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Find video protocols related to scientific articles indexed in Pubmed.
Hierarchical HMM based learning of navigation primitives for cooperative robotic endovascular catheterization.
Med Image Comput Comput Assist Interv
PUBLISHED: 10-22-2014
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Despite increased use of remote-controlled steerable catheter navigation systems for endovascular intervention, most current designs are based on master configurations which tend to alter natural operator tool interactions. This introduces problems to both ergonomics and shared human-robot control. This paper proposes a novel cooperative robotic catheterization system based on learning-from-demonstration. By encoding the higher-level structure of a catheterization task as a sequence of primitive motions, we demonstrate how to achieve prospective learning for complex tasks whilst incorporating subject-specific variations. A hierarchical Hidden Markov Model is used to model each movement primitive as well as their sequential relationship. This model is applied to generation of motion sequences, recognition of operator input, and prediction of future movements for the robot. The framework is validated by comparing catheter tip motions against the manual approach, showing significant improvements in the quality of catheterization. The results motivate the design of collaborative robotic systems that are intuitive to use, while reducing the cognitive workload of the operator.
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The effect of prasugrel on ADP-stimulated markers of platelet activation in patients with sickle cell disease.
Platelets
PUBLISHED: 08-20-2014
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Abstract Platelets of patients with sickle cell disease (SCD) show evidence of mild activation in the non-crisis steady state and greater activation during vaso-occlusive crises (VOC). Prasugrel, a potent inhibitor of ADP-mediated platelet activation and aggregation, may be useful in attenuating VOC. We compared platelet responses to ADP stimulation in patients with SCD and healthy subjects before and after treatment with prasugrel. In a phase 1 study, platelet biomarker levels were assessed in 12 adult patients with SCD and 13 healthy subjects before and after 12?±?2 days of 5.0 or 7.5?mg/day prasugrel. The following were determined in whole blood samples stimulated with 20?µM ADP: (i) percentages of monocytes and neutrophils with adherent platelets (cell-platelet aggregates); (ii) the relative number (mass) of platelets associated with each monocyte and neutrophil as reported by CD61 mean fluorescence intensity (MFI) of the monocyte-platelet and neutrophil-platelet aggregates; (iii) the percentages of platelets positive for surface expression of CD40 ligand (CD40L), P-selectin (CD62p) and activated glycoprotein IIb-IIIa (GPIIb-IIIa); and (iv) the percentages of platelets and monocyte-platelet aggregates positive for surface tissue factor (TF) expression. At baseline, there were no significant differences between cohorts in the percentages of platelets expressing activation biomarkers. Following 12 days of prasugrel administration, the percentages of platelets expressing activation biomarkers following ADP stimulation were reduced in both cohorts, and there were no significant differences between groups. Both patients with SCD and healthy subjects had significant reductions in the monocyte-platelet and neutrophil-platelet aggregate MFI and the percentage of platelets expressing P-selectin and activated GPIIb-IIIa (all p?
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A novel flexible hyper-redundant surgical robot: prototype evaluation using a single incision flexible access pelvic application as a clinical exemplar.
Surg Endosc
PUBLISHED: 08-09-2014
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The flexible endoscope is increasingly being considered as a surgical tool to enable innovative natural orifice or flexible access techniques. These experiences have exposed unique advantages but also significant challenges. Major current technical drawbacks in this setting relate to uncontrolled flexibility, inaccurate sustained target localization, unreliable navigation and overall platform instability. In striving to address existing technical limitations, this paper introduces a novel flexible hyper-redundant surgical robot and evaluates its clinical potential using a focused clinical application.
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Hand-held medical robots.
Ann Biomed Eng
PUBLISHED: 03-31-2014
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Medical robots have evolved from autonomous systems to tele-operated platforms and mechanically-grounded, cooperatively-controlled robots. Whilst these approaches have seen both commercial and clinical success, uptake of these robots remains moderate because of their high cost, large physical footprint and long setup times. More recently, researchers have moved toward developing hand-held robots that are completely ungrounded and manipulated by surgeons in free space, in a similar manner to how conventional instruments are handled. These devices provide specific functions that assist the surgeon in accomplishing tasks that are otherwise challenging with manual manipulation. Hand-held robots have the advantages of being compact and easily integrated into the normal surgical workflow since there is typically little or no setup time. Hand-held devices can also have a significantly reduced cost to healthcare providers as they do not necessitate the complex, multi degree-of-freedom linkages that grounded robots require. However, the development of such devices is faced with many technical challenges, including miniaturization, cost and sterility, control stability, inertial and gravity compensation and robust instrument tracking. This review presents the emerging technical trends in hand-held medical robots and future development opportunities for promoting their wider clinical uptake.
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MIR146A inhibits JMJD3 expression and osteogenic differentiation in human mesenchymal stem cells.
FEBS Lett.
PUBLISHED: 03-13-2014
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Chromatin remodeling is important for cell differentiation. Histone methyltransferase EZH2 and histone demethylase JMJD3 (KDM6B) modulate levels of histone H3 lysine 27 trimethylation (H3K27me3). Interplay between the two modulators influence lineage specification in stem cells. Here, we identified microRNA MIR146A to be a negative regulator of JMJD3. In the osteogenic differentiation of human mesenchymal stem cells (hMSCs), we observed an upregulation of JMJD3 and a downregulation of MIR146A. Blocking JMJD3 activity in differentiating hMSCs reduced transcript levels of osteogenic gene RUNX2. H3K27me3 levels decreased at the RUNX2 promoter during cell differentiation. Modulation of MIR146A levels in hMSCs altered JMJD3 and RUNX2 expression and affected osteogenic differentiation. We conclude that JMJD3 promotes osteogenesis in differentiating hMSCs, with MIR146A regulating JMJD3.
