tbuckley/cabot-search huggingface dataset:
A step test to assess exercise-related oxygen desaturation in interstitial lung disease
Authors: S. Dal Corso, S. R. Duarte, J. A. Neder, C. Malaguti, M. B. de Fuccio, C. A. de Castro Pereira, L. E. Nery
Journal: European Respiratory Journal (2006)

A 6-min step test (6MST) may constitute a practical method for routinely assessing effort tolerance and exercise-related oxyhaemoglobin desaturation (ERD) in the primary care of patients with interstitial lung disease. In total, 31 patients (19 males) with idiopathic pulmonary fibrosis (n = 25) and chronic hypersensitivity pneumonia were submitted, on different days, to two 6MSTs. Physiological responses were compared with those found on maximal and submaximal cycle ergometer tests at the same oxygen uptake ( V ′ O 2 ). Chronic breathlessness was also determined, as measured by the baseline dyspnoea index (BDI). Responses to 6MST were highly reproducible: 1.3±2.0 steps·min -1 , ±5 beats·min -1 (cardiac frequency), ±50 mL·min -1 ( V ′ O 2 ), ±7 L·min -1 (minute ventilation) and ±2% (arterial oxygen saturation measured by pulse oximetry ( S p,O 2 )). The number of steps climbed in 6 min was correlated to peak V ′ O 2 and the BDI. There were significant associations among the tests in relation to presence (change in S p,O 2 between rest and exercise ≥4%) and severity ( S p,O 2 &lt;88%) of ERD. Four patients, however, presented ERD only in response to 6MST. Resting diffusing capacity of the lung for carbon monoxide and alveolar–arterial oxygen tension difference were the independent predictors of the number of steps climbed. A single-stage, self-paced 6-min step test provided reliable and reproducible estimates of exercise capacity and exercise-related oxyhaemoglobin desaturation in interstitial lung disease patients.
The first 15 years of the American Academy of Dermatology skin cancer screening programs: 1985-1999
Authors: Alan C Geller, Zi Zhang, Arthur J Sober, Allan C Halpern, Martin A Weinstock, Simone Daniels, Donald R Miller, Marie-France Demierre, Daniel R Brooks, Barbara A Gilchrest
Journal: Journal of the American Academy of Dermatology (2003)
Improving Adolescent Health Policy: Incorporating a Framework for Assessing State-Level Policies
Authors: Claire D. Brindis, Kristin Moore
Journal: Annual Review of Public Health (2014)

Many US policies that affect health are made at the state, not the federal, level. Identifying state-level policies and data to analyze how different policies affect outcomes may help policy makers ascertain the usefulness of their public policies and funding decisions in improving the health of adolescent populations. A framework for describing and assessing the role of federal and state policies on adolescent health and well-being is proposed; an example of how the framework might be applied to the issue of teen childbearing is included. Such a framework can also help inform analyses of whether and how state and federal policies contribute to the variation across states in meeting adolescent health needs. A database on state policies, contextual variables, and health outcomes data can further enable researchers and policy makers to examine how these factors are associated with behaviors they aim to impact.
Direct interaction with filamins modulates the stability and plasma membrane expression of CFTR
Authors: William R. Thelin, Yun Chen, Martina Gentzsch, Silvia M. Kreda, Jennifer L. Sallee, Cameron O. Scarlett, Christoph H. Borchers, Ken Jacobson, M. Jackson Stutts, Sharon L. Milgram
Journal: Journal of Clinical Investigation (2007)

The role of the cystic fibrosis transmembrane conductance regulator (CFTR) as a cAMP-dependent chloride channel on the apical membrane of epithelia is well established. However, the processes by which CFTR is regulated on the cell surface are not clear. Here we report the identification of a protein-protein interaction between CFTR and the cytoskeletal filamin proteins. Using proteomic approaches, we identified filamins as proteins that associate with the extreme CFTR N terminus. Furthermore, we identified a disease-causing missense mutation in CFTR, serine 13 to phenylalanine (S13F), which disrupted this interaction. In cells, filamins tethered plasma membrane CFTR to the underlying actin network. This interaction stabilized CFTR at the cell surface and regulated the plasma membrane dynamics and confinement of the channel. In the absence of filamin binding, CFTR was internalized from the cell surface, where it prematurely accumulated in lysosomes and was ultimately degraded. Our data demonstrate what we believe to be a previously unrecognized role for the CFTR N terminus in the regulation of the plasma membrane stability and metabolic stability of CFTR. In addition, we elucidate the molecular defect associated with the S13F mutation.
Expression of Extracellular Matrix Components Versican, Chondroitin Sulfate, Tenascin, and Hyaluronan, and Their Association with Disease Outcome in Node-Negative Breast Cancer
Authors: Supaporn Suwiwat, Carmela Ricciardelli, Raija Tammi, Markku Tammi, Paivi Auvinen, Veli-Matti Kosma, Richard G. LeBaron, Wendy A. Raymond, Wayne D. Tilley, David J. Horsfall
Journal: Clinical Cancer Research (2004)

