tbuckley/cabot-search huggingface dataset:
Causes and Timing of Death in Extremely Premature Infants from 2000 through 2011
Authors: Ravi M. Patel, Sarah Kandefer, Michele C. Walsh, Edward F. Bell, Waldemar A. Carlo, Abbot R. Laptook, Pablo J. Sánchez, Seetha Shankaran, Krisa P. Van Meurs, M. Bethany Ball, Ellen C. Hale, Nancy S. Newman, Abhik Das, Rosemary D. Higgins, Barbara J. Stoll
Journal: New England Journal of Medicine (2015)

Understanding the causes and timing of death in extremely premature infants may guide research efforts and inform the counseling of families. We analyzed prospectively collected data on 6075 deaths among 22,248 live births, with gestational ages of 22 0/7 to 28 6/7 weeks, among infants born in study hospitals within the National Institute of Child Health and Human Development Neonatal Research Network. We compared overall and cause-specific in-hospital mortality across three periods from 2000 through 2011, with adjustment for baseline differences. The number of deaths per 1000 live births was 275 (95% confidence interval [CI], 264 to 285) from 2000 through 2003 and 285 (95% CI, 275 to 295) from 2004 through 2007; the number decreased to 258 (95% CI, 248 to 268) in the 2008-2011 period (P=0.003 for the comparison across three periods). There were fewer pulmonary-related deaths attributed to the respiratory distress syndrome and bronchopulmonary dysplasia in 2008-2011 than in 2000-2003 and 2004-2007 (68 [95% CI, 63 to 74] vs. 83 [95% CI, 77 to 90] and 84 [95% CI, 78 to 90] per 1000 live births, respectively; P=0.002). Similarly, in 2008-2011, as compared with 2000-2003, there were decreases in deaths attributed to immaturity (P=0.05) and deaths complicated by infection (P=0.04) or central nervous system injury (P<0.001); however, there were increases in deaths attributed to necrotizing enterocolitis (30 [95% CI, 27 to 34] vs. 23 [95% CI, 20 to 27], P=0.03). Overall, 40.4% of deaths occurred within 12 hours after birth, and 17.3% occurred after 28 days. We found that from 2000 through 2011, overall mortality declined among extremely premature infants. Deaths related to pulmonary causes, immaturity, infection, and central nervous system injury decreased, while necrotizing enterocolitis-related deaths increased. (Funded by the National Institutes of Health.).
Sweating and Water Loss Through the Skin
Authors: E. William Rosenberg
Journal: JAMA (1962)

SOME recent engineering advances in the field of electrical hygrometry have made possible a rapid and precise determination of the relative humidity of any given atmosphere. It has long been appreciated that by measuring the change in relative humidity inside a chamber held against an area of skin, it is possible to determine the amount of water escaping from the skin. Kuno cites experiments done in 1790 by Segium and Lavoisier who used this technique to study cutaneous water loss. Sulzberger and Herrmann recently described studies of this type with a hygrometer but were limited by technical difficulties. For the past 3 years we have been working with one of these newer systems of electrical hygrometry in an attempt to improve present techniques for quantitating the amounts of water lost from human skin during life. A detailed account of the technical system involved was recently presented elsewhere. In this report
Histone deacetylase inhibitor, Trichostatin A induces ubiquitin-dependent cyclin D1 degradation in MCF-7 breast cancer cells
Authors: John P Alao, Alexandra V Stavropoulou, Eric W-F Lam, R Charles Coombes, David M Vigushin
Journal: Molecular Cancer (2006)

