US Dept Research Articles

Abstract 1672: Ganoderma lucidum (Reishi) induces autophagy in inflammatory breast cancer cells to promote cell death.

Abstract Autophagic cell death is an important physiological cell death process that is characterized by massive degradation of cellular contents by means of intracellular membrane/vesicle reorganization and lysosomal activity. Herein, we test the autophagy inducing effects of the medicinal mushroom Ganoderma lucidum (Reishi) in the inflammatory breast cancer (IBC) cell line, SUM-149. IBC is a rare, lethal and aggressive form of advanced breast cancer with poor prognosis and no targeted therapy. Because the mechanism is not well defined, some autophagic cell death events might be attributed to apoptosis. This death or survival mechanism depends on cell type and cells stress, since in such cases the induction of both, autophagy and other pro-death signals (i.e. BAX), occur in parallel. Our hypothesis is that Reishi induces autophagy in IBC cells to promote cell death. SUM-149 cells were treated with 0.5mg/mL of Reishi for 2h, 4h, 6h, 8h, 12h and 24h. Cells were lysed and equal total protein was western blotted against Beclin-1, Atg5, Atg12 and LC3B autophagy proteins. To confirm autophagy effects on cell viability, cells were treated with 3-methyladenine (3-MA), chloroquine (CQ) and PP242 with or without Reishi for 24 hours. Cells were fixed and stained with propidium iodide to assess viable nuclei. Herein we show that Reishi affects the expression of autophagy-associated molecules depending on treatment time. Reishi increases the expression of autophagy proteins in IBC. Moreover, the autophagy inhibitors increased cell viability after 24h, while cancer cell viability decreased when Reishi was added. Autophagy inducer PP242 alone and in combination with Reishi decreased cell viability and induced the expression of the pro-apoptotic protein, BAX. Thus, we demonstrate that Reishi induces autophagy, promoting cell death in IBC cells, as cancer cell viability is reduced, with a subsequent increase in pro-apoptotic protein expression when Reishi is added. Our findings are the first to show a novel mechanism responsible for the inhibition of IBC cell viability by Reishi demonstrating its potential for use in treatment of cancer. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM. Citation Format: Raysa Rosario-Acevedo, Tiffany Rios, Ivette Suarez-Arroyo, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) induces autophagy in inflammatory breast cancer cells to promote cell death. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1672. doi:10.1158/1538-7445.AM2013-1672

Abstract 2247: Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib.

Abstract Inflammatory Breast Cancer (IBC) is a unique and aggressive cancer where tumor spheroids invade the dermal lymphatics causing the inflammatory phenotype. IBC cell lines and human tissues overexpress plasma membrane proteins such as E-cadherin and Epidermal Growth Factor Receptor (EGFR), which are associated with maintaining tumor spheroid integrity, increased IBC tumor growth rate, invasion and metastasis. Since IBC tumor cell emboli are more efficient at forming metastases and are more resistant to chemo and radiotherapy than single cells, it seems feasible to prevent IBC with a compound that has the ability to disintegrate the cell spheroids. Our published data shows that the medicinal mushroom, Ganoderma lucidum (Reishi), inhibits IBC progression via disintegration of tumor spheroids. Thus, we aimed to investigate Reishi's in vitro and in vivo therapeutic potential in IBC, focusing on the regulation of E-cadherin and EGFR and its contribution to the IBC cellular response when treated with the EGFR Tyrosine Kinase Inhibitor (TKI), erlotinib (commercially known as Tarceva®). Herein, we show that Reishi downregulates E-cadherin and EGFR abundance in vitro, significantly reduces tumor growth by 58%, and downregulates in vivo EGFR, and E-cadherin protein expression. Moreover, a synergistic effect is observed when erlotinib and Reishi are used simultaneously after 72 hours of treatment. Since Reishi downregulates the expression of E-cadherin and EGFR, our subsequent investigations will focus on the identification of PM proteins using stable isotope labeling with amino acids in cell culture (SILAC). Our results provide evidence that Reishi downregulates key proteins overexpressed in IBC, and chemosensitizes IBC cells to erlotinib therapy, highlighting its anti-IBC-therapeutic potential. This project was sponsored by Title V PPOHA US Dept of Education #P031M105050 to UCC, NIH/RCMI #2G12RR003035 to UCC, NIH/INBRE #5P20RR016470 to UPR/UCC, NIH/NCRR #U54RR026139 to UPR/UCC, and a research donation from the Commonwealth of Puerto Rico to UCC-Centro Universitario de Medicina Integral y Complementaria (CUMIC) / MMM. Citation Format: Ivette Suarez-Arroyo, Raysa Rosario-Acevedo, Alexandra Aguilar-Pérez, Luis A. Cubano, Michelle M. Martínez-Montemayor. Ganoderma lucidum (Reishi) downregulates key proteins overexpressed in IBC and chemosensitizes EGFR-overexpressing cells to erlotinib. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 2247. doi:10.1158/1538-7445.AM2013-2247

