tbuckley/cabot-search huggingface dataset:
Recreational football for disease prevention and treatment in untrained men: a narrative review examining cardiovascular health, lipid profile, body composition, muscle strength and functional capacity
Authors: Jens Bangsbo, Peter Riis Hansen, Jiri Dvorak, Peter Krustrup
Journal: British Journal of Sports Medicine (2015)

Over the past 10 years, researchers have studied the effects of recreational football training as a health-promoting activity for participants across the lifespan. This has important public health implications as over 400 million people play football annually. Results from the first randomised controlled trial, published in the BJSM in January 2009, showed that football increased maximal oxygen uptake and muscle and bone mass, and lowered fat percentage and blood pressure, in untrained men, and since then more than 70 articles about football for health have been published, including publications in two supplements of the Scandinavian Journal of Medicine and Science in Sports in 2010 and 2014, prior to the FIFA World Cup tournaments in South Africa and Brazil. While studies of football training effects have also been performed in women and children, this article reviews the current evidence linking recreational football training with favourable effects in the prevention and treatment of disease in adult men.
Basoluminal Carcinoma: A New Biologically and Prognostically Distinct Entity Between Basal and Luminal Breast Cancer
Authors: Mervi Laakso, Minna Tanner, Jonas Nilsson, Tom Wiklund, Björn Erikstein, Pirkko Kellokumpu-Lehtinen, Per Malmström, Nils Wilking, Jonas Bergh, Jorma Isola
Journal: Clinical Cancer Research (2006)

Abstract Purpose: Breast carcinomas expressing basal epithelium cytokeratins constitute a tumor subgroup that is typically hormone receptor negative and shows a distinct gene expression profile. Based on variable basal cytokeratin immunostaining patterns, we hypothesized that the “basal phenotype” tumor group may comprise more than one biological entity. Experimental Design: Basal cytokeratins 5 and 14 (CK5/14) were stained by immunohistochemistry and the percentage of positive cells was defined by image analysis. The results thus obtained were compared with clinicopathologic characteristics and relapse-free survival. Results: Of the 506 breast tumors, 53 (10.5%) showed immunoreactivity for CK5/14. Basal cytokeratin expression showed up as two microscopically distinguishable subtypes, i.e., a uniformly positive type (“basal”) and a partially positive type (“basoluminal”) often displaying a checkerboard-type intratumoral heterogeneity. These subgroups could also be separated with a third basal cytokeratin (CK17, P &amp;lt; 0.0001). Both basal and basoluminal subtypes were hormone receptor negative and of high grade, but differed with respect to the Ki-67 labeling index (P = 0.0014), vimentin (P = 0.005), and c-kit (P = 0.02), which were more frequently expressed in basal than in basoluminal tumors. In contrast, the amplification of HER-2 was found almost exclusively in the basoluminal subgroup (P = 0.009). Compared with the basal tumors, basoluminal tumors associated with significantly shorter relapse-free survival (P = 0.01), which was not explained by their more frequent HER-2 amplification. Conclusions: We conclude that the intratumoral heterogeneity in basal cytokeratin expression can be used to define two distinct breast cancer subtypes, basal and basoluminal, with distinctive features related to proliferation activity, oncogene and biomarker status, and patient survival.
An Individual Person Data Meta-Analysis of Preoperative Magnetic Resonance Imaging and Breast Cancer Recurrence
Authors: Nehmat Houssami, Robin Turner, Petra Macaskill, Lindsay W. Turnbull, David R. McCready, Todd M. Tuttle, Neha Vapiwala, Lawrence J. Solin
Journal: Journal of Clinical Oncology (2014)

