tbuckley/cabot-search huggingface dataset:
PTU-014 The Use Of Kinematic Analysis Of Bile Duct Cannulation As A Means Of Objectively Assessing Endoscopic Skill At Ercp
Authors: SJL Ralphs, O North, M Ristic, SD Taylor-Robinson
Journal: Gut (2014)

<h3>Introduction</h3> Training in ERCP has become more challenging due to a reduction in diagnostic cases following the introduction of MRCP. There is a need to explore options to assist with basic training and the assessment of competency. There are currently no validated objective tools for this purpose. Simulators have been shown to enhance surgical skill and some there is some evidence to suggest that they can assist training in ERCP.<sup>1</sup> Kinematics, the study of motion, has been used in the objective assessment of surgical skill and endoscopic skill during colonoscopy on simulators but no studies have been done on ERCP.<sup>2</sup> <h3>Methods</h3> 23 candidates perform bile duct cannulation on a modified ERCP simulator. Endoscopic experience ranged from complete novices to HPB consultants. Radiofrequency sensors were attached to the duodenoscope tip and catheter, and the procedures were videoed. Six parameters were measured from a starting point at the pylorus until bile duct cannulation was achieved. These included mean speed, total distance travelled, trajectory corrections, time to cannulation, time spent planning and number of papilla contacts. A performance score was calculated so that, with the exception of mean speed, a decrease in each parameter equated to an exponentially higher score, equating to greater skill. <h3>Results</h3> Kinematic data showed that HPB consultants performed better than other participants at all 6 measures used to calculate the objective performance score. The greatest difference noted was for distance travelled (mean 3976 mm v 720 mm for novices and HPB consultants respectively) and procedure time (318s v 50s for the same two groups). The overall objective performance scores attained by subjects correlated well with their level of experience, and produced significant differences between the three least experienced groups (p &lt; 0.05). The mean performance scores were; HPB consultants: 18.9 (n = 5), HPB trainees: 17.5 (n = 5), general gastroenterology trainees: 13.0 (n = 7), novices: 11.1 (n = 6). <h3>Conclusion</h3> Kinematic analysis of a simulated bile duct cannulation enables the endoscopist’s skill to be measured objectively. This method could be used to assist with the training and assessment of this advanced endoscopic procedure. <h3>References</h3> Lim BS, Leung JW, Lee J, Yen D, Beckett L, Tancredi D, Leung FW. Effect of ERCP mechanical simulator (EMS) practice on trainees’ ERCP performance in the early learning period: US multicenter randomized controlled trial. <i>Am J Gastroenterol</i><i>.</i> 2011 Feb;106(2):300–6. Obstein KL, Patil VD, Jayender J, San José Estépar R, Spofford IS, Lengyel BI, Vosburgh KG, Thompson CC. Evaluation of colonoscopy technical skill levels by use of an objective kinematic-based system. <i>Gastrointest Endosc</i>. 2011 Feb;73(2):315-21 <h3>Disclosure of Interest</h3> None Declared.
Abstract 250: Vinculin is a putative amplification target gene at 10q22 in advanced prostate cancer
Authors: Christian Ruiz, Irma M. Gonzales, Martin Oeggerli, Sandra Schneider, Jeffrey A. Kiefer, Spyro Mousses, Michael T. Barrett, David O. Azorsa, Lukas Bubendorf
Journal: Cancer Research (2010)