State of Medical Home Education in Pediatric Residency Programs

The US Dept of Health and Human Services, via Healthy People 2020 (HP 2020), identifies health goals for the coming decade. One goal is fostering medical homes that are family-centered, culturally-competent, comprehensive, coordinated systems for all children, including those with special health needs. To achieve this goal, physicians must understand the medical home, beginning in training. A workgroup comprised of members from the AAP, National Center for Medical Home Implementation, APPD, APA, residents, national experts and families was established to create a flexible, standardized medical home curriculum for training programs.

Abstract 1987: Ganoderma lucidum (Reishi) suppresses key protein synthesis initiation molecules in inflammatory breast cancer

Abstract Inflammatory breast cancer (IBC) is an aggressive and lethal type of breast cancer. IBC's lethality originates from its nature of invading the lymphatic system and to the absence of a palpable tumor mass. Pathogenic properties of IBC result in part from deregulation of the eukaryotic translation initiation factor (eIF4G), which is activated via the mammalian target of rapamycin (mTOR) pathway. Active mTOR signaling liberates eukaryotic translation initiation factor 4E (eIF4E) through the hierarchical phosphorylation of eIF4E binding protein (4E-BP). When hypophosphorylated, 4E-BP associates with eIF4E, preventing eIF4E from binding eIF4G, blocking the formation of the eIF4F translation initiation complex; thus, impeding protein translation. Therefore therapeutics that target eIF4G in IBC are of great interest. Ganoderma lucidum (Reishi) is a medicinal mushroom used to prevent and treat many diseases including cancer. We recently reported that Reishi inhibits eIF4G expression after 24h of treatment in the SUM-149 IBC patient derived cell line. Therefore, we investigated the therapeutic potential of Reishi mushroom in IBC cells in vitro and in vivo, focusing on the regulation of mTOR and direct downstream effectors: 4E-BP1 and the ribosomal protein p70S6K. Herein, we show that Reishi treatment of SUM-149 cells impacts protein synthesis initiation via inhibition of the mTOR pathway leading to hypophosphorylation of 4E-BP1. Accordingly, Reishi downregulates mTOR protein levels, 4E-BP1 phosphorylation, maintains eIF4E levels and decreases p70S6k and eIF4G expression, potentially leading to reduced eIF4F translation initiation complex levels after 6h of treatment. To further investigate Reishi's therapeutic effects in vivo, we studied IBC progression of SUM-149 subcutaneous tumors in severe combined immunocompromised (SCID) mice. Following tumor establishment, mice were gavaged every day with vehicle or Reishi at 28mg/kg BW for 13 weeks. Tumor progression was quantified by caliper measurements, followed by analysis of excised organs for protein expression. Results show that Reishi significantly reduced tumor growth by 58% compared to vehicle controls. Moreover, mTOR, eIF4E, eIF4G, E-cadherin, p4E-BP1 and p70S6k expression decreases in the SUM-149 tumors from mice treated with Reishi. Our results provide evidence that Reishi suppresses key molecules that are important for protein synthesis initiation in IBC, thus highlighting the potential of Reishi as a natural anti-IBC-therapeutic. This project was sponsored by Title V PPOHA grant number P031M105050 from the US Dept of Education to UCC, and NIH/RCMI 2G12RR003035 to UCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1987. doi:1538-7445.AM2012-1987