Abstract Purpose: The purpose is to determine whether the levels of expression of extracellular matrix components in peritumoral stroma are predictive of disease outcome for women with node-negative breast cancer. Experimental Design: Tumor tissue from 86 patients with node-negative breast cancer was examined by immunohistochemical staining for the expression of versican, chondroitin sulfate (CS), tenascin, and hyaluronan (HA). With the exception of HA, the expression of the extracellular matrix components was measured by video image analysis. Statistical correlation of the immunohistochemical data with clinicopathological characteristics and disease outcome was performed. Results: All of the extracellular matrix components were present in the peritumoral stroma of the entire study cohort. In contrast, immunoreactivity within the cancer cell was observed in 82% of tumors for HA, 12% for CS, and 4% for tenascin; no immunostaining of cancer cells for versican was observed for any of the tumors. Cox regression and Kaplan-Meier analyses indicated that elevated expression of stromal versican predicted increased risk and rate of relapse in this cohort. Elevated expression of tenascin was predictive of increased risk and rate of death only. Although neither CS nor HA were predictive of disease outcome in this cohort, tumor size was predictive of increased risk and rate of both relapse and survival. Conclusions: Elevated expression within peritumoral stromal matrix of versican and tenascin was predictive of relapse-free and overall survival, respectively, in women with node-negative breast cancer.
Morphological and molecular characteristics of living human fetuses between Carnegie stages 7 and 23: immunolocalization of inhibin and a subunits
Authors: L M Harkness, D T Baird
Journal: Human Reproduction Update (1997)

Transforming growth factor (TGF) is known to have the ability to modify mitogenic responses of tissues to other peptide growth factors and therefore may contribute to the rapid growth rate of an embryo. Throughout the TGF superfamily there is a similar fundamental molecular architecture. Included in this superfamily are inhibin A, activin A and activin B. It has been shown that activin is a powerful mesodermal inducing factor in the early embryo. The human embryo has shown localization of inhibin in the gonads after 16 weeks gestation but it has not been previously identified in earlier embryos. The inhibin-activin protein was found in a range of tissues including the liver stages 19-21 (alpha) and stages 19-22 (beta); oesophagus stages 19-22 (alpha and beta); stomach stages 21 and 22 (alpha and beta); gut stages 16-22 (alpha) and 21 and 22 (beta); pericardium stages 12-22 (alpha and beta); gonad stages 21 and 22 (beta) stage 22 (alpha); adrenal stages 19-22 (alpha and beta); urogenital system stages 21 and 22 (alpha and beta); yolk sac stage 12 (alpha and beta); mesenchyme stages 16-22 (alpha); surface ectoderm stages 13-22 (alpha) and stages 16-22 (beta a); notocord stages 13-22 (beta) and stages 21 and 22 (alpha); nasal, trachea and bronchi stages 19-22 (alpha and beta) leading to speculation of the role of both subunits.
Thromboxane Receptor Mediates Renal Vasoconstriction and Contributes to Acute Renal Failure in Endotoxemic Mice
Authors: Jean-Jacques Boffa, Armin Just, Thomas M. Coffman, William J. Arendshorst
Journal: Journal of the American Society of Nephrology (2004)