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A review of the current status of laparoscopic and robot-assisted sacrocolpopexy for pelvic organ prolapse.
Eur. Urol.
PUBLISHED: 01-08-2014
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Abdominal sacrocolpopexy (ASC) represents the superior treatment for apical pelvic organ prolapse (POP) but is associated with increased length of stay, analgesic requirement, and cost compared with transvaginal procedures. Laparoscopic sacrocolpopexy (LSC) and robot-assisted sacrocolpopexy (RSC) may offer shorter postoperative recovery while maintaining equivalent rates of cure.
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A phase 1 study of prasugrel in patients with sickle cell disease: pharmacokinetics and effects on ex vivo platelet reactivity.
Br J Clin Pharmacol
PUBLISHED: 10-31-2013
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Prasugrel is a novel thienopyridine P2Y12 adenosine diphosphate (ADP) receptor antagonist that inhibits ADP-mediated platelet activation and aggregation. Accordingly, it may be useful in reducing platelet-related ischaemia in sickle cell disease (SCD). Exposure to prasugrels active metabolite (Pras-AM) and its antiplatelet activity in SCD have not been investigated.
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A phase 1 study of prasugrel in patients with sickle cell disease: Effects on biomarkers of platelet activation and coagulation.
Thromb. Res.
PUBLISHED: 08-20-2013
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Prasugrel, a P2Y12 adenosine diphosphate (ADP) receptor antagonist effectively inhibits ADP-mediated platelet activation and aggregation, and may be useful in reducing vaso-occlusive crises in sickle cell disease (SCD). In this study, we assess the effect of prasugrel on biomarkers of platelet activation and coagulation in patients with SCD.
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Current and Emerging Robot-Assisted Endovascular Catheterization Technologies: A Review.
Ann Biomed Eng
PUBLISHED: 08-13-2013
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Endovascular techniques have been embraced as a minimally-invasive treatment approach within different disciplines of interventional radiology and cardiology. The current practice of endovascular procedures, however, is limited by a number of factors including exposure to high doses of X-ray radiation, limited 3D imaging, and lack of contact force sensing from the endovascular tools and the vascular anatomy. More recently, advances in steerable catheters and development of master/slave robots have aimed to improve these practices by removing the operator from the radiation source and increasing the precision and stability of catheter motion with added degrees-of-freedom. Despite their increased application and a growing research interest in this area, many such systems have been designed without considering the natural manipulation skills and ergonomic preferences of the operators. Existing studies on tool interactions and natural manipulation skills of the operators are limited. In this manuscript, new technical developments in different aspects of robotic endovascular intervention including catheter instrumentation, intra-operative imaging and navigation techniques, as well as master/slave based robotic catheterization platforms are reviewed. We further address emerging trends and new research opportunities towards more widespread clinical acceptance of robotically assisted endovascular technologies.
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Transcriptional analysis of histone deacetylase family members reveal similarities between differentiating and aging spermatogonial stem cells.
Stem Cell Rev
PUBLISHED: 07-16-2013
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The differentiation of adult stem cells involves extensive chromatin remodeling, mediated in part by the gene products of histone deacetylase (HDAC) family members. While the transcriptional downregulation of HDACs can impede stem cell self-renewal in certain contexts, it may also promote stem cell maintenance under other circumstances. In self-renewing, differentiating, and aging spermatogonial stem cells (SSCs), the gene expression dynamics of HDACs have not yet been characterized. To gain further insight with these studies, we analyzed the transcriptional profiles of six HDAC family members, previously identified to be the most highly expressed in self-renewing SSCs, during stem cell differentiation and aging. Here we discovered that in both differentiating and aging SSCs the expression of Sirt4 increases, while the expression of Hdac2, Hdac6, and Sirt1 decreases. When SSCs are exposed to the lifespan-enhancing drug rapamycin in vivo, the resultant HDAC gene expression patterns are opposite of those seen in the differentiating and aging SSCs, with increased Hdac2, Hdac6, and Sirt1 and decreased Hdac8, Hdac9, and Sirt4. Our findings suggest that HDACs important for stem cell maintenance and oxidative capacity are downregulated as adult stem cells differentiate or age. These results provide important insights into the epigenetic regulation of stem cell differentiation and aging in mammals.
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Cycling to and from a stem cell niche: the temporal and spatial odyssey of mitotic male germ cells.
Int. J. Dev. Biol.
PUBLISHED: 06-21-2013
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The development of male germ cells within the prenatal and prepubertal periods in mammals combines multiple biological events that integrate cell cycle regulation, epigenetic reprogramming, and cell migration along temporally and spatially dynamic lines. Germ cells arise from their precursor primordial germ cells in the mid-gestation embryo, forming gonocytes that enter G0 phase cell cycle arrest within the fetal testis. Cyclin-dependent kinase inhibitors, activated retinoblastoma 1 protein, and increased levels of transforming growth factor beta 2 collectively influence this cell cycle arrest. Gonocyte quiescence persists until shortly after birth, whereupon the cells concomitantly re-enter the cell cycle and migrate towards a niche that establishes and maintains self-renewing spermatogonial stem cells and balances them with differentiating spermatogonia. Platelet-derived growth factor signaling is one of the mechanisms that regulates both mitotic activation and migration in neonatal gonocytes, along with mitogens, 17?-estradiol and retinoic acid, and chemoattractants C-C-motif ligand 9 and members of the ADAM, integrin, and tetraspanin families. Numerous germ cell-intrinsic proteins have been identified that ensure the retention of germ cells within the spermatogonial stem cell niche. Sertoli cells are a significant component of this niche, contributing essential growth factors and chemokines to spermatogonia. This review focuses on the dynamic events that occur to mitotic male germ cells before and during their arrival at this niche, with an emphasis on the cell cycle and directed migration.