Abstract Patients with advanced prostate cancer are usually treated with androgen withdrawal. Although this therapy is effective at the beginning, nearly all prostate cancers become refractory to it. Approximately 15% of these hormone-refractory prostate cancers contain a genomic amplification at 10q22. Aim of this study was to explore the structure of the 10q22 amplicon and to determine the major driving gene. We applied high-resolution array-CGH using the 244k Agilent microarrays to cell lines harboring 10q22 amplification. We identified a common amplified region (CAR) and silenced each of the 26 genes in this region by an RNAi screen in the prostate cancer cell lines PC-3 and 22rv1. Genes with a significant growth reduction in the 10q22 amplified cell line PC-3 but not in the non-amplified 22rv1 cells were selected as putative candidate genes of this amplicon. They were further investigated in vivo by functional assays and in vitro by immunohistochemical analysis of the protein expression in more than 500 human prostate cancers on a tissue microarray (TMA). We could narrow down the CAR to a region of 5.8 Mb. The siRNA screening experiments revealed Vinculin (VCL) as the most promising candidate gene of this amplicon. Immunohistochemical analysis of the Vinculin protein expression on a TMA enriched for 10q22 amplified prostate cancers showed a strong association between VCL gene amplification and overexpression (p &amp;lt; 0.001). Further analysis of 443 specimens from across all stages of prostate cancer progression showed that Vinculin expression was highest in hormone-refractory prostate cancers, but negative or very low in benign prostatic hyperplasia (p &amp;lt; 0.0001). Notably, high tumor cell proliferation measured by Ki67 expression was significantly associated with high Vinculin expression in prostate cancer (p &amp;lt; 0.0001). Although there are countless reports on Vinculin as a cytoskeletal protein, its role in prostate cancer has previously not been investigated. Our data strongly suggest Vinculin as a major driving gene of the 10q22 amplification in prostate cancer and that Vinculin overexpression might contribute to prostate cancer progression by enhancing tumor cell proliferation. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 250.
Abstract B37: PSCA haploinsufficiency enhances prostate tumor growth in prostate-specific Pten knockout mice
Authors: Miranda L. Moore, Shuai Tang, Mark C. Willingham, Purnima Dubey
Journal: Cancer Research (2009)

Abstract Prostate cancer is a heterogeneous disease, with multiple stages of cancer evident within an individual organ. Although some of the genetic changes necessary to initiate or advance prostate cancer have been identified, in order to develop effective therapies, it is critical to understand the different means by which this disease develops and progresses. Prostate Stem Cell Antigen (PSCA) is a GPI-anchored cell surface protein that is expressed in the normal epithelial cells of a restricted set of organs, including prostate, bladder, stomach, kidney and pancreas. Over-expression of PSCA is found in all stages of prostate cancer, from PIN to metastasis. We are investigating the biological function of PSCA in prostate tumorigenesis. We recently reported that deletion of PSCA increases metastasis of TRAMP-induced prostate tumors in mice, suggesting that PSCA may function as a tumor suppressor. To determine the effect of modulating PSCA dosage in the context of another oncogenic signal implicated in human prostate cancer development, we crossed PSCA knockout mice to prostate-specific Pten knockout mice, and analyzed the animals at 30 weeks of age. Pten −/−;PSCA +/− mice developed significantly larger prostate tumors than Pten −/− mice that are wild-type for PSCA. These results also suggest that PSCA may function as a tumor suppressor. In contrast, mice with deletion of both copies of the PSCA gene (Pten −/−; PSCA −/− mice) developed tumors similar in size to Pten −/−;PSCA +/+ animals, consistent with the possibility that PSCA function may contribute to the early stages of cancer development. Together, our results suggest that modulation of PSCA gene dosage affects cancer initiation and progression, indicating a putative dual role for PSCA in epithelial cancer. Our current experiments are designed to determine the molecular mechanism of PSCA function. Citation Information: Cancer Res 2009;69(23 Suppl):B37.
Abstract IA25: Using old mouse models to identify new cancer drug targets
Authors: Michael T. Hemann
Journal: Cancer Research (2011)

