Science.gov

Sample records for prevention targets examples

  1. Research-to-policy translation for prevention of disordered weight and shape control behaviors: A case example targeting dietary supplements sold for weight loss and muscle building.

    PubMed

    Austin, S Bryn; Yu, Kimberly; Tran, Alvin; Mayer, Beth

    2017-04-01

    New approaches to universal eating disorders prevention and interventions targeting macro-environmental change are greatly needed, and research-to-policy translation efforts hold promise for advancing both of these goals. This paper describes as a policy-translation case example an academic-community-government partnership of the Strategic Training Initiative for the Prevention of Eating Disorders, Multi-Service Eating Disorders Association, and the office of Massachusetts Representative Kay Khan, all based in Massachusetts, USA. The partnership's research-to-policy translation project focused on dietary supplements sold for weight loss and muscle building, which have been linked with serious injury and death in consumers. Youth and people of all ages with eating disorders and body dysmorphic disorder may be especially vulnerable to use these products due to deceptive promises of fast and safe weight loss and muscle gain. The research-to-policy translation project was informed by a triggers-to-action framework to establish the evidentiary base of harm to consumers, operationalize policy solutions to mitigate harm through legislation, and generate political will to support action through legislation introduced in the Massachusetts legislature to restrict sales of weight-loss and muscle-building dietary supplements. The paper concludes with lessons learned from this unique policy translation effort for the prevention of disordered weight and shape control behaviors and offers recommendations for next steps for the field to advance research and practice for universal, macro-environmentally targeted prevention. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Bioinformatics by Example: From Sequence to Target

    NASA Astrophysics Data System (ADS)

    Kossida, Sophia; Tahri, Nadia; Daizadeh, Iraj

    2002-12-01

    With the completion of the human genome, and the imminent completion of other large-scale sequencing and structure-determination projects, computer-assisted bioscience is aimed to become the new paradigm for conducting basic and applied research. The presence of these additional bioinformatics tools stirs great anxiety for experimental researchers (as well as for pedagogues), since they are now faced with a wider and deeper knowledge of differing disciplines (biology, chemistry, physics, mathematics, and computer science). This review targets those individuals who are interested in using computational methods in their teaching or research. By analyzing a real-life, pharmaceutical, multicomponent, target-based example the reader will experience this fascinating new discipline.

  3. A state-based model of prevention: Indiana's example.

    PubMed

    Agley, Jon; Gassman, Ruth

    2008-04-01

    Public health officials in the United States have battled alcohol, tobacco, and other drug (ATOD) use among adolescents for the past few decades, but only in 2002 did they begin to see a decline in rates of use. ATOD use and abuse are associated with numerous problems, including criminal behavior and increased adolescent morbidity and mortality rates. Researchers have sought to identify best-practice procedures for ATOD prevention; the state of Indiana has a strong ATOD prevention system in place that has the potential to serve as a model for other U.S. localities because of its best-practice approach to public health services. This article outlines the activities of the Indiana Prevention Resource Center to provide an example to strengthen public health professionals' ability to prevent ATOD use and abuse and to provide for a healthy adolescent population.

  4. Strategies for universalistic and targeted HIV prevention.

    PubMed

    Des Jarlais, D C; Padian, N

    1997-10-01

    The controversy over "targeted" versus "universalistic" programs for HIV prevention has persisted throughout the history of the HIV/AIDS epidemic in the United States and in some European countries. Building on previous analyses, we outline methods for integrating universalistic and targeted HIV prevention programming. The outline considers possible synergy between targeted and universalistic programs, rather than a forced choice between the two. Components within this framework include a continuum of the intensity of targeted programs, specification of local risk behavior populations, categories of risk behavior, and HIV seroprevalence within local risk-behavior populations. Given the scarce resources currently available, preventing all new HIV infections is not a realistic public health goal, but with better use of current scientific knowledge, it should be possible to greatly reduce the rate of new HIV infections.

  5. Targeted Therapy for Breast Cancer Prevention

    PubMed Central

    den Hollander, Petra; Savage, Michelle I.; Brown, Powel H.