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Pharmacokinetic and pharmacodynamic effects of prasugrel in healthy Korean males.
J. Cardiovasc. Pharmacol.
PUBLISHED: 04-19-2013
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Prasugrel is a thienopyridine for treatment of acute coronary syndromes in patients undergoing percutaneous coronary intervention. Higher concentrations of prasugrels active metabolite (R-138727) have been observed in Asian than white subjects. The primary objective was to investigate pharmacokinetics of R-138727 in healthy Korean males. Thirty subjects were randomized (1:2) to a 60 or 30 mg loading dose, subsequently (1:1:1) to 10-, 7.5-, or 5-mg maintenance doses. R-138727 plasma concentrations were analyzed with liquid chromatography/mass spectrometry. Platelet aggregation was measured with Accumetrics VerifyNow. Mean (coefficient of variation) exposure to R-138727 was 600 ng·h/mL (16%) after 60 mg prasugrel and 283 ng·h/mL (17%) after 30 mg. After 10, 7.5, and 5 mg, mean exposures were 78.1 (24%), 58.4 (21%), and 38.3 ng·h/mL (24%). Pharmacokinetics were linear over this range. Daily 5 mg doses maintained a 65% (SD = 14.5%) inhibition of adenosine diphosphate-induced platelet aggregation; all other doses produced ?90%. Prasugrel was well tolerated with no serious adverse events. Results are consistent with other studies of Asian subjects administered prasugrel. Although further guidance will be provided by a recently completed phase 3 study, these preliminary data suggest that dosing strategies approved for white patients with acute coronary syndromes are applicable to Asian patients.
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Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.
J. Urol.
PUBLISHED: 02-12-2013
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We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes.
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Iron limitation modulates ocean acidification effects on southern ocean phytoplankton communities.
PLoS ONE
PUBLISHED: 01-01-2013
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The potential interactive effects of iron (Fe) limitation and Ocean Acidification in the Southern Ocean (SO) are largely unknown. Here we present results of a long-term incubation experiment investigating the combined effects of CO2 and Fe availability on natural phytoplankton assemblages from the Weddell Sea, Antarctica. Active Chl a fluorescence measurements revealed that we successfully cultured phytoplankton under both Fe-depleted and Fe-enriched conditions. Fe treatments had significant effects on photosynthetic efficiency (Fv/Fm; 0.3 for Fe-depleted and 0.5 for Fe-enriched conditions), non-photochemical quenching (NPQ), and relative electron transport rates (rETR). pCO2 treatments significantly affected NPQ and rETR, but had no effect on Fv/Fm. Under Fe limitation, increased pCO2 had no influence on C fixation whereas under Fe enrichment, primary production increased with increasing pCO2 levels. These CO2-dependent changes in productivity under Fe-enriched conditions were accompanied by a pronounced taxonomic shift from weakly to heavily silicified diatoms (i.e. from Pseudo-nitzschia sp. to Fragilariopsis sp.). Under Fe-depleted conditions, this functional shift was absent and thinly silicified species dominated all pCO2 treatments (Pseudo-nitzschia sp. and Synedropsis sp. for low and high pCO2, respectively). Our results suggest that Ocean Acidification could increase primary productivity and the abundance of heavily silicified, fast sinking diatoms in Fe-enriched areas, both potentially leading to a stimulation of the biological pump. Over much of the SO, however, Fe limitation could restrict this possible CO2 fertilization effect.
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MicroRNA 146 (Mir146) modulates spermatogonial differentiation by retinoic acid in mice.
Biol. Reprod.
PUBLISHED: 01-01-2013
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Impaired biogenesis of microRNAs disrupts spermatogenesis and leads to infertility in male mice. Spermatogonial differentiation is a key step in spermatogenesis, yet the mechanisms that control this event remain poorly defined. In this study, we discovered microRNA 146 (Mir146) to be highly regulated during spermatogonial differentiation, a process dependent on retinoic acid (RA) signaling. Mir146 transcript levels were diminished nearly 180-fold in differentiating spermatogonia when compared with undifferentiated spermatogonia. Luciferase assays revealed the direct binding of Mir146 to the 3 untranslated region of the mediator complex subunit 1 (Med1), a coregulator of retinoid receptors (RARs and RXRs). Overexpression of Mir146 in cultured undifferentiated spermatogonia reduced Med1 transcript levels, as well as those of differentiation marker kit oncogene (Kit). MED1 protein was also diminished. Conversely, inhibition of Mir146 increased the levels of Kit. When undifferentiated spermatogonia were exposed to RA, Mir146 was downregulated along with a marker for undifferentiated germ cells, zinc finger and BTB domain containing 16 (Zbtb16; Plzf); Kit was upregulated. Overexpression of Mir146 in RA-treated spermatogonia inhibited the upregulation of Kit, stimulated by retinoic acid gene 8 (Stra8), and spermatogenesis- and oogenesis-specific basic helix-loop-helix 2 (Sohlh2). Inhibition of Mir146 in RA-treated spermatogonia greatly enhanced the upregulation of these genes. We conclude that Mir146 modulates the effects of RA on spermatogonial differentiation.
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Is there still a role for preoperative 12-lead electrocardiography?
World J Surg
PUBLISHED: 10-13-2011
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Twelve-lead electrocardiography is a standard preoperative investigation for patients undergoing major surgery. There is uncertainty and debate over the usefulness of this test for stratifying postoperative cardiac risk. The aim of this study was to investigate the correlation between an abnormal electrocardiogram (ECG) and the postoperative cardiac event rate.
