tbuckley/cabot-search huggingface dataset:
An analysis of impact forces in an active shoulder tackle in rugby
Authors: J Usman, A S McIntosh, B Fréchède
Journal: British Journal of Sports Medicine (2011)

Background The incidence of shoulder injury resulting from the tackle in rugby union football is high and the tackle is as well the main cause of injury. Little is known about the magnitude of tackle forces and influencing factors. Objective To measure the force applied to the shoulder in the tackle, the effect of shoulder padding, skill level, side of body, and player size. Design Repeated measures design. In counterbalanced order, participants tackled a 45 kg tackle bag five times in the four conditions: dominant versus non-dominant sides; with and without shoulder pads. Setting Community level rugby football. The selection criteria were: (1) age 18–25 years old, (2) played at least 3 years of rugby, and (3) played at least a season of rugby within the last 3 years. Participants 35 participants were recruited. Interventions IRB approved shoulder pads. Main outcome measurements Maximum impact force was measured with a custom built forceplate incorporated into a 45 kg tackle bag. Results The overall average shoulder force was 1660 N. The average impact force for tackling without shoulder pads was 1684 N compared to 1635 N for wearers. Shoulder pads reduced the peak impact forces by 3% (p&gt;0.05). There was a 6% difference in the average impact force between the dominant (1708 N) and non-dominant sides (1611 N). Tackle repetition was found to be a statistically significant factor as the impact forces reduced from the first tackle (1743 N) to the fifth tackle (1571 N) (p&lt;0.05). No relationship was observed between player skill level and size. Conclusion Shoulder pad performance needs to be improved. Although the shoulder force in the tackle is normally tolerated without injury, its magnitude is within the reported tolerance threshold range for sternoclavicular joint and glenohumeral joint. Fatigue may be an injury risk factor in the tackle.
Noninvasive Evaluation of Neural Impairment in Subjects With Impaired Glucose Tolerance
Authors: Zsuzsanna Putz, Ádám G Tabák, Nelli Tóth, Ildikó Istenes, Nóra Németh, Rajiv A. Gandhi, Zsolt Hermányi, Katalin Keresztes, György Jermendy, Solomon Tesfaye, Péter Kempler
Journal: Diabetes Care (2008)

To evaluate neural dysfunction in subjects with impaired glucose tolerance (IGT).For this study, 46 subjects with IGT and 45 healthy volunteers underwent detailed neurological assessment. Cardiovascular autonomic function was assessed by standard cardiovascular reflex tests, and heart rate variability was characterized by the triangle index. Sensory nerve function was assessed using Neurometer (for current perception threshold) and Medoc devices. Peak plantar pressure was measured by dynamic pedobarography, and symptoms were graded using the neuropathy total symptom score.Subjects with IGT had significantly greater abnormalities detected by four of five cardiovascular reflex tests and greater heart rate variability characterized by the triangle index. They had a higher frequency of both hyperesthesia and hypoesthesia as detected by current perception threshold testing at 5 Hz, as well as increased heat detection thresholds.This study provides evidence that subclinical neural dysfunction is present in subjects with IGT and can be detected noninvasively. Cardiovascular autonomic neuropathy may contribute to increased cardiovascular risk in IGT subjects.
Mechanisms of Endocrine Resistance in Breast Cancer
Authors: C. Kent Osborne, Rachel Schiff
Journal: Annual Review of Medicine (2010)

The estrogen receptor (ER) pathway plays a pivotal role in breast cancer development and progression. Endocrine therapy to block the ER pathway is highly effective, but its usefulness is limited by common intrinsic and acquired resistance. Multiple mechanisms responsible for endocrine resistance have been proposed and include deregulation of various components of the ER pathway itself, alterations in cell cycle and cell survival signaling molecules, and the activation of escape pathways that can provide tumors with alternative proliferative and survival stimuli. Among these, increased expression or signaling of growth factor receptor pathways, especially the EGFR/HER2 pathway, has been associated with both experimental and clinical endocrine therapy resistance. New treatment combinations targeting both ER and growth factor receptor signaling to block the crosstalk between these pathways and eliminate escape routes have been proven highly effective in preclinical models. Results of recent clinical studies, while partly supporting this approach, also highlight the need to better identify a priori the patients whose tumors are most likely to benefit from these specific cotargeting strategies.
Treatment with Chemotherapy and Dendritic Cells Pulsed with Multiple Wilms' Tumor 1 (WT1)–Specific MHC Class I/II–Restricted Epitopes for Pancreatic Cancer
Authors: Shigeo Koido, Sadamu Homma, Masato Okamoto, Kazuki Takakura, Masako Mori, Shinji Yoshizaki, Shintaro Tsukinaga, Shunichi Odahara, Seita Koyama, Hiroo Imazu, Kan Uchiyama, Mikio Kajihara, Hiroshi Arakawa, Takeyuki Misawa, Yoichi Toyama, Satoru Yanagisawa, Masahiro Ikegami, Shin Kan, Kazumi Hayashi, Hideo Komita, Yuko Kamata, Masaki Ito, Takefumi Ishidao, Sei-ichi Yusa, Shigetaka Shimodaira, Jianlin Gong, Haruo Sugiyama, Toshifumi Ohkusa, Hisao Tajiri
Journal: Clinical Cancer Research (2014)

