tbuckley/cabot-search huggingface dataset:
States As the Laboratory for Democracy: Is Anybody Paying Attention, and Does Anybody Care?
Authors: Blase N. Polite
Journal: Journal of Clinical Oncology (2015)

It is important to not lose sight of the methodologically simplistic but still powerful take-home points from the report by Jemal et al, 1 which accompanies this editorial.Between 2008 and 2010, Ͼ 23,000 deaths resulting from colon cancer (50% of total) could have been prevented if all states had colon cancer death rates equal to the five states with the lowest rates for the most educated whites.An equally important point is the variation among the states; 69% of deaths could have been prevented in Mississippi, compared with only 29% in Utah.An often-repeated concept of our nation, attributed to Justice Louis Brandeis, is that the states are the laboratory for democracy.Implicit in this is that other states and the federal government should be able to learn from and adapt the successful experiments.To achieve this is complicated, and true parity is unlikely in the foreseeable future, but the lessons are out there if policymakers are willing to pay attention.Jemal et al 1 obtained mortality data for colorectal cancer from 2008 through 2010 by age, sex, race/ethnicity, educational attainment, and state of residence from the National Vital Statistics System of the National Center for Health Statistics.For the population denominator, the authors used estimates derived from the Annual Social and Economic Supplement to the Current Population Survey.From these data, they calculated age-adjusted colorectal cancer death rates by race/ethnicity and educational level.Within each racial/ethnic category (non-Hispanic black, non-Hispanic white, and Hispanic), they calculated a rate ratio for each state, comparing those with Ն 16 years of education with those with Յ 12 years of education.States were ranked based on the rate ratio.To determine preventable deaths, the authors took the colorectal cancer death rates for the five states with the lowest rates among the most educated non-Hispanic whites and calculated what would happen if all other groups achieved these lower death rates.Many of the results are predictable and will come as no surprise to those who follow these data.Blacks or those with lower levels of education had higher colorectal cancer death rates than whites.Also nicely highlighted in Figure 1 of the report is that even controlling for education, blacks did worse.For example, the age-adjusted death rate for whites with Յ 12 years of education was 11.3 per 100,000, compared with 16.7 per 100,000 for blacks.3][4] The low colorectal cancer death rates for Hispanics is quite encouraging.However, this category is complicated by limited data, heterogeneity of the country of origin, and differences in immi-
CONCENTRATION OF SERUM PROTEIN-BOUND IODINE IN NORMAL MEN 12
Authors: Robert G. Tucker, Ancel Keys
Journal: Journal of Clinical Investigation (1951)

During recent years the determination of the protein-bound iodine (PBI) in the serum or plasma has been used with increasing frequency as a diagnostic aid.Various limits have been sug- gested for the serum PBI concentration in eu- thyroidism.The range most frequently recorded in the literature is from 4 to 8 gamma per cent of PBI.These values are not fiducial expressions of full statistical analyses of adequate numbers of persons; they are based on observations made by several groups of workers on limited numbers of persons judged to be euthyroid but otherwise not fully characterized (Table I).The present paper TABLE ILiterature values for normal serum PBI in man All values in micrograms per 100 ml. of serum.Authors N Mean S. D. Range Salter, Bassett, and Sapping-21 5.7* 1.0* 4.0-8.0ton (1) Talbot and associates (2) 11 7.0 6.0-8.4Perry and Cosgrove (3) 34 5.9 1.3 4.0-9.3Conner and associates (4) 4.8 4.0-6.0Kydd, Man, and Peters (5) 83 5.3t 1.0t 3.8-8.5Starr and associates (6) 100 5.6 0.9t 4.0-8.5 Calculated from Figure 2. t Calculated from Figure 1.reports the results, including statistical analysis, from 402 young and middle-aged men who are clinically "normal" in all respects and who repre- sent active urban "white collar" workers in the upper Midwest.
Exposure to Bisphenol A and Other Phenols in Neonatal Intensive Care Unit Premature Infants
Authors: Antonia M. Calafat, Jennifer Weuve, Xiaoyun Ye, Lily T. Jia, Howard Hu, Steven Ringer, Ken Huttner, Russ Hauser
Journal: Environmental Health Perspectives (2008)