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Pharmacokinetics and tissue penetration of vancomycin continuous infusion as prophylaxis for vascular surgery.
J. Antimicrob. Chemother.
PUBLISHED: 08-12-2011
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To determine the tissue penetration of vancomycin into perivascular fat and arterial wall during a continuous infusion of vancomycin, given as prophylaxis for vascular surgery.
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A hand-held instrument to maintain steady tissue contact during probe-based confocal laser endomicroscopy.
IEEE Trans Biomed Eng
PUBLISHED: 07-14-2011
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Probe-based confocal laser endomicroscopy (pCLE) provides high-resolution in vivo imaging for intraoperative tissue characterization. Maintaining a desired contact force between target tissue and the pCLE probe is important for image consistency, allowing large area surveillance to be performed. A hand-held instrument that can provide a predetermined contact force to obtain consistent images has been developed. The main components of the instrument include a linear voice coil actuator, a donut load-cell, and a pCLE probe. In this paper, detailed mechanical design of the instrument is presented and system level modeling of closed-loop force control of the actuator is provided. The performance of the instrument has been evaluated in bench tests as well as in hand-held experiments. Results demonstrate that the instrument ensures a consistent predetermined contact force between pCLE probe tip and tissue. Furthermore, it compensates for both simulated physiological movement of the tissue and involuntary movements of the operators hand. Using pCLE video feature tracking of large colonic crypts within the mucosal surface, the steadiness of the tissue images obtained using the instrument force control is demonstrated by confirming minimal crypt translation.
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Colonic and parastomal ulceration related to nicorandil.
Surg Laparosc Endosc Percutan Tech
PUBLISHED: 06-10-2011
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Nicorandil is an antianginal medication increasingly used in the treatment of severe ischemic heart disease. It has been implicated in the pathogenesis of perianal and perioral ulceration. We report 2 patients with atypical gastrointestinal ulceration due to nicorandil.
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Robot-assisted versus open sacrocolpopexy: a cost-minimization analysis.
J. Urol.
PUBLISHED: 05-20-2011
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Abdominal sacrocolpopexy is considered a standard of care operation for apical vaginal vault prolapse repair. Using outcomes at our center we evaluated whether the robotic approach to sacrocolpopexy is as cost-effective as the open approach.
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Effect of intrinsic and extrinsic factors on the clinical pharmacokinetics and pharmacodynamics of prasugrel.
Clin Pharmacokinet
PUBLISHED: 11-09-2010
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Thienopyridines are inactive prodrugs that are converted in vivo to active metabolites, which irreversibly bind to and inactivate platelet P2Y(12) receptors, and inhibit platelet activation and aggregation. Prasugrel is a third-generation thienopyridine, recently approved for prevention of thrombotic cardiovascular complications in patients with an acute coronary syndrome undergoing percutaneous coronary intervention. Prasugrel is converted to its active metabolite (Pras-AM; compound R-138727) in two sequential steps: (i) rapid and complete hydrolysis by intestinal human carboxylesterase-2 to form a thiolactone intermediate; and (ii) oxidation of the thiolactone by cytochrome P450 (CYP) enzymes in the gut and/or the liver. CYP3A and CYP2B6 are the primary CYPs contributing to Pras-AM formation, with smaller contributions from CYP2C9 and CYP2C19. Prasugrel is rapidly absorbed and metabolized, with Pras-AM plasma concentrations peaking at about 0.5 hours after oral administration; this helps to account for the rapid onset of inhibition of platelet aggregation (IPA) achieved by prasugrel. In the clinical pharmacology programme for prasugrel, bodyweight had the greatest effect of all covariates that were tested. In the phase III TRITON-TIMI 38 trial, the mean exposure to Pras-AM was 42% greater in patients weighing < 60 kg than in patients with the study population median bodyweight of 85 kg. In a pharmacodynamic meta-analysis of data from healthy subjects a decrease of 1 kg in bodyweight was associated with an increase in IPA of approximately 0.26 percentage points (p < 0.0001). Pras-AM exposure was greater in subjects aged ? 75 years, but exposure differences were not as large as those for bodyweight. Pras-AM exposure was greater in Asians than in Caucasians, but this appeared to result from a disproportionately greater exposure difference in Asian subjects with low bodyweight. Sex and allelic variation in CYPs 1A2, 2B6, 2C19, 2C9, 3A4 and 3A5 appeared to have no clinically relevant effect on Pras-AM exposure or IPA. Consistent with the lack of association between genetic status and these pharmacokinetic and pharmacodynamic results in healthy subjects, no significant association was detected between these allelic variants and the composite primary endpoint (cardiovascular death, non-fatal myocardial infarction or non-fatal stroke) in the TRITON-TIMI 38 trial. Studies in renally impaired subjects and subjects with mild or moderate hepatic impairment have indicated that dose adjustment is not required in these patient populations. Prasugrel has few clinically significant drug-drug interactions. Potent CYP3A inhibitors, gastric acid suppressants and food have been shown to reduce the rate of formation of Pras-AM but not its overall exposure. This pharmacokinetic effect reduced the rate of onset of IPA after a loading dose but did not affect the peak IPA after a loading dose or the IPA during maintenance dosing. Potent induction of CYP3A, as well as smoking--which induces CYP1A2--did not affect Pras-AM exposure or IPA. Prior treatment with clopidogrel did not influence tolerability to prasugrel and did not appear to alter IPA during prasugrel treatment. Prasugrel did not affect the activities of CYP2C9, CYP2C19 or P-glycoprotein, but it weakly inhibited CYP2B6. The inhibition of CYP2B6 is potentially clinically significant only for drugs that have a narrow therapeutic window and have CYP2B6 as the primary elimination pathway. No interaction was detected between prasugrel and heparin. Although prasugrel did not alter warfarin pharmacokinetics, prasugrel and warfarin should not be used together, because of an increased bleeding risk associated with their concomitant use.