Abstract 1992: Ganoderma lucidum (Reishi) induces autophagy in inflammatory breast cancer by regulation of the mTOR signaling pathway

Abstract The control of cell growth by the mammalian target of rapamycin (mTOR) signaling pathway and autophagy are relevant to disease, as altered regulation of either pathway may result in tumorigenesis. Autophagy is a regulated pathway involving the lysosomal degradation of cytoplasmic components and organelles. Activation of the human autophagy-initiation kinase (ULK1) is directly controlled by mTOR and is a critical part of the autophagy machinery. In this study we test the autophagy inducing effects of the medicinal mushroom Ganoderma lucidum (Reishi) in the patient derived inflammatory breast cancer (IBC) cell line SUM-149 and in the non-cancerous mammary epithelial cell line MCF10A. IBC is a rare, lethal and aggressive form of locally advanced breast cancer that has a poor prognosis and no targeted therapy. Herein, we demonstrate that Reishi modulates the expression of autophagy related molecules depending on treatment time. At 2h post-Reishi treatment SUM-149 cells show that ULK1, Atg5, Atg12, Beclin1 and the microtubule-associated protein 1 light chain 3 (LC3) are α1.2 fold upregulated. Furthermore, autophagosomal structures were identified in SUM-149 but not in MCF10A Reishi treated cells. At 4h post-Reishi Atg5 and Atg12 (required for phagophore formation) are ∼1.5 fold upregulated, while at 6h LC3 expression (involved in autophagosome formation) is ∼2 fold upregulated compared to vehicle. We also show that autophagy induction in SUM-149 cells is mediated via downregulation of the PI3K/mTOR signaling pathway. Reishi downregulates PI3K (p85 and p110), mTOR phosphorylation and reduces the expression of Raptor, which is the regulatory subunit of mTORC1, the complex that directly regulates proteins involved in autophagy. Rictor, the regulatory subunit of the mTORC2 complex, which inhibits autophagy indirectly through Akt is also downregulated by Reishi. We demonstrate that Reishi has great potential to be used as an anti-IBC-therapeutic. This project was sponsored by Title V PPOHA grant number P031M105050 from the US Dept of Education to UCC, and NIH/RCMI 2G12RR003035 to UCC. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1992. doi:1538-7445.AM2012-1992

Treatment-Refractory OCD Responding to Maintenance Electroconvulsive Therapy

Treatment-Refractory OCD Responding to Maintenance Electroconvulsive Therapy

Mass‐spectrometric analysis of changes in brain lipid expression and distribution after brain injury

Mechanical impact injuries to the cortex of rats induce neuronal loss, vascular damage, glial activation, infiltration of circulating immune cells, and edema, followed by partial revascularization, partial neuronal recovery and remodeling of neuronal connectivity. We report here changes in lipid metabolism in the region of injury after a controlled cortical impact (CCI) injury to the cortex of anesthetized Sprague‐Dawley rats. At selected time points after induction of a CCI injury inducing tissue damage and subsequent loss of some cortical tissue but not major functional impairment, brains were removed and processed for imaging mass spectrometry of 16 μm coronal sections through the region of injury. Following injury, significant time‐related changes in numerous lipid species in both gray and white matter around and through the site of injury were observed. Specifically, increases and decreases in the levels of specific sphingomyelin species were noted at 24 hrs, 3 days and 7 days after CCI injury. Phosphatidylcholine 36a:2 was found in greater abundance in both grey and white matter in the area of injury than in the contralateral cortex, while another phosphatidylcholine 38:4 showed no change in distribution between sham and injured animals. Lipid imaging presents new insights into the cellular consequences of injury, (Supported by US Dept of Defense through the CNRM).