Abstract Effective cancer therapy, using surgery, radiotherapy, or chemotherapy results in the absence of macroscopic disease either at the site of the primary tumor or common distal sites of disease dissemination. Despite this initial tumor clearance, many patients will eventually relapse. Thus, small cohorts of tumor cells can survive in cryptic anatomical loci following therapy. These surviving cancer cells represent minimal residual disease (MRD). While cell-intrinsic processes are known to play decisive roles in chemotherapeutic response and drug resistance, relatively little is known about the impact of the tumor microenvironment on the persistence of MRD. Using a preclinical model of B cell lymphoma, we have been able to show that paracrine release of prosurvival cytokines protects subsets of lymphoma cells from cell death induced by genotoxic chemotherapy. Thus, while genotoxic damage can eradicate systemic disease, it can also, paradoxically, elicit prosurvival signaling in select anatomical sites. To further examine the role of the tumor microenvironment on therapeutic response, we have adapted large-scale loss of function genetic screen approaches for use in models of B cell malignancy in vivo. Specifically, we have made use of comprehensive shRNA libraries to target the genome in an unbiased manner. By introducing large shRNA pools into leukemia cells and transplanting modified cells into syngeneic recipients, we could identify up to 9,000 unique hairpins in individual mice, suggesting that library diversity can be maintained in this setting, and that genome-scale shRNA libraries can be screened in vivo. Genes identified using this approach represent central mediators of leukemia cell survival and potential cancer drug targets. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the Second AACR International Conference on Frontiers in Basic Cancer Research; 2011 Sep 14-18; San Francisco, CA. Philadelphia (PA): AACR; Cancer Res 2011;71(18 Suppl):Abstract nr IA25.
Effects of Ursodeoxycholic Acid and Aspirin on the Formation of Lithogenic Bile and Gallstones during Loss of Weight
Authors: Paul H. Broomfield, Rakesh Chopra, Richard C. Sheinbaum, George G. Bonorris, Alan Silverman, Leslie J. Schoenfield, Jay W. Marks
Journal: New England Journal of Medicine (1988)

We attempted to determine whether the administration of aspirin or ursodeoxycholic acid during loss of weight could prevent the development of lithogenic changes in bile and the formation of gallstones. Sixty-eight obese subjects without gallstones who were entered in a program (520 kcal per day) to lose weight were randomly assigned to receive ursodeoxycholic acid (1200 mg per day), aspirin (1300 mg per day), or placebo in double-blind fashion for up to 16 weeks. At entry, at four weeks of treatment, and at three weeks after the completion of treatment, the subjects underwent ultrasonography to detect gallstones and duodenal drainage of bile to detect cholesterol crystals and to determine the bile saturation index and glycoprotein concentration. No gallstones or cholesterol crystals formed in the patients treated with ursodeoxycholic acid. Among the patients given placebo, gallstones formed in five (P<0.05 vs. ursodeoxycholic acid) and cholesterol crystals in six (P<0.001 vs. ursodeoxycholic acid); among those given aspirin, gallstones formed in two and cholesterol crystals in one (no significant difference from ursodeoxycholic acid treatment). By the fourth week, the bile saturation index increased in the placebo group (from 1.07±0.26 to 1.29±0.27; P<0.001), decreased in the ursodeoxycholic acid group (from 1.11±0.34 to 0.91±0.24; P<0.001), and did not change significantly in the aspirin group. The concentration of glycoprotein in bile increased in the placebo group (27.9±14.5 percent; P<0.001) but did not change significantly in the groups treated with ursodeoxycholic acid or aspirin. We conclude that ursodeoxycholic acid prevents lithogenic changes in bile and the formation of gallstones in obese subjects during loss of weight. (N Engl J Med 1988; 319:1567–72.)
Psychosocial factors associated with outcomes of sports injury rehabilitation in competitive athletes: a mixed studies systematic review
Authors: Dale Forsdyke, Andy Smith, Michelle Jones, Adam Gledhill
Journal: British Journal of Sports Medicine (2016)

Background The prime focus of research on sports injury has been on physical factors. This is despite our understanding that when an athlete sustains an injury it has psychosocial as well as physical impacts. Psychosocial factors have been suggested as prognostic influences on the outcomes of rehabilitation. The aim of this work was to address the question: are psychosocial factors associated with sports injury rehabilitation outcomes in competitive athletes? Study design Mixed studies systematic review (PROSPERO reg.CRD42014008667). Method Electronic database and bibliographic searching was undertaken from the earliest entry until 1 June 2015. Studies that included injured competitive athletes, psychosocial factors and a sports injury rehabilitation outcome were reviewed by the authors. A quality appraisal of the studies was undertaken to establish the risk of reporting bias. Results 25 studies were evaluated that included 942 injured competitive athletes were appraised and synthesised. Twenty studies had not been included in previous reviews. The mean methodological quality of the studies was 59% (moderate risk of reporting bias). Convergent thematic analysis uncovered three core themes across the studies: (1) emotion associated with rehabilitation outcomes; (2) cognitions associated with rehabilitation outcomes; and (3) behaviours associated with rehabilitation outcomes. Injury and performance-related fears, anxiety and confidence were associated with rehabilitation outcomes. There is gender-related, age-related and injury-related bias in the reviewed literature. Conclusions Psychosocial factors were associated with a range of sports injury rehabilitation outcomes. Practitioners need to recognise that an injured athlete's thoughts, feelings and actions may influence the outcome of rehabilitation.
Case 6-2003
Authors: Howard W. Sander, E. Tessa Hedley-Whyte
Journal: New England Journal of Medicine (2003)

