controlled trial in a population sample of 504 children aged 6-9years at baseline. The children were allocated to a combined physical activity and dietary intervention group (306 children at baseline, 261 children at 2-year follow-up) or a control group (198 children, 177 children) without blinding. We measured fasting insulin and fasting glucose, calculated HOMA-IR, assessed physical activity and sedentary time by combined heart rate and body movement monitoring, assessed dietary factors by a 4day food record, used the Finnish Children Healthy Eating Index (FCHEI) as a measure of overall diet quality, and measured body fat percentage (BF%) and lean body mass by dual-energy x-ray absorptiometry. The intervention effects on insulin, glucose and HOMA-nd 2year follow-up. The intervention had no effect on fasting glucose, BF% or lean body mass. Changes in total physical activity energy expenditure, light physical activity, moderate-to-vigorous physical activity, total sedentary time, the reported consumption of high-fat (≥60%) vegetable oil-based spreads, and FCHEI, but not a change in BF% or lean body mass, partly explained the intervention effects on fasting insulin and HOMA-IR.

The combined physical activity and dietary intervention attenuated the increase in insulin resistance over 2years in a general population of predominantly normal-weight children. This beneficial effect was partly mediated by changes in physical activity, sedentary time and diet but not changes in body composition.

ClinicalTrials.gov NCT01803776 Graphical abstract.
ClinicalTrials.gov NCT01803776 Graphical abstract.Preventing clinical drug-induced liver injury (DILI) remains a major challenge, because DILI develops via multifactorial mechanisms. Immune and inflammatory reactions are considered important mechanisms of DILI; however, biomarkers from in vitro systems using immune cells have not been comprehensively studied. The aims of this study were (1) to identify promising biomarker genes for predicting DILI in an in vitro coculture model of peripheral blood mononuclear cells (PBMCs) with a human liver cell line, and (2) to evaluate these genes as predictors of DILI using a panel of drugs with different clinical DILI risk. Transcriptome-wide analysis of PBMCs cocultured with HepG2 or differentiated HepaRG cells that were treated with several drugs revealed an appropriate separation of DILI-positive and DILI-negative drugs, from which 12 putative biomarker genes were selected. To evaluate the predictive performance of these genes, PBMCs cocultured with HepG2 cells were exposed to 77 different drugs, and gene expression levels in PBMCs were determined. The MET proto-oncogene receptor tyrosine kinase (MET) showed the highest area under the receiver-operating characteristic curve (AUC) value of 0.81 among the 12 genes with a high sensitivity/specificity (85/66%). However, a stepwise logistic regression model using the 12 identified genes showed the highest AUC value of 0.94 with a high sensitivity/specificity (93/86%). Taken together, we established a coculture system using PBMCs and HepG2 cells and selected biomarkers that can predict DILI risk. The established model would be useful in detecting the DILI potential of compounds, in particular those that involve an immune mechanism.Methylmercury (MeHg) can elicit cognitive and motor deficits due to its developmental neuro- and myotoxic properties. While previous work has demonstrated that Nrf2 antioxidant signaling protects from MeHg toxicity, in vivo tissue-specific studies are lacking. In Drosophila, MeHg exposure shows greatest developmental toxicity in the pupal stage resulting in failed eclosion (emergence of adults) and an accompanying 'myosphere' phenotype in indirect flight muscles (IFMs). To delineate tissue-specific contributions to MeHg-induced motor deficits, we investigated the potential of Nrf2 signaling in either muscles or neurons to moderate MeHg toxicity. Larva were exposed to various concentrations of MeHg (0-20 µM in food) in combination with genetic modulation of the Nrf2 homolog cap-n-collar C (CncC), or its negative regulator Keap1. Eclosion behavior was evaluated in parallel with the morphology of two muscle groups, the thoracic IFMs and the abdominal dorsal internal oblique muscles (DIOMs). CncC signaling activity was reported with an antioxidant response element construct (ARE-GFP). We observed that DIOMs are distinguished by elevated endogenous ARE-GFP expression, which is only transiently seen in the IFMs. Dose-dependent MeHg reductions in eclosion behavior parallel formation of myospheres in the DIOMs and IFMs, while also increasing ARE-GFP expression in the DIOMs. Modulating CncC signaling via muscle-specific Keap1 knockdown and upregulation gives a rescue and exacerbation, respectively, of MeHg effects on eclosion and myospheres. Interestingly, muscle-specific CncC upregulation and knockdown both induce lethality. In contrast, neuron-specific upregulation of CncC, as well as Keap1 knockdown, rescued MeHg effects on eclosion and myospheres. find more Our findings indicate that enhanced CncC signaling localized to either muscles or neurons is sufficient to rescue muscle development and neuromuscular function from a MeHg insult. Additionally, there may be distinct roles for CncC signaling in myo-morphogenesis.The current study is proposing a design envelope for porous Ti-6Al-4V alloy femoral stems to survive under fatigue loads. Numerical computational analysis of these stems with a body-centered-cube (BCC) structure is conducted in ABAQUS. Femoral stems without shell and with various outer dense shell thicknesses (0.5, 1.0, 1.5, and 2 mm) and inner cores (porosities of 90, 77, 63, 47, 30, and 18%) are analyzed. A design space (envelope) is derived by using stem stiffnesses close to that of the femur bone, maximum fatigue stresses of 0.3σys in the porous part, and endurance limits of the dense part of the stems. The Soderberg approach is successfully employed to compute the factor of safety Nf > 1.1. Fully porous stems without dense shells are concluded to fail under fatigue load. It is thus safe to use the porous stems with a shell thickness of 1.5 and 2 mm for all porosities (18-90%), 1 mm shell with 18 and 30% porosities, and 0.5 mm shell with 18% porosity. The reduction in stress shielding was achieved by 28%. Porous stems incorporated BCC structures with dense shells and beads were successfully printed.
Few studies have examined the geometry of endovascular mechanical thrombectomy pathways. Here we examine the tortuosity and angulations of catheter pathways from the aortic arch to the termination of the internal carotid artery (ICA) and its association with thrombectomy performance.