    2013-01-01

    With a better understanding of the etiology of breast cancer, molecularly targeted drugs have been developed and are being testing for the treatment and prevention of breast cancer. Targeted drugs that inhibit the estrogen receptor (ER) or estrogen-activated pathways include the selective ER modulators (tamoxifen, raloxifene, and lasofoxifene) and aromatase inhibitors (AIs) (anastrozole, letrozole, and exemestane) have been tested in preclinical and clinical studies. Tamoxifen and raloxifene have been shown to reduce the risk of breast cancer and promising results of AIs in breast cancer trials, suggest that AIs might be even more effective in the prevention of ER-positive breast cancer. However, these agents only prevent ER-positive breast cancer. Therefore, current research is focused on identifying preventive therapies for other forms of breast cancer such as human epidermal growth factor receptor 2 (HER2)-positive and triple-negative breast cancer (TNBC, breast cancer that does express ER, progesterone receptor, or HER2). HER2-positive breast cancers are currently treated with anti-HER2 therapies including trastuzumab and lapatinib, and preclinical and clinical studies are now being conducted to test these drugs for the prevention of HER2-positive breast cancers. Several promising agents currently being tested in cancer prevention trials for the prevention of TNBC include poly(ADP-ribose) polymerase inhibitors, vitamin D, and rexinoids, both of which activate nuclear hormone receptors (the vitamin D and retinoid X receptors). This review discusses currently used breast cancer preventive drugs, and describes the progress of research striving to identify and develop more effective preventive agents for all forms of breast cancer. PMID:24069582

  6. Defining and targeting an audience for cancer-prevention messages.

    PubMed

    Bettinghaus, E P

    1992-01-01

    The target audience for cancer-prevention messages is not the cancer patient. Cancer-prevention messages should be designed for and directed toward groups of people who have been determined to be at risk for the disease. Potential audiences may vary widely in size and nature, depending on the specific cancer, its cause, and its etiology. The prevention of specific disease, eg, lung cancer, typically demands some behavior on the part of the recipient of a cancer-prevention message. Thus, members of a target audience may be asked to stop smoking or to refrain from starting. Each potential target audience is likely to be unique and cannot always be reached with typical mass-media campaigns. Messages designed to be effective for such special audiences may be required if a significant impact on behavior is to be obtained. This article attempts to identify potential audiences for cancer-prevention messages and develops the nature of the media to be used, the sources to be employed, and the arguments to be developed in such a campaign. Characteristics (eg, sex, race, age, marital status, and socioeconomic status) are used as examples of variables that may dictate the nature of cancer-prevention campaigns.

  7. [The IDEFICS primary prevention as a good practice example].

    PubMed

    Pigeot, Iris; De Henauw, Stefaan; Ahrens, Wolfgang

    2016-11-01

    Worldwide the prevalence of childhood overweight and obesity is strikingly high. Prevention programs are therefore of high priority at a national and international level. In the framework of the IDEFICS study a primary prevention program was developed, implemented and evaluated. This paper investigates to what degree the IDEFICS intervention may serve as good practice example. For this purpose, the single modules are described and the achieved effects are discussed. In eight European countries 16,228 children aged 2 to 9.9 years were recruited from kindergartens and schools. About half of them participated in a primary prevention program. In each country the intervention region was matched to a control region with a similar socio-demographic profile. All children participated in an extensive examination program at baseline, which was repeated two years later to assess the development of the children and the intervention effects. In addition, a further follow-up examination took place five years after the intervention in the framework of the I.Family study. After two years the IDEFICS intervention showed only minor effects on an individual level, but sustainable effects on the community and the setting level. After five years a beneficial change in the consumption of sugar and water could be observed in the intervention families and children who were overweight and obese at baseline showed favorable weight trajectories. The reasons for the weak intervention effects may be, among others, due to the limited penetration of intervention messages, an insufficient intensity of local intervention activities and our limited ability to induce structural changes of the obesogenic environment.