Abstract Purpose: We performed a phase I trial to investigate the safety, clinical responses, and Wilms' tumor 1 (WT1)-specific immune responses following treatment with dendritic cells (DC) pulsed with a mixture of three types of WT1 peptides, including both MHC class I and II–restricted epitopes, in combination with chemotherapy. Experimental Design: Ten stage IV patients with pancreatic ductal adenocarcinoma (PDA) and 1 patient with intrahepatic cholangiocarcinoma (ICC) who were HLA-positive for A*02:01, A*02:06, A*24:02, DRB1*04:05, DRB1*08:03, DRB1*15:01, DRB1*15:02, DPB1*05:01, or DPB1*09:01 were enrolled. The patients received one course of gemcitabine followed by biweekly intradermal vaccinations with mature DCs pulsed with MHC class I (DC/WT1-I; 2 PDA and 1 ICC), II (DC/WT1-II; 1 PDA), or I/II–restricted WT1 peptides (DC/WT1-I/II; 7 PDA), and gemcitabine. Results: The combination therapy was well tolerated. WT1-specific IFNγ-producing CD4+ T cells were significantly increased following treatment with DC/WT1-I/II. WT1 peptide-specific delayed-type hypersensitivity (DTH) was detected in 4 of the 7 patients with PDA vaccinated with DC/WT1-I/II and in 0 of the 3 patients with PDA vaccinated with DC/WT1-I or DC/WT1-II. The WT1-specific DTH-positive patients showed significantly improved overall survival (OS) and progression-free survival (PFS) compared with the negative control patients. In particular, all 3 patients with PDA with strong DTH reactions had a median OS of 717 days. Conclusions: The activation of WT1-specific immune responses by DC/WT1-I/II combined with chemotherapy may be associated with disease stability in advanced pancreatic cancer. Clin Cancer Res; 20(16); 4228–39. ©2014 AACR.
Elafin Reverses Pulmonary Hypertension via Caveolin-1–Dependent Bone Morphogenetic Protein Signaling
Authors: Nils P. Nickel, Edda Spiekerkoetter, Mingxia Gu, Caiyun G. Li, Hai Li, Mark Kaschwich, Isabel Diebold, Jan K. Hennigs, Ki-Yoon Kim, Kazuya Miyagawa, Lingli Wang, Aiqin Cao, Silin Sa, Xinguo Jiang, Raymond W. Stockstill, Mark R. Nicolls, Roham T. Zamanian, Richard D. Bland, Marlene Rabinovitch
Journal: American Journal of Respiratory and Critical Care Medicine (2015)

