tbuckley/cabot-search huggingface dataset:
Abstract P5-10-16: Iodine/Anthracyclines Is the Best Combination Against Mammary Cancer. Antineoplastic Synergism and Cardioprotection
Authors: Y Alfaro, G Delgado, C. Aceves
Journal: Cancer Research (2010)

Abstract Mammary cancer is the world's most common malignant neoplasia for women. Recently, the mortality for breast cancer has fallen due principally to early detection and to use of neoadjuvant chemotherapy. Anthracycline antibiotics are the most commonly used anticancer drugs, and Doxorubicin (DOX) is the first choice to treat mammary cancer. Nevertheless, its use has limited by its cadiotoxic side effects, which are generated by free radicals. Our studies in methylnitrosourea (MNU)-induced mammary cancer models have shown that supplementation with moderately high doses of molecular iodine (I2) exhibits two distinctive and beneficial effects: antineoplastic and antioxidant. In the present work we explored these dual characteristic of I2 (0.05%) as an adjuvant to DOX16 (therapeutic dose of 16 mg/kg) and DOX8 (8 mg/kg) in female Sprague Dawley rats (200 g) with tumors induced by a single dose of 50 mg MNU per Kg. Iodine intake is initiated 2 days before DOX application and continues up to sacrifice 7 days later. The following parameters were registered: body weight, tumor size, tumor proliferation rate (proliferating cell nuclear antigen, PCNA), serum creatinine kinase-MB activity (CK-MB), cardiac lipoperoxidation (cLPO), and cardiac catalase activity (cCAT). Values correspond to mean± SD. Different superscripts represent significant (p≥0.05). Tumor reduction was greater in the DOX16 + I2 group than in the DOX 16 group (75% vs. 50%, respectively), and was associated with a significantly greater decrease in the rate of tumor cell proliferation (25% vs 10% decrease in PCNA-positive cells), showing the synergistic effect of I2. In contrast, at both DOX doses, the DOX + I2, groups had lower body weight loss and less cardiac damage (CK-MB; 280% vs 100%, cLPO 100% vs 0%) than with DOX alone. cCAT was not changed by any of the treatments.Conclusions: Iodine acts as an adjuvant by significantly enhancing the antiproliferative effect of DOX at a therapeutic dose (DOX16), and it exerts significant general and cardiac protective effects that do not involve catalase activation. Cellular and molecular mechanisms involved in these dual effects of iodine are currently being analyzed. The authors thank Drs. Mauricio Diaz, Marcela Lizano, and Brenda Anguiano as well as Biol. Felipe Ortiz for their technical assistance and Leonor Casanova for academic supports. We also thank Dr. Dorothy Pless for proof-reading. Supported in part by PAPIIT/UNAM 201210 and CONACYT 78955 and 47928/47928. Figure available in online version. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P5-10-16.
Brief Report: Association of Myositis Autoantibodies, Clinical Features, and Environmental Exposures at Illness Onset With Disease Course in Juvenile Myositis
Authors: G. Esther A. Habers, Adam M. Huber, Gulnara Mamyrova, Ira N. Targoff, Terrance P. O'Hanlon, Sharon Adams, Janardan P. Pandey, Chantal Boonacker, Marco van Brussel, Frederick W. Miller, Annet van Royen‐Kerkhof, Lisa G. Rider
Journal: Arthritis & Rheumatology (2015)