  8. Targeting AMPK for cancer prevention and treatment

    PubMed Central

    Young, Matthew R.; Chen, Guohong; Hua, Baojin

    2015-01-01

    AMP-activated protein kinase (AMPK) is an important mediator in maintaining cellular energy homeostasis. AMPK is activated in response to a shortage of energy. Once activated, AMPK can promote ATP production and regulate metabolic energy. AMPK is a known target for treating metabolic syndrome and type-2 diabetes; however, recently AMPK is emerging as a possible metabolic tumor suppressor and target for cancer prevention and treatment. Recent epidemiological studies indicate that treatment with metformin, an AMPK activator reduces the incidence of cancer. In this article we review the role of AMPK in regulating inflammation, metabolism, and other regulatory processes with an emphasis on cancer, as well as, discuss the potential for targeting AMPK to treat various types of cancer. Activation of AMPK has been found to oppose tumor progression in several cancer types and offers a promising cancer therapy. This review evaluates the evidence linking AMPK with tumor suppressor function and analyzes the molecular mechanisms involved. AMPK activity opposes tumor development and progression in part by regulating inflammation and metabolism. PMID:25812084

  9. Social class and preventive health behaviour: a British example.

    PubMed Central

    Pill, R; Peters, T J; Robling, M R

    1995-01-01

    STUDY OBJECTIVE--To test the relationship between social class and preventive health behaviour in a British national sample and identify which set of more specific socioeconomic factors best "explained" any observed relationship(s). DESIGN--Secondary analysis from a national cross sectional survey of the health attitudes and health behaviour of men and women aged 18 years and over living in private households in England, Scotland, and Wales. A selection of addresses was made randomly from the electoral register using a three stage design, and then one individual in each household was sampled. A total of 12,254 addresses yielded interviews with 9003 individuals, a response rate of 73.5%. Compared with the census population, the single and divorced/separated are slightly under-represented but otherwise sources of bias are small. PARTICIPANTS--The subset selected was 1671 women and 1026 men aged between 20-45 years with at least one child under 17 living at home. MAIN RESULTS--Social class was strongly associated with the health practices index (HPI, used as a measure of health behaviour) both for women and men (p < 0.001). The set of factors identified for both sexes as having an impact on this relationship were education, tenure, residential overcrowding index, and salience of lifestyle. In addition, their partner's employment status and household income were relevant for women only. These groups of factors did not totally explain the observed relationship but the proportion of variance in HPI attributable to social class was considerably reduced. CONCLUSIONS--Descriptions of the association between social class and health behaviour(s) are of little use to those wishing to mount more effective interventions in health promotion. Multivariable analysis can indicate which specific factors account for much of the social class effect on health behaviour and thereby assist better understanding and targeting of resources. PMID:7707001

  10. Identifying Molecular Targets of Lifestyle Modifications in Colon Cancer Prevention

    PubMed Central

    Derry, Molly M.; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

    2013-01-01

    One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals. PMID:23675573

  11. Identifying molecular targets of lifestyle modifications in colon cancer prevention.

    PubMed

    Derry, Molly M; Raina, Komal; Agarwal, Chapla; Agarwal, Rajesh

    2013-01-01

    One in four deaths in the United States is cancer-related, and colorectal cancer (CRC) is the second leading cause of cancer-associated deaths. Screening strategies are utilized but have not reduced disease incidence or mortality. In this regard, there is an interest in cancer preventive strategies focusing on lifestyle intervention, where specific etiologic factors involved in cancer initiation, promotion, and progression could be targeted. For example, exposure to dietary carcinogens, such as nitrosamines and polycyclic aromatic hydrocarbons influences colon carcinogenesis. Furthermore, dietary deficiencies could alter sensitivity to genetic damage and influence carcinogen metabolism contributing to CRC. High alcohol consumption increases the risk of mutations including the fact that acetaldehyde, an ethanol metabolite, is classified as a group 1 carcinogen. Tobacco smoke exposure is also a risk factor for cancer development; approximately 20% of CRCs are associated with smoking. Additionally, obese patients have a higher risk of cancer development, which is further supported by the fact that physical activity decreases CRC risk by 55%. Similarly, chronic inflammatory conditions also increase the risk of CRC development. Moreover, the circadian clock alters digestion and regulates other biochemical, physiological, and behavioral processes that could influence CRC. Taken together, colon carcinogenesis involves a number of etiological factors, and therefore, to create effective preventive strategies, molecular targets need to be identified and beleaguered prior to disease progression. With this in mind, the following is a comprehensive review identifying downstream target proteins of the above lifestyle risk factors, which are modulated during colon carcinogenesis and could be targeted for CRC prevention by novel agents including phytochemicals.

