tbuckley/cabot-search huggingface dataset:
Changes in the perception and attitude toward tobacco use among elementary students in Texas following an intervention
Authors: Sean Hesselbacher, Sara Surani, Amina Khimani, Salim Surani
Journal: European Respiratory Journal (2013)

Introduction: The majority of tobacco users begin before the age of 18. A preventative intervention targeted at elementary school children has been previously reported (Surani S. et al. Int J Pediatr. 2011; 584589), though the changes attributable to the intervention are not known.  Objectives: The purpose of this study is to assess the effect of the intervention on the perception and knowledge of, and attitudes toward, tobacco use.  Methods: After permission from the school districts, children from second and third grade underwent an educational program. The “AntE tobacco” program, a 13-minute educational cartoon video depicting the ill effects of smoking by a colony of ants, was presented to the students. A 17-point questionnaire assessing 4 categories related to tobacco use (perceptions of the smoking prototype, behavioral willingness to smoke, attitudes toward use, and knowledge about risks) was administered before and after the intervention.  Results: Pre- and post-intervention questionnaires were completed by 447 students. Following the intervention, children who smoked were felt to be significantly less popular and cool, and more boring than before the intervention. However, children were more likely to agree that smoking makes them look cool, have more friends, and look more grown-up following the intervention. There was little to no change in responses in behavioral willingness to smoke or knowledge of tobacco use risks.  Conclusions: The effects of the intervention were contradictory on the perception and attitudes toward tobacco use among elementary students. Other interventions may be needed to address willingness to use tobacco and knowledge of the risks.
Macitentan, a Dual Endothelin Receptor Antagonist, in Combination with Temozolomide Leads to Glioblastoma Regression and Long-term Survival in Mice
Authors: Sun-Jin Kim, Ho Jeong Lee, Mark Seungwook Kim, Hyun Jin Choi, Junqin He, Qiuyu Wu, Kenneth Aldape, Jeffrey S. Weinberg, W.K. Alfred Yung, Charles A. Conrad, Robert R. Langley, François Lehembre, Urs Regenass, Isaiah J. Fidler
Journal: Clinical Cancer Research (2015)

Abstract Purpose: The objective of the study was to determine whether astrocytes and brain endothelial cells protect glioma cells from temozolomide through an endothelin-dependent signaling mechanism and to examine the therapeutic efficacy of the dual endothelin receptor antagonist, macitentan, in orthotopic models of human glioblastoma. Experimental Design: We evaluated several endothelin receptor antagonists for their ability to inhibit astrocyte- and brain endothelial cell–induced protection of glioma cells from temozolomide in chemoprotection assays. We compared survival in nude mice bearing orthotopically implanted LN-229 glioblastomas or temozolomide-resistant (LN-229Res and D54Res) glioblastomas that were treated with macitentan, temozolomide, or both. Tumor burden was monitored weekly with bioluminescence imaging. The effect of therapy on cell division, apoptosis, tumor-associated vasculature, and pathways associated with cell survival was assessed by immunofluorescent microscopy. Results: Only dual endothelin receptor antagonism abolished astrocyte- and brain endothelial cell–mediated protection of glioma cells from temozolomide. In five independent survival studies, including temozolomide-resistant glioblastomas, 46 of 48 (96%) mice treated with macitentan plus temozolomide had no evidence of disease (P &amp;lt; 0.0001), whereas all mice in other groups died. In another analysis, macitentan plus temozolomide therapy was stopped in 16 mice after other groups had died. Only 3 of 16 mice eventually developed recurrent disease, 2 of which responded to additional cycles of macitentan plus temozolomide. Macitentan downregulated proteins associated with cell division and survival in glioma cells and associated endothelial cells, which enhanced their sensitivity to temozolomide. Conclusions: Macitentan plus temozolomide are well tolerated, produce durable responses, and warrant clinical evaluation in glioblastoma patients. Clin Cancer Res; 21(20); 4630–41. ©2015 AACR.
Prevention of Postpartum Psychosis and Mania in Women at High Risk
Authors: Veerle Bergink, Paul F. Bouvy, Jeroen S.P. Vervoort, Kathelijne M. Koorengevel, Eric A.P. Steegers, Steven A. Kushner
Journal: American Journal of Psychiatry (2012)