There is little consensus regarding preoperative magnetic resonance imaging (MRI) in breast cancer (BC). We examined the association between preoperative MRI and local recurrence (LR) as primary outcome, as well as distant recurrence (DR), in patients with BC.An individual person data (IPD) meta-analysis, based on preoperative MRI studies that met predefined eligibility criteria, was performed. Survival analysis (Cox proportional hazards modeling) was used to investigate time to recurrence and to estimate the hazard ratio (HR) for MRI. We modeled the univariable association between LR (or DR) and MRI, and covariates, and fitted multivariable models to estimate adjusted HRs. Sensitivity analysis was based on women who had breast conservation with radiotherapy.Four eligible studies contributed IPD on 3,180 affected breasts in 3,169 subjects (median age, 56.2 years). Eight-year LR-free survival did not differ between the MRI (97%) and no-MRI (95%) goups (P = .87), and the multivariable model showed no significant effect of MRI on LR-free survival: HR for MRI (versus no-MRI) was 0.88 (95% CI, 0.52 to 1.51; P = .65); age, margin status, and tumor grade were associated with LR-free survival (all P < .05). HR for MRI was 0.96 (95% CI, 0.52 to 1.77; P = .90) in sensitivity analysis. Eight-year DR-free survival did not differ between the MRI (89%) and no-MRI (93%) groups (P = .37), and the multivariable model showed no significant effect of MRI on DR-free survival: HR for MRI (v no-MRI) was 1.18 (95% CI, 0.76 to 2.27; P = .48) or 1.31 (95% CI, 0.76 to 2.27; P = .34) in sensitivity analysis.Preoperative MRI for staging the cancerous breast does not reduce the risk of LR or DR.
Beneficial effects of air inclusions on the performance of ethylene vinyl acetate (EVA) mouthguard material
Authors: B Westerman, P M Stringfellow, J A Eccleston
Journal: British Journal of Sports Medicine (2002)

Objective: To investigate the impact characteristics of an ethylene vinyl acetate (EVA) mouthguard material with regulated air inclusions, which included various air cell volumes and wall thickness between air cells. In particular, the aim was to identify the magnitude and direction of forces within the impacts. Method: EVA mouthguard material, 4 mm thick and with and without air inclusions, was impacted with a constant force impact pendulum with an energy of 4.4 J and a velocity of 3 m/s. Transmitted forces through the EVA material were measured using an accelerometer, which also allowed the determination of force direction and magnitude within the impacts. Results: Statistically significant reductions in the transmitted forces were observed with all the air inclusion materials when compared with EVA without air inclusions. Maximum transmitted force through one air inclusion material was reduced by 32%. Force rebound was eliminated in one material, and reduced second force impulses were observed in all the air inclusion materials. Conclusion: The regulated air inclusions improved the impact characteristics of the EVA mouthguard material, the material most commonly used in mouthguards world wide.
An Oral Spleen Tyrosine Kinase (Syk) Inhibitor for Rheumatoid Arthritis
Authors: Michael E. Weinblatt, Arthur Kavanaugh, Mark C. Genovese, Theresa K. Musser, Elliott B. Grossbard, Daniel B. Magilavy
Journal: New England Journal of Medicine (2010)

Spleen tyrosine kinase (Syk) is an important modulator of immune signaling. The objective of this phase 2 study was to evaluate the efficacy and safety of R788, an oral inhibitor of Syk, in patients with active rheumatoid arthritis despite methotrexate therapy.We enrolled 457 patients who had active rheumatoid arthritis despite long-term methotrexate therapy in a 6-month, double-blind, placebo-controlled trial. The primary outcome was the American College of Rheumatology (ACR) 20 response (which indicates at least a 20% reduction in the number of both tender and swollen joints and improvement in at least three of five other criteria) at month 6.R788, at a dose of 100 mg twice daily and at a dose of 150 mg once daily, was significantly superior to placebo at month 6 (ACR 20 response rates of 67% and 57%, respectively, vs. 35%; P<0.001 for the comparison of both doses with placebo). It was also significantly superior with respect to ACR 50, which indicates at least a 50% improvement (43% and 32% vs. 19%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.007 for the comparison of the 150-mg dose with placebo) and ACR 70 (28% and 14% vs. 10%; P<0.001 for the comparison of the 100-mg dose with placebo, P=0.34 for the comparison of the 150-mg dose with placebo). A clinically significant effect was noted by the end of the first week of treatment. Adverse effects included diarrhea (in 19% of subjects taking the 100-mg dose of R788 vs. 3% of those taking placebo), upper respiratory infections (14% vs. 7%), and neutropenia (6% vs. 1%). R788 was associated with an increase in systolic blood pressure of approximately 3 mm Hg between baseline and month 1, as compared with a decrease of 2 mm Hg with placebo; 23% of the patients taking R788 vs. 7% of the patients receiving placebo required the initiation of or a change in antihypertensive therapy.In this phase 2 study, a Syk inhibitor reduced disease activity in patients with rheumatoid arthritis; adverse events included diarrhea, hypertension, and neutropenia. Additional studies will be needed to further assess the safety and efficacy of Syk-inhibition therapy in patients with rheumatoid arthritis. (Funded by Rigel; ClinicalTrials.gov number, NCT00665925.)
Induction of de novo bone formation in the beagle. A novel effect of aluminum.
Authors: L D Quarles, H J Gitelman, M K Drezner
Journal: Journal of Clinical Investigation (1988)