  12. Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

    DTIC Science & Technology

    2014-10-01

    Exosome Secretion PRINCIPAL INVESTIGATOR: Christine Vogel CONTRACTING ORGANIZATION: New York University, New York, NY 10012...30 Sep 2013 - 29 Sep 2014 4. TITLE AND SUBTITLE Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5a. CONTRACT...NUMBER Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion 5b. GRANT NUMBER W81XWH-13-1-0467 5c. PROGRAM ELEMENT

  13. Prevention 2.0: targeting cyberbullying @ school.

    PubMed

    Wölfer, Ralf; Schultze-Krumbholz, Anja; Zagorscak, Pavle; Jäkel, Anne; Göbel, Kristin; Scheithauer, Herbert

    2014-12-01

    Although cyberbullying is characterized by worrying prevalence rates and associated with a broad range of detrimental consequences, there is a lack of scientifically based and evaluated preventive strategies. Therefore, the present study introduces a theory-based cyberbullying prevention program (Media Heroes; German original: Medienhelden) and evaluates its effectiveness. In a pretest-posttest design (9-month interval), schools were asked to randomly assign their participating classes to either control or intervention group. Longitudinal data were available from 593 middle school students (M Age = 13.3 years, 53 % girls) out of 35 classes, who provided information on cyberbullying behavior as well as socio-demographic and psychosocial variables. While the present results revealed worrying prevalence rates of cyberbullying in middle school, multilevel analyses clearly demonstrate the program's effectiveness in reducing cyberbullying behavior within intervention classes in contrast to classes of the control group. Hence, this study presents a promising program which evidentially prevents cyberbullying in schools.

  14. Evaluating HIV prevention strategies for populations in key affected groups: The example of Cabo Verde

    PubMed Central

    Monteiro, João Filipe G.; Galea, Sandro; Flanigan, Timothy; Monteiro, Maria de Lourdes; Friedman, Samuel R.; Marshall, Brandon DL

    2015-01-01

    Objectives We used an individual-based model to evaluate the effects of hypothetical prevention interventions on HIV incidence trajectories in a concentrated, mixed epidemic setting from 2011 to 2021, and using Cabo Verde as an example. Methods Simulations were conducted to evaluate the extent to which early HIV treatment and optimization of care, HIV testing, condom distribution, and substance abuse treatment could eliminate new infections (i.e., reduce incidence to less than 10 cases per 10,000 person-years) among non-drug users, female sex workers (FSW), and people who use drugs (PWUD). Results Scaling up all four interventions resulted in the largest decreases in HIV, with estimates ranging from 1.4 (95%CI:1.36–1.44) per 10,000 person-years among non-drug users to 8.2 (95%CI:7.8–8.6) per 10,000 person-years among PWUD in 2021. Intervention scenarios targeting FWS and PWUD also resulted in HIV incidence estimates at or below 10 per 10,000 person-years by 2021 for all population sub-groups. Conclusions Our results suggest that scaling up multiple interventions among entire population is necessary to achieve elimination. However, prioritizing key populations with this combination prevention strategy may also result in a substantial decrease in total incidence. PMID:25838121