To identify early factors associated with disease course in patients with juvenile idiopathic inflammatory myopathies (IIMs).Univariable and multivariable multinomial logistic regression analyses were performed in a large juvenile IIM registry (n = 365) and included demographic characteristics, early clinical features, serum muscle enzyme levels, myositis autoantibodies, environmental exposures, and immunogenetic polymorphisms.Multivariable associations with chronic or polycyclic courses compared to a monocyclic course included myositis-specific autoantibodies (multinomial odds ratio [OR] 4.2 and 2.8, respectively), myositis-associated autoantibodies (multinomial OR 4.8 and 3.5), and a documented infection within 6 months of illness onset (multinomial OR 2.5 and 4.7). A higher overall clinical symptom score at diagnosis was associated with chronic or monocyclic courses compared to a polycyclic course. Furthermore, severe illness onset was associated with a chronic course compared to monocyclic or polycyclic courses (multinomial OR 2.1 and 2.6, respectively), while anti-p155/140 autoantibodies were associated with chronic or polycyclic courses compared to a monocyclic course (multinomial OR 3.9 and 2.3, respectively). Additional univariable associations of a chronic course compared to a monocyclic course included photosensitivity, V-sign or shawl sign rashes, and cuticular overgrowth (OR 2.2-3.2). The mean ultraviolet index and highest ultraviolet index in the month before diagnosis were associated with a chronic course compared to a polycyclic course in boys (OR 1.5 and 1.3), while residing in the Northwest was less frequently associated with a chronic course (OR 0.2).Our findings indicate that myositis autoantibodies, in particular anti-p155/140, and a number of early clinical features and environmental exposures are associated with a chronic course in patients with juvenile IIM. These findings suggest that early factors, which are associated with poorer outcomes in juvenile IIM, can be identified.
POST-MARKET EVALUATION OF A FULLY REPOSITIONABLE AND RETRIEVABLE AORTIC VALVE IN 750 PATIENTS TREATED IN ROUTINE CLINICAL PRACTICE: AN UPDATE FROM THE RESPOND STUDY
Authors: Nicolas M. Van Mieghem, David Hildick-Smith, Sabine Bleiziffer, Jochen Woehrle, Daniel J. Blackman, Mohamed Abdel-Wahab, Ulrich Gerckens, Axel Linke, Peter Wenaweser, Oyvind Bleie, Karl E. Hauptmann, Hueseyin Ince, Dominic Allocco, Keith Dawkins, Volkmar Falk
Journal: Journal of the American College of Cardiology (2016)
Abstract 217: Modulation of Hsp90 chaperone activity by hypoxic condition: Hypoxia stimulates ARD1-mediated Hsp90 post-translational modification
Authors: Jong Kyu Woo, Ho-Young Lee
Journal: Cancer Research (2012)

Abstract Arrest defective-1 protein (ARD1, also known Naa10p) is an N-acetyltransferase known to be involved in cell cycle control. Several reports have implicated ARD1 in regulation of cell proliferation and apoptosis in mammalian cells. Although a potential role for ARD1 in controlling cell proliferation and apoptosis has been identified, little is known about the relevance of ARD1 to cancer development. Heat Shock Protein 90 (Hsp90), an essential molecular chaperone in eukaryotic cells, maintains the functional conformation of a subset of proteins that are typically key components of multiple regulatory and signaling networks mediating cancer cell proliferation, survival and metastasis. Reversible acetylation has been implicated as a regulatory post-translational modification of Hsp90. Although an acetyltransferase responsible for acetylating Hsp90 has yet to be identified, several groups recently identified Histone deacetylase 6 (HDAC6) as an one of the Hsp90 deacetylase. This study, we show that hypoxia leads to increased Hsp90 acetylation via ARD1 binding to Hsp90 and disrupted interaction between Hsp90 and client proteins and co-chaperone proteins. We found that treatment with the HDAC inhibitor trichostatin A (TSA) or sodium butyrate (NaB) enhanced Hsp90 acetylation and led to the dissociation of Hsp90 and client protein Hif-1a. To gain further insight into protein acetylation in the cytoplasm, we searched cellular targets for Hypoxia. By using an immunoprecipitation approach, we identified ARD1 as a prominent Hsp90 interacting partner. Transfection of ARD1 leads to Hsp90 hyperacetylation, its dissociation from an essential co-chaperone proteins and a loss of chaperone activity. Transfected ARD1 and Hsp90 can be abundantly and specifically co-immunoprecipitated under hypoxia condition. Those interactions prevented the formation of the Hsp90 chaperon complex, resulting in reduced chaperone function of Hsp90. We suggest that ARD1 functions as a tumor suppressor by disrupting the function of Hsp90, and thus inactivating of PI3K/Akt pathway and Hif-1a in cancer cells under hypoxic condition. We conclude that a coordinated interaction between Hsp90 and ARD1 under hypoxic condition may be an important mechanism for hypoxic cell signal to homeostasis. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 217. doi:1538-7445.AM2012-217
P248 Barriers to uptake of oxygen therapy in Malawi: a qualitative study
Authors: AC Stevenson, C Edwards, J Langton, N Kennedy
Journal: Thorax (2012)

