tbuckley/cabot-search huggingface dataset:
Mechanical properties of the patellar tendon in elite volleyball players with and without patellar tendinopathy
Authors: Christian Helland, Jens Bojsen-Møller, Truls Raastad, Olivier R Seynnes, Marie M Moltubakk, Vidar Jakobsen, Håvard Visnes, Roald Bahr
Journal: British Journal of Sports Medicine (2013)

Background Although differences in mechanical properties between symptomatic and healthy tendons have been observed for the Achilles tendon, the impact of tendinopathy on patellar tendon mechanics is not fully documented. The aim of the present case–control study was to assess the mechanical properties of the tendon and jump performance in elite athletes with and without patellar tendinopathy. Methods We identified 17 male volleyball players with patellar tendinopathy and 18 healthy matched controls from a 5-year prospective cohort study on junior elite volleyball players. Outcome variables included three measures of maximal vertical jump performance and ultrasound-based assessments of patellar tendon cross-sectional area, stiffness and Young's modulus. Results The proximal cross-sectional area of the patellar tendon was significantly larger in the tendinopathic group (133±11 vs 112±9 mm 2 , respectively; p&lt;0.001). Pathological tendons presented lower stiffness (2254±280 vs 2826±603 N/mm, respectively; p=0.006) and Young's modulus (0.99±0.16 vs 1.17±0.25 GPa, respectively; p=0.04) than healthy tendons. However, the difference between the countermovement jump height and the squat jump height (3.4±2.2 vs 1.2±1.5 cm, p=0.005) was significantly higher in the tendinopathic group compared with the control group. Conclusions Patellar tendinopathy is associated with a decrease in the mechanical and material properties of the tendon in elite athletes subjected to a high volume of jumping activity. However, compared with their healthy counterparts, tendinopathic volleyball players have a better ability to utilise the stretch-shortening cycle when jumping.
Visceral sensation and emotion: a study using hypnosis
Authors: L A Houghton
Journal: Gut (2002)

<b>Background and objectives:</b> We have previously shown that hypnosis can be used to study the effect of different emotions on the motility of the gastrointestinal tract. These studies demonstrated that both anger and excitement increased colonic motility while happiness led to a reduction. The purpose of this study was to investigate the effect of hypnotically induced emotion on the visceral sensitivity of the gut. <b>Methods:</b> Sensory responses to balloon distension of the rectum and compliance were assessed in 20 patients with irritable bowel syndrome (IBS) (aged 17–64 years; 17 female) diagnosed by the Rome I criteria. Patients were studied on four separate occasions in random order either awake (control) or in hypnosis, during which anger, happiness, or relaxation (neutral emotion) were induced. <b>Results:</b> Hypnotic relaxation increased the distension volume required to induce discomfort (p=0.05) while anger reduced this threshold compared with relaxation (p&lt;0.05), happiness (p&lt;0.01), and awake conditions (p&lt;0.001). Happiness did not further alter sensitivity from that observed during relaxation. There were no associated changes in rectal compliance or wall tension. <b>Conclusions:</b> Further to our previous observations on motility, this study shows that emotion can also affect an IBS patient's perception of rectal distension and demonstrates the critical role of the mind in modulating gastrointestinal physiology. These results emphasise how awareness of the emotional state of the patient is important when either measuring visceral sensitivity or treating IBS.
CXCL4 Downregulates the Atheroprotective Hemoglobin Receptor CD163 in Human Macrophages
Authors: Christian A. Gleissner, Iftach Shaked, Christian Erbel, Dittmar Böckler, Hugo A. Katus, Klaus Ley
Journal: Circulation Research (2009)