To define the primary effects of aluminum on bone in the mammalian species, we examined the dose/time-dependent actions of aluminum in normal beagles. Administration of low dose aluminum (0.75 mg/kg) significantly elevated the serum aluminum (151.7 +/- 19.9 micrograms/liter) compared with that in controls (4.2 +/- 1.35 micrograms/liter) but did not alter the calcium, creatinine, or parathyroid hormone. After 8 wk of therapy, bone biopsies displayed reduced bone resorption (2.6 +/- 0.63 vs. 4.5 +/- 0.39%) and osteoblast covered bone surfaces (2.02 +/- 0.51 vs. 7.64 +/- 1.86%), which was indicative of low turnover. In contrast, prolonged treatment resulted in increased bone volume and trabecular number (38.9 +/- 1.35 vs. 25.2 +/- 2.56% and 3.56 +/- 0.23 vs. 2.88 +/- 0.11/mm) which was consistent with uncoupled bone formation. Administration of higher doses of aluminum (1.20 mg/kg) increased the serum aluminum further (1242.3 +/- 259.8 micrograms/liter) but did not affect calcium, creatinine, or parathyroid hormone. However, after 8 wk of treatment, bone biopsies displayed changes similar to those after long-term, low-dose therapy. In this regard, an increased trabecular number (3.41 +/- 0.18/mm) and bone volume (36.5 +/- 2.38%) again provided evidence of uncoupled bone formation. In contrast, in this instance poorly mineralized woven bone contributed to the enhanced bone volume. High-dose treatment for 16 wk further enhanced bone volume (50.4 +/- 4.61%) and trabecular number (3.90 +/- 0.5/mm). These observations illustrate that aluminum may stimulate uncoupled bone formation and induce a positive bone balance. This enhancement of bone histogenesis contrasts with the effects of pharmacologic agents that alter the function of existing bone remodeling units.
Book: Spike Island: The Memory of a Military Hospital
Authors: A. Paton
Journal: BMJ (2002)

Philip Hoare Fourth Estate, £8.99, pp 423 ISBN 1 84115 294 3 ——————— Rating: ![Graphic][1]</img> On 19 May 1856 Queen Victoria sailed across the Solent from Osborne House on the Isle of Wight to lay the foundation stone of the Royal Victoria Hospital at Netley. The site was on a spit of land—between the Itchen and Hamble rivers overlooking Southampton Water—known as Spike Island, a name which Philip Hoare, who grew up nearby, says is shrouded in mystery, although a glance at the map suggests that the area looks like a spike. The dimensions of the new hospital were awesome: said to … [1]: /embed/inline-graphic-1.gif
Recent attempts at RNAi‐mediated P‐glycoprotein downregulation for reversal of multidrug resistance in cancer
Authors: Meysam Abbasi, Afsaneh Lavasanifar, Hasan Uludaˇ
Journal: Medicinal Research Reviews (2011)

Multidrug resistance (MDR) is among the major mechanisms leading to failure in chemotherapy of cancer patients. The ATP-binding cassette proteins are major contributors to MDR, involved in the active efflux of xenobiotics out of cancer cells. Among them, P-glycoprotein (P-gp) is the most dominant protein involved in the efflux of drugs. For more than 30 years, scientists have searched for the ideal P-gp inhibitor to modulate drug resistance activity of P-gp. This inhibitor should be tissue and cell specific with side effects on other tissues, must not provoke immune responses from the host, should provide sustained inhibition, and must be synthesized readily with low cost. Chemical P-gp inhibitors tested to date, have shown nonspecific toxic effects limiting their clinical applications. Sequence-specific P-gp gene silencing by RNA interference (RNAi) may provide a more effective approach for downregulation of specific protein targets due to high specificity, limited toxicity and immunogenicity, and relative ease in synthesis. RNAi can be implemented by delivery of synthetic small interfering RNAs (siRNAs) or by gene expression of short hairpin RNAs using gene expressing vectors. Specific delivery systems and expression vectors have been designed for this purpose and many researchers have explored their effectiveness for P-gp downregulation. In this report, we review the efficiency of various methods for siRNA delivery and transfection for P-gp downregulation in cancer cells for MDR reversal. Novel ideas and observations by different research groups were discussed for future improvement in this essential field.
Activation of Spinal NF‐κB/p65 Contributes to Peripheral Inflammation and Hyperalgesia in Rat Adjuvant‐Induced Arthritis
Authors: Jian‐Gang Luo, Xu‐Li Zhao, Wei‐Cheng Xu, Xue‐Jun Zhao, Jun‐Nan Wang, Xiao‐Wen Lin, Tao Sun, Zhi‐Jian Fu
Journal: Arthritis & Rheumatology (2013)