Presentation of CaseA nine-year-old right-handed girl from the United Arab Emirates was admitted to the hospital because of progressive weakness and areflexia.The patient had been well until three months earlier, when a gait difficulty developed. A physician diagnosed a vitamin deficiency, and treatment was instituted but without benefit. One month later, progressive weakness and a slapping gait developed; she was unable to walk on her toes and could barely rise from a full squat. Another physician found that she had both proximal and distal weakness in the arms and legs, that the reflexes were absent throughout, and that . . .
Production of Recombinant Adeno-Associated Type 5 (rAAV5) Vectors Using Recombinant Herpes Simplex Viruses Containing rep and cap
Authors: Jason T. Wustner, Susan Arnold, Martin Lock, James C. Richardson, Vaughn B. Himes, Gary Kurtzman, Richard W. Peluso
Journal: Molecular Therapy (2002)

We developed a scaleable production system for adeno-associated virus type 5 (AAV5)-based vectors using a replication-defective recombinant herpes simplex type 1 virus (rHSV) containing the rep and cap genes of AAV5. Multiple rHSV isolates containing AAV5 rep and cap with normal or altered p5 promoter elements were constructed and tested in vector production. Compared with rAAV5 vector yields obtained by plasmid transfection, yields of rAAV5 using any of the rHSV isolates were low. Evidence suggests that the low vector yields are a consequence of the extensive and early cytopathology induced by the rHSV isolates. In addition, we found a correlation between the amount of Rep52 or Rep40 proteins and the amount of vector produced by each rHSV isolate, suggesting that packaging of vector DNA into virus particles is rate-limiting when using rHSV to generate rAAV5 vectors.
PWE-163 The Excitatory Effects Of Repetitive Cerebellar Brain Stimulation On Human Swallowing Motor Pathways Are Critically Dependent On Stimulus Duration
Authors: DH Vasant, E Michou, S Mistry, S Hamdy
Journal: Gut (2014)

<h3>Introduction</h3> Previously we have demonstrated frequency-specific effects of cerebellar repetitive transcranial magnetic stimulation (rTMS) in enhancing human cortical swallowing pathways,<sup>1</sup> as a prelude to developing therapeutic parameters for post-stroke dysphagia. Here, we investigate the durational parameters of 10Hz cerebellar rTMS on pharyngeal motor excitability. <h3>Methods</h3> Healthy subjects (n = 12, 7 male, 5 female, mean age 31 ± 4 years), were intubated with an intraluminal catheter to record pharyngeal electromyography before bilateral MRI-guided single-pulse TMS mapping of pharyngeal motor evoked potentials (PMEPs) to co-localise optimal cortical and cerebellar sites for pharyngeal activity. Baseline cortical PMEPs were then recorded followed by one of the four cerebellar interventions; sham (coil tilted to 90°), short duration (50-pulses), intermediate duration (250-pulses) or longer-train (500-pulses) at 10 Hz frequency, received on separate randomised visits. Post-intervention PMEPs were recorded for up to an hour as a measure of cortical excitability. Normalised (percentage change from baseline) PMEP data were then compared to sham using repeated measures ANOVA (factors of time, hemispheric site, intervention). <h3>Results</h3> Intermediate train-length (250-pulses: F<sub>1,11</sub>=7.3, <i>p</i> = 0.02) was most effective at increasing pharyngeal cortical excitability bilaterally compared to longer (500-pulses: F<sub>1,11</sub>=4.5, p = 0.058) and shorter (50 pulses; F<sub>1,11</sub>=1.7, p = 0.21) 10-Hz cerebellar interventions (Figure 1). <h3>Conclusion</h3> Our data confirm that sustained facilitation of the pharyngeal motor cortex to cerebellar rTMS is not only dependent on the stimulation frequency, but also the duration of stimulation. We therefore propose that 250-pulses of 10 Hz cerebellar rTMS to be the optimal parameters for future therapeutic studies in post-stroke dysphagia. <h3>Reference</h3> 1 Vasant DH, <i>et al</i>. Neuronavigated repetitive cerebellar stimulation produces long-lasting activation of human cortical swallowing projections<i>.</i><i>Gut</i> 2013;62:A16-A17 <h3>Disclosure of Interest</h3> None Declared.
AB0116 Expression of rictor in rheumatoid arthritis fibroblast-like synoviocytes
Authors: L. Fang, X. Guo, Y. Pan
Journal: Annals of the Rheumatic Diseases (2013)