ABSTRACT. Sepsis is a major cause of acute renal failure (ARF) and death. Thromboxane A2 (TxA2) may mediate decreases of renal blood flow (RBF) and/or GFR associated with LPS-induced sepsis. This study tested whether TxA2 receptor blockade, with the use of TxA2 receptor knockout (TP-KO) mice or a selective TP receptor antagonist (SQ29,548), would alleviate LPS-induced renal vasoconstriction and ARF. Under basal conditions, anesthetized TP-KO mice displayed a lower mean arterial pressure than wild-type (WT) mice (102 versus 94 mmHg; P < 0.05). RBF, renal vascular resistance (RVR), GFR, and urine flow did not differ among groups under basal conditions, suggesting little tonic influence of TxA2 on renal TP receptors in health. In endotoxemic WT mice, 14 h after LPS (Escherichia coli LPS 8.5 mg/kg intraperitoneally), mean arterial pressure was reduced to 85 mmHg (P < 0.001), as were RBF (5.0 versus 9.3 ml/min per g kidney wt; P < 0.001) and GFR (0.38 versus 1.03 ml/min per g kidney wt; P < 0.001). Heart rate and RVR (71 versus 47 mmHg/ml per min; P < 0.05) increased. The decreases in RBF and GFR after LPS were attenuated in TP-KO mice versus WT mice (both P < 0.05). In both TP-KO and TP antagonist-treated mice, RVR remained stable in response to LPS versus WT mice that did not receive LPS. Delayed TP-antagonist treatment (12 h after LPS injection) ameliorated RBF and RVR but did not restore GFR. In other WT animals, TP-antagonist treatment for 2 h before intravenous LPS abolished the early renal vasoconstriction and alleviated the decrease in GFR. These results demonstrate that renal vasoconstriction during endotoxemic shock induced by LPS is mediated by TP receptors as indicated by pharmacologic blockade and genetic disruption of TP receptors.
Obstructive jaundice following a myocardial infarct
Authors: J N Khan, R Sanyal, A Pallan, J Ferrando, J Ment, S Roy-Choudhury
Journal: Gut (2008)

A 70-year-old man presented with a non-ST elevation myocardial infarction. Physical examination, ECG and blood tests including liver function tests were normal. Treatment with aspirin, clopidrogel and enoxaparin was commenced.

The chest pain …
Injury rates in Shotokan karate.
Authors: G R Critchley, S Mannion, C Meredith
Journal: British Journal of Sports Medicine (1999)

OBJECTIVE: To document the injury rate in three British Shotokan karate championships in consecutive years. In these tournaments strict rules governed contact, with only "light" or "touch" contact allowed. Protective padding for the head, hands, or feet was prohibited. METHODS: Prospective recording of injuries resulting from 1770 bouts in three national competitions of 1996, 1997, and 1998. Details of ages and years of karate experience were also obtained. RESULTS: 160 injuries were sustained in 1770 bouts. The overall rate of injury was 0.09 per bout and 0.13 per competitor. 91 (57%) injuries were to the head. The average age of those injured was 22 years, with an average of nine years of experience in karate. CONCLUSIONS: The absence of protective padding does not result in higher injury rates than in most other series of Shotokan karate injuries. Strict refereeing is essential, however, to maintain control and minimise contact.
Update in Palliative Medicine and End-of-Life Care
Authors: Janet L. Abrahm
Journal: Annual Review of Medicine (2003)

Palliative medicine includes clinical palliative care, education, and research that focus on the quality of life of patients with advanced disease and their families. The domain of palliative medicine is the relief of suffering: physical, psychological, social, and spiritual. Palliative medicine and care for patients at the end of life and their families include the following key components: compassionate communication; exploration of patient and family values and goals of care; expert attention to relief of suffering; management of pain, depression, delirium, and other symptoms; awareness of the manifestations of grief; and sensitivity to the concerns of bereaved survivors.
Effect of Verification Bias on Screening for Prostate Cancer by Measurement of Prostate-Specific Antigen
Authors: Rinaa S. Punglia, Anthony V. D'Amico, William J. Catalona, Kimberly A. Roehl, Karen M. Kuntz
Journal: New England Journal of Medicine (2003)

The sensitivity and specificity of a screening test are biased when disease status is not verified in all subjects and when the likelihood of confirmation depends on the test result itself. We assessed the screening characteristics of the prostate-specific antigen (PSA) measurement after correction for verification bias.Between 1995 and 2001, 6691 men underwent PSA-based screening for prostate cancer. Of these men, 705 (11 percent) subsequently underwent biopsy of the prostate. Under the assumption that the chance of undergoing a biopsy depends only on the PSA-test result and other observed clinical variables, we used a mathematical model to estimate adjusted receiver-operating-characteristic (ROC) curves.Adjusting for verification bias significantly increased the area under the ROC curve (i.e., the overall diagnostic performance) of the PSA test, as compared with an unadjusted analysis (0.86 vs. 0.69, P<0.001, for men less than 60 years of age; 0.72 vs. 0.62, P=0.008, for men 60 years of age or older). If the threshold PSA value for undergoing biopsy were set at 4.1 ng per milliliter, 82 percent of cancers in younger men and 65 percent of cancers in older men would be missed. A digital rectal examination that is abnormal but not suspicious for cancer does not affect the overall performance characteristics of the test.A lower threshold level of PSA for recommending prostate biopsy, particularly in younger men, may improve the clinical value of the PSA test.
<i>IRF-1</i> Gene Variations Influence IgE Regulation and Atopy
Authors: Michaela Schedel, Leonardo A Pinto, Bianca Schaub, Philip Rosenstiel, Dmitry Cherkasov, Lisa Cameron, Norman Klopp, Thomas Illig, Christian Vogelberg, Stephan K Weiland, Erika von Mutius, Michael Lohoff, Michael Kabesch
Journal: American Journal of Respiratory and Critical Care Medicine (2007)