We previously demonstrated that exposure to polyvinyl chloride plastic medical devices containing di(2-ethylhexyl) phthalate (DEHP) was associated with higher urinary concentrations of several DEHP metabolites in 54 premature infants in two neonatal intensive care units than in the general population. For 42 of these infants, we evaluated urinary concentrations of several phenols, including bisphenol A (BPA), in association with the use of the same medical devices.
A haplotype of the endothelial protein C receptor gene is associated with reduced risk of acute lung injury in critically ill patients
Authors: Aliki Vassiliou, Nikolaos Maniatis, Anastasia Kotanidou, Eleftheria Letsiou, Marina Kallergi, Foteini Karystinaki, Christina Sotiropoulou, Konstantinos Glynos, Ioanna Dimopoulou, Charalambos Roussos, Apostolos Armaganidis, Stylianos Orfanos
Journal: European Respiratory Journal (2011)

Background:  Activation of the coagulation system is present in the pulmonary circulation of patients with acute lung injury and acute respiratory distress syndrome (ALI/ARDS). Endothelial Protein C Receptor (EPCR) is involved in the activation of the protein C cytoprotective and anticoagulant pathway. Functionally relevant EPCR gene mutations have been described but their impact on ALI/ARDS development remains unclear.   Aims and objectives:  To investigate the role of EPCR mutations as predisposing factors to ALI development in severely ill critically ill patients.   Methods:  92 severely ill (APACHE score ≥25) ICU patients were screened for variations in the EPCR gene. Multivariate logistic regression analysis was performed in order to determine the prognostic significance of EPCR haplotypes compared to other potential risk factors, including disease severity, age and the presence of sepsis, to the development of ALI/ARDS.   Results:  Depending on the presence of haplotype-defining point-mutations, patients were divided into three haplotypes: H1 (n=59), H2 (n=17) and recombinant H1/H3 (n=16). ALI occurred in 53% of H2 carriers, 24% of H1 carriers and 50% of H1/H3 carriers with odds ratios 1.0, 0.284 (Confidence Interval= 0.090-0.904) and 0.963, respectively (p=0.033). Severe sepsis/septic shock was positively correlated with ALI/ARDS development, while APACHE II, SOFA, age and soluble EPCR levels were not independent predictors of ALI/ARDS.   Conclusion:  EPCR genotype seems to be a determinant of ALI/ARDS development in critically ill patients. H1 haplotype carriers have a reduced risk of ALI/ARDS, as compared to H2 haplotype and H1/H3 carriers.
For and against: Doctors should advise adolescents to abstain from sex For Against
Authors: T. Stammers
Journal: BMJ (2000)

Thank you for your interest in spreading the word about The BMJ.NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address. Username * Your Email * Send To * You are going to email the following Doctors should advise adolescents to abstain from sexForAgainst Your Personal Message CAPTCHA This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
Dose-Dependent Effects of Sirolimus on mTOR Signaling and Polycystic Kidney Disease
Authors: Zlata Novalic, Annemieke M. van der Wal, Wouter N. Leonhard, Gudrun Koehl, Martijn H. Breuning, Edward K. Geissler, Emile de Heer, Dorien J.M. Peters
Journal: Journal of the American Society of Nephrology (2012)

Inhibition of the mammalian target of rapamycin (mTOR) shows beneficial effects in animal models of polycystic kidney disease (PKD); however, two clinical trials in patients with autosomal dominant PKD failed to demonstrate a short-term benefit in either the early or progressive stages of disease. The stage of disease during treatment and the dose of mTOR inhibitors may account for these differing results. Here, we studied the effects of a conventional low dose and a higher dose of sirolimus (blood levels of 3 ng/ml and 30–60 ng/ml, respectively) on mTOR activity and renal cystic disease in two Pkd1-mutant mouse models at different stages of the disease. When initiated at early but not late stages of disease, high-dose treatment strongly reduced mTOR signaling in renal tissues, inhibited cystogenesis, accelerated cyst regression, and abrogated fibrosis and the infiltration of immune cells. In contrast, low-dose treatment did not significantly reduce renal cystic disease. Levels of p-S6RpSer240/244, which marks mTOR activity, varied between kidneys; severity of the renal cystic phenotype correlated with the level of mTOR activity. Taken together, these data suggest that long-term treatment with conventional doses of sirolimus is insufficient to inhibit mTOR activity in renal cystic tissue. Mechanisms to increase bioavailability or to target mTOR inhibitors more specifically to kidneys, alone or in combination with other compounds, may improve the potential for these therapies in PKD.
Phytoestrogen Intake and Endometrial Cancer Risk
Authors: P. L. Horn-Ross, E. M. John, A. J. Canchola, S. L. Stewart, M. M. Lee
Journal: JNCI Journal of the National Cancer Institute (2003)