Pulmonary arterial hypertension is characterized by endothelial dysfunction, impaired bone morphogenetic protein receptor 2 (BMPR2) signaling, and increased elastase activity. Synthetic elastase inhibitors reverse experimental pulmonary hypertension but cause hepatotoxicity in clinical studies. The endogenous elastase inhibitor elafin attenuates hypoxic pulmonary hypertension in mice, but its potential to improve endothelial function and BMPR2 signaling, and to reverse severe experimental pulmonary hypertension or vascular pathology in the human disease was unknown.To assess elafin-mediated regression of pulmonary vascular pathology in rats and in lung explants from patients with pulmonary hypertension. To determine if elafin amplifies BMPR2 signaling in pulmonary artery endothelial cells and to elucidate the underlying mechanism.Rats with pulmonary hypertension induced by vascular endothelial growth factor receptor blockade and hypoxia (Sugen/hypoxia) as well as lung organ cultures from patients with pulmonary hypertension were used to assess elafin-mediated reversibility of pulmonary vascular disease. Pulmonary arterial endothelial cells from patients and control subjects were used to determine the efficacy and mechanism of elafin-mediated BMPR2 signaling.In Sugen/hypoxia rats, elafin reduced elastase activity and reversed pulmonary hypertension, judged by regression of right ventricular systolic pressure and hypertrophy and pulmonary artery occlusive changes. Elafin improved endothelial function by increasing apelin, a BMPR2 target. Elafin induced apoptosis in human pulmonary arterial smooth muscle cells and decreased neointimal lesions in lung organ culture. In normal and patient pulmonary artery endothelial cells, elafin promoted angiogenesis by increasing pSMAD-dependent and -independent BMPR2 signaling. This was linked mechanistically to augmented interaction of BMPR2 with caveolin-1 via elafin-mediated stabilization of endothelial surface caveolin-1.Elafin reverses obliterative changes in pulmonary arteries via elastase inhibition and caveolin-1-dependent amplification of BMPR2 signaling.
Hypertrophic agonists induce the binding of c-Fos to an AP-1 site in cardiac myocytes: implications for the expression of GLUT1
Authors: T Santalucía
Journal: Cardiovascular Research (2003)

Serum is among the agents known to induce hypertrophy of cardiac myocytes, which occurs concomitant with an increase in AP-1-mediated transcription. We have examined if this effect correlates with changes in the relative abundance of particular AP-1 heterodimers, as their exact composition under these conditions is unknown. Furthermore, we obtained insight on the specific role of c-Fos from studying the induction of the glucose transporter GLUT1 by serum in fibroblasts.We characterised the AP-1 heterodimers expressed in neonatal cardiac myocytes by supershift electrophoretic mobility shift assay (EMSA) analysis. Quantitative changes in transcription were measured using a luciferase reporter vector, and we examined the expression of the glucose transporter GLUT1 in cardiac myocytes and a c-Fos knockout-derived fibroblast cell line by western blotting.Transcriptionally active AP-1 in combinations of c-Jun, JunD and JunB with Fra1, Fra2 and possibly FosB, are expressed in cardiac myocytes. Hypertrophic stimuli transiently induced AP-1 dimers containing c-Fos, and this was dependent on the ERK mitogen-activated protein kinase pathway and coincided with the activation of AP-1-mediated transcription and the induction of GLUT1 in cardiac myocytes. In fibroblasts, the induction of GLUT1 by serum required the specific expression of c-Fos.Our data suggest that induction of c-Fos containing AP-1 heterodimers may partly activate AP-1-mediated transcription in cardiac myocytes treated with hypertrophic agonists under conditions known to induce GLUT1. Data obtained in fibroblasts treated with serum lead us to hypothesise that c-Fos might play a major role in the regulation of GLUT1 expression.
Oxidised lipids present in ascitic fluid interfere with the regulation of the macrophages during acute pancreatitis, promoting an exacerbation of the inflammatory response
Authors: P. T. Gutierrez, E. Folch-Puy, O. Bulbena, D. Closa
Journal: Gut (2008)

<h3>Background:</h3> Pancreatitis-associated ascitic fluid (PAAF) plays a critical role in the pathogenesis of acute pancreatitis. Taking into consideration that damaged pancreas exudes high concentrations of lipolytic enzymes in the peritoneal cavity, large amounts of lipid metabolism derived products could occur in PAAF. In this study, we have examined the involvement of the lipid fraction of PAAF generated in the early stages of experimental acute pancreatitis. <h3>Methods:</h3> Pancreatitis was induced in rats by intraductal administration of 5% sodium taurocholate. After 3 h, PAAF was collected and its lipid fraction was obtained. Lipid composition and levels of lipid peroxidation were measured. Toxicity was evaluated by measuring the effects of the PAAF lipid fraction on cell viability of hepatic and macrophage cell lines. <i>In vivo</i> effects on the liver were also evaluated. Effects on the inflammatory response were determined by measuring the levels of nuclear factor kappa B (NFκB) activation, the effect on the inhibitory activity of 15-deoxy-PGJ<sub>2</sub> and the possible interference on PPARγ activation. <h3>Results:</h3> High concentrations of oxidised free fatty acids were detected in PAAF. Besides the direct cell toxicity, the PAAF-derived lipid extract interfered with the anti-inflammatory pathway mediated by PPARγ. Addition of this lipid extract to macrophage cell cultures had no direct effect on the activation of NFκB, but abolished the inhibitory activity of endogenous PPARγ agonists such as 15-deoxy-PGJ<sub>2</sub>. <h3>Conclusions:</h3> Oxidised free fatty acids present in PAAF interfere with the endogenous regulatory mechanism of the inflammatory response, thus promoting an exacerbation of macrophage activation in acute pancreatitis.
Between Death and Survival: Retinoic Acid in Regulation of Apoptosis
Authors: Noa Noy
Journal: Annual Review of Nutrition (2010)