Abstract Background Cyclin D1 is an important regulator of G1-S phase cell cycle transition and has been shown to be important for breast cancer development. GSK3β phosphorylates cyclin D1 on Thr-286, resulting in enhanced ubiquitylation, nuclear export and degradation of the cyclin in the cytoplasm. Recent findings suggest that the development of small-molecule cyclin D1 ablative agents is of clinical relevance. We have previously shown that the histone deacetylase inhibitor trichostatin A (TSA) induces the rapid ubiquitin-dependent degradation of cyclin D1 in MCF-7 breast cancer cells prior to repression of cyclin D1 gene ( CCND1 ) transcription. TSA treatment also resulted in accumulation of polyubiquitylated GFP-cyclin D1 species and reduced levels of the recombinant protein within the nucleus. Results Here we provide further evidence for TSA-induced ubiquitin-dependent degradation of cyclin D1 and demonstrate that GSK3β-mediated nuclear export facilitates this activity. Our observations suggest that TSA treatment results in enhanced cyclin D1 degradation via the GSK3β/CRM1-dependent nuclear export/26S proteasomal degradation pathway in MCF-7 cells. Conclusion We have demonstrated that rapid TSA-induced cyclin D1 degradation in MCF-7 cells requires GSK3β-mediated Thr-286 phosphorylation and the ubiquitin-dependent 26S proteasome pathway. Drug induced cyclin D1 repression contributes to the inhibition of breast cancer cell proliferation and can sensitize cells to CDK and Akt inhibitors. In addition, anti-cyclin D1 therapy may be highly specific for treating human breast cancer. The development of potent and effective cyclin D1 ablative agents is therefore of clinical relevance. Our findings suggest that HDAC inhibitors may have therapeutic potential as small-molecule cyclin D1 ablative agents.
How Does Neuroscience Affect Our Conception of Volition?
Authors: Adina L. Roskies
Journal: Annual Review of Neuroscience (2010)

Although there is no clear concept of volition or the will, we do have intuitive ideas that characterize the will, agency, and voluntary behavior. Here I review results from a number of strands of neuroscientific research that bear upon our intuitive notions of the will. These neuroscientific results provide some insight into the neural circuits mediating behaviors that we identify as related to will and volition. Although some researchers contend that neuroscience will undermine our views about free will, to date no results have succeeded in fundamentally disrupting our commonsensical beliefs. Still, the picture emerging from neuroscience does raise new questions, and ultimately may put pressure on some intuitive notions about what is necessary for free will.
Lung function effects of chronic exposure to air pollution
Authors: J. Sunyer
Journal: Thorax (2009)

Lung function is an excellent operative marker of the effects of air pollution in the general population. It is objective and quantitative, an early predictor of cardiorespiratory morbidity and mortality, able to describe trajectories to the occurrence of chronic obstructive pulmonary disease (COPD) and coherent with experimental data on deposition and accumulation of pollutants in airways and lungs and the resulting systemic inflammation and oxidative stress.1 2

Acute effects of air pollution are well established, whereas long-term effects are less certain. There is strong evidence of long-term effects of current levels of air pollution on lung function growth in children, resulting in deficits of lung function at the end of adolescence.3 However, there are no data about the potential reversibility of the deleterious effect afterwards. In adults, there is only one large long-term follow-up study.4 The strongest evidence for adverse long-term effects of air pollution on lung function in adults comes from cross-sectional investigations. In Europe, these studies were limited to a few residential areas.5 6

Forbes et al have published in this issue ( see page 657 ) the largest cross-sectional study in adults in Europe, comprising four English surveys conducted between the years 1995 and 2001 in 648–720 postcode areas, adding 41 329 subjects older than age 16 and living in around 30 000 households.7 Individual residential exposure to air pollutants was based on dispersion modelling including meteorological and emission data for each postcode. Air pollution levels are moderate (median particulate matter <10 μm (PM10) and NO2 around 20 and 30 μg/m3, respectively). An increase in 10 μg/m3 of PM10 and NO2 was associated with a decrease of about 3% and 0.7% in FEV1 …
DOES THE PRESENCE OF MICROALBUMINURIA PORTEND A WORSE OUTCOME IN NON-DIABETIC PATIENTS WITH METABOLIC SYNDROME?
Authors: Pawan K. Hari, Vikas Veeranna, Rajeev Sudhakar, Palaniappan Manickam, Ramanjit Kaur, Jyotiranjan Pradhan, Sony Jacob, Luis Afonso
Journal: Journal of the American College of Cardiology (2010)
Users' Guides to the Medical Literature
Authors: Heiner C. Bucher, Gordon H. Guyatt, Deborah J. Cook, Anne Holbrook, Finlay A. McAlister, None for the Evidence-Based Medicine Working Group
Journal: JAMA (1999)