The development of endometrial cancer is largely related to prolonged exposure to unopposed estrogens. Phytoestrogens (i.e., weak estrogens found in plant foods) may have antiestrogenic effects. We evaluated the associations between dietary intake of seven specific compounds representing three classes of phytoestrogens (isoflavones, coumestans, and lignans) and the risk of endometrial cancer.In a case-control study from the greater San Francisco Bay Area, we collected dietary information from 500 African American, Latina, and white women aged 35-79 years who were diagnosed with endometrial cancer between 1996 and 1999 and from 470 age- and ethnicity-matched control women identified through random-digit dialing. Unconditional logistic regression analyses were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs).Isoflavone (OR = 0.59, 95% CI = 0.37 to 0.93 for the highest versus lowest quartile of exposure) and lignan (OR = 0.68, 95% CI = 0.44 to 1.1) consumptions were inversely related to the risk of endometrial cancer. These associations were slightly stronger in postmenopausal women (OR = 0.44, 95% CI = 0.26 to 0.77 and OR = 0.57, 95% CI = 0.34 to 0.97 for isoflavones and lignans, respectively). Obese postmenopausal women consuming relatively low amounts of phytoestrogens had the highest risk of endometrial cancer (OR = 6.9, 95% CI = 3.3 to 14.5 compared with non-obese postmenopausal women consuming relatively high amounts of isoflavones); however, the interaction between obesity and phytoestrogen intake was not statistically significant.Some phytoestrogenic compounds, at the levels consumed in the typical American-style diet, are associated with reduced risk of endometrial cancer.
An NKG2D-Mediated Human Lymphoid Stress Surveillance Response with High Interindividual Variation
Authors: Seema Shafi, Pierre Vantourout, Graham Wallace, Ayman Antoun, Robert Vaughan, Miles Stanford, Adrian Hayday
Journal: Science Translational Medicine (2011)

Humans mount lymphocyte stress surveillance responses to MICA, but they are individually tuned to optimal bandwidths.
Recent Developments in Vascular Endothelial Cell Transient Receptor Potential Channels
Authors: Xiaoqiang Yao, Christopher J. Garland
Journal: Circulation Research (2005)

Among the 28 identified and unique mammalian TRP (transient receptor potential) channel isoforms, at least 19 are expressed in vascular endothelial cells. These channels appear to participate in a diverse range of vascular functions, including control of vascular tone, regulation of vascular permeability, mechanosensing, secretion, angiogenesis, endothelial cell proliferation, and endothelial cell apoptosis and death. Malfunction of these channels may result in disorders of the human cardiovascular system. All TRP channels, except for TRPM4 and TRPM5, are cation channels that allow Ca 2+ influx. However, there is a daunting diversity in the mode of activation and regulation in each case. Specific TRP channels may be activated by different stimuli such as vasoactive agents, oxidative stress, mechanical stimuli, and heat. TRP channels may then transform these stimuli into changes in the cytosolic Ca 2+ , which are eventually coupled to various vascular responses. Evidence has been provided to suggest the involvement of at least the following TRP channels in vascular function: TRPC1, TRPC4, TRPC6, and TRPV1 in the control of vascular permeability; TRPC4, TRPV1, and TRPV4 in the regulation of vascular tone; TRPC4 in hypoxia-induced vascular remodeling; and TRPC3, TRPC4, and TRPM2 in oxidative stress–induced responses. However, in spite of the large body of data available, the functional role of many endothelial TRP channels is still poorly understood. Elucidating the mechanisms regulating the different endothelial TRP channels, and the associated development of drugs selectively to target the different isoforms, as a means to treat cardiovascular disease should, therefore, be a high priority.
Spondyloarthritis: may the force be with you?
Authors: Dennis McGonagle, Rebecca C Thomas, Georg Schett
Journal: Annals of the Rheumatic Diseases (2013)