Rationale : CXCL4 is a platelet-derived chemokine that promotes macrophage differentiation from monocytes. Deletion of the PF4 gene that encodes CXCL4 reduces atherosclerotic lesions in ApoE −/− mice. Objective : We sought to study effects of CXCL4 on macrophage differentiation with possible relevance for atherogenesis. Methods and Results : Flow cytometry for expression of surface markers in macrophage colony–stimulating factor (M-CSF)– and CXCL4-induced macrophages demonstrated virtually complete absence of the hemoglobin scavenger receptor CD163 in CXCL4-induced macrophages. mRNA for CD163 was downregulated as early as 2 hours after CXCL4. CD163 protein reached a minimum after 3 days, which was not reversed by treatment of cells with M-CSF. The CXCL4 effect was entirely neutralized by heparin, which bound CXCL4 and prevented CXCL4 surface binding to monocytes. Pretreatment of cells with chlorate, which inhibits glycosaminoglycan synthesis, strongly inhibited CXCL4-dependent downregulation of CD163. Similar to recombinant CXCL4, releasate from human platelets also reduced CD163 expression. CXCL4-differentiated macrophages were unable to upregulate the atheroprotective enzyme heme oxygenase-1 at the RNA and protein level in response to hemoglobin–haptoglobin complexes. Immunofluorescence of human atherosclerotic plaques demonstrated presence of both CD68 + CD163 + and CD68 + CD163 − macrophages. PF4 and CD163 gene expression within human atherosclerotic lesions were inversely correlated, supporting the in vivo relevance of CXCL4-induced downregulation of CD163. Conclusions : CXCL4 may promote atherogenesis by suppressing CD163 in macrophages, which are then unable to upregulate the atheroprotective enzyme heme oxygenase-1 in response to hemoglobin.
Prevalence and predictors of disability in valued life activities among individuals with rheumatoid arthritis
Authors: P P Katz
Journal: Annals of the Rheumatic Diseases (2005)

To identify the prevalence of disability in a wide range of life activities and identify factors associated with such disability using the Verbrugge and Jette disablement model as a framework.Data were from a panel study of 548 individuals with rheumatoid arthritis, interviewed annually by telephone. Valued life activity (VLA) disability was assessed using a 26-item scale rating difficulty in carrying out each activity. Three types of summary measure were calculated: activities unable to perform, activities affected, and mean difficulty. Subscale scores were also calculated, corresponding to obligatory, committed, and discretionary activities, as defined in the disablement model. Disease status measures were examined as predictors of VLA disability using multiple regression analyses.Half the subjects were unable to do at least one VLA. Approximately 2%, 31.3%, and 40.2% were unable to do at least one obligatory, committed, and discretionary activity, respectively. Almost all (95%) reported at least one VLA affected by rheumatoid arthritis; 68.4%, 91.4%, and 92.5% reported at least one obligatory, committed, and discretionary activity, respectively, affected. Disease status measures were robust predictors of VLA disability, accounting for 22-47% of the variation in VLA disability (with one exception). Adding the health assessment questionnaire (HAQ) to these models increased (p<0.0001) all model R2 values. HAQ score mediated the effects of many disease measures, consistent with the disablement model.VLA disability was common, with more disability noted in committed and discretionary than obligatory activities. Because VLA disability has been linked to psychological wellbeing in previous studies, identification of factors that may protect against such disability is important.
Carbon dioxide laser treatment of extramammary Paget's disease guided by photodynamic diagnosis
Authors: None Becker-Wegerich, None Fritsch, None Schulte, None Megahed, None Neuse, None Goerz, None Stahl, None Ruzicka
Journal: British Journal of Dermatology (1998)

Extramammary Paget's disease (EPD) is a rare malignancy occurring mainly in apocrine gland-bearing regions. Surgical excision is the treatment of choice. This may be very difficult or even impossible if the disease is widespread or located in a critical anatomical site. We report on the successful treatment of a 71-year-old man with EPD in the suprapubic region with CO2 laser guided by photodynamic diagnosis.
Factors for Hematopoietic Toxicity of Carboplatin: Refining the Targeting of Carboplatin Systemic Exposure
Authors: Antonin Schmitt, Laurence Gladieff, Céline M. Laffont, Alexandre Evrard, Jean-Christophe Boyer, Amélie Lansiaux, Christine Bobin-Dubigeon, Marie-Christine Etienne-Grimaldi, Michèle Boisdron-Celle, Mireille Mousseau, Frédéric Pinguet, Anne Floquet, Eliane M. Billaud, Catherine Durdux, Chantal Le Guellec, Julien Mazières, Thierry Lafont, Florent Ollivier, Didier Concordet, Etienne Chatelut
Journal: Journal of Clinical Oncology (2010)