Our website uses cookies to enhance your experience. By continuing to use our site, or clicking "Continue," you are agreeing to our Cookie Policy | Continue JAMA HomeNew OnlineCurrent IssueFor Authors Publications JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry (1919-1959) Podcasts Clinical Reviews Editors' Summary Medical News Author Interviews More JN Learning / CMESubscribeJobsInstitutions / LibrariansReprints & Permissions Terms of Use | Privacy Policy | Accessibility Statement 2023 American Medical Association. All Rights Reserved Search All JAMA JAMA Network Open JAMA Cardiology JAMA Dermatology JAMA Forum Archive JAMA Health Forum JAMA Internal Medicine JAMA Neurology JAMA Oncology JAMA Ophthalmology JAMA Otolaryngology–Head & Neck Surgery JAMA Pediatrics JAMA Psychiatry JAMA Surgery Archives of Neurology & Psychiatry Input Search Term Sign In Individual Sign In Sign inCreate an Account Access through your institution Sign In Purchase Options: Buy this article Rent this article Subscribe to the JAMA journal
<i>MicroRNA-34b</i> and <i>MicroRNA-34c</i> Are Targets of p53 and Cooperate in Control of Cell Proliferation and Adhesion-Independent Growth
Authors: David C. Corney, Andrea Flesken-Nikitin, Andrew K. Godwin, Wei Wang, Alexander Yu. Nikitin
Journal: Cancer Research (2007)

MicroRNAs (miRNA) are a recently discovered class of noncoding RNAs that negatively regulate gene expression. Recent evidence indicates that miRNAs may play an important role in cancer. However, the mechanism of their deregulation in neoplastic transformation has only begun to be understood. To elucidate the role of tumor suppressor p53 in regulation of miRNAs, we have analyzed changes in miRNA microarray expression profile immediately after conditional inactivation of p53 in primary mouse ovarian surface epithelium cells. Among the most significantly affected miRNAs were miR-34b and miR-34c, which were down-regulated 12-fold according to quantitative reverse transcription-PCR analysis. Computational promoter analysis of the mir-34b/mir-34c locus identified the presence of evolutionarily conserved p53 binding sites approximately 3 kb upstream of the miRNA coding sequence. Consistent with evolutionary conservation, mir-34b/mir-34c were also down-regulated in p53-null human ovarian carcinoma cells. Furthermore, as expected from p53 binding to the mir-34b/c promoter, doxorubicin treatment of wild-type, but not p53-deficient, cells resulted in an increase of mir-34b/mir-34c expression. Importantly, miR-34b and miR-34c cooperate in suppressing proliferation and soft-agar colony formation of neoplastic epithelial ovarian cells, in agreement with the partially overlapping spectrum of their predicted targets. Taken together, these results show the existence of a novel mechanism by which p53 suppresses such critical components of neoplastic growth as cell proliferation and adhesion-independent colony formation.
Transforming growth factor β<sub>1</sub> and laminin-111 cooperate in the induction of interleukin-16 expression in synovial fibroblasts from patients with rheumatoid arthritis
Authors: K Warstat, M Hoberg, M Rudert, S Tsui, T Pap, B Angres, M Essl, T J Smith, W W Cruikshank, G Klein, S Gay, W K Aicher
Journal: Annals of the Rheumatic Diseases (2009)

