tbuckley/cabot-search huggingface dataset:
Risk factors for injuries in a high-altitude ultramarathon
Authors: M Khodaee, R Myers, J Spittler, J A Lee, J C Hill, D Yeakel
Journal: British Journal of Sports Medicine (2011)

Background Risk factors for ultramarathon injuries are poorly understood. Objective Effects of human and environmental factors on predicting injuries. Design Observational study using electronic surveys prior and 10-days post-race. Setting Leadville-100 is a difficult high-altitude trail ultramarathon (160.9 km) with a course elevation of 2804–3840 m in Leadville, Colorado. Participants All runners completed the pre-race survey and half (n=308, 48%) completed the post-race survey. Assessment of risk factors The dependent variable was visiting a physician/health care provider for injuries due to the race. The independent variables were age, gender, prior completion of the race, foot type (normal, flat feet, high arch), Body Mass Index (BMI), height, weight, wearing orthotics, shoe type, changing shoes during the race. Main outcome measurements The primary outcome measure was whether stability running shoes are correlated with fewer injuries compared to other types of shoes. Results Out of 646 participants, 361 (55.9%) runners finished the race under the 30-h time cut-off. Majority (n=676, 84.9%) were male with average age of 41 years (range 21–73). Majority were first time participants (n=468, 73%). Among those who completed the post-race survey, 109 (35%) visited the aid stations during the race and 37 (12%) sought medical attention after the race. Runners primarily visited aid stations for musculoskeletal, gastrointestinal, and respiratory complaints. Half (n=171, 55%) were able to walk without assistance and majority (n=216, 72%) return to work after 1 day of rest. Runners with cushion shoes were more likely to seek medical attention compared to those with instability shoes (p&lt;0.005; OR=3.59; CI 1.33 to 9.66). There were no correlations between gender, foot type, BMI, height, weight, having orthotics, and prior race completion and seeking medical attention post-race. Conclusion Compared to other running shoes, the stability type is correlated with fewer injuries requiring medical visits among participants in a high-altitude ultramarathon.
Acute Effects of N-Methyl-N′-nitro-N-nitrosoguanidine on Canine Gastric Mucosa
Authors: Yuh-Jyh Kuo, Alec C. Chou, Linda L. Shanbour
Journal: JNCI Journal of the National Cancer Institute (1977)

The electrophysiological effects of the chemical gastric carcinogen N-methyl-N′-nitro-N-nitrosoguanidine (MNNG) were determined in an in vivo chambered canine stomach and in an in vitro canine gastric mucosal preparation. In the in vivo stomach, the topical application of 2.5 mg MNNG/ml decreased the transmural electrical potential difference, and the systemic blood pressure was essentially unchanged. In the in vitro preparation, exposure of the mucosal side of the isolated canine gastric mucosa to 0.25 and 2.5 mg MNNG/ml for 1 hour sequentially or exposure of the serosal side to 2.5 mg MNNG/ml for 2 hours inhibited net Na+ and CI- fluxes. With longer duration, the undirectional fluxes of Na+ and CI- increased, indicating an increase in permeability. These findings suggested that inhibition of active transport in the gastric mucosa may have an important function in the gastric carcinogenicity of MNNG.
Effects of Perioperative Administration of a Selective Cyclooxygenase 2 Inhibitor on Pain Management and Recovery of Function After Knee Replacement
Authors: Asokumar Buvanendran, Jeffrey S Kroin, Kenneth J Tuman, Timothy R Lubenow, Dalia Elmofty, Mario Moric, Aaron G Rosenberg
Journal: JAMA (2003)