Objective It is known that noxious stimuli from inflamed tissue may increase the excitability of spinal dorsal horn neurons (a process known as central sensitization), which can signal back and contribute to peripheral inflammation. However, the underlying mechanisms have yet to be fully defined. A number of recent studies have indicated that spinal NF‐κB/p65 is involved in central sensitization, as well as pain‐related behavior. Thus, the aim of this study was to determine whether NF‐κB/p65 can facilitate a peripheral inflammatory response in rat adjuvant‐induced arthritis (AIA). Methods Lentiviral vectors encoding short hairpin RNAs that target NF‐κB/p65 (LV‐shNF‐κB/p65) were constructed for gene silencing. The spines of rats with AIA were injected with LV‐shNF‐κB/p65 on day 3 or day 10 after treatment with Freund's complete adjuvant (CFA). During an observation period of 20 days, pain‐related behavior, paw swelling, and joint histopathologic changes were evaluated. Moreover, the expression levels of spinal tumor necrosis factor α (TNFα), interleukin‐1β (IL‐1β), and cyclooxygenase 2 (COX‐2) were assessed on day 14 after CFA treatment. Results The presence of peripheral inflammation in rats with AIA induced an increase in NF‐κB/p65 expression in the spinal cord, mainly in the dorsal horn neurons and astrocytes. Delivery of LV‐shNF‐κB/p65 to the spinal cord knocked down the expression of NF‐κB/p65 and significantly attenuated hyperalgesia, paw edema, and joint destruction. In addition, spinal delivery of LV‐shNF‐κB/p65 reduced the overexpression of spinal TNFα, IL‐1β, and COX‐2. Conclusion These findings indicate that spinal NF‐κB/p65 plays an important role in the initiation and development of both peripheral inflammation and hyperalgesia. Thus, inhibition of spinal NF‐κB/p65 expression may provide a potential treatment to manage painful inflammatory disorders.
Protective Role of Hypoxia-Inducible Factor-2α against Ischemic Damage and Oxidative Stress in the Kidney
Authors: Ichiro Kojima, Tetsuhiro Tanaka, Reiko Inagi, Hideki Kato, Toshiharu Yamashita, Ai Sakiyama, Osamu Ohneda, Norihiko Takeda, Masataka Sata, Toshio Miyata, Toshiro Fujita, Masaomi Nangaku
Journal: Journal of the American Society of Nephrology (2007)

Central to cellular responses to hypoxic environment is the hypoxia-inducible factor (HIF) transcriptional control system. A role for HIF-2α was investigated in a model of renal ischemia-reperfusion injury (IRI) associated with oxidative stress using HIF-2α knockdown mice. In these mice, HIF-2α expression was approximately one half that of wild-type mice, whereas HIF-1α expression was equivalent. HIF-2α knockdown mice were more susceptible to renal IRI, as indicated by elevated blood urea nitrogen levels and semiquantitative histologic analysis. Immunostaining with markers of oxidative stress showed enhanced oxidative stress in the kidney of HIF-2α knockdown mice, which was associated with peritubular capillary loss. Real-time quantitative PCR analysis showed decreased expression of antioxidative stress genes in the HIF-2α knockdown kidneys. Studies that used small interference RNA confirmed regulation of the antioxidative stress genes in cultured endothelial cells. Although HIF-2α knockdown mice were anemic, serum erythropoietin levels were not significantly increased, reflecting inappropriate response to anemia as a result of HIF-2α knockdown. Experiments that used hemodiluted mice with renal ischemia demonstrated that anemia of this degree did not affect susceptibility to ischemia. Knockdown of HIF-2α in inflammatory cells by bone marrow transplantation experiments demonstrated that HIF-2α in inflammatory cells did not contribute to susceptibility to renal IRI. Restoration of HIF-2α in endothelium by intercrossing with Tie1-Cre mice ameliorated renal injury by IRI, demonstrating a specific role of endothelial HIF-2α. These results suggest that HIF-2α in the endothelium has a protective role against ischemia of the kidney <i>via</i> amelioration of oxidative stress.
Effects of Imipramine and Dextroamphetamine on Behavior of Neuropsychiatrically Impaired Children
Authors: BERTRAND G. WINSBERG, IRV BIALER, SAMUEL KUPIETZ, JACK TOBIAS
Journal: American Journal of Psychiatry (1972)