Distance Education: Current Issues and Future Implications

This paper will explore the current state and literature regarding distance education in higher education. The US Department of Education reports, “In the 2006-2007 academic year, institutions reported an estimated 12.2 million enrollments in college-level credit-granting distance education courses” (US Dept of Education, 2009. p.3). With the steady rise of access to education, programs have been developed at most institutions to remain competitive and prepare to accommodate an increase of adult learners and students in remote locations. However, with quick growth, critics have questioned everything about distance education. Problems with quality, support services and developing new learning techniques to engage and encourage learners in a completely online setting have been at the forefront of the debate. This paper will review the successes and challenges associated with online learning and provide a basis for future implications of how higher education can embrace and promote distance learning.

Coitus Interruptus Is Not Contraception

To the Editor: In the article by Sznitman et al.,1 the authors suggest that because 60% of the adolescents in their study reported use of coitus interruptus, “sexual educators need to honestly acknowledge withdrawal can prevent pregnancy.” The probability of coitus interruptus failure is estimated to be 18.8% during the first 12 months of use.2 Furthermore, an estimated 27% of women users of coitus interruptus have an unintended pregnancy during the first year of use.3 We assert that coitus interruptus should never be presented to adolescents, or any person, as a valid method of contraception. The American College of Obstetrics and Gynecology, Planned Parenthood Federation of America, the Office of Women's Health (in the US Dept of Health and Human Services) (available at: http://www.womenshealth.gov/faq/birth-control-methods.cfm, accessed July 10, 2009) and US Centers for Disease Control and Prevention (available at: http://www.cdc.gov/reproductivehealth/UnintendedPregnancy/Contraception.htm, accessed July 10, 2009) do not include coitus interruptus in their lists of contraceptive methods. Planned Parenthood, in fact, strongly recommends to adolescents not to practice coitus interruptus because of their inexperience (available at: http://www.plannedparenthood.org/teen-talk/birth-control-teens/teens-pull-out-method-25381.htm, accessed July 10, 2009). Sznitman et al.1 rightly advocate for condom promotion as respondents who reported inconsistent condom use and withdrawal were 2.22 (95%CI [1.06, 4.66]) times as likely to have a sexually transmitted infection as consistent condom users. Condoms alone, however, are not a highly effective method for preventing pregnancy, especially among adolescents; an estimated 15% to 17% of condom users will become pregnant during the first year of use.2,4 Up to 7.5% of adolescent girls, ages 15 to 19, become pregnant in 1 year5; about half of them give birth, one-third have abortions, and the remainder miscarry (or have stillbirths).5 Furthermore, between 2005 and 2007, the teen birth rate increased by 5% and, in 2007, 4.2% of adolescents gave birth.6 These statistics signal the need for renewed action of promoting dual method use of condoms and contraceptive methods.7,8 Because adolescents experience elevated rates of sexually transmitted infections and unintended pregnancy, health practitioners and educators must provide a holistic approach to protecting the reproductive health of adolescents. Irene A. Doherty, PhD, MPH Department of Medicine Division of Infectious Diseases School of Medicine University of North Carolina Chapel Hill, NC Gretchen S. Stuart, MD, MPHTM, FACOG Department of Obstetrics and Gynecology School of Medicine University of North Carolina Chapel Hill, NC

Commentary: Making a Difference in Emergency Medical Services

Commentary: Making a Difference in Emergency Medical Services

Commentary

Commentary

Exploratory Analyses of the U.S. Housing Bubble with Kolmogorov Entropy and Principal Component Analysis (PCA)

In this paper we develop an exploratory non-parametric clustering model of spatial and/or spatio-temporal phenomena based on Kolmogorov entropy. The methodology will be tested using quarterly HPI (Housing Price Index) data for 350 plus cities in the US from the Federal Financing and Housing Administration (FHFA), an agency of HUD (US Dept of Housing and Urban Development). This multivariate data will be also analyzed with Principal Component Analysis (PCA) techniques to identify key regions involved in creating the housing bubble and its spread to the rest of cities.