Purpose Area under the curve (AUC) dosing is routinely carried out for carboplatin, but the chosen target AUC values remain largely empirical. This multicenter pharmacokinetic-pharmacodynamic (PK-PD) study was performed to determine the covariates involved in the interindividual variability of carboplatin hematotoxicity that should be considered when choosing individual target AUCs. Patients and Methods Three hundred eighty-three patients received carboplatin as part of established regimens. A semi-physiologic population PK-PD model was applied to describe separately the time course of absolute neutrophil and platelet counts using NONMEM software. The plasma ultrafiltrable carboplatin concentration (C Carbo ) was assumed to inhibit the proliferation of blood cell precursors through a linear model: drug effect = slope × C Carbo . The slope corresponds to the patients' sensitivity to carboplatin hematotoxicity. The relationships between the patients' sensitivity to the neutropenic or thrombopenic effects of carboplatin and various covariates, including associated chemotherapies, demographic, biologic, and pharmacogenetic data, were studied. Results The sensitivity of carboplatin-induced thrombocytopenia decreased in the case of concomitant paclitaxel chemotherapy (slope decreased by 24%), whereas it increased with coadministration of etoposide and gemcitabine (slope increased by 45% and 133%, respectively). For neutropenia, the sensitivity increased when carboplatin was combined with other cytotoxics (slope increased by 76%). Conclusion This study provides useful information to clinicians to better estimate the hematopoietic toxicity of carboplatin and thus choose more rationally carboplatin target AUCs as a function of pretreatment or concomitantly administered chemotherapies. For example, an AUC of 5 mg/mL · min is associated with a risk of grade 3 or 4 thrombocytopenia of 2% in combination with paclitaxel versus 38% with gemcitabine in a non-pretreated patient.
Computational and transcriptional evidence for microRNAs in the honey bee genome
Authors: Daniel B Weaver, Juan M Anzola, Jay D Evans, Jeffrey G Reid, Justin T Reese, Kevin L Childs, Evgeny M Zdobnov, Manoj P Samanta, Jonathan Miller, Christine G Elsik
Journal: Genome biology (2007)

Abstract Background Non-coding microRNAs (miRNAs) are key regulators of gene expression in eukaryotes. Insect miRNAs help regulate the levels of proteins involved with development, metabolism, and other life history traits. The recently sequenced honey bee genome provides an opportunity to detect novel miRNAs in both this species and others, and to begin to infer the roles of miRNAs in honey bee development. Results Three independent computational surveys of the assembled honey bee genome identified a total of 65 non-redundant candidate miRNAs, several of which appear to have previously unrecognized orthologs in the Drosophila genome. A subset of these candidate miRNAs were screened for expression by quantitative RT-PCR and/or genome tiling arrays and most predicted miRNAs were confirmed as being expressed in at least one honey bee tissue. Interestingly, the transcript abundance for several known and novel miRNAs displayed caste or age-related differences in honey bees. Genes in proximity to miRNAs in the bee genome are disproportionately associated with the Gene Ontology terms 'physiological process', 'nucleus' and 'response to stress'. Conclusion Computational approaches successfully identified miRNAs in the honey bee and indicated previously unrecognized miRNAs in the well-studied Drosophila melanogaster genome despite the 280 million year distance between these insects. Differentially transcribed miRNAs are likely to be involved in regulating honey bee development, and arguably in the extreme developmental switch between sterile worker bees and highly fertile queens.
Comparison of energy expenditure in adolescents when playing new generation and sedentary computer games: cross sectional study
Authors: Lee Graves, Gareth Stratton, N D Ridgers, N T Cable
Journal: BMJ (2007)

<b>Objective</b> To compare the energy expenditure of adolescents when playing sedentary and new generation active computer games. <b>Design</b> Cross sectional comparison of four computer games. <b>Setting</b> Research laboratories. <b>Participants</b> Six boys and five girls aged 13-15 years. <b>Procedure</b> Participants were fitted with a monitoring device validated to predict energy expenditure. They played four computer games for 15 minutes each. One of the games was sedentary (XBOX 360) and the other three were active (Wii Sports). <b>Main outcome measure</b> Predicted energy expenditure, compared using repeated measures analysis of variance. <b>Results</b> Mean (standard deviation) predicted energy expenditure when playing Wii Sports bowling (190.6 (22.2) kJ/kg/min), tennis (202.5 (31.5) kJ/kg/min), and boxing (198.1 (33.9) kJ/kg/min) was significantly greater than when playing sedentary games (125.5 (13.7) kJ/kg/min) (P&lt;0.001). Predicted energy expenditure was at least 65.1 (95% confidence interval 47.3 to 82.9) kJ/kg/min greater when playing active rather than sedentary games. <b>Conclusions</b> Playing new generation active computer games uses significantly more energy than playing sedentary computer games but not as much energy as playing the sport itself. The energy used when playing active Wii Sports games was not of high enough intensity to contribute towards the recommended daily amount of exercise in children.
Clinical and genetic features of pediatric acute lymphoblastic leukemia in Down syndrome in the Nordic countries
Authors: Catarina Lundin, Erik Forestier, Mette Klarskov Andersen, Kirsi Autio, Gisela Barbany, Lucia Cavelier, Irina Golovleva, Sverre Heim, Kristiina Heinonen, Randi Hovland, Johann H Johannsson, Eigil Kjeldsen, Ann Nordgren, Lars Palmqvist, Bertil Johansson
Journal: Journal of Hematology & Oncology (2014)