Controlling postoperative pain after knee replacement while reducing opioid-induced adverse effects and improving outcomes remains an important challenge.To assess the effect of combined preoperative and postoperative administration of a selective inhibitor of cyclooxygenase 2 on opioid consumption and outcomes after total knee arthroplasty (TKA).Randomized, placebo-controlled, double-blind trial conducted June 2001 through September 2002, enrolling 70 patients aged 40 to 77 years and undergoing TKA at a university hospital in the United States.Patients were randomly assigned to receive 50 mg of oral rofecoxib at 24 hours and at 1 to 2 hours before TKA, 50 mg daily for 5 days postoperatively, and 25 mg daily for another 8 days, or matching placebo at the same times.Postoperative outcomes including postsurgical analgesic consumption and pain scores achieved, nausea and vomiting, joint range of motion, sleep disturbance, patient satisfaction with analgesia, and hematologic and coagulation parameters.Total epidural analgesic consumption and in-hospital opioid consumption were less in the group receiving rofecoxib compared with the group receiving placebo (P<.05). Median pain score (visual analog scale [VAS], 0-10) achieved for the knee was lower in the rofecoxib group compared with the placebo group during hospital stay (2.2 [interquartile range [IQR], 1.4-3.2] vs 3.5 [IQR, 2.7-4.3], P<.001) and 1 week after discharge (2.6 [IQR, 1.4-3.5] vs 3.7 [IQR, 2.9-4.7], P =.03). There was less postoperative vomiting in the rofecoxib group (6%) compared with the placebo group (26%) (P =.047), as well as a decrease in sleep disturbance compared with the placebo group on the night of surgery (P =.006) and on the first (P =.047) and second (P<.001) days postoperatively. Knee flexion was increased in the rofecoxib group compared with the placebo group at discharge (active flexion: mean [SD], 84.2 degrees [11.1 degrees ] vs 73.2 degrees [13.6 degrees ], P =.03; passive flexion: 90.5 degrees [6.8 degrees ] vs 81.8 degrees [13.4 degrees ], P =.05) and at 1 month postoperatively (109.3 degrees [8.5 degrees ] vs 100.8 degrees [11.8 degrees ], P =.01), with shorter time in physical therapy to achieve effective joint range of motion. The rofecoxib group was more satisfied with analgesia and anesthesia at discharge compared with the placebo group (median satisfaction score, 4.3 [IQR, 3.0-4.7] vs 3.3 [IQR, 2.3-4.3], respectively; P =.03), and the differences persisted at 2-week and at 1-month follow-up. There was no intergroup difference in surgical blood loss (P>.05 for both intraoperative and postoperative blood loss).Perioperative use of an inhibitor of cyclooxygenase 2 is an effective component of multimodal analgesia that reduces opioid consumption, pain, vomiting, and sleep disturbance, with improved knee range of motion after TKA.
Heart Failure
Authors: David A. Kass
Journal: Circulation (2012)

T he pathologically hypertrophied and failing heart is a battlefield in a war that would make even George Lucas proud.On the one side, you have hemodynamic, neurohormonal, morphological, and cellular/molecular dark forces urging the ventricle toward decompensation and ultimate demise.On the other, Jedi signaling cascades try valiantly to stave off the impending disaster.Alas, unlike the movies, the dark side often wins, and we need better-equipped counterforces to change this.Current heart failure therapies are fairly defensive-blocking neurohumoral stimuli and hemodynamic overload.However, adaptive/offensive strategies are advancing, including those aimed at enhancing metabolism, vascular supply, and cell regeneration, and those activating molecular signaling to counter maladaptation.
Relationship Between Peer Victimization, Cyberbullying, and Suicide in Children and Adolescents
Authors: Mitch van Geel, Paul Vedder, Jenny Tanilon
Journal: JAMA Pediatrics (2014)