<h3>Background</h3> RICTOR (rapamycin-insensitive companion of mTOR) is a key component of mTORC2 (mammalian target of rapamycin complex 2), which can regulate the organization of actin cytoskeleton and phosphorylate/activate Akt. Akt signaling is activated in rheumatoid arthritis fibroblast-like synoviocytes (RA-FLS) and plays an important role in the pathogenesis of RA. We hypothesized that RICTOR might be involved in the long-lasting changed phenotype of RA-FLS. <h3>Objectives</h3> To investigate the expression of RICTOR in RA-FLS. <h3>Methods</h3> FLS were isolated from the primary synovial tissues, which were obtained during joint replacement surgery or arthroscopy from seven patients with RA, four patients with osteoarthritis (OA), and four patients with joint trauma (Trauma group). The expression of RICTOR in FLS from the three groups was evaluated at the protein level by western blotting and at the mRNA level by Real-time PCR. Three of the RA-FLS samples were selected randomly for being treated with 10ng/ml TNF-alpha, 4nM Akt pathway blocker MK-2206 with or without 10ng/ml TNF-alpha. The expression of RICTOR was detected by western blotting after 24h. <h3>Results</h3> 1) Western blotting and Realtime-PCR showed that the expression of RICTOR was elevated in RA-FLS compared with that in Trauma-FLS (both <i>p</i>&lt;0.05) at protein and mRNA level. But no difference was found between RA-FLS and OA-FLS. 2) Compared with the control group, treatment with MK-2206 (with or without TNF-alpha) for 24h decreased the expression of RICTOR protein (both <i>p</i>&lt;0.01), while the expression of RICTOR in RA-FLS was not influenced by stimulation with TNF-alpha. <h3>Conclusions</h3> Expression of RICTOR is elevated in RA-FLS in vitro. The increase is due to the activation of Akt signaling. The results suggest that RICTOR may contribute to the stable activation of RA-FLS. <h3>References</h3> Bayascas JR, Alessi DR. Regulation of Akt/PKB Ser473 phosphorylation. Mol Cell. 2005, 18(2):143-145. Zhang HG, Wang Y, Xie JF, et al. Regulation of tumor necrosis factor alpha-mediated apoptosis of rheumatoid arthritis synovial fibroblasts by the protein kinase Akt. Arthritis Rheum. 2001, 44(7):1555-1567. <h3>Disclosure of Interest</h3> None Declared
The L-Arginine-Nitric Oxide Pathway
Authors: Franklin H. Epstein, Salvador Moncada, Annie Higgs
Journal: New England Journal of Medicine (1993)

The discovery that mammalian cells generate nitric oxide, a gas previously considered to be merely an atmospheric pollutant, is providing important information about many biologic processes. Nitric oxide is synthesized from the amino acid L-arginine by a family of enzymes, the nitric oxide synthases, through a hitherto unrecognized metabolic route -- namely, the L-arginine-nitric oxide pathway18.The synthesis of nitric oxide by vascular endothelium is responsible for the vasodilator tone that is essential for the regulation of blood pressure. In the central nervous system nitric oxide is a neurotransmitter that underpins several functions, including the formation of memory. . . .