Nursing policy research: turning evidence-based research into health policy

This book describes key issues related to the dwindling nurse supply, most of the causes of which are well known, and outlines recent research and strategies to enhance the recruitment, education, and retention of the nursing workforce. It emphasizes the role of doctoral prepared nurses in health care policy development and illustrates how research findings can be utilized to generate evidence-based policies that support growth in the workforce. It fosters improvements in all nursing work environments to assure long-term retention.Contributors represent leading academic institutions, foundations, health policy groups including the Agency for Healthcare Research & Quality (US Dept of Health & Human Services), and nursing centers focusing on workforce research and policy.This book covers latest research findings on nurse staffing levels and patient outcomes and nurse recruitment and retention. It examines nursing education issues such as the faculty shortage, recruitment of high school students, and the role of clinical simulation in teaching. It describes how nursing workforce centers are combating the nursing shortage, effective methods to forecast nurse supply and demand, and how to secure funding for workforce projects.

The Economics of Enteric Infections: Human Foodborne Disease Costs

The World Health Organization estimates that in 2005, 1.5 million people died, worldwide, from diarrheal diseases. A separate study estimated that 70% of diarrheal diseases are foodborne. The widely cited US estimate is that there are 76 million foodborne illnesses annually, resulting in 325,000 hospitalizations and 5200 deaths. However, there are epidemiologic and methodologic challenges to accurately estimate the economic burden of foodborne disease on society, either in terms of monetary costs or non-monetary units of measurement. Studies on the economic burden of foodborne disease vary considerably: some analyze the effects of a single pathogen or a single outbreak, whereas others attempt to estimate all foodborne disease in a country. Differences in surveillance systems, methodology, and other factors preclude meaningful comparisons across existing studies. However, if it were possible to completely estimate the societal costs for all acute foodborne diseases and their chronic sequelae worldwide, on the basis of currently available data, worldwide costs from these illnesses would be substantial. Moreover, foodborne infections are largely manifested as intestinal illnesses and are largely preventable. Total costs of foodborne disease would be much smaller in the United States and the world if economic incentives for industry to produce safer food were improved. However, costs of implementing new food safety prevention and control rules must be weighed against the estimated benefits of reducing foodborne disease to determine net benefits so that governments have information to efficiently allocate funds among competing programs.

Misunderstanding Of SPF Sunscreen Rating Among Varying Sport And Physical Activity Participants

PURPOSE: The purpose of this study was to evaluate knowledge of the skin protection factor (SPF) rating among various physical activity groups. The SPF factor is commonly used in labeling for sunscreens and, now, for clothing. METHODS: A total of 1208 submitted answers to a demographic and 10 question T/F survey. Each participant listed activities in which they participate. Surveys were distributed during regional health fairs, skin cancer screenings, medical school classes, and dermatology and surgical oncology patient visits. Knowledge of SPF was measured by the true/false survey statement: "SPF (sun protection factor) represents the number of minutes a person can be out in the sun with sunscreen on and be getting the same amount of UV rays as if they were out in the sun with no sunscreen on for one minute." RESULTS: In the groups listed, the above true statement was the most or 2nd to most incorrectly answered. In this survey, all ten statements are true for the purpose of being an educational tool. Participants may have been able to discern the answer pattern. Because of this, the percentage of correct answers to the SPF question is probably skewed high. In a future study, we plan to administer a revised survey instrument with a mix of true and false statements to specific sports teams.Table: No caption providedCONCLUSION: Even though "SPF" is a commonly used acronym indicating the level of sun protection offered in sunscreen and clothing, many people do not understand what SPF actually means. With ACSM and AHA guidelines and their support of the US Dept of Health and Human Services (DHHS) physical activity guidelines, we recommend that the ACSM address skin cancer prevention education, and, in particular, the promotion of accurate understanding of SPF nomenclature.