<h3>Introduction and Objectives</h3> Oxygen is a scarce resource in many developing countries and there are current efforts to increase its availability. Clinicians in Malawi often report refusal of oxygen by patients. This qualitative study explores attitudes to oxygen therapy in Malawi. <h3>Method</h3> Focus group discussions involving 86 participants were held in rural and urban communities in Malawi until no new ideas were found. Framework analysis of transcripts of the audio recordings was carried out by at least two researchers to identify recurring themes. <h3>Results</h3> We found that participants’ knowledge of oxygen was limited, although many recognised that oxygen is used for respiratory diseases in adults and children. Knowledge of oxygen arose from personal experience, observation in hospital and discussion in local communities. Participants were keen to receive further education about oxygen therapy. Attitudes to oxygen varied. Some participants recognised that it could benefit those with respiratory and other diseases, and had positive experiences of using it. Others expressed fear or anxiety about using oxygen and cited this as a reason for refusing it. Many of the participants had witnessed a patient’s death following the use of oxygen: “<i>they are afraid that the patient is going to die ... because they had previously seen another patient dying after being placed on the machine”</i>. Some had heard in their local communities that oxygen was used prior to the death of a patient: “<i>even at the funeral ceremony people are told that the deceased went to the hospital and there he was put on oxygen and he died there, so this message terrifies people</i>”. Participants found the appearance and noise from oxygen concentrators alarming: “<i>that device is fearsome just by looking at it. When you think of someone inserting this device in the nose or mouth, you may think they want to finish off the life of your child</i>”. <h3>Conclusion</h3> This study impacts on efforts to increase the use of oxygen in Malawi and other developing countries. We have shown a need for education at a community level and for guidance for health workers seeking to increase the uptake of oxygen.
Predictive Biomarkers for Anti-Epidermal Growth Factor Receptor Therapy: Beyond<i>KRAS</i>Testing
Authors: Noman Ashraf, Nishi Kothari, Richard Kim
Journal: Journal of the National Comprehensive Cancer Network (2014)

In an era of personalized medicine, an increased effort is being made to identify patients likely to benefit from targeted therapy. By limiting treatment to selected patients, both unnecessary cost and toxicity may be avoided. Restricting the use of anti-epidermal growth factor receptor (anti-EGFR)-targeted agents in metastatic colorectal cancer to only patients with KRAS exon 2 wild-type tumors has become well-established in clinical practice. However, lack of KRAS exon 2 mutations does not necessarily predict response, and a significant proportion of patients with KRAS wild-type tumors do not benefit from therapy with cetuximab or panitumumab. Further characterization is needed of the subset of patients with KRAS exon 2 wild-type tumors who are likely to benefit from anti-EGFR therapy. Recent data suggest that patients with KRAS mutations at loci other than exon 2, and those with other RAS mutations, might not benefit from EGFR-directed therapy. This article briefly reviews established work on KRAS exon 2 mutations, but focuses primarily on emerging data on non-exon 2 KRAS mutations and additional RAS and BRAF mutations and how this information may impact clinical decision-making.
The State of Outcome Research: Are We on Target?
Authors: Sheldon Greenfield
Journal: New England Journal of Medicine (1989)

The time when medicine could afford the luxury of a leisurely pace in identifying optimal practices at a reasonable cost has passed. Payers, providers, health care organizations, and more recently patients are clamoring for ways to deliver maximally effective care for the fewest dollars. How to identify the practices that represent such care is among the most pressing problems facing American medicine.An exclusive reliance on randomized controlled trials to provide definite information about effectiveness is not the answer. We cannot afford to conduct randomized controlled trials for every test, procedure, or medication in use. To do so would require . . .
SP0006 Interstitial lung disease in rheumatic diseases: What do we know?
Authors: E.L. Matteson
Journal: Annals of the Rheumatic Diseases (2013)

Respiratory manifestations cause significant morbidity and mortality in patients with connective tissue diseases (CTDs). Not infrequently, respiratory involvement may be the presenting manifestation of CTDs. These disease features occurring in a patient with known CTD may be due to the underlying CTD, a treatment-related adverse effect such as a drug reaction, opportunistic infection, or an unrelated process. Clinical features of ILD include exertional dyspnea and/or chronic cough and inspiratory crackles There is a relatively high prevalence of subclinical intersitial lung disease (ILD) in patients with CTDs. The frequency of ILD in rheumatoid arthritis is about 20 to 30% of patients, while ILD may occur in 20 to 50% of patients with idiopathic inflammatory myositis, 40-50% or more of patients with systemic sclerosis, 2 to 5% of patients with systemic lupus erythematosus, 20 to 60% of patients with mixed connective tissue disease, and up to 25% of patients with Sjögren’s syndrome. The spectrum of ILD varies depending on the underlying CTD. The histologic pattern seen in the lung biopsy is usually not diagnostic of the underlying CTD, however, the histologic pattern of disease can determine the radiologic features and influences clinical presentation, response to therapy, and prognosis. Beyond what is known about the genetics of the underlying CTD, no specific genetic associations have been identified for CTD ILD. A few simple diagnostic procedures may address &gt;95% of pulmonary consultation questions related to ILD in the CTDs. These include CBC with differential, pulmonary function tests with DLCO, high resolution computed tomography of the chest, and appropriate serologies. Secondary tests can include echocardiogram and bronchoscopy with bronchioalveolar lavage. Corticosteroids and immunosuppressive/immunomodulatory therapy are commonly used in management of CTD-ILD, with variable response. <h3>Disclosure of Interest</h3> None Declared
530Extracellular ATP induces atherosclerosis and vascular inflammation via purinergic receptor 2 (P2Y2) in mice
Authors: P Stachon, A Peikert, A Michel, D Wolf, N Hoppe, B Dufner, C Bode, M Idzko, A Zirlik
Journal: Cardiovascular Research (2014)