Objectives: In synovial tissues of patients with rheumatoid arthritis (RA), strong expression of laminins and integrins co-localises with increased expression of inflammatory cytokines. Synovial fibroblasts (SF) contribute to the pathogenesis of RA through increased expression of cytokines and chemoattractant factors, one of which is interleukin-16 (IL16). A study was undertaken to investigate the regulatory pathways of IL16 in SF from patients with RA (RA-SF) and osteoarthritis (OA-SF). Methods: SF were seeded in laminin-coated flasks and activated by the addition of cytokines. The expression of IL16 was investigated by quantitative RT-PCR, immunoblotting and ELISA; its biological activity was determined by a cell migration assay. Cell–matrix interactions were investigated by cell binding and attachment assays. Relevant intracellular signalling pathways were studied by immunoblotting and with pharmacological blocking reagents. Results: Stimulation of SF with transforming growth factor β 1 (TGF-β 1 ) and growth on laminin-111 (LM-111) significantly increased the expression of IL16. Binding to LM-111 induced significantly more IL16 mRNA in RA-SF than in OA-SF (p&lt;0.05). The IL16 cytokine was detected in supernatants of TGF-β 1 -activated and in LM-111+TGF-β 1 -activated RA-SF (38 to 62 pg/ml), but not in supernatants of OA-SF. This IL16 regulation involved p38MAPK, ERK1/2 and SMAD2 signalling, but not NFκB. Conclusions: Binding of RA-SF to LM-111 in the presence of TGF-β 1 triggers a significant IL16 response and thus may contribute to the infiltration of CD4+ lymphocytes into synovial tissues. This mode of IL16 induction represents a novel pathway leading to IL16 production in RA-SF but not in OA-SF, which operates independently of NFκB signalling.
How can we improve patient use of inhaler devices in COPD
Authors: Mathieu Molimard, Karen Giorgi-Vigo
Journal: European Respiratory Journal (2011)

Introduction:  “Ease of use” is traditionally seen as a key factor in COPD inhaler choice. Our aim was to assess patient and healthcare professional (HCP) needs and problems with inhalers and to assess options to satisfy these needs, enabling better patient adherence with maintenance inhalers.   Methods:  1008 HCPs and 490 patients (≥18 yrs) participated in an online survey. Sawtooth Software9s ACA and CBC products were used to collect, randomize and measure relative impact of features in utility values (positive vs. negative choice impacts).   Results:  Overall, with current devices, patients indicate a lack of full certainty that they have taken the full dose correctly (rating of only 4.3 for Asthma, 5.3 for COPD; 1–7 scale). HCPs place far more importance on increasing patient satisfaction and demand than other attributes, reasoning this aids adherence. Similarly, patients want ease of use and features to aid adherence (a dose reminder and improvements over dose counters) to address their primary unmet need of uncertainty in inhaling all doses fully. Device type (MDI, DPI, multidose, singledose) has little impact in HCP choice (COPD HCP utilities: patient satisfaction and demand +92, multidose DPI –6, dose counter –3).   Conclusion:  Issues such as dose counters and multidose vs. singledose have little impact on physician demand. Satisfying patient need for true dose confirmation can drive patient satisfaction and adherence. Patients need devices that assure them that they have taken the full dose to be more adherent, and HCPs need devices that drive patient demand and adherence.
ACC/AHA/ESC 2006 Guidelines for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death
Authors: Douglas P. Zipes, A. John Camm, Martin Borggrefe, Alfred E. Buxton, Bernard Chaitman, Martin Fromer, Gabriel Gregoratos, George Klein, Robert J. Myerburg, Miguel A. Quinones, Dan M. Roden, Michael J. Silka, Cynthia Tracy, Sidney C. Smith, Alice K. Jacobs, Cynthia D. Adams, Elliott M. Antman, Jeffrey L. Anderson, Sharon A. Hunt, Jonathan L. Halperin, Rick Nishimura, Joseph P. Ornato, Richard L. Page, Barbara Riegel, Silvia G. Priori, Arthur J. Moss, Silvia G. Priori, Jean-Jacques Blanc, Andrzej Budaj, A. John Camm, Veronica Dean, Jaap W. Deckers, Catherine Despres, Kenneth Dickstein, John Lekakis, Keith McGregor, Marco Metra, Joao Morais, Ady Osterspey, Juan Luis Tamargo, José Luis Zamorano
Journal: Journal of the American College of Cardiology (2006)
Approaches to Uncertainty in Exposure Assessment in Environmental Epidemiology
Authors: Donna Spiegelman
Journal: Annual Review of Public Health (2010)