Diagnostic Errors—The Next Frontier for Patient Safety

1. Vevers V. Obama says WH will remain smoke-free. http://www.cbsnews.com /blogs/2008/12/08/politics/politicalhotsheet/entry4654231.shtml. Accessed December 9, 2008. 2. Reinberg S. Cancer to surpass heart disease as world’s leading killer. washingtonpost .com Web page. December 9, 2008. http://www.washingtonpost.com /wp-dyn/content/article/2008/12/09/AR2008120901814.html. Accessed December 10, 2008. 3. Centers for Disease Control and Prevention. Cigarette smoking among adults—United States, 2007 [published correction appears in MMWR Morb Mortal Wkly Rep. 2008;57(47):1281]. MMWR Morb Mortal Wkly Rep. 2008; 57(45):1221-1226. 4. Centers for Disease Control and Prevention. Smoking-attributable mortality, years of potential life lost, and productivity losses—United States, 2000-2004. MMWR Morb Mortal Wkly Rep. 2008;57(45):1226-1228. 5. American Nonsmokers’ Rights Foundation. Summary of 100% smokefree state laws and population protected by 100% US smokefree laws. January 4, 2009. http: //www.no-smoke.org/pdf/SummaryUSPopList.pdf. Accessed December 12, 2009. 6. Risbeck CA. ADHA smoking cessation initiative liaisons, II: partnering with tobacco quitlines. November 2007. http://findarticles.com/p/articles/mi_m1ANQ /is_/ai_n25015057. Accessed December 9, 2008. 7. WHO Framework Convention on Tobacco Control: third session of the conference of the parties to the WHO FCTC. http://www.who.int/fctc/en/. Accessed January 10, 2009. 8. Fiore M, Croyle RT, Curry SJ, et al. Preventing 3 million premature deaths and helping 5 million smokers quit: a national action plan for tobacco cessation. Am J Public Health. 2004;94(2):205-210. 9. Peto R, Lopez A. The future worldwide health effects of current smoking patterns. In: Boyle P, Gray N, Henningfield J, Seffrin J, Zatonski W, eds. Tobacco and Public Health: Science and Policy. New York, NY: Oxford University Press; 2004: 281-286. 10. Mackay J, Erikson M, Shafey O. The Tobacco Atlas. 2nd ed. Atlanta, GA: American Cancer Society; 2006. 11. Fiore MC, Jaen CR, Baker TB, et al. Treating tobacco use and dependence: 2008 update. Rockville, MD: US Dept of Health and Human Services; May 2008. http://www.surgeongeneral.gov/tobacco/. Accessed February 5, 2009. 12. National Institute of Allergy and Infectious Dieseases. Treatment of HIV infection. http://www.niaid.nih.gov/factsheets/treat-hiv.htm. Updated November 8, 2007. Accessed February 8, 2009. 13. CEO Roundtable on Cancer Web page. http://www.ceoroundtableoncancer .org. Accessed December 19, 2008.

Statement of EFSA on a study associating bisphenol A with medical disorders

EFSA JournalVolume 6, Issue 10 838 GuidanceOpen Access Statement of EFSA on a study associating bisphenol A with medical disorders European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author European Food Safety Authority (EFSA), European Food Safety Authority (EFSA)Search for more papers by this author First published: 24 October 2008 https://doi.org/10.2903/j.efsa.2008.838Citations: 2 Acknowledgement: This statement was prepared by the EFSA Unit on food contact materials, enzymes, flavourings and processing aids (CEF) and the Unit on Assessment Methodology (AMU). EFSA wishes to thank the following members of the CEF Panel for their scientific advice during the drafting of this statement: Jean-Claude Lhuguenot, Wim Mennes and Detlef Woelfle. Adoption date: 22 October 2008 Published date: 24 October 2008 Question number: EFSA-Q-2008-702 AboutPDF ToolsExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinkedInRedditWechat No abstract is available for this article. References Centers for Disease Control and Prevention (CDC). 2004. National Health and Nutrition Examination Survey Data 2003–04. Hyattsville, MD: US Dept of Health and Human Services, CDC; 2004. EFSA (2006). Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to 2,2-BIS(4-HYDROXYPHENYL) PROPANE (Bisphenol A). The EFSA Journal (2006), 428, 1– 75. www.efsa.europa.eu/EFSA/efsa_locale-1178620753812_1178620772817.htm Lang, I., Galloway, T., Scarlet, A., Henley, W., Depledge, M., Wallace R. and Melzer, D. 2008. Association of Urinary Bisphenol A Concentration With Medical Disorders and Laboratory Abnormalities in Adults. Journal of the American Medical Association. 2008; 300(11): 1303– 1310 jama.ama-assn.org/cgi/content/full/300.11.1303 Citing Literature Volume6, Issue10October 2008838 ReferencesRelatedInformation