Rationale: The development of atopic diseases is characterized by skewed immune responses to common allergens. Only recently, interferons have been identified to play a crucial role in these mechanisms.Objectives: Because interferon regulatory factor (IRF)-1 is critical for interferon expression, we tested the hypotheses that genetic changes in this essential transcription factor may have consequences for the development of atopy.Methods: The IRF-1 gene locus was resequenced in 80 human chromosomes. Association and haplotype analyses were performed in a cross-sectional study population of German children from Dresden (n = 1,940), and results were replicated in a second population sample from Munich (n = 1,159), both part of the ISAAC (International Study of Asthma and Allergy in Childhood) phase II. Promoter polymorphism effects were studied using electrophoretic mobility shift assay and colorimetric binding assays. Allele-specific IRF-1 gene expression was studied in vitro using luciferase reporter assays, whereas we assessed ex vivo expression of IRF-1 by real-time polymerase chain reaction and IFN-γ protein by Luminex technology (Bio-Rad, Hercules, CA). Statistical analyses were performed using SAS/Genetics (SAS 9.1.3; SAS Institute, Cary, NC).Measurements and Main Results: By resequencing, 49 polymorphisms were identified within the IRF-1 gene. Four blocks containing 11 polymorphisms were significantly associated with atopy, total IgE levels, or specific IgE levels in both populations (P < 0.05). Two polymorphisms changed transcription factor binding of nuclear factor (NF)-κB and EGR1 (early growth response 1) to the IRF-1 promoter, altered gene expression in vitro (P = 0.0004), and altered IRF-1 mRNA and IFN-γ protein expression ex vivo.Conclusions: Our results suggest that functionally relevant IRF-1 polymorphisms influence atopy risk, potentially by altering transcription factor binding, IRF-1 gene expression, and IFN-γ regulation.
OC-064 Hepatic fibrosis in people with type 2 diabetes mellitus: the Edinburgh type 2 diabetes study
Authors: J R Morling, M W Strachan, R M Williamson, J F Price, J A Fallowfield, I N Guha
Journal: Gut (2012)

<h3>Introduction</h3> People with type 2 diabetes mellitus (T2DM) have a higher prevalence of and higher mortality rates from liver-associated disease than the non-diabetic population of equivalent age. Early identification of liver disease followed by appropriate surveillance and intervention should be beneficial to the expanding population of older people with T2DM. We aimed to determine the prevalence and progression of hepatic fibrosis in a representative sample of older adults with T2DM. <h3>Methods</h3> 1066 participants of the Edinburgh Type 2 Diabetes Study, a large, randomly-selected population of patients with T2DM aged 60–75 years were invited to assessment on two occasions. At baseline, the Enhanced Liver Fibrosis Panel (ELF) was measured and demographics and diabetes history were recorded. ELF was repeated approximately 3 years later. The presence of fibrosis was determined as: none/mild &lt;7.7, moderate 7.7–&lt;9.8, severe ≥9.8. Fibrosis progression was investigated for association with demographics, diabetes history and alcohol intake using logistic regression. <h3>Results</h3> Average follow-up was 2.7 years. At baseline (n=530), 3.1% subjects had no/mild fibrosis, 85.1% moderate fibrosis and 11.9% severe fibrosis. Follow-up prevalences (n=806) were 1.9%, 79.3%, and 18.9% respectively. 489 subjects had both baseline and follow-up ELF results. 61 (12.5%) patients progressed to the most severe fibrosis stage between baseline and follow-up. None of the factors investigated were independently associated with progression to severe fibrosis: age, sex, social deprivation, diabetes-related factors (fasting glucose, HbA1c, diabetes duration, treatment type or location) or alcohol use. <h3>Conclusion</h3> These preliminary data suggest that considerable hepatic fibrosis is present in older patients with T2DM. ELF is well validated for diagnosing severe hepatic fibrosis and it is of concern that in &lt;3 years, almost 13% of patients progressed to this level. Further work is planned to determine factors affecting progression and to develop prognostic models for the development of hepatic fibrosis in people with T2DM. <h3>Competing interests</h3> None declared.
Development and validation of a polycystic liver disease complaint-specific assessment (POLCA)
Authors: Frederik Temmerman, Fabienne Dobbels, Thien Anh Ho, Yves Pirson, Ragna Vanslembrouck, Walter Coudyzer, Bert Bammens, Jos van Pelt, Jacques Pirenne, Frederik Nevens
Journal: Journal of Hepatology (2014)
Eosinophil Degranulation, Gastric Eosinophil-Derived Neurotoxin (gEDN) Levels and Dysphagia Score in Patients with Eosinophilic Esophagitis (EE)
Authors: C WEILER, D SQUILLACE, G KEPHART, Y ROMERO, J ALEXANDER, H KITA
Journal: Journal of Allergy and Clinical Immunology (2008)
Bradycardia and Slowing of the Atrioventricular Conduction in Mice Lacking Ca <sub>V</sub> 3.1/α <sub>1G</sub> T-Type Calcium Channels
Authors: Matteo E. Mangoni, Achraf Traboulsie, Anne-Laure Leoni, Brigitte Couette, Laurine Marger, Khai Le Quang, Elodie Kupfer, Anne Cohen-Solal, José Vilar, Hee-Sup Shin, Denis Escande, Flavien Charpentier, Joël Nargeot, Philippe Lory
Journal: Circulation Research (2006)