We included 100 consecutive anterior circulation large vessel occlusion thrombectomy patients over 12 months. Computed tomography angiograms (CTA) were used for 3D segmentation of catheter pathway from the aortic arch to ICA termination. Tortuosity index (TI) and angulations of the catheter pathway were measured in a semi-automated fashion. TI and angulation degree were compared between sides and correlated with age and procedural measures.

We analyzed 188 catheter pathways in 100 patients. Severe angulation (≤ 30°) was present in 5.8% and 39.4% of common carotid artery (CCA) and extracranial ICA segments, respectively. Five pathways (2.6%) had 360° loop. CCA and extracranial ICA tortuosity had a weak but significant correlation with age (r = 0.17, 0.21, p value = 0.05, 0.02 respectively), time from groin puncture to the site of occlusion (r = 0.29, 0.25, p values = 0.008, 0.026 respectively), and fluoroscopy time (r = 0.022, 0.31, p values = 0.016, 0.001 respectively). There was a significant difference in the pattern of angulation (p value = 0.04) and tortuosity between right and left side in CCA segment (TI = 0.20 ± 0.086 vs. 0.15 ± 0.82, p value < 0.001).

There was a significant difference in CCA angulation between right and left sides. TI of extracranial CCA and ICA correlated with age and influenced time from groin puncture to the occlusion site and total fluoroscopy time.
There was a significant difference in CCA angulation between right and left sides. TI of extracranial CCA and ICA correlated with age and influenced time from groin puncture to the occlusion site and total fluoroscopy time.In this work, a two-step sequential extraction scheme for the determination of trace elements in Arctic PM10 samples was optimized by using two certified reference materials (CRMs). By means of an experimental design for qualitative variables, the five most common extracting solutions for particulate matter (PM) sequential extraction (high purity water (HPW), 0.032 M HNO3, 0.022 M HCl, 0.11 M CH3COOH, and 0.012 M CH3COOH/CH3COONH4 buffer) and two different extraction methods (stirring and ultrasounds) were compared. The purpose of the study was the identification of the procedure which gives the best estimation of the anthropogenic portion of the elements present in PM10 samples. The use of ultrasounds instead of stirring induced a low but significant decrease of the extraction of all the elements and a decrease in the repeatability of the procedure. Diluted HNO3 was the extractant which allowed to maximize the extraction of anthropogenic elements (As, Cd, Pb, Zn) with respect to crustal ones (Al, Si, Ti). The optimized procedure proved successful in avoiding contaminations and, therefore, suitable to be applied to PM samples having extremely low concentrations, such as samples collected in polar or other remote areas. The chosen procedure was applied to ten Arctic PM10 samples, allowing for a better identification of their sources. Indeed, it was possible to hypothesize that even though the concentrations of As, Cd, K, Mg, Mn, and Ni in spring and summer were different, their mobility and, therefore, their chemical form in the analyzed PM10 samples were probably similar. Graphical abstract.Several challenging biological sensing concepts have been realized using electrolyte-gated reduced graphene oxide field effect transistors (rGO-FETs). In this work, we demonstrate the interest of rGO-FET for the sensing of human papillomavirus (HPV), one of the most common sexually transmitted viruses and a necessary factor for cervical carcinogenesis. The highly sensitive and selective detection of the HPV-16 E7 protein relies on the attractive semiconducting characteristics of pyrene-modified rGO functionalized with RNA aptamer Sc5-c3. The aptamer-functionalized rGO-FET allows for monitoring the aptamer-HPV-16 E7 protein binding in real time with a detection limit of about 100 pg mL-1 (1.75 nM) for HPV-16 E7 from five blank noise signals (95% confidence level). The feasibility of this method for clinical application in point-of-care technology is evaluated using HPV-16 E7 protein suspended in saliva and demonstrates the successful fabrication of a promising field effect transistor biosensor for HPV diagnosis.
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