This study assessed the comparative effectiveness of imipramine, placebo, and dextroamphetamine as therapeutic agents for the control of hyperkinetic and aggressive behaviors in children. Behavioral change under the drug conditions was evaluated using a 39-item behavior rating scale. The results indicate that imipramine is an effective agent for the control of hyperactivity and aggression in behaviorally impaired children. Implications of the findings for clinical application in pediatric psychopharmacology are presented and discussed.
Construction of Optimized Bispecific Antibodies for Selective Activation of the Death Receptor CD95
Authors: Tanja Herrmann, Ludger Große-Hovest, Tina Otz, Peter H. Krammer, Hans-Georg Rammensee, Gundram Jung
Journal: Cancer Research (2008)

Abstract We have previously reported that bispecific antibodies directed to different target antigens on lymphoma cells and to the death receptor CD95/Fas/Apo-1 selectively kill these cells, thus providing an attractive strategy for the selective stimulation of CD95 on the surface of tumor cells. Here, we further explore the general applicability of this approach under more stringent conditions using various bispecific antibodies directed to different target antigens on glioblastoma cells which express relatively low levels of CD95. We found that bispecific CD95 antibodies targeting the neuronal glial antigen-2 induce CD95-mediated apoptosis selectively in glioblastoma cells expressing this target antigen. A recombinant bispecific single-chain antibody was as effective as a chemically hybridized F(ab′)2 fragment with identical specificities. In contrast, a bispecific F(ab′)2 fragment binding to the epidermal growth factor receptor on the glioblastoma cells failed to induce apoptosis. This is most likely due to the exclusively unicellular binding of this particular fragment to target cells expressing both the epidermal growth factor receptor and CD95. If this type of binding in a cis configuration is favored by a particular bispecific antibody, rather than a bicellular binding in trans, effective cross-linking of CD95 does not occur and apoptosis is not induced. To facilitate bicellular binding in a trans configuration, we constructed a bispecific antibody directed to the extracellular matrix protein tenascin. As expected, this reagent was the most effective of all the antibodies tested. The presence of sensitizing reagents such as cycloheximide and various cytostatic drugs further enhanced antibody-mediated killing of the tumor cells. We believe that these results may point the way to a successful application of bispecific CD95 antibodies in experimental tumor therapy. [Cancer Res 2008;68(4):1221–7]
Lipid Depletion in Atheromatous Coronary Arteries in Rhesus Monkeys after Regression Diets
Authors: MARK L. ARMSTRONG, MARJORIE B. MEGAN
Journal: Circulation Research (1972)

Lipids were measured in the coronary arteries of monkeys on an atherogenic diet and in the arteries of matched monkeys on the atherogenic diet followed by regression diets. Cholesterol content was 51 mg/g dry weight in the arteries of monkeys with atheromatosis; after 40 months on the regression diets it was 18 mg/g. Cholesteryl ester was 69% lower and free cholesterol 53% lower after the regression diets. Decreases in triglycerides and phospholipids were not significant. The cholesterol content of the arteries of two monkeys autopsied after 20 months on the regression diets was close to the mean value after 40 months. The data show that cholesterol in both its free form and its ester form is depleted from experimentally induced coronary atheromatosis by dietary regression regimens. The data also suggest that most of the cholesterol depletion occurs during the first half of regression; the susceptibility of the residual excess arterial cholesterol to mobilization from the vessel wall by dietary means is questionable.