The generation of the mammalian heartbeat is a complex and vital function requiring multiple and coordinated ionic channel activities. The functional role of low-voltage activated (LVA) T-type calcium channels in the pacemaker activity of the sinoatrial node (SAN) is, to date, unresolved. Here we show that disruption of the gene coding for CaV3.1/alpha1G T-type calcium channels (cacna1g) abolishes T-type calcium current (I(Ca,T)) in isolated cells from the SAN and the atrioventricular node without affecting the L-type Ca2+ current (I(Ca,L)). By using telemetric electrocardiograms on unrestrained mice and intracardiac recordings, we find that cacna1g inactivation causes bradycardia and delays atrioventricular conduction without affecting the excitability of the right atrium. Consistently, no I(Ca,T) was detected in right atrium myocytes in both wild-type and CaV3.1(-/-) mice. Furthermore, inactivation of cacna1g significantly slowed the intrinsic in vivo heart rate, prolonged the SAN recovery time, and slowed pacemaker activity of individual SAN cells through a reduction of the slope of the diastolic depolarization. Our results demonstrate that CaV3.1/T-type Ca2+ channels contribute to SAN pacemaker activity and atrioventricular conduction.
Phenobarbital Effects in Cholestatic Liver Disease
Authors: JOSEPH R. BLOOMER
Journal: Annals of Internal Medicine (1975)

Fifteen patients with cholestatic disorders were treated for 1 to 5 months with phenobarbital. Primary biliary cirrhosis was diagnosed in seven, sclerosing cholangitis in two, intrahepatic biliary hypoplasia in three, and cholestatic hepatitis in three. Except for the patients with cholestatic hepatitis, in whom marked cholestasis was virtually the only abnormality in liver biopsy specimens, serum bilirubin and bile acid concentrations were diminished during therapy, the hepatic clearance of sulfobromophthalein and 131-I-rose bengal was variably enhanced, and there was relief from pruritus. Serum cholesterol concentrations and other measures of hepatic function were not significantly changed during therapy except for serum alkaline phosphatase activity, which rose in twelve patients. Parallel changes occurred in 5'-nucleotidase, suggesting a hepatic origin for the alkaline phosphatase activity. These studies indicate that phenobarbital therapy is associated with improvement in organic anion clearance in some patients with cholestatic disorders and may be beneficial to such patients.
From Dysfunction to Adaptation: An Interactionist Model of Dependency
Authors: Robert F Bornstein
Journal: Annual Review of Clinical Psychology (2012)

Contrary to clinical lore, a dependent personality style is associated with active as well as passive behavior and may be adaptive in certain contexts (e.g., in fostering compliance with medical and psychotherapeutic treatment regimens). The cognitive/interactionist model conceptualizes dependency-related responding in terms of four components: (a) motivational (a marked need for guidance, support, and approval from others); (b) cognitive (a perception of oneself as powerless and ineffectual); (c) affective (a tendency to become anxious when required to function autonomously); and (d) behavioral (use of diverse self-presentation strategies to strengthen ties to potential caregivers). Clinicians' understanding of the etiology and dynamics of dependency has improved substantially in recent years; current challenges include delineating useful subtypes of dependency, developing valid symptom criteria for Dependent Personality Disorder in DSM-5 and beyond, and working effectively with dependent patients in the age of managed care.