Jacques et al 1 provide proof of concept that experimental spondyloarthritis (SpA) may be a biomechanically triggered process. The implication is that an aberrant mesenchymal tissue response to physiological mechanical forces that occur during joint movement may trigger inflammation associated with SpA. Given the long-known genetic association of human SpA with human leukocyte antigen (HLA)-B27,2 which governs initiation of adaptive immune responses, the concept that SpA resembles a biomechanically driven rather than autoimmune disease may come as a great surprise. The en face argument that mechanically driven animal models bear no resemblance to human SpA, however, has to be taken with caution, given that the role of mechanics in human SpA has several supporting strands of evidence that date back over 50 years.

Jacques and colleagues show that the earliest lesions in their model are localised at the Achilles tendon. As far back as 1959, La Cava, in his prophetic commentary on enthesitis, but not specifically in relationship to SpA, recognised that “the continually recurring concentration of muscle stress at these points provokes a reaction of inflammation with a strong tendency to the formation of fibrosis and calcification”.3 He also stated that insertions appeared to show ‘a peculiar reaction to irritative stimuli’ and that such stimuli were most frequently ‘microtraumatic in origin’. Since that time evidence has accumulated that supports all aspects of these suppositions.

In the 1970s, Moll and Wright deduced the clinical concept of SpA.4–6 Although they did not pinpoint the ‘invisible unifying concept’, which appears to be mechanical stress, they recognised that physical trauma to joints appeared to trigger psoriatic arthritis and speculated that psoriatic arthritis (PsA) represented a ‘Deep Koebner response’. However, they did not specifically recognise the importance of the entheseal organ as the link between biomechanics and inflammation. Likewise, nail …
Computerized quantitative analysis of left ventricular wall motion by two-dimensional echocardiography.
Authors: I Schnittger, P J Fitzgerald, E P Gordon, E L Alderman, R L Popp
Journal: Circulation (1984)

Quantitative detection of left ventricular segmental wall motion abnormalities by any modality depends on the reference system used because of the dynamic geometry of contraction and cardiac motion within the thorax. To assess the feasibility and accuracy of quantitative analysis of left ventricular wall motion by two-dimensional echocardiography, we studied 61 subjects with the use of 44 different reference methods in each of three echocardiographic views: the parasternal short-axis view at the levels of the mitral valve and of the papillary muscles and an apical four-chamber view. The three major groups of reference systems used were those with a fixed external reference, a floating reference correcting for translation, and systems correcting for both translation and rotation. In the first part of this study the end-diastolic and end-systolic outlines of 20 normal subjects were stored in a computer and composite data of these 20 subjects were plotted to obtain a 95% confidence interval for measured normal fractional change for each reference method. In the second part of the project an additional prospective group of 10 normal subjects and a group of 31 "abnormal" patients had their left ventricular wall motion analyzed by similar methods and the results were compared with all the confidence intervals. One reference method was selected for each two-dimensional echocardiographic view based on the highest sensitivity and specificity found by statistical analysis; a floating-reference system including translation was found to be optimal for the apical four-chamber and parasternal short-axis views at the level of the mitral valve and a fixed external reference system was optimal for the short-axis view at the papillary level. The percent fractional shortening of radial dimensions (radial methods) and the percent fractional change in area measurements (area methods) during the cardiac cycle were also calculated at 5, 10, 20, 30 and 45 degree intervals around the outline perimeter for each subject according to each of the 44 different methods. Area methods yielded the same specificity and sensitivity as radial dimension analysis methods at 5 to 45 degree intervals. Ten normal subjects underwent repeat echocardiography within 2 days of their first study to examine day-to-day variation. Average change in mean contraction from day to day was 7% to 9% for radial methods and 9% to 13% for area methods. In conclusion, we present a computerized system for unbiased selection of optimal methods of analysis of left ventricular wall motion by two-dimensional echocardiography.(ABSTRACT TRUNCATED AT 400 WORDS)
Stimulatory effects of distinct members of the bone morphogenetic protein family on ligament fibroblasts
Authors: K Bobacz, R Ullrich, L Amoyo, L Erlacher, J S Smolen, W B Graninger
Journal: Annals of the Rheumatic Diseases (2005)