The vitamin A metabolite all-trans-retinoic acid (RA) regulates multiple biological processes by virtue of its ability to regulate gene expression. It thus plays critical roles in embryonic development and is involved in regulating growth, remodeling, and metabolic responses in adult tissues. RA can also suppress carcinoma cell growth and is currently used in treatment of some cancers. Growth inhibition by RA may be exerted by induction of differentiation, cell cycle arrest, or apoptosis, or by a combination of these activities. Paradoxically, in the context of some cells, RA not only fails to inhibit growth but, instead, enhances proliferation and survival. This review focuses on the involvement of RA in regulating apoptotic responses. It includes brief overviews of transcriptional signaling by RA and of apoptotic pathways, and then addresses available information on the mechanisms by which RA induces apoptosis or, conversely, inhibits cell death and enhances survival.
Risk Assessment for and Strategies to Reduce Perioperative Pulmonary Complications
Authors: Amir Qaseem, Vincenza Snow
Journal: Annals of Internal Medicine (2006)

Letters3 October 2006Risk Assessment for and Strategies to Reduce Perioperative Pulmonary ComplicationsAmir Qaseem, MD, PhD, MHA and Vincenza Snow, MDAmir Qaseem, MD, PhD, MHAFrom the American College of Physicians, Philadelphia, PA 19106. and Vincenza Snow, MDFrom the American College of Physicians, Philadelphia, PA 19106.Author, Article, and Disclosure Informationhttps://doi.org/10.7326/0003-4819-145-7-200610030-00017 SectionsAboutFull TextPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissions ShareFacebookTwitterLinkedInRedditEmail IN RESPONSE: Dr. Qaseem makes an important point about acid suppression prophylaxis in a subset of patients at increased risk for pulmonary aspiration of gastric contents during surgery. Although we agree, acid suppression is widely used for gastrointestinal prophylaxis. As Dr. Qaseem pointed out, even though the acid aspiration syndrome is a critical perioperative complication, it is limited to a very small subset of patients. The use of acid suppression solely as a preventive strategy for pulmonary complications was excluded from our review. These patients need to be individually evaluated and managed appropriately. Author, Article, and Disclosure InformationAffiliations: From the American College of Physicians, Philadelphia, PA 19106.Disclosures: None disclosed. PreviousarticleNextarticle Advertisement FiguresReferencesRelatedDetailsSee AlsoRisk Assessment for and Strategies to Reduce Perioperative Pulmonary Complications Tahir Qaseem Metrics Cited byLaringectomie parziali sopracricoidee (cricoioidopessia e crico-ioido-epiglottopessia)Laringectomías parciales supracricoideas (cricohioidopexia y cricohioidoepiglotopexia)Preoperative EvaluationPreoperative cardiac risk factors associated with in-hospital mortality in elderly patients without heart failure undergoing hip fracture surgery: a single-centre studyMedical Care of the Surgical PatientRapid Geriatric Assessment of Hip FracturePreoperative EvaluationOptimal Preoperative Assessment of the Geriatric Surgical Patient: A Best Practices Guideline from the American College of Surgeons National Surgical Quality Improvement Program and the American Geriatrics SocietyPostoperative morbidity after fast-track laparoscopic resection of rectal cancerAnesthetic Management of Patients Undergoing Aortic Valve Bypass (Apicoaortic Conduit) Surgery 3 October 2006Volume 145, Issue 7Page: 553KeywordsConflicts of interestProphylaxisSurgery ePublished: 3 October 2006 Issue Published: 3 October 2006 Copyright & PermissionsCopyright © 2006 by American College of Physicians. All Rights Reserved.PDF downloadLoading ...
Duodenal ulcer, Helicobacter pylori, and gastric secretion.
Authors: K Chandrakumaran, D Vaira, M Hobsley
Journal: Gut (1994)