Beyond Established and Novel Risk Factors

Dyslipidemia, hypertension, and diabetes mellitus have been appropriately highlighted as established predictors of cardiovascular disease. These risk factors have become preeminent targets for influencing cardiovascular risk; their assessment, treatment, and monitoring are major emphases of clinical care, research investigation, treatment guidelines, organization position papers, and measures of physician and hospital performance. Notably, lifestyle risk factors, including dietary habits, physical inactivity, smoking, and adiposity, strongly influence the established cardiovascular risk factors and also affect novel pathways of risk such as inflammation/oxidative stress, endothelial function, thrombosis/coagulation, and arrhythmia. Furthermore, modest alterations of these lifestyle risk factors are achievable and have substantial effects on cardiovascular risk. Thus, basic lifestyle habits should be considered fundamental risk factors for cardiovascular disease. Although efforts to combat established and novel risk factors with pharmacological treatments are important and should continue, we call for a systematic rebalancing of current research, clinical care, and policy efforts to focus more on lifestyle. The rising costs of healthcare and the epidemics of overweight and obesity highlight the inadequacies of our current strategy. Substantially more resources should be directed toward research on lifestyle risk factors, their determinants, and effective interventions to change them. The clinical evaluation and treatment of dietary, physical activity, and smoking habits must become as routine and familiar as assessment of blood pressure, cholesterol, and glucose levels. Major policy initiatives and reimbursement guidelines must also be rebalanced to emphasize lifestyle risk factors. Cardiovascular diseases are leading causes of death and disability among men and women in nearly all nations.1 Identification of persons at higher or lower risk for cardiovascular events is important to facilitate effective use of resources and interventions to reduce disease burden among individuals and in society. Each of the established risk factors for cardiovascular disease—age, gender, dyslipidemia, hypertension, diabetes mellitus, and smoking—have been appropriately highlighted …

Treatment of Tobacco Dependence

Cigarette smoking continues to cause substantial death and disability, but more than 1 in 5 adults smoke despite the desire among most smokers to stop and the availability of effective treatments. A systematic process to identify all smokers is crucial. Because tobacco dependence is characterized by relapses and remissions, clinicians should be ready to engage smokers and reengage relapsed smokers with options for new medication strategies and additional counseling resources.

Smooth muscle responsiveness to IL-13 is sufficient for IL-13 induction of airway hyperresponsiveness (AHR) (39.6)

Abstract IL-13 is the primary inducer of AHR in mouse models of asthma and increases contractility of isolated muscle cells in vitro and the contractility of intestinal smooth muscle in worm-infected mice. Consequently, we evaluated whether smooth muscle responsiveness to IL-13 is sufficient for development of AHR in mice inoculated intratracheally with IL-13. The smooth muscle-specific promoter SMP8 was used to generate mice that express IL-4Rα only on smooth muscle cells (SMonly mice, produced by crossing SMP8-IL-4Rα transgenic mice to IL-4Rα-deficient mice). SMonly mice failed to develop goblet cell hyperplasia or BAL eosinophilia in response to intratracheal IL-13 but developed AHR to inhaled methacholine to the same extent as wild-type mice when tested by barometric plethysmography with a Buxco apparatus and significant, albeit reduced AHR to injected acetylcholine when anesthetized, intubated and evaluated by the airway time-pressure index (APTI) technique. Thus, smooth muscle expression of IL-4Rα is sufficient for IL-13 induction of AHR and this is not dependent on goblet cell hyperplasia or pulmonary eosinophilia. Studies designed to determine whether smooth muscle expression of IL-4Rα is necessary for IL-13 induction of AHR are in progress. Supported by the US Dept of Veterans Affairs and NIH.