Peer victimization is related to an increased chance of suicidal ideation and suicide attempts among children and adolescents. OBJECTIVE To examine the relationship between peer victimization and suicidal ideation or suicide attempts using meta-analysis. DATA SOURCES Ovid MEDLINE, PsycINFO, and Web of Science were searched for articles from 1910 to 2013. The search terms were bully*, teas*, victim*, mobbing, ragging, and harassment in combination with the term suic*. Of the 491 studies identified, 34 reported on the relationship between peer victimization and suicidal ideation, with a total of 284,375 participants. Nine studies reported on the relationship between peer victimization and suicide attempts, with a total of 70,102 participants. STUDY SELECTION Studies were eligible for inclusion if they reported an effect size on the relationship between peer victimization and suicidal ideation or suicide attempt in children or adolescents.Two observers independently coded the effect sizes from the articles. Data were pooled using a random effects model. MAIN OUTCOMES AND MEASURES This study focused on suicidal ideation and suicide attempts. Peer victimization was hypothesized to be related to suicidal ideation and suicide attempts. RESULTS Peer victimization was found to be related to both suicidal ideation (odds ratio, 2.23 [95% CI, 2.10-2.37]) and suicide attempts (2.55 [1.95 -3.34]) among children and adolescents. Analyses indicated that these results were not attributable to publication bias. Results were not moderated by sex, age, or study quality. Cyberbullying was more strongly related to suicidal ideation compared with traditional bullying. CONCLUSIONS AND RELEVANCE Peer victimization is a risk factor for child and adolescent suicidal ideation and attempts. Schools should use evidence-based practices to reduce bullying.
Treatment of Diabetic Gastroparesis by High-Frequency Gastric Electrical Stimulation
Authors: Zhiyue Lin, Jameson Forster, Irene Sarosiek, Richard W. McCallum
Journal: Diabetes Care (2004)

OBJECTIVE—To investigate the long-term efficacy of high-frequency gastric electrical stimulation (GES) for treating diabetic gastroparesis. RESEARCH DESIGN AND METHODS—This is a retrospective review of 48 adult diabetic patients with refractory gastroparesis who had a GES system implanted surgically and had follow-up evaluations at 6 and 12 months. The outcome measures were total symptom score (TSS), derived from six upper gastrointestinal (GI) symptom subscores; health-related quality of life (HQOL), including physical composite score (PCS) and mental composite score (MCS) assessed by SF-36 questionnaire, radionuclide gastric emptying test, nutritional status, HbA1c, and adverse events. RESULTS—In comparison with baseline, TSS, all six upper GI symptom subscores, PCS, and MCS were significantly improved at 6 months, with the improvement sustained at 12 months. Of 13 patients receiving nutritional support at baseline by tube feeding, only 5 required supplemental enteral feeding at 12 months, and none of the 9 on total parenteral nutrition continued this support. The mean number of hospitalization days during the year after GES was significantly reduced by 52 days compared with the prior year. HbA1c levels were significantly reduced at 12 months. Gastric emptying was only minimally and not significantly faster. Because of infections at the pulse generator pocket site, four patients had their GES systems removed 3–17 months postsurgery. CONCLUSIONS—In diabetic patients with refractory gastroparesis, high-frequency GES by a permanently implanted system significantly improved upper GI symptoms, HQOL, nutritional status, glucose control, and hospitalizations with an acceptably low complication rate.
Plasma MicroRNAs as Novel Biomarkers for Endometriosis and Endometriosis-Associated Ovarian Cancer
Authors: Swati Suryawanshi, Anda M. Vlad, Hui-Min Lin, Gina Mantia-Smaldone, Robin Laskey, MinJae Lee, Yan Lin, Nicole Donnellan, Marcia Klein-Patel, Ted Lee, Suketu Mansuria, Esther Elishaev, Raluca Budiu, Robert P. Edwards, Xin Huang
Journal: Clinical Cancer Research (2013)