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Sin3a is required by sertoli cells to establish a niche for undifferentiated spermatogonia, germ cell tumors, and spermatid elongation.
Stem Cells
PUBLISHED: 06-24-2010
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Microenvironments support the maintenance of stem cells and the growth of tumors through largely unknown mechanisms. While cell-autonomous chromatin modifications have emerged as important determinants for self-renewal and differentiation of stem cells, a role for non-cell autonomous epigenetic contributions is not well established. Here, we genetically ablated the chromatin modifier Swi-independent 3a (Sin3a) in fetal Sertoli cells, which partly comprise the niche for male germline stem cells, and investigated its impact on spermatogenic cell fate and teratoma formation in vivo. Sertoli cell-specific Sin3a deletion resulted in the formation of few undifferentiated spermatogonia after birth while initially maintaining spermatogenic differentiation. Stem cell-associated markers Plzf, Gfra1, and Oct4 were downregulated in the mutant fetal gonad, while Sertoli cell markers Steel and Gdnf, which support germ cells, were not diminished. Following birth, markers of differentiating spermatogonia, Kit and Sohlh2, exhibited normal levels, but chemokine-signaling molecules chemokine (C-X-C motif) ligand 12 (CXCL12)/stromal cell-derived factor 1 (SDF1) and chemokine (C-X-C motif) receptor 4 (CXCR4), expressed in Sertoli cells and germ cells, respectively, were not detected. In the juvenile, mutant testes exhibited a progressive loss of differentiating spermatogonia and a block in spermatid elongation, followed by extensive germ cell degeneration. Sertoli cell-specific Sin3a deletion also suppressed teratoma formation by fetal germ cells in an in vivo transplantation assay. We conclude that the epigenome of Sertoli cells influences the establishment of a niche for germline stem cells as well as for tumor initiating cells.
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Treatment choice, duration, and cost in patients with interstitial cystitis and painful bladder syndrome.
Int Urogynecol J
PUBLISHED: 06-12-2010
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In order to better understand provider treatment patterns for interstitial cystitis (IC)/painful bladder syndrome, we sought to document the therapies utilized and their associated expenditures using a national dataset.
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Integrated analysis of pharmacokinetic data across multiple clinical pharmacology studies of prasugrel, a new thienopyridine antiplatelet agent.
J Clin Pharmacol
PUBLISHED: 04-21-2010
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An integrated analysis of pharmacokinetic (PK) parameter estimates for prasugrel, from 16 phase I clinical pharmacology studies, consolidated exposure estimates from 506 healthy male and female participants and evaluated the effect of specific intrinsic and extrinsic factors on exposure to prasugrels active metabolite (AM, R-138727). A linear mixed effect model was fitted with study and subject nested within study as random effects and subject factors as fixed effects. Prasugrel AM exposure was similar in males and females, in participants <65 years and ?65 years, in smokers and nonsmokers, in drinkers and nondrinkers of alcohol, and in Asians, Caucasians, and participants of African and Hispanic descent. Prasugrel AM exposure increased as body weight decreased and was 40% higher in participants <60 kg than in participants ?60 kg. Exposure in Asians was 40% higher than that in Caucasians, but this difference could be explained by the lower overall weight of the Asian participants and a disproportionately large difference between ethnic groups in lighter participants, especially those <60 kg. These results characterize prasugrels PK across a range of studies and highlight body weight as the most influential covariate on prasugrel AM exposure, with implications for prasugrel maintenance dosing in clinical practice.
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A comparison of the VerifyNow P2Y12 point-of-care device and light transmission aggregometry to monitor platelet function with prasugrel and clopidogrel: an integrated analysis.
J. Cardiovasc. Pharmacol.
PUBLISHED: 04-14-2010
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We compared platelet function results obtained with the VerifyNow P2Y12 (VN-P2Y12) point-of-care device and the light transmission aggregometry (5 and 20 microM adenosine diphosphate) method using an integrated database of eight clinical trials with a total of 591 subjects. The study was performed in healthy subjects, patients with coronary artery disease, patients with end-stage renal disease, and patients with acute coronary syndrome after treatment with prasugrel or clopidogrel. Analyses focused on loading doses of 60 mg prasugrel or 600 mg clopidogrel and daily maintenance doses of 10 mg prasugrel or 75 or 150 mg clopidogrel. Similar patterns of platelet inhibition were observed for light transmission aggregometry versus VN-P2Y12 and assay results were well correlated (r approximately 0.7), although a sigmoidal model may more accurately represent the relationship between light transmission aggregometry and VN-P2Y12, because VN-P2Y12 was relatively less sensitive to low and high levels of inhibition. The percentage of poor responders was less with prasugrel compared with clopidogrel by both assays, but the percentages tended to differ between the assays. The VN-P2Y12 "BASE" channel appeared to be susceptible to high levels of P2Y12 blockade, which would underestimate the VN-P2Y12-reported percent inhibition in individuals who respond well to loading doses of thienopyridines. This integrated analysis supports the findings of earlier individual studies comparing these methodologies that assess platelet function.
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Aging well--the role of minimally invasive aesthetic dermatological procedures in women over 65.
J Cosmet Dermatol
PUBLISHED: 04-07-2010
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The western world is getting older. Aging well has become the new target of preventative medicine. Aesthetic dermatology can contribute to this quest. Females over 65 represent an important and growing group of consumers of cosmetic procedures. In this group, there is a paucity of scientific evaluation of aesthetic procedures.