Introduction: A solid body of basic evidence support a role for extracellular ATP and its receptors as danger signals in various chronic inflammatory diseases including asthma, chronic obstructive pulmonary disease (COPD), arthritis, allergic dermatitis, graft versus host disease and other entities. The ATP- binding P2Y2- receptor is involved in inflammatory cell recruitment and chronic inflammatory diseases like COPD. Hypothesis: Atherosclerosis represents a chronic inflammatory disease and several lines of evidence suggest that extracellular ATP and the P2Y2- receptor may contribute to atherogenesis. Methods: The expression of P2Y2 was determinded by realtime PCR and immune histology in aortas after feeding LDLR- deficient mice (LDLR-/-) a high (HCD) or low (LCD) cholesterol diet for 16 weeks. To gain into the functional role of extracellular ATP in atherogenesis, LDLR-/- mice on HCD for 18 weeks received either ATP or PBS intraperitoneally 3 times per week. Furthermore, P2Y2 knockout mice (P2Y2-/-) were crossed with LDLR-/- and fed a HCD for 18 weeks. LDLR-/- served as control group. Atherosclerosis was determined histologically. To evaluate the role of ATP and P2Y2 in vascular inflammation, intravital microscopy was performed in P2Y2-/- and LDLR-/- mice stimulated with ATP or vehicle. Results: P2Y2 is overexpressed in murine atherosclerotic aortas compared to healthy vessels indicating a relevant role in atherosclerosis. Stimulation of the P2Y2- receptor by ATP increases atherosclerotic lesions in aortic arches (N=15, control: 0.30mm2, ATP- group: 0.35 mm2, p=0.04) and abdominal aortas (N=15, control: 0, 0.34mm2, ATP- group: 0.18mm2, p<0.01) significantly. However, the knockout of the ATP- binding P2Y2- receptor reduces atherosclerosis in aortic arches compared to the LDLR-/- control group (N= 10, LDLR-/- :0.26mm2, P2Y2-/-/LDLR-/-: 0.14mm2, p = 0.03). Since leukocyte recruitment to the vessel wall is the crucial step in atherogenesis, we examined ATP and its P2Y2- receptor in vascular inflammation. Stimulating mice with ATP intraperitoneally induces leukocyte adhesion and rolling in wildtype mice. In P2Y2-/- mice this effect of ATP is reduced indicating a relevant role of P2Y2 in ATP dependent vascular inflammation. Conclusion: Extracellular ATP acts as a danger signal in vascular inflammation and induces atherosclerosis in mice via purinergic receptor 2. The ATP- P2Y2 axis represents a potential new pathway in pathogenesis of atherosclerosis.
Comparison of Two Fluid-Management Strategies in Acute Lung Injury
Authors: Herbert P Wiedemann, Arthur P Wheeler, Gordon R Bernard, B Taylor Thompson, Douglas Hayden, Ben deBoisblanc, Alfred F Connors, R Duncan Hite, Andrea L Harabin
Journal: New England Journal of Medicine (2006)