Women with a history of bipolar disorder or postpartum psychosis are at extremely high risk of relapse postpartum. Although lithium prophylaxis has demonstrated efficacy in reducing postpartum relapse, the timing of prophylaxis remains controversial given the balance of risks and benefits for the mother and fetus. The authors compared lithium use during pregnancy to its initiation postpartum in women at high risk for postpartum psychosis.Between 2003 and 2010, 70 pregnant women at high risk for postpartum psychosis were referred to the authors' psychiatric outpatient clinic. Women who were initially medication free were advised to start lithium prophylaxis immediately postpartum. Women already taking maintenance lithium during pregnancy were advised to continue treatment.All women with a history of psychosis limited to the postpartum period (N=29) remained stable throughout pregnancy despite being medication free. Of the women with bipolar disorder (N=41), 24.4% relapsed during pregnancy, despite prophylaxis use by the majority throughout pregnancy. The postpartum relapse rate was highest in women with bipolar disorder who experienced mood episodes during pregnancy (60.0%). In contrast, none of the 20 women with a history of postpartum psychosis only who used postpartum prophylaxis relapsed, compared to 44.4% of patients with postpartum psychosis only who declined prophylaxis.The authors recommend initiating prophylactic treatment immediately postpartum in women with a history of psychosis limited to the postpartum period, to avoid in utero fetal exposure to medication. Patients with bipolar disorder require continuous prophylaxis throughout pregnancy and the postpartum period to reduce peripartum relapse risk.
Bone Disease, Gestational Diabetes Mellitus, and Health Care
Authors: Zachary T. Bloomgarden
Journal: Diabetes Care (2009)

This is the seventh of a series of articles based on presentations at the American Diabetes Association (ADA) Scientific Sessions held 6–10 June 2008 in San Francisco, California.

### Type 2 diabetes and bone disease

Robert Josse (Toronto, Canada) discussed new concepts of skeletal homeostasis and its disorders in a symposium addressing the relationship of type 2 diabetes, and in particular that of thiazolidinedione (TZD) treatment, to bone disease. Remodeling is the process of combined osteoclast and osteoblast activity that optimizes bone structure to improve strength and mechanical function and repair microdamage, fulfills metabolic functions, and acts as an important source of growth factors. The basic multicellular units of bone contain osteoclasts that excavate bone, mononuclear cells that remove cellular debris, and osteoblasts that replace the removed bone. Receptor activator of nuclear factor-κB (RANK) ligand is a transmembrane protein belonging to the tumor necrosis factor superfamily that specifically binds RANK and osteoprotegerin and plays an important role in regulating osteoclast differentiation and activation, whereas the Wnt (related to a gene controlling wing forming in fruit flies) system controls osteoblast activity with complex signals linking osteoblasts and osteoclasts (1). An LDL receptor–related protein (LRP)5 mutation is associated with increased bone mass. The LRP5/Wnt signaling pathway increases activity of the multifunctional protein β-catenin that participates in cell adhesion and nuclear signaling and is inhibited by an osteocyte product sclerostin (defects in this are associated with sclerositis) and by the antagonist Dickkopf (DKK) proteins. DKK1 is a myeloblast product that helps explain the failure of multiple myeloma lesions to show activity on bone scan.

Osteoporosis may be caused by increased osteoclast or decreased osteoblast activity, compromising bone strength, which Josse suggested be seen as an integrated measure of bone density and bone quality, recognizing that standard bone density measurement fails to assess the latter component. Bones break when the applied …
Celecoxib versus diclofenac in long-term management of rheumatoid arthritis: randomised double-blind comparison
Authors: Paul Emery, Henning Zeidler, Tore K Kvien, Mario Guslandi, Raphael Naudin, Helen Stead, Kenneth M Verburg, Peter C Isakson, Richard C Hubbard, G Steven Geis
Journal: The Lancet (1999)
THE OCCURRENCE OF CARRIERS OF DISEASE-PRODUCING TYPES OF PNEUMOCOCCUS
Authors: A. R. Dochez, O. T. Avery
Journal: The Journal of Experimental Medicine (1915)