Endometriosis, a largely benign, chronic inflammatory disease, is an independent risk factor for endometrioid and clear cell epithelial ovarian tumors. We aimed to identify plasma miRNAs that can be used to differentiate patients with endometriosis and ovarian cancer from healthy individuals.We conducted a two-stage exploratory study to investigate the use of plasma miRNA profiling to differentiate between patients with endometriosis, patients with endometriosis-associated ovarian cancer (EAOC), and healthy individuals. In the first stage, using global profiling of more than 1,000 miRNAs via reverse transcriptase quantitative PCR (RT-qPCR) in a 20-patient initial screening cohort, we identified 23 candidate miRNAs, which are differentially expressed between healthy controls (n = 6), patients with endometriosis (n = 7), and patients with EAOC (n = 7) based on the fold changes. In the second stage, the 23 miRNAs were further tested in an expanded cohort (n = 88) of healthy individuals (n = 20), endometriosis (n = 33), EAOC (n = 14), and serous ovarian cancer cases (SOC; n = 21, included as controls).We identified three distinct miRNA signatures with reliable differential expression between healthy individuals, patients with endometriosis, and patients with EAOC. When profiled against the control SOC category, our results revealed different miRNAs, suggesting that the identified signatures are reflective of disease-specific pathogenic mechanisms. This was further supported by the fact that the majority of miRNAs differentially expressed in human EAOCs were mirrored in a double transgenic mouse EAOC model.Our study reports for the first time that distinct plasma miRNA expression patterns may serve as highly specific and sensitive diagnostic biomarkers to discriminate between healthy, endometriosis, and EAOC cases.
Substitution of the carboxyl-terminal domain of apo AI with apo AII sequences restores the potential of HDL to reduce the progression of atherosclerosis in apo E knockout mice.
Authors: P Holvoet, S Danloy, E Deridder, M Lox, H Bernar, A Dhoest, D Collen
Journal: Journal of Clinical Investigation (1998)

HDL metabolism and atherosclerosis were studied in apo E knockout (KO) mice overexpressing human apo AI, a des- (190-243)-apo AI carboxyl-terminal deletion mutant of human apo AI or an apo AI-(1-189)-apo AII-(12-77) chimera in which the carboxyl-terminal domain of apo AI was substituted with the pair of helices of apo AII. HDL cholesterol levels ranked: apo AI/apo E KO approximately apo AI-(1-189)-apo AII- (12-77)/apo E KO > > des-(190-243)-apo AI/apo E KO > apo E KO mice. Progression of atherosclerosis ranked: apo E KO > des-(190-243)-apo AI/apo E KO > > apo AI-(1-189)- apo AII-(12-77)/apo E KO approximately apo AI/apo E KO mice. Whereas the total capacity to induce cholesterol efflux from lipid-loaded THP-1 macrophages was higher for HDL of mice overexpressing human apo AI or the apo AI/apo AII chimera, the fractional cholesterol efflux rate, expressed in percent cholesterol efflux/microg apolipoprotein/h, for HDL of these mice was similar to that for HDL of mice overexpressing the deletion mutant and for HDL of apo E KO mice. This study demonstrates that the tertiary structure of apo AI, e.g., the number and organization of its helices, and not its amino sequence is essential for protection against atherosclerosis because it determines HDL cholesterol levels and not cholesterol efflux. Amino acid sequences of apo AII, which is considered to be less antiatherogenic, can be used to restore the structure of apo AI and thereby its antiatherogenicity.
Hyper-CVAD and high-dose methotrexate/cytarabine followed by stem-cell transplantation: an active regimen for aggressive mantle-cell lymphoma.
Authors: I F Khouri, J Romaguera, H Kantarjian, J L Palmer, W C Pugh, M Korbling, F Hagemeister, B Samuels, A Rodriguez, S Giralt, A Younes, D Przepiorka, D Claxton, F Cabanillas, R Champlin
Journal: Journal of Clinical Oncology (1998)