Optimal fluid management in patients with acute lung injury is unknown. Diuresis or fluid restriction may improve lung function but could jeopardize extrapulmonary-organ perfusion.In a randomized study, we compared a conservative and a liberal strategy of fluid management using explicit protocols applied for seven days in 1000 patients with acute lung injury. The primary end point was death at 60 days. Secondary end points included the number of ventilator-free days and organ-failure-free days and measures of lung physiology.The rate of death at 60 days was 25.5 percent in the conservative-strategy group and 28.4 percent in the liberal-strategy group (P=0.30; 95 percent confidence interval for the difference, -2.6 to 8.4 percent). The mean (+/-SE) cumulative fluid balance during the first seven days was -136+/-491 ml in the conservative-strategy group and 6992+/-502 ml in the liberal-strategy group (P<0.001). As compared with the liberal strategy, the conservative strategy improved the oxygenation index ([mean airway pressure x the ratio of the fraction of inspired oxygen to the partial pressure of arterial oxygen]x100) and the lung injury score and increased the number of ventilator-free days (14.6+/-0.5 vs. 12.1+/-0.5, P<0.001) and days not spent in the intensive care unit (13.4+/-0.4 vs. 11.2+/-0.4, P<0.001) during the first 28 days but did not increase the incidence or prevalence of shock during the study or the use of dialysis during the first 60 days (10 percent vs. 14 percent, P=0.06).Although there was no significant difference in the primary outcome of 60-day mortality, the conservative strategy of fluid management improved lung function and shortened the duration of mechanical ventilation and intensive care without increasing nonpulmonary-organ failures. These results support the use of a conservative strategy of fluid management in patients with acute lung injury. (ClinicalTrials.gov number, NCT00281268 [ClinicalTrials.gov].).
AB1185-HPR Psychological and Sleep Disorders in Patients with Rheumatoid Arthritis and It's Relationship with Disease Activity
Authors: G. Saavedra-Martinez, L. Villarreal, A. Palomino, V. Giraldo, D. Gomez, J. Bello-Gualtero, P. Santos-Moreno
Journal: Annals of the Rheumatic Diseases (2014)

<h3>Background</h3> Emotional stability is an important dimension of personality, therefore any involvement in this area should be considered as important. Psychological an sleep disorders in rheumatoid arthritis (RA) are poorly described in literature. <h3>Objectives</h3> The aim of this study was to describe psychological and sleep disturbances using CIE-10 classification in a population with RA and a possible correlation with disease activity. <h3>Methods</h3> A descriptive cross-sectional study was performed in a specialized clinic dedicated to care patients with RA. 349 patients were included in the study, which were seen by the area of psychology, which information was collected through semi-structured interviews and non-probability sampling. Descriptive epidemiology was applied for continuous variables, measures of central tendency and dispersion for categorical and qualitative variables (averages/percentages) and Pearson9s statistics for bi-variated analysis. <h3>Results</h3> The total sample of patients was 349, 287 (82.2%) were women and 62 (17.8%) were men, average DAS28- 2.46. Average age is 58.1 years. 52.7% of patients were medium socio-economical level and the 47% were low socio-economical level; Related with the occupation, 30.5% is retired because age and the 19.8% have handicap retirement pay; 26.9% is dedicated to the housekeeping and 20.1% were working. <i>Psychological disorders:</i> 72 (18.4% of women and 36.8% of men) reported no psychological disorders, while 262 (81.5% of women and 63.1% of men) report psychological disorders. women: 143 (57.1% of women and 38.8%) mood disorder (depression/anxiety), 60 (24.7% of women and 11.1% of men) somatoform disorders, 13 (4.8% of women and 5.5% of men) disorders of food intake, 17 (7.5% in woman only) sleep disorders, 6 (1.7% of women and 5.5% of men) sexual dysfunction, 10 (3.9% of women and 2.7% of men) dementia. The mean of DAS was 2.49 <i>Sleep disorders:</i> primary insomnia 122 patients (84.4% of women and 15.6% of men), related sleep disorder breathing (OSAS) 18 Patients (77.7% of women and 22.3% of men) and 12 patients with circadian rhythm disorder (83.3% of women and 16.7% of men), and hypersomnia 8 patients (100% of women). It was not established a correlation between psychological and sleep disorders and disease activity. <h3>Conclusions</h3> According to these findings most of patient who were in remission no report psychological disorders and most of patients in moderate disease activity present somatoform disorders. Women have many psychological disorders in relation to RA; there is a prevalence of depressive episode. A higher DAS28 is expected to be associated with restless sleep. <h3>Disclosure of Interest</h3> None declared <h3>DOI</h3> 10.1136/annrheumdis-2014-eular.5373
Précis of<i>Darwin, sex and status: Biological approaches to mind and culture</i>
Authors: Jerome H. Barkow
Journal: Behavioral and Brain Sciences (1991)

Abstract Darwin, Sex and Status argues that a human sociobiology that mistakes evolutionary theory for theories of psychology and culture is wrong, as are psychologies that could never have evolved or social sciences that posit impossible psychologies. Status develops theories of human self-awareness, cognition, and cultural capacity that are compatible with evolutionary theory. Recurring themes include: the importance of sexual selection in human evolution; our species' preoccupation with self-esteem and relative standing; the individual as an active strategist, regularly revising culturally provided information; and awareness as an impressionmanagement device. Culture is a somewhat structured information pool that itself evolves, often in ways that reduce the genetic fitness of its participants.