Lobar pneumonia in 75 per cent of instances is due to specific types of pneumococci possessed of a high degree of pathogenicity. Although pneumococci occur in the mouths of 60 per cent of normal individuals, such organisms are readily distinguishable from the highly parasitic types of pneumococcus responsible for the severe forms of lobar pneumonia, a convincing proof that infection in this disease is, in the majority of instances, not autogenic in nature, but is derived from some extraneous source. In a high percentage of instances healthy persons intimately associated with cases of lobar pneumonia harbor the disease-producing types of pneumococcus. In every such instance the pneumococcus isolated has corresponded in type with that of the infected individual. Convalescents from pneumonia carry for a considerable length of time the type of pneumococcus with which they have been infected. The existence of the carrier state among healthy persons and among those recently recovered from pneumonia establishes a basis for understanding the mechanism by means of which lobar pneumonia spreads and maintains its high incidence from year to year.
An index of the contractile state of the myocardium in man
Authors: Martin J. Frank, Gilbert E. Levinson
Journal: Journal of Clinical Investigation (1968)

There is a profound need, on both clinical and physiologic grounds, for a measure of the contractile state of the intact ventricle. Such a measure can be obtained by evaluating the force-velocity relationship with a correction for myocardial fiber length. The force-velocity relation can be expressed as the ratio of maximum rate of pressure rise to maximum isovolumetric pressure, a quantity which was described by Hill as the maximum rate of proportional rise of pressure and which is similar to the velocity constant of a chemical reaction. Division of this ratio by an estimate of ventricular circumference corrects for variations due to differences in initial fiber length. This index was evaluated in 11 normal subjects and 46 patients with cardiac disease during left heart catheterization. Maximum rate of pressure rise was obtained by electronic differentiation of the ventricular pressure pulse, and ventricular circumference, assuming a spherical ventricle, was calculated from volumes measured by indicator washout. The contractility index of normal subjects did not differ from that of patients with mitral stenosis, atrial septal defect, or chronic pulmonary disease (patients without left ventricular overloading). In contrast, in patients with left ventricular failure, the indices were more than two standard deviations below the mean value for normal subjects. Such a reduction was not noted in patients with pressure or volume overloading of the left ventricle before the onset of myocardial failure. During exercise, the index rose uniformly in patients without left ventricular disease, responded variably in compensated patients with volume or pressure overloading, and was virtually unchanged in patients with left ventricular decompensation. The administration of isoproterenol or digitalis resulted in increased contractility regardless of the patient's status. It is concluded that the use of this index in physiologic studies of the ventricle and in diagnostic and therapeutic decisions is justified.
Effects of Varenicline on Smoking Cessation in Adults With Stably Treated Current or Past Major Depression
Authors: Robert M. Anthenelli, Chad Morris, Tanya S. Ramey, Sarah J. Dubrava, Kostas Tsilkos, Cristina Russ, Carla Yunis
Journal: Annals of Internal Medicine (2013)

Chinese translationDepression is overrepresented in smokers.To evaluate smoking abstinence and changes in mood and anxiety levels in smokers with depression treated with varenicline versus placebo.Phase 4, multicenter, parallel, 1:1 allocation, double-blind, randomization trial. Randomization, stratified by antidepressant use and depression score at baseline, was blocked in sizes of 4. (ClinicalTrials.gov: NCT01078298).38 centers in 8 countries.525 adult smokers with stably treated current or past major depression and no recent cardiovascular events.Varenicline, 1 mg twice daily, or placebo for 12 weeks, with 40-week nontreatment follow-up.Primary outcome was carbon monoxide-confirmed continuous abstinence rate (CAR) for weeks 9 to 12. Other outcomes included CARs assessed during nontreatment follow-up and ratings of mood, anxiety, and suicidal ideation or behavior.68.4% versus 66.5% of the varenicline and placebo groups, respectively, completed the study. Varenicline-treated participants had higher CARs versus placebo at weeks 9 to 12 (35.9% vs. 15.6%; odds ratio [OR], 3.35 [95% CI, 2.16 to 5.21]; P < 0.001), 9 to 24 (25.0% vs. 12.3%; OR, 2.53 [CI, 1.56 to 4.10]; P < 0.001), and 9 to 52 (20.3% vs. 10.4%; OR, 2.36 [CI, 1.40 to 3.98]; P = 0.001). There were no clinically relevant differences between groups in suicidal ideation or behavior and no overall worsening of depression or anxiety in either group. The most frequent adverse event was nausea (varenicline, 27.0%; placebo, 10.4%). Two varenicline-group participants died during the nontreatment phase.Some data were missing, and power to detect differences between groups was low in rare events. Smokers with untreated depression, with co-occurring psychiatric conditions, or receiving mood stabilizers and antipsychotics were not included.Varenicline increased smoking cessation in smokers with stably treated current or past depression without exacerbating depression or anxiety.Pfizer.
Establishing a Milk Specific IgE Decision Point in IgE Mediated Cow'S Milk Allergy (CMA) Patients from a Tertiary Pediatric Brazilian Center
Authors: A.K.F. Gushken, A.P.M. Castro, A.C. Pastorino, E. Ciccone, R.F.F. Gonçalves, C.M.A. Jacob
Journal: Journal of Allergy and Clinical Immunology (2006)
Toward Advancing Nano-Object Count Metrology: A Best Practice Framework
Authors: Scott C. Brown, Volodymyr Boyko, Greg Meyers, Matthias Voetz, Wendel Wohlleben
Journal: Environmental Health Perspectives (2013)