<b>Objective:</b> To investigate effects of cartilage derived morphogenetic protein-1 and -2 (CDMP-1, CDMP-2), bone morphogenetic protein (BMP)-7 and BMP-6 on metabolism of ligament fibroblasts and their osteogenic or chondrogenic differentiation potential. <b>Methods:</b> Ligament fibroblasts were obtained from 3 month old calves, plated as monolayers or micromass cultures, and incubated with or without CDMP-1, CDMP-2, BMP-7, and BMP-6. Expression of the indicated growth factors was assessed by RT-PCR and western immunoblotting. The presence of their respective type I and II receptors, and lineage related markers, was investigated in stimulated and unstimulated cells by RT-PCR and northern blotting. Biosynthesis of matrix proteoglycans was assessed by [<sup>35</sup>S]sulphate incorporation in monolayers. Alcian blue and toluidine blue staining was done in micromass cultures. <b>Results:</b> CDMP-1, CDMP-2, BMP-7, and BMP-6 were detected on mRNA and on the protein level. Type I and II receptors were endogenously expressed in unstimulated ligament fibroblasts. The growth factors significantly stimulated total proteoglycan synthesis as assessed by [<sup>35</sup>S]sulphate incorporation. Toluidine blue staining showed cartilage-specific metachromasia in the growth factor treated micromass cultures. Transcription analysis of stimulated ligament fibroblasts demonstrated coexpression of chondrocyte markers but no up regulation of osteogenic markers. <b>Conclusion:</b> CDMP-1, CDMP-2, BMP-7, and BMP-6 and their receptors were expressed in ligament tissue. These growth factors induced matrix synthesis in fibroblasts derived from bovine ligament. The preferential expression of cartilage markers in vitro suggests that CDMP-1, CDMP-2, BMP-7, and BMP-6 have the potential to induce differentiation towards a chondrogenic phenotype in ligament fibroblasts. Thus, fibroblasts from ligaments may serve as a source for chondrogenesis and tissue repair.
Initial Assessment, Surveillance, and Management of Blood Pressure in Patients Receiving Vascular Endothelial Growth Factor Signaling Pathway Inhibitors
Authors: Michael L. Maitland, George L. Bakris, Henry R. Black, Helen X. Chen, Jean-Bernard Durand, William J. Elliott, S. Percy Ivy, Carl V. Leier, JoAnn Lindenfeld, Glenn Liu, Scot C. Remick, Richard Steingart, W. H. Wilson Tang
Journal: JNCI Journal of the National Cancer Institute (2010)

Hypertension is a mechanism-based toxic effect of drugs that inhibit the vascular endothelial growth factor signaling pathway (VSP). Substantial evidence exists for managing hypertension as a chronic condition, but there are few prospectively collected data on managing acute hypertension caused by VSP inhibitors. The Investigational Drug Steering Committee of the National Cancer Institute convened an interdisciplinary cardiovascular toxicities expert panel to evaluate this problem, to make recommendations to the Cancer Therapy Evaluation Program on further study, and to structure an approach for safe management by treating physicians. The panel reviewed: the published literature on blood pressure (BP), hypertension, and specific VSP inhibitors; abstracts from major meetings; shared experience with the development of VSP inhibitors; and established principles of hypertension care. The panel generated a consensus report including the recommendations on clinical concerns summarized here. To support the greatest possible number of patients to receive VSP inhibitors safely and effectively, the panel had four recommendations: 1) conduct and document a formal risk assessment for potential cardiovascular complications, 2) recognize that preexisting hypertension will be common in cancer patients and should be identified and addressed before initiation of VSP inhibitor therapy, 3) actively monitor BP throughout treatment with more frequent assessments during the first cycle of treatment, and 4) manage BP with a goal of less than 140/90 mmHg for most patients (and to lower, prespecified goals in patients with specific preexisting cardiovascular risk factors). Proper agent selection, dosing, and scheduling of follow-up should enable maintaining VSP inhibition while avoiding the complications associated with excessive or prolonged elevation in BP.