  15. Molecular targets of aspirin and cancer prevention

    PubMed Central

    Alfonso, L; Ai, G; Spitale, R C; Bhat, G J

    2014-01-01

    Salicylates from plant sources have been used for centuries by different cultures to treat a variety of ailments such as inflammation, fever and pain. A chemical derivative of salicylic acid, aspirin, was synthesised and mass produced by the end of the 19th century and is one of the most widely used drugs in the world. Its cardioprotective properties are well established; however, recent evidence shows that it can also act as a chemopreventive agent. Its antithrombotic and anti-inflammatory actions occur through the inhibition of cyclooxygenases. The precise mechanisms leading to its anticancer effects are not clearly established, although multiple mechanisms affecting enzyme activity, transcription factors, cellular signalling and mitochondrial functions have been proposed. This review presents a brief account of the major COX-dependent and independent pathways described in connection with aspirin's anticancer effects. Aspirin's unique ability to acetylate biomolecules besides COX has not been thoroughly investigated nor have all the targets of its primary metabolite, salicylic acid been identified. Recent reports on the ability of aspirin to acetylate multiple cellular proteins warrant a comprehensive study to investigate the role of this posttranslational modification in its anticancer effects. In this review, we also raise the intriguing possibility that aspirin may interact and acetylate cellular molecules such as RNA, and metabolites such as CoA, leading to a change in their function. Research in this area will provide a greater understanding of the mechanisms of action of this drug. PMID:24874482

  16. Targeting CD81 to Prevent Metastases in Breast Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0398 TITLE: Targeting CD81 to Prevent Metastases in Breast Cancer PRINCIPAL INVESTIGATOR: Dr. Stefanie Jeffrey...Targeting CD81 to Prevent Metastases in Breast Cancer 5b. GRANT NUMBER W81XWH-14-1-0398 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Stefanie Jeffrey 5d...SUPPLEMENTARY NOTES None 14. ABSTRACT During the research period, we tested a role for CD81 in breast cancer metastases and found that loss of CD81

  17. Targeting Structural Change for HIV Prevention: A Process and Tool for Community Application

    PubMed Central

    Willard, Nancy; Chutuape, Kate; Stewart-Campbell, Rachel; Boyer, Cherrie B.; Ellen, Jonathan

    2015-01-01

    To address the persistent HIV epidemic in the United States, prevention efforts are focusing on social determinants related to HIV risk by targeting systems and structures, such as organizational and institutional policies, practices and programs, and legislative and regulatory approaches to modify features of the environment that influence HIV risk. With limited evidenced-based examples, communities can benefit from strategic planning resources that help them consider developing structural-level changes that target root causes of HIV risk. In this article, we present the Connect to Protect® project that outlines a process and a tool to move from general ideas to specific structural changes. Examples from 14 coalitions are also provided. Using the process and tools presented here can provide a launching pad for other coalitions seeking to build an HIV prevention agenda and for practitioners seeking to incorporate structural changes for community health promotion. PMID:25776019

  18. Targeting Structural Change for HIV Prevention: A Process and Tool for Community Application.

    PubMed

    Willard, Nancy; Chutuape, Kate; Stewart-Campbell, Rachel; Boyer, Cherrie B; Ellen, Jonathan

    2015-11-01

    To address the persistent HIV epidemic in the United States, prevention efforts are focusing on social determinants related to HIV risk by targeting systems and structures, such as organizational and institutional policies, practices and programs, and legislative and regulatory approaches to modify features of the environment that influence HIV risk. With limited evidenced-based examples, communities can benefit from strategic planning resources that help them consider developing structural-level changes that target root causes of HIV risk. In this article, we present the Connect to Protect® project that outlines a process and a tool to move from general ideas to specific structural changes. Examples from 14 coalitions are also provided. Using the process and tools presented here can provide a launching pad for other coalitions seeking to build an HIV prevention agenda and for practitioners seeking to incorporate structural changes for community health promotion.

  19. 40 CFR Appendix L to Part 51 - Example Regulations for Prevention of Air Pollution Emergency Episodes

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Air Pollution Emergency Episodes L Appendix L to Part 51 Protection of Environment ENVIRONMENTAL... IMPLEMENTATION PLANS Pt. 51, App. L Appendix L to Part 51—Example Regulations for Prevention of Air Pollution... air pollution from reaching levels that would cause imminent and substantial endangerment to...