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Effect of amitriptyline on symptoms in treatment naïve patients with interstitial cystitis/painful bladder syndrome.
J. Urol.
PUBLISHED: 03-29-2010
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Amitriptyline is frequently used to treat patients with interstitial cystitis/painful bladder syndrome. The evidence to support this practice is derived mainly from a small, single site clinical trial and case reports.
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Pharmacodynamics and pharmacokinetics of single doses of prasugrel 30 mg and clopidogrel 300 mg in healthy Chinese and white volunteers: an open-label trial.
Clin Ther
PUBLISHED: 01-29-2010
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Prasugrel is an oral antiplatelet agent approved for the reduction of atherothrombotic cardiovascular events in patients presenting with acute coronary syndrome and undergoing percutaneous coronary intervention. Although the approved loading dose is 60 mg, earlier studies of prasugrel suggested that active-metabolite exposure and pharmacodynamic response may be higher in Asian subjects than in white subjects.
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Vancomycin continuous infusion as prophylaxis for vascular surgery.
Ther Drug Monit
PUBLISHED: 10-08-2009
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Prosthetic graft infection is a devastating complication of vascular surgery that occurs in 3%-5% of clean prosthetic procedures. Staphylococci are the most frequently isolated pathogens, and thus surgical prophylaxis regimens often include vancomycin. However, the efficacy of these regimens in ensuring a required concentration of antibiotic is uncertain. This study aimed to determine if a continuous vancomycin infusion regimen administered perioperatively as surgical prophylaxis for vascular procedures maintained an adequate serum concentration. Thirty-four consecutive patients undergoing a vascular procedure requiring a prosthetic graft or patch were given vancomycin prophylaxis. Each patient received a loading dose calculated according to body weight 12 hours before surgery. A 24-hour continuous infusion was then started, based on calculated creatinine clearance. Serum vancomycin concentrations were checked on induction of anesthesia, 2 hours postoperatively, and at the end of the infusion. Perioperative fluid administration and blood loss were recorded. An estimated creatinine clearance was repeated on the second postoperative day. Of the 34 patients recruited, 7 did not have the anticipated procedure and 6 patients had incomplete sample collection. Twenty-one patients with complete sample collection were analyzed. The target concentration (10-25 mg/L) was achieved in 81% of all samples. All patients achieved the target concentration at 1 or more time points. The regimen employed provided appropriate concentrations at the time of intervention. No potentially toxic concentrations or adverse reactions to vancomycin were encountered. Vancomycin given as a continuous infusion delivers adequate serum concentration. Long-term graft infection rates are needed to show a clinical effect.
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Effect of age on the pharmacokinetics and pharmacodynamics of prasugrel during multiple dosing: an open-label, single-sequence, clinical trial.
Drugs Aging
PUBLISHED: 09-05-2009
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A substantial portion of patients at risk for acute coronary syndrome (ACS) are >65 years old. Prasugrel is a novel antiplatelet agent approved for the treatment of ACS patients undergoing percutaneous coronary intervention, and will be used in this population.
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Inhibition of platelet aggregation with prasugrel and clopidogrel: an integrated analysis in 846 subjects.
Platelets
PUBLISHED: 07-29-2009
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This integrated analysis compared speed of onset, level of platelet inhibition, and response variability to prasugrel and clopidogrel in healthy subjects and in patients with stable coronary artery disease with data pooled from 24 clinical pharmacology studies. Data from subjects (N = 846) were categorized into the following treatment groups: prasugrel 60 mg loading dose (LD)/10 mg maintenance dose (MD), clopidogrel 300 mg LD/75 mg MD, or clopidogrel 600 mg LD/75 mg MDs. Maximum platelet aggregation (MPA) and inhibition of platelet aggregation (IPA) to 5 and 20 muM ADP were assessed by turbidimetric aggregometry. A linear mixed-effect model compared the MPA and IPA between treatments over time points evaluated in the integrated database, and covariates affecting platelet inhibition were identified. Prasugrel 60 mg LD resulted in faster onset, greater magnitude, and more consistent levels of inhibition of platelet function compared to either clopidogrel 300 mg or 600 mg LDs. Greater and more consistent levels of platelet inhibition were observed with the prasugrel 10 mg MD compared to the clopidogrel 75 mg MD. This integrated analysis confirms the findings of earlier individual studies, that prasugrel achieves faster onset of greater extent and more consistent platelet inhibition compared to the approved and higher loading doses of clopidogrel. Gender, race, body weight, and age were identified as statistically significant covariates impacting platelet inhibition.
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Randomized multicenter feasibility trial of myofascial physical therapy for the treatment of urological chronic pelvic pain syndromes.
J. Urol.
PUBLISHED: 06-17-2009
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We determined the feasibility of conducting a randomized clinical trial designed to compare 2 methods of manual therapy (myofascial physical therapy and global therapeutic massage) in patients with urological chronic pelvic pain syndromes.
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The pharmacokinetics and pharmacodynamics of prasugrel in healthy Chinese, Japanese, and Korean subjects compared with healthy Caucasian subjects.
Eur. J. Clin. Pharmacol.
PUBLISHED: 05-21-2009
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Prasugrel is a novel thienopyridine prodrug metabolised to an active metabolite that binds irreversibly to the platelet P2Y(12) receptor and inhibits adenosine diphosphate (ADP)-induced platelet aggregation. We compared prasugrel pharmacokinetics, pharmacodynamics, and tolerability in healthy Chinese, Japanese, Korean and Caucasian subjects.
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Mechanisms of pelvic floor muscle function and the effect on the urethra during a cough.
Eur. Urol.