Uncertainty in assessment of individual exposure levels leads to bias, often, but not always, toward the null in estimates of health effects, and to underestimation of the variability of the estimates, leading to anticonservative p-values. In the absence of data on the uncertainty in individual exposure estimates, sensitivity analysis, also known as uncertainty analysis and bias analysis, is available. Hypothesized values of key parameters of the model relating the observed exposure to the true exposure are used to assess the resulting amount of bias in point and interval estimates. In general, the relative risk estimates can vary from zero to infinity as the hypothesized values of key parameters of the measurement error model vary. Thus, we recommend that exposure validation data be used to empirically adjust point and interval estimates of health effects for measurement error. The remainder of this review gives an overview of available methods for doing so. Just as we routinely adjust for confounding, we can and should routinely adjust for measurement error.
Nationwide prevalence of rheumatoid arthritis and penetration of disease-modifying drugs in Sweden
Authors: Martin Neovius, Julia F Simard, Johan Askling
Journal: Annals of the Rheumatic Diseases (2010)

Objective To provide Swedish nationwide data on the prevalence of rheumatoid arthritis (RA), including variations by age, sex, geography, demography and education level, and assess antirheumatic treatment penetration. Methods Patients ≥16 years assigned an RA diagnosis were identified from inpatient (n=96 560; 1964–2007) and specialist outpatient care (n=56 336; 2001–2007) in the Swedish National Patient Register, and the Swedish Rheumatology Quality Register (n=21 242; 1995–2007). Data on prescriptions, demography, vital status and educational level were retrieved from national registers. Results A total of 58 102 individuals (mean age 66 years; 73% women) assigned an RA diagnosis were alive in Sweden in 2008, corresponding to a cumulative prevalence of 0.77% (women 1.11%, men 0.43%). The 2001–2007 period prevalence was 0.70%. Restriction to patients with ≥2 visits or diagnosis from a rheumatologist/internist reduced the overall cumulative prevalence to 0.68%. Whereas urban/rural differences (crude 0.65–1.00%) were explained by age differences, the age/sex-adjusted prevalence remained higher in patients with ≤9 years education (0.86%) than for those with 10–12 years (0.82%) and &gt;12 years (0.65%). Treatment exposures (76% any disease-modifying antirheumatic drugs (DMARDs) or steroids, 64% any DMARD, 15% biological agents) varied with age; use of biological agents decreased from 22% in 16–59 years olds to 3% in ≥80 years olds. Any DMARD use correspondingly decreased from 71% to 43%. Applying age cut-off points from previous northern European and North American prevalence studies reduced or eliminated between-study differences. Conclusion This nationwide approach yielded a prevalence of RA similar to previous regional assessments. While displaying only modest geographical variation and no urban/rural gradient, prevalence was associated with educational level. Although most patients received antirheumatic drugs, age was a strong treatment determinant.
Allergen Specific IgE Response Is Similar in HIV-1 Seropositive and Seronegative Adults: Implications for HAART Induced Th2 to Th1 Switching
Authors: Mili Shum, Ashlei Mathew, Maja Nowakowski, Hamid Moallem, Tamar A. Smith-Norowitz, Helen G. Durkin, Rauno O. Joks
Journal: Journal of Allergy and Clinical Immunology (2015)
Vascular responses to vasopressin are tone-dependent in the cerebral circulation of the newborn pig.
Authors: W M Armstead, R Mirro, D W Busija, C W Leffler
Journal: Circulation Research (1989)