A movement among international agencies and policy makers to classify industrial materials by their number content of sub-100-nm particles could have broad implications for the development of sustainable nanotechnologies.
Subclinical Pellagra and Idiopathic Hypogeusia
Authors: R. F. Green
Journal: JAMA (1971)

To the Editor.—  Idiopathic hypogeusia with dysgeusia, hyposmia and dysosmia cannot be called a new syndrome or a new disease. Frostig and Spies mentioned these psychosensory disturbances in 1939. 1   They are but a part of a very old disease which causes the perception to change—perceptual dysfunction, as result of a vitamin B 3 deficiency. The disease is subclinical pellagra and the cure is niacin.  Subclinical pellagra is a deficiency syndrome characterized by the presence of perceptual changes affecting any or all of the special and properioceptive senses, associated with neurasthenia. It is due to a deficiency of or an increased demand for niacin, the administration of which causes prompt disappearance of the symptom complex. 2   Henkin et al have discovered changes in perception involving only two of the special senses—taste and smell. I would predict that 90% of these cases could fulfill the criteria for subclinical pellagra. In my
The Impact of the Capability of Circulating Progenitor Cell to Differentiate on Myocardial Salvage in Patients With Primary Acute Myocardial Infarction
Authors: Yasushi Numaguchi, Takahito Sone, Kenji Okumura, Masakazu Ishii, Yasuhiro Morita, Ryuji Kubota, Kazuhiko Yokouchi, Hajime Imai, Mitsunori Harada, Hiroyuki Osanai, Takahisa Kondo, Toyoaki Murohara
Journal: Circulation (2006)

Circulating endothelial progenitor cells (EPCs) are known to be involved in vasculogenesis and mobilized after acute myocardial infarction (AMI). To test the hypothesis that the angiogenic function of EPCs affects post-myocardial infarction (MI) myocardial salvage, we evaluated the number and potential differentiation of EPCs and compared these data with clinical parameters 6 months after MI.Consecutive 51 patients (age, 61+/-8 years, mean+/-SD) with primary AMI who were successfully treated with stenting were enrolled. EPC identified as CD45low, CD34+, CD133+, and VEGFR2+ was quantified by a flow cytometry. The potential of EPCs to differentiate into endothelial cells (EPC differentiation) was also confirmed by the upregulation of CD31 and VEGFR2 after 7 days of culture. According to the proportion of EPC fraction, patients were divided into 2 groups (cut-off value=median). Although no difference was seen in myocardial damage shown by mean peak CK leakage and mean area at risk between the differentiated group (n=26) and nondifferentiated group (n=25), the number of attached cell was greater in differentiated group than in the nondifferentiated group (P=0.023). Left ventricular function and ischemic damaged area were assessed by scintigraphic images of (123)I-BMIPP in the acute phase and (99m)Tc-tetrofosmin in the chronic phase. We found that a greater increase in myocardial salvage (P=0.0091), decrease in end-systolic volume (P=0.012), and recovery of ejection fraction (P=0.011) occurred in the group with differentiated EPCs than in the nondifferentiated group.In patients with primary AMI, the capability of EPCs to differentiate influences the functional improvement and infarct size reduction, indicating that manipulation of EPCs could be a novel therapeutic target to salvage ischemic damage.
Serine/Arginine Protein–Specific Kinase 2 Promotes Leukemia Cell Proliferation by Phosphorylating Acinus and Regulating Cyclin A1
Authors: Sung-Wuk Jang, Seung-ju Yang, Åsa Ehlén, Shaozhong Dong, Hanna Khoury, Jing Chen, Jenny L. Persson, Keqiang Ye
Journal: Cancer Research (2008)