PUBLISHED: 05-19-2009
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Current measurement tools have difficulty identifying the automatic physiologic processes maintaining continence, and many questions still remain about pelvic floor muscle (PFM) function during automatic events.
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The relationship among symptoms, sleep disturbances and quality of life in patients with interstitial cystitis.
J. Urol.
PUBLISHED: 04-16-2009
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We conducted a retrospective analysis to determine associations among symptoms, sleep disturbances and quality of life in responder and nonresponder groups of patients with interstitial cystitis.
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Randomized controlled multisite trial of injected bulking agents for women with intrinsic sphincter deficiency: mid-urethral injection of Zuidex via the Implacer versus proximal urethral injection of Contigen cystoscopically.
Urology
PUBLISHED: 03-24-2009
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To determine whether Zuidex using a non-cystoscopy mid-urethral injection technique produces as good a result (i.e. was not inferior) as Contigen injected endoscopically at the bladder neck in the treatment of urinary stress incontinence secondary to intrinsic sphincter deficiency in adult women.
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Laparoscopic management of ureteral endometriosis: the Stanford University hospital experience with 96 consecutive cases.
J. Urol.
PUBLISHED: 02-13-2009
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We report the clinical characteristics and the principles of laparoscopic management of ureteral endometriosis at our institution.
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Goal achievement provides new insights into interstitial cystitis/painful bladder syndrome symptoms and outcomes.
Neurourol. Urodyn.
PUBLISHED: 02-06-2009
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Goal Assessment Scaling (GAS), wherein patients specify goals then evaluate treatments with regard to goal achievement, has proven utility in assessing treatment of complex conditions such as chronic pain, rheumatoid arthritis, and incontinence. We used surveys and focus groups to characterize the goals of patients with interstitial cystitis/painful bladder syndrome (IC/PBS) in order to create a pilot GAS.
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Epidural steroid injections in the management of a patient with spinal stenosis and urinary urgency.
Nat Clin Pract Urol
PUBLISHED: 01-20-2009
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A 79-year-old woman with a history of chronic back pain and urinary urgency presented to a spine center for treatment and evaluation for axial low back pain. The patient described the back pain as severe with intermittent radiation into the right leg; her pain intensity was 7 out of 10 on a visual analog scale. She described her sense of urgency as severe, and could delay urination for 10 min or less. She described her bladder control as 6 out of 10 on the urgency perception score (with 0 being perfect control).
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Enhanced recovery programme in colorectal surgery: does one size fit all?
World J. Gastroenterol.
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Enhanced recovery after surgery (ERAS) employs a multimodal perioperative care pathway with the aim of attenuating the stress response to surgery and accelerating recovery. It has been difficult to determine the relative importance of some of the individual components of these pathways such as epidural analgesia and laparoscopic colorectal surgery. Some argue that only a rigid adherence to the published ERAS protocol can achieve the proposed benefits of fast-track surgery. In this article, we explore some of the areas where the evidence base may be changing and ask whether a more flexible and individualised approach should be considered.
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Distinct requirements for Sin3a in perinatal male gonocytes and differentiating spermatogonia.
Dev. Biol.
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Chromatin modifier Swi-independent 3a (SIN3A), together with associated histone deacetylases, influences gene expression during development and differentiation through a variety of transcription factors in a cell-specific manner. Sin3a is essential for the maintenance of inner cell mass cells of mouse blastocysts, embryonic fibroblasts, and myoblasts, but is not required for the survival of trophectoderm or Sertoli cells. To better understand how this transcriptional regulator modulates cells at different developmental stages within a single lineage, we used conditional gene targeting in mice to ablate Sin3a from perinatal quiescent male gonocytes and from postnatal differentiating spermatogonia. Mitotic germ cells expressing stimulated by retinoic acid gene 8 (Stra8) that lacked Sin3a exhibited increased DNA damage and apoptosis, yet collectively progressed through meiosis and spermiogenesis and generated epididymal sperm at approximately 50% of control levels, sufficient for normal fertility. In contrast, perinatal gonocytes lacking Sin3a underwent rapid depletion that coincided with cell cycle reentry, exhibiting 2.5-fold increased histone H3 phosphorylation upon cycling that suggested a prophase/metaphase block; germ cells were almost entirely absent two weeks after birth, resulting in sterility. Gene expression profiling of neonatal testes containing Sin3a-deleted gonocytes identified upregulated transcripts highly associated with developmental processes and pattern formation, and downregulated transcripts involved in nuclear receptor activity, including Nr4a1 (Nur77). Interestingly, Nr4a1 levels were elevated in testes containing Stra8-expressing, Sin3a-deleted spermatogonia. SIN3A directly binds to the Nr4a1 promoter, and Nr4a1 expression is diminished upon spermatogonial differentiation in vitro. We conclude that within the male germline, Sin3a is required for the mitotic reentry of gonocytes, but is dispensable for the maintenance of differentiating spermatogonia and subsequent spermatogenic processes.
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B-type natriuretic peptide predicts postoperative cardiac events and mortality after elective open abdominal aortic aneurysm repair.
J. Vasc. Surg.
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The aim of this study was to determine if a single preoperative B-type natriuretic peptide (BNP) level correlated with perioperative cardiac events, cardiac death, and all-cause mortality in elective open abdominal aortic aneurysm (AAA) repair in the short term, intermediate term, and long term.
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Interstitial cystitis and the overlap with overactive bladder.
Curr Urol Rep
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The overlap between interstitial cystitis-painful bladder syndrome and overactive bladder can present a diagnostic challenge to the treating practitioner. Both can present with similar patient symptoms. Further compounding this dilemma is the fact that no gold standard test exists to differentiate one from the other. This review will serve to highlight their similarities and distinguishing features.