PURPOSE Diffuse and nodular forms of mantle-cell lymphoma (MCL) are consistently associated with poor prognosis. In an effort to improve the outcome, we adopted a treatment plan that consisted of four courses of fractionated cyclophosphamide (CY) 1,800 mg/m2 administered with doxorubicin (DOX), vincristine (VCR), and dexamethasone (Hyper-CVAD) that alternated with high-dose methotrexate (MTX) and cytarabine (Ara-C). After four courses, patients were consolidated with high-dose CY, total-body irradiation, and autologous or allogeneic blood or marrow stem-cell transplantation. PATIENTS AND METHODS Forty-five patients were enrolled; 25 patients were previously untreated, 43 patients had Ann Arbor stage IV disease, and 42 patients had marrow involvement. Forty-one patients had diffuse histology, two patients had nodular, and two patients had blastic variants. RESULTS Hyper-CVAD/MTX-Ara-C induced a response rate of 93.5% (complete response [CR], 38%; partial response [PR], 55.5%) after four cycles of pretransplantation induction chemotherapy. All patients who went on to undergo transplantation achieved CRs. For the 25 previously untreated patients, the overall survival (OS) and event-free survival (EFS) rates at 3 years were 92% (95% confidence interval [CI], 80 to 100) and 72% (95% CI, 45 to 98) compared with 25% (95% CI, 12 to 62; P = .005) and 17% (95% CI, 10 to 43; P = .007), respectively, for the previously treated patients. When compared with a historic control group who received a CY, DOX, VCR, and prednisone (CHOP)-like regimen, untreated patients in the study had a 3-year EFS rate of 72% versus 28% (P = .0001) and a better OS rate (92% v 56%; P = .05). Treatment-related death occurred in five patients: all were previously treated and two received allogeneic transplants. CONCLUSION The Hyper-CVAD/MTX-Ara-C program followed by stem-cell transplantation is a promising new therapy for previously untreated patients with MCL.
Intracellular adhesion molecule-1 modulates β-chemokines and directly costimulates T cells in vivo
Authors: Jong J. Kim, Anthony Tsai, Liesl K. Nottingham, Lake Morrison, Devin M. Cunning, Jim Oh, Daniel J. Lee, Kesen Dang, Tzvete Dentchev, Ara A. Chalian, Michael G. Agadjanyan, David B. Weiner
Journal: Journal of Clinical Investigation (1999)

The potential roles of adhesion molecules in the expansion of T cell–mediated immune responses in the periphery were examined using DNA immunogen constructs as model antigens. We coimmunized cDNA expression cassettes encoding the adhesion molecules intracellular adhesion molecule-1 (ICAM-1), lymphocyte function associated-3 (LFA-3), and vascular cell adhesion molecule-1 (VCAM-1) along with DNA immunogens, and we analyzed the resulting antigen-specific immune responses. We observed that antigen-specific T-cell responses can be enhanced by the coexpression of DNA immunogen and adhesion molecules ICAM-1 and LFA-3. Coexpression of ICAM-1 or LFA-3 molecules along with DNA immunogens resulted in a significant enhancement of T-helper cell proliferative responses. In addition, coimmunization with pCICAM-1 (and more moderately with pCLFA-3) resulted in a dramatic enhancement of CD8-restricted cytotoxic T-lymphocyte responses. Although VCAM-1 and ICAM-1 are similar in size, VCAM-1 coimmunization did not have any measurable effect on cell-mediated responses. These results suggest that ICAM-1 and LFA-3 provide direct T-cell costimulation. These observations are further supported by the finding that coinjection with ICAM-1 dramatically enhanced the level of interferon-γ (IFN-γ) and β-chemokines macrophage inflammatory protein-1α (MIP-1α), MIP-1β, and regulated on activation normal T-cell expression and secreted (RANTES) produced by stimulated T cells. Through comparative studies, we observed that ICAM-1/LFA-1 T-cell costimulatory pathways are independent of CD86/CD28 pathways and that they may synergistically expand T-cell responses in vivo.
Deoxycholate is an important releaser of peptide YY and enteroglucagon from the human colon.
Authors: T E Adrian, G H Ballantyne, W E Longo, A J Bilchik, S Graham, M D Basson, R P Tierney, I M Modlin
Journal: Gut (1993)