Abstract Serine/arginine (SR) protein–specific kinase (SRPK), a family of cell cycle–regulated protein kinases, phosphorylate SR domain–containing proteins in nuclear speckles and mediate the pre-mRNA splicing. However, the physiologic roles of this event in cell cycle are incompletely understood. Here, we show that SRPK2 binds and phosphorylates acinus, an SR protein essential for RNA splicing, and redistributes it from the nuclear speckles to the nucleoplasm, resulting in cyclin A1 but not A2 up-regulation. Acinus S422D, an SRPK2 phosphorylation mimetic, enhances cyclin A1 transcription, whereas acinus S422A, an unphosphorylatable mutant, blocks the stimulatory effect of SRPK2. Ablation of acinus or SRPK2 abrogates cyclin A1 expression in leukemia cells and arrest cells at G1 phase. Overexpression of acinus or SRPK2 increases leukemia cell proliferation. Furthermore, both SRPK2 and acinus are overexpressed in some human acute myelogenous leukemia patients and correlate with elevated cyclin A1 expression levels, fitting with the oncogenic activity of cyclin A1 in leukemia. Thus, our findings establish a molecular mechanism by which SR splicing machinery regulates cell cycle and contributes to leukemia tumorigenesis. [Cancer Res 2008;68(12):4559–70]
Liddle’s syndrome mutations disrupt cAMP-mediated translocation of the epithelial Na+ channel to the cell surface
Authors: Peter M. Snyder
Journal: Journal of Clinical Investigation (2000)

The epithelial Na+ channel (ENaC) plays a critical role in Na+ absorption, and mutations in this channel cause diseases of Na+ homeostasis, including a genetic form of hypertension (Liddle's syndrome). To investigate cAMP-mediated stimulation of ENaC, α, β, and γENaC were coexpressed in Fischer rat thyroid epithelia to generate apical Na+ channels and transepithelial Na+ current. cAMP agonists stimulated Na+ current by 70%. Following covalent modification of cysteines introduced into ENaC, cAMP increased the rate of appearance of unmodified channels at the cell surface. In addition, cAMP increased the fluorescent labeling of ENaC at the apical cell surface. Inhibition of vesicle trafficking by incubating epithelia at 15°C prevented the cAMP-mediated stimulation of ENaC. These results suggest that cAMP stimulates Na+ absorption in part by increasing translocation of ENaC to the cell surface. Stimulation of ENaC by cAMP was dependent on a sequence (PPPXY) in the COOH terminus of each subunit. This sequence is the target for mutations that cause Liddle's syndrome, suggesting that cAMP-mediated translocation of ENaC to the cell surface is defective in this genetic form of hypertension.
Analysis of cranial neural crest distribution in the developing heart using quail-chick chimeras.
Authors: M T Phillips, M L Kirby, G Forbes
Journal: Circulation Research (1987)

Previous studies have shown that ablation of cranial neural crest results in heart malformations in chick embryos. Cranial neural crest cells populate all of the pharyngeal arches and provide the mesenchymal walls of the aortic arch arteries. Neural crest cells migrate from the pharyngeal apparatus into the outflow region of the heart. However, it is not known which of the pharyngeal arches contribute ectomesenchyme to the developing heart nor has a pattern of distribution in the outflow region been established. In the present study, premigratory presumptive arch neural crest from quail embryos was grafted homotopically onto early chick embryos. On Day 6 of incubation, the chimeric embryos were fixed and processed for histological evaluation. The neural crest providing mesenchyme to pharyngeal arches 1 and 2 was not associated with the developing heart. Neural crest presumptive for arches 3, 4, and 6 was found distributed to the outflow region of the heart. Neural crest from arch 4 contributed the largest number of cells to the developing aorticopulmonary and conotruncal septa. This information indicates that ablations of neural crest presumptive for arches 3, 4, and 6 influence heart development directly while lesions of other areas of cranial neural crest probably influence heart development only secondarily with the primary effects occurring in the pharyngeal arches.