Patients with chronic dyspepsia were categorised by macroscopic appearance at oesophagogastroduodenoscopy as having duodenal ulceration (DU), other diagnosed lesions such as reflux oesophagitis, carcinoma of stomach, etc, or no organic lesion (non-ulcer dyspepsia, NUD). Material was collected to identify gastric infection with Helicobacter pylori (H pylori) by CP urease test, culture, and histological examination and to make the microscopic diagnosis of active chronic gastritis. Each patient in the DU and NUD categories was then invited to volunteer for a gastric secretion study in which maximal gastric secretion in response to histamine was measured. Sixty two gastric secretion tests were performed (31 DU, 31 NUD). The presence of H pylori was associated with active chronic gastritis (100%). DU patients secreted more acid than the NUD patients. H pylori positivity was associated with decreased maximal gastric secretion in both groups. There was a positive correlation between smoking and maximal acid output shown only in H pylori negative but not in H pylori positive patients. These findings were clear cut when all corrections of maximal gastric secretion were made for pyloric loss, duodenogastric reflux, and stature. This study failed to show any aetiological link between H pylori and DU by increased maximal gastric secretion.
Serum Dioxin, Testosterone, and Subsequent Risk of Benign Prostatic Hyperplasia: A Prospective Cohort Study of Air Force Veterans
Authors: Amit Gupta, Norma Ketchum, Claus G. Roehrborn, Arnold Schecter, Corinne C. Aragaki, Joel E. Michalek
Journal: Environmental Health Perspectives (2006)

Operation Ranch Hand veterans were involved in spraying herbicides, including Agent Orange, during the Vietnam War in 1962-1971; Agent Orange was contaminated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD). It has been hypothesized that dioxins may be partially responsible for an increase of male reproductive tract disorders such as testicular cancer, cryptorchidism, and hypospadias.In this study, our objective was to assess the effect of serum TCDD concentration on the risk of development of benign prostatic hyperplasia (BPH) and on serum testosterone levels.This study was a longitudinal, prospective cohort study made up of U.S. Air Force veterans involved in Operation Ranch Hand. Other Air Force veterans who did not spray herbicides were included as comparisons. BPH was determined by medical record review and by medical examinations conducted during the study. Data were available for 971 Ranch Hand and 1,266 comparison veterans. We investigated the relationship between BPH and serum TCDD level using the Cox proportional hazards models adjusted for testosterone levels, body mass index (BMI), and the percentage change in BMI per year.In univariate and multivariate analyses, the risk of BPH decreased with increasing serum TCDD in the comparison group. The multivariate risk ratio for BPH in the comparison group was 0.84 (95% confidence interval, 0.73-0.98). Excluding men with prostate cancer, inflammatory or other prostatic diseases did not substantially alter the association. Serum testosterone levels were inversely associated with serum TCDD levels in both Ranch Hand and comparison groups.TCDD exposure at general population levels is associated with a decreasing risk of BPH with higher exposure levels. TCDD exposure is also negatively associated with serum testosterone levels.
Yellow fever 17D as a vaccine vector for microbial CTL epitopes
Authors: Deng Tao, Giovanna Barba-Spaeth, Urvashi Rai, Victor Nussenzweig, Charles M. Rice, Ruth S. Nussenzweig
Journal: The Journal of Experimental Medicine (2005)

The yellow fever vaccine 17D (17D) is safe, and after a single immunizing dose, elicits long-lasting, perhaps lifelong protective immunity. One of the major challenges facing delivery of human vaccines in underdeveloped countries is the need for multiple injections to achieve full efficacy. To examine 17D as a vector for microbial T cell epitopes, we inserted the H-2Kd–restricted CTL epitope of the circumsporozoite protein (CS) of Plasmodium yoelii between 17D nonstructural proteins NS2B and NS3. The recombinant virus, 17D-Py, was replication competent and stable in vitro and in vivo. A single subcutaneous injection of 105 PFU diminished the parasite burden in the liver by ∼70%. The high level of protection lasted between 4 and 8 wk after immunization, but a significant effect was documented even 24 wk afterwards. Thus, the immunogenicity of a foreign T cell epitope inserted into 17D mimics some of the remarkable properties of the human vaccine. Priming with 17D-Py followed by boosting with irradiated sporozoites conferred sterile immunity to 90% of the mice. This finding indicates that the immune response of vaccine-primed individuals living in endemic areas could be sustained and magnified by the bite of infected mosquitoes.