Peptide YY (PYY) and enteroglucagon are hormonal peptides found in endocrine cells of the distal intestinal mucosa. Although it is known that plasma concentrations of both peptides increase in response to feeding, the mechanism by which ingested food causes release of colonic hormones is not understood. The release of PYY and enteroglucagon was measured in response to intraluminal stimuli in 176 patients having investigative colonoscopy. Introduction of air, saline (isotonic and hypertonic), glucose (isotonic and hypertonic), oleic acid (without bile salts), and casein hydrolysate all failed to release PYY but glucose caused a small but significant increase in enteroglucagon concentrations. In contrast with the lack of effect of nutrients, infusion of deoxycholic acid produced a rapid and marked dose responsive increase in plasma PYY concentrations when introduced into the sigmoid colon. PYY release was statistically significant at doses between 3.3 mM to 30 mM; for example 10 mM deoxycholate caused a sixfold increase in plasma PYY concentrations. Infusion of 10 mM deoxycholate into the transverse colon or caecum produced an increase of PYY that was similar to the responses in the sigmoid colon. There was also a significant release of enteroglucagon in response to infusion of this bile salt into the sigmoid colon at doses between 3.3 mM and 30 mM. The enteroglucagon response to 10 mM deoxycholate was similar in all three colonic regions. When oleic acid was added to deoxycholate as an emulsion, the release of PYY and enteroglucagon was similar to that seen with the bile salt alone. These findings suggest that bile salts may play an important part in the control of colonic endocrine function and may explain the increased circulating concentrations of colonic regulatory peptides that are seen in malabsorption states and after small bowel resection in humans.
The Mitochondrial Death Pathway and Cardiac Myocyte Apoptosis
Authors: Michael T. Crow, Kartik Mani, Young-Jae Nam, Richard N. Kitsis
Journal: Circulation Research (2004)

Apoptosis has been causally linked to the pathogenesis of myocardial infarction and heart failure in rodent models. This death process is mediated by two central pathways, an extrinsic pathway involving cell surface receptors and an intrinsic pathway using mitochondria and the endoplasmic reticulum. Each of these pathways has been implicated in myocardial pathology. In this review, we summarize recent advances in the understanding of the intrinsic pathway and how it relates to cardiac myocyte death and heart disease.
Integrin-Linked Kinase at the Heart of Cardiac Contractility, Repair, and Disease
Authors: Gregory E. Hannigan, John G. Coles, Shoukat Dedhar
Journal: Circulation Research (2007)

Recent advances in cardiac physiology identify the integrin-linked kinase (ILK) as an essential molecule regulating cardiac growth, contractility, and repair. A key transducer of biochemical signals initiated at the plasma membrane by cell–matrix interactions, ILK now emerges as a crucial player in mechanotransduction by integrins. Animal models have been particularly instructive in dissecting the cardiac functions of ILK and its associated proteins, such as parvins and PINCH, and have clearly established ILK as a major contributor to cardiac health. ILK gene knockouts in mice, flies, and worms result in early embryonic lethality because of cell adhesion defects and cytoskeletal disorganization. Although widely distributed in mammalian tissues, ILK expression is highest in the heart, and cardiac-specific ablation of ILK causes cardiomyopathy and sudden death in mice. ILK protein complexes are found in the sarcomere, which is the basic contractile unit of myocytes. A natural inactivating mutation in the kinase domain of ILK disrupts ILK protein interactions in the sarcomere, causing a contractile defect in the zebrafish heart. The relatively subtle phenotype of mutant ILK hearts, compared with ILK-ablated hearts, suggests multiple cardiac ILK functions. Cardiac-specific expression of ILK in transgenic mice induces a hypertrophic program, pointing to ILK as a proximal regulator of multiple hypertrophic signal transduction pathways. ILK protein interactions may also be important in mediating postinfarct cell migration and myocardial repair.