Children with Down syndrome (DS) have an increased risk for acute lymphoblastic leukemia (ALL). Although previous studies have shown that DS-ALL differs clinically and genetically from non-DS-ALL, much remains to be elucidated as regards genetic and prognostic factors in DS-ALL. To address clinical and genetic differences between DS-ALL and non-DS-ALL and to identify prognostic factors in DS-ALL, we ascertained and reviewed all 128 pediatric DS-ALL diagnosed in the Nordic countries between 1981 and 2010. Their clinical and genetic features were compared with those of the 4,647 B-cell precursor (BCP) ALL cases diagnosed during the same time period. All 128 DS-ALL were BCP ALL, comprising 2.7% of all such cases. The 5-year event-free survival (EFS) and overall survival (OS) were significantly (P = 0.026 and P = 0.003, respectively) worse for DS-ALL patients with white blood cell counts ≥50 × 109/l. The age distributions varied between the DS and non-DS cases, with age peaks at 2 and 3 years, respectively; none of the DS patients had infant ALL (P = 0.029). The platelet counts were lower in the DS-ALL group (P = 0.005). Abnormal karyotypes were more common in non-DS-ALL (P < 0.0001), and there was a significant difference in the modal number distribution, with only 2% high hyperdiploid DS-ALL cases (P < 0.0001). The 5-year EFS and 5-year OS were significantly worse for DS-ALL (0.574 and 0.691, respectively) compared with non-DS-ALL (0.783 and 0.894, respectively) in the NOPHO ALL-1992/2000 protocols (P < 0.001). The present study adds further support for genetic and clinical differences between DS-ALL and non-DS-ALL.
Inhibition of thrombosis by a novel platelet selective S-nitrosothiol compound without hemodynamic side effects
Authors: G Vilahur
Journal: Cardiovascular Research (2004)

Platelet and endothelial production of bioactive nitric oxide (NO) is known to be impaired in acute coronary syndromes, thus compounds that release NO are useful candidates to restore NO-vascular functions. Objective: We have studied whether donation of NO with a novel platelet-selective S-nitrosothiol compound (LA810) at a systemic level can inhibit thrombosis elicited by damaged vessel wall (eroded and disrupted vessel wall) at hemodynamic conditions typical of patent and stenotic coronary arteries. Methods: Thrombogenicity was measured in the porcine experimental model and assessed as platelet–thrombus formation in the ex vivo Badimon perfusion chamber. After baseline perfusions, female pigs (Large White × Landrace) were given intravenous infusion of LA810 or GSNO standard S-nitrosothiol during 2 h. Changes in blood pressure, heart rate and in vitro platelet aggregation were measured. Results: LA810 significantly decreased thrombus formation at any degree of vascular damage and shear rate (p<0.001) without hypotensive side-effects or heart rate variations. In contrast, inhibition of thrombus formation by GSNO required high doses associated to hypotensive episodes. Platelet aggregation induced by collagen was inhibited after nitrosothiol infusion in whole blood (LA810) and platelet rich plasma (LA810 and GSNO). In addition, there was a drug-dependent rise in platelet guanosine 3′,5′-cyclic monophosphate (cGMP) levels. Conclusions: This new anti-ischemic NO-donor (NOd) LA810 that inhibits platelet function without hypotensive side-effects seems a highly efficacious strategy to reduce acute thrombosis triggered by coronary artery disease.
Proteolytic activity in cowshed dust extracts induces C5a release in murine bronchoalveolar lavage fluids which may account for its protective properties in allergic airway inflammation
Authors: Matthias Stiehm, Albrecht Bufe, Marcus Peters
Journal: Thorax (2012)