The effects of lysine vasopressin (LVP) on pial arteriolar diameter and cortical periarachnoid fluid prostanoid concentrations were investigated in newborn pigs. Chloralose-anesthetized piglets were equipped with closed cranial windows over the parietal cortex for observation of pial arterioles and collection of cerebrospinal fluid (CSF) passing over the cerebral surface. Prostanoids in the CSF were determined by radioimmunoassay. LVP (10-1,000 microU/ml) elicited concentration-dependent increases in pial arteriolar diameter associated with increased levels of 6-keto-prostaglandin (PG)F1 alpha, PGE2, thromboxane B2, and PGF2 alpha. LVP-induced pial arteriolar dilation was unchanged after intravenous indomethacin (5 mg/kg). Conversely, LVP constricts pial arterioles previously dilated by physiological (hemorrhagic hypotension) and pharmacological (topically applied PGE2 or isoproterenol) intervention. This constriction is potentiated by indomethacin. Vascular and biochemical changes elicited by LVP were blocked by intravenous [1-(beta-mercapto-beta beta-cyclopentamethylene propionic acid),2,(O-methyl)-Tyr-AVP] (5 micrograms/kg), a putative V1 receptor antagonist, whereas vascular effects of norepinephrine and U46619, a thromboxane A2 mimic, were unchanged. Therefore, the degree of vascular tone appears to influence responses of the newborn pig cerebral circulation to LVP.
Platelet-Derived Growth Factor–Induced p42/44 Mitogen-Activated Protein Kinase Activation and Cellular Growth Is Mediated by Reactive Oxygen Species in the Absence of <i>TSC2</i>/Tuberin
Authors: Geraldine A. Finlay, Victor J. Thannickal, Barry L. Fanburg, David J. Kwiatkowski
Journal: Cancer Research (2005)

Abstract Tuberous sclerosis complex (TSC) is a genetic disorder caused by inactivating mutations in the TSC1 or TSC2 genes, which encode hamartin and tuberin, respectively. TSC is characterized by multiple tumors of the brain, kidney, heart, and skin. Tuberin and hamartin inhibit signaling by the mammalian target of rapamycin (mTOR) but there are limited studies of their involvement in other pathways controlling cell growth. Using ELT-3 cells, which are Eker rat–derived smooth muscle cells, we show that ELT-3 cells expressing tuberin (TSC2+/+) respond to platelet-derived growth factor (PDGF) stimulation by activating the classic mitogen-activated protein (MAP)/extracellular signal-regulated kinase kinase (MEK)-1–dependent phosphorylation of p42/44 MAP kinase (MAPK) with nuclear translocation of phosphorylated p42/44 MAPK. In contrast, in tuberin-deficient ELT-3 cells (TSC2−/−), PDGF stimulation results in MEK-1–independent p42/44 MAPK phosphorylation with reduced nuclear localization of phosphorylated p42/44 MAPK. Moreover, in TSC2−/− cells but not in TSC2+/+ cells, cellular growth and activation of p42/44 MAPK by PDGF requires the reactive oxygen species intermediate, superoxide anion (O2·−). Both baseline and PDGF-induced O2·− levels were significantly higher in TSC2−/− cells and were reduced by treatment with rapamycin and inhibitors of mitochondrial electron transport. Furthermore, the exogenous production of O2·− by the redox cycling compound menadione induced MEK-1–independent cellular growth and p42/44 MAPK phosphorylation in TSC2−/− cells but not in TSC2+/+ cells. Together, our data suggest that loss of tuberin, which causes mTOR activation, leads to a novel cellular growth-promoting pathway involving mitochondrial oxidant–dependent p42/44 MAPK activation and mitogenic growth responses to PDGF.