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Cyclosporine A for refractory interstitial cystitis/bladder pain syndrome: experience of 3 tertiary centers.
J. Urol.
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Cyclosporine A is a fifth-tier treatment option in the American Urological Association guidelines for interstitial cystitis/bladder pain syndrome. It was more effective than pentosanpolysulfate in a Finnish trial, but experience elsewhere is limited. Some centers use cyclosporine A off label for carefully selected patients but the number of patients in each center is small. We performed a retrospective review combining data from 3 tertiary centers that focus on interstitial cystitis/bladder pain syndrome.
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Geminin is required for mitotic proliferation of spermatogonia.
Dev. Biol.
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Spermatogonial stem cells divide throughout life, maintaining their own population and giving rise to differentiated gametes. The unstable regulatory protein Geminin is thought to be one of the factors that determine whether stem cells continue to divide or terminally differentiate. Geminin regulates the extent of DNA replication and is thought to maintain cells in an undifferentiated state by inhibiting various transcription factors and chromatin remodeling proteins. To examine how Geminin might regulate spermatogenesis, we developed two conditional mouse models in which the Geminin gene (Gmnn) is deleted from either spermatogonia or meiotic spermatocytes. Deleting Geminin from spermatogonia causes complete sterility in male mice. Gmnn(-/-) spermatogonia disappear during the initial wave of mitotic proliferation that occurs during the first week of life. Gmnn(-/-) spermatogonia exhibit more double-stranded DNA breaks than control cells, consistent with a defect in DNA replication. They maintain expression of genes associated with the undifferentiated state and do not prematurely express genes characteristic of more differentiated spermatogonia. In contrast, deleting Geminin from spermatocytes does not disrupt meiosis or the differentiation of spermatids into mature sperm. In females, Geminin is not required for meiosis, oocyte differentiation, or fertility after the embryonic period of mitotic proliferation has ceased. We conclude that Geminin is absolutely required for mitotic proliferation of spermatogonia but does not regulate their differentiation. Our results suggest that Geminin maintains replication fidelity during the mitotic phase of spermatogenesis, ensuring the precise duplication of genetic information for transmission to the next generation.
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Understanding your capital options.
Healthc Financ Manage
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When planning capital expenditures, hospitals and health systems should understand the following financing considerations: Traditional fixed-rate tax-exempt bonds; Variable-rate financing alternatives; Basel III Accord requirements; Direct tax-exempt bank loans; Total return swaps Taxable financings; Interest-rate swaps and collateral requirements
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Robot-assisted transvaginal peritoneoscopy using confocal endomicroscopy: a feasibility study in a porcine model.
Surg Endosc
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Optical biopsy methods such as probe-based confocal laser endomicroscopy (pCLE) provide useful intraoperative real-time information, especially during minimally invasive surgery with flexible endoscopic or robotic platforms. By translating the probe at constant pressure across the target tissue, undistorted "mosaics" can be produced. However, this poses ergonomic challenges with a conventional flexible endoscope.
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Rapamycin increases oxidative stress response gene expression in adult stem cells.
Aging (Albany NY)
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Balancing quiescence with proliferation is of paramount importance for adult stem cells in order to avoid hyperproliferation and cell depletion. In some models, stem cell exhaustion may be reversed with the drug rapamycin, which was shown can suppress cellular senescencein vitro and extend lifespan in animals. We hypothesized that rapamycin increases the expression of oxidative stress response genes in adult stem cells, and that these gene activities diminish with age. To test our hypothesis, we exposed mice to rapamycin and then examined the transcriptome of their spermatogonial stem cells (SSCs). Gene expression microarray analysis revealed that numerous oxidative stress response genes were upregulated upon rapamycin treatment, including superoxide dismutase 1, glutathione reductase, and delta-aminolevulinate dehydratase. When we examined the expression of these genes in 55-week-old wild type SSCs, their levels were significantly reduced compared to 3-week-old SSCs, suggesting that their downregulation is coincident with the aging process in adult stem cells. We conclude that rapamycin-induced stimulation of oxidative stress response genes may promote cellular longevity in SSCs, while a decline in gene expression in aged stem cells could reflect the SSCs diminished potential to alleviate oxidative stress, a hallmark of aging.
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Robotics in Keyhole Transcranial Endoscope-assisted Microsurgery: A Critical Review of Existing Systems and Proposed Specifications for New Robotic Platforms.
Neurosurgery
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Over the last decade, advances in image guidance, endoscopy and tube-shaft instruments have allowed for the development of keyhole transcranial endoscope-assisted microsurgery, utilizing smaller craniotomies, and minimizing exposure and manipulation of unaffected brain tissue. Although such approaches offer the possibility of shorter operating times, reduced morbidity and mortality, and improved long-term outcomes, the technical skills required to perform such surgery are inevitably greater than for traditional open surgical techniques, and they have not been widely adopted by neurosurgeons. Surgical robotics, which has the ability to improve visualization and increase dexterity, therefore has the potential to enhance surgical performance.
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What is Visualize?

JoVE Visualize is a tool created to match the last 5 years of PubMed publications to methods in JoVE's video library.

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We use abstracts found on PubMed and match them to JoVE videos to create a list of 10 to 30 related methods videos.

Video X seems to be unrelated to Abstract Y...

In developing our video relationships, we compare around 5 million PubMed articles to our library of over 4,500 methods videos. In some cases the language used in the PubMed abstracts makes matching that content to a JoVE video difficult. In other cases, there happens not to be any content in our video library that is relevant to the topic of a given abstract. In these cases, our algorithms are trying their best to display videos with relevant content, which can sometimes result in matched videos with only a slight relation.