<h3>Objective</h3> Intranasal application of cowshed dust extract (CDE) during sensitisation in a murine model of experimental asthma leads to a significant alleviation of the clinical parameters of the allergic immune response. However, neither the immunological mechanisms underlying this protective effect nor all of the protective substances included in CDE have yet been described. Recently, complement factor 5a (C5a) receptor signalling has been identified to play a regulatory role in allergic airway disease. Thus we investigated whether CDE can activate the complement system to release biologically active C5a in the lung. <h3>Methods</h3> Proteins included in CDE were identified by mass spectrometry. Complement cleaving activity of a serine protease identified in CDE was validated with the purified enzyme, and the biological activity of the released C5a was determined. C5a was applied in a murine model of allergy to prove its protective impact on allergic airway disease. <h3>Results</h3> CDE induced the release of C5a in murine bronchoalveolar lavages (BAL). We identified a serine protease from the midgut of <i>tenebrio molitor larvae</i> in CDEs which was able to induce the release of biologically active C5a in murine BAL. We applied C5a in different doses to female Balb/c mice during the sensitisation phase and during the first antigen challenge and showed that C5a has the ability to dampen important parameters of allergic airway inflammation, such as infiltration of proinflammatory cells into lung tissue or Th2 cytokine secretion by lung cells. <h3>Conclusions</h3> We conclude that the C5a generating enzyme included in CDE might account for some of the allergy protective effects of CDE by generation of C5a in murine lungs.
Modulation of prostate cancer genetic risk by omega-3 and omega-6 fatty acids
Authors: Isabelle M. Berquin, Younong Min, Ruping Wu, Jiansheng Wu, Donna Perry, J. Mark Cline, Mike J. Thomas, Todd Thornburg, George Kulik, Adrienne Smith, Iris J. Edwards, Ralph D’Agostino, Hao Zhang, Hong Wu, Jing X. Kang, Yong Q. Chen
Journal: Journal of Clinical Investigation (2007)

Although a causal role of genetic alterations in human cancer is well established, it is still unclear whether dietary fat can modulate cancer risk in a predisposed population. Epidemiological studies suggest that diets rich in omega-3 polyunsaturated fatty acids reduce cancer incidence. To determine the influence of fatty acids on prostate cancer risk in animals with a defined genetic lesion, we used prostate-specific Pten-knockout mice, an immune-competent, orthotopic prostate cancer model, and diets with defined polyunsaturated fatty acid levels. We found that omega-3 fatty acids reduced prostate tumor growth, slowed histopathological progression, and increased survival, whereas omega-6 fatty acids had opposite effects. Introducing an omega-3 desaturase, which converts omega-6 to omega-3 fatty acids, into the Pten-knockout mice reduced tumor growth similarly to the omega-3 diet. Tumors from mice on the omega-3 diet had lower proportions of phosphorylated Bad and higher apoptotic indexes compared with those from mice on omega-6 diet. Knockdown of Bad eliminated omega-3-induced cell death, and introduction of exogenous Bad restored the sensitivity to omega-3 fatty acids. Our data suggest that modulation of prostate cancer development by polyunsaturated fatty acids is mediated in part through Bad-dependent apoptosis. This study highlights the importance of gene-diet interactions in prostate cancer.
Early or pre-coeliac mucosa: development of gluten enteropathy.
Authors: B Egan-Mitchell, P F Fottrell, B McNicholl
Journal: Gut (1981)

Duodenal mucosa showed normal morphology, interepithelial lymphocytes, alkaline phosphatase, and sucrase in a girl with growth retardation and iron deficiency, but normal absorption of lactose and xylose after two years of abnormal stools. Mucosal lactase was low. Fourteen months later mucosal damage consistent with coeliac disease was evident, and gluten intolerance was subsequently confirmed by gluten challenge. It is probable that, in some children, the mucosal lesion occurs very gradually, so that at an early stage with normal morphology, suppression of lactase activity and possibly interference with iron absorption may be the only abnormalities.
Diabetes a growing problem in United States
Authors: Janice Hopkins Tanne
Journal: BMJ (2001)

The United States, like many other industrialised countries, faces a diabetes epidemic. “Sixteen million Americans—6% of the population—have diabetes, and one third of them don't even realise it; 800 000 will be diagnosed this year. It is the leading cause of blindness, end stage renal disease, and leg amputations and the seventh leading cause of death,” Dr Susan Hershberg Adelman told a seminar in New York last week.

Dr Adelman, a trustee of the American Medical Association, spoke at a meeting jointly sponsored by that association, the American Diabetes Association, and the pharmaceutical firm Aventis.

Worldwide, about 140 million …
Incidence and outcome of cytomegalovirus infections following nonmyeloablative compared with myeloablative allogeneic stem cell transplantation, a matched control study
Authors: Christian Junghanss, Michael Boeckh, Rachel A. Carter, Brenda M. Sandmaier, Michael B. Maris, David G. Maloney, Thomas Chauncey, Peter A. McSweeney, Marie-Térèse Little, Lawrence Corey, Rainer Storb
Journal: Blood (2002)