  20. 40 CFR Appendix L to Part 51 - Example Regulations for Prevention of Air Pollution Emergency Episodes

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... Air Pollution Emergency Episodes L Appendix L to Part 51 Protection of Environment ENVIRONMENTAL... IMPLEMENTATION PLANS Pt. 51, App. L Appendix L to Part 51—Example Regulations for Prevention of Air Pollution... air pollution from reaching levels that would cause imminent and substantial endangerment to...

  1. 40 CFR Appendix L to Part 51 - Example Regulations for Prevention of Air Pollution Emergency Episodes

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... Air Pollution Emergency Episodes L Appendix L to Part 51 Protection of Environment ENVIRONMENTAL... IMPLEMENTATION PLANS Pt. 51, App. L Appendix L to Part 51—Example Regulations for Prevention of Air Pollution... air pollution from reaching levels that would cause imminent and substantial endangerment to...

  2. 40 CFR Appendix L to Part 51 - Example Regulations for Prevention of Air Pollution Emergency Episodes

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... Air Pollution Emergency Episodes L Appendix L to Part 51 Protection of Environment ENVIRONMENTAL... IMPLEMENTATION PLANS Pt. 51, App. L Appendix L to Part 51—Example Regulations for Prevention of Air Pollution... air pollution from reaching levels that would cause imminent and substantial endangerment to...

  3. 40 CFR Appendix L to Part 51 - Example Regulations for Prevention of Air Pollution Emergency Episodes

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... Air Pollution Emergency Episodes L Appendix L to Part 51 Protection of Environment ENVIRONMENTAL... IMPLEMENTATION PLANS Pt. 51, App. L Appendix L to Part 51—Example Regulations for Prevention of Air Pollution... air pollution from reaching levels that would cause imminent and substantial endangerment to...

  4. Federal Involvement in Preventive Health Care for Children: The EPSDT Example.

    ERIC Educational Resources Information Center

    Maslin, Christine

    This paper critically reviews the federally funded Early and Periodic Screening, Diagnosis and Testing (EPSDT) program, and highlights problems in its design and functioning. A prime example of a preventive health program that is commendable in intent but ineffective in actual practice, the EPSDT program's failure was prompted by factors which…

  5. The Implementation of the Fast Track Program: An Example of a Large-Scale Prevention Science Efficacy Trial

    PubMed Central

    2009-01-01

    In 1990, the Fast Track Project was initiated to evaluate the feasibility and effectiveness of a comprehensive, multicomponent prevention program targeting children at risk for conduct disorders in four demographically diverse American communities (Conduct Problems Prevention Research Group [CPPRG], 1992). Representing a prevention science approach toward community-based preventive intervention, the Fast Track intervention design was based upon the available data base elucidating the epidemiology of risk for conduct disorder and suggesting key causal developmental influences (R. P. Weissberg & M. T. Greenberg, 1998). Critical questions about this approach to prevention center around the extent to which such a science-based program can be effective at (1) engaging community members and stakeholders, (2) maintaining intervention fidelity while responding appropriately to the local norms and needs of communities that vary widely in their demographic and cultural/ethnic composition, and (3) maintaining community engagement in the long-term to support effective and sustainable intervention dissemination. This paper discusses these issues, providing examples from the Fast Track project to illustrate the process of program implementation and the evidence available regarding the success of this science-based program at engaging communities in sustainable and effective ways as partners in prevention programming. PMID:11930968

  6. Targeting early infection to prevent HIV-1 mucosal transmission.

    PubMed

    Haase, Ashley T

    2010-03-11

    Measures to prevent sexual mucosal transmission of human immunodeficiency virus (HIV)-1 are urgently needed to curb the growth of the acquired immunodeficiency syndrome (AIDS) pandemic and ultimately bring it to an end. Studies in animal models and acute HIV-1 infection reviewed here reveal potential viral vulnerabilities at the mucosal portal of entry in the earliest stages of infection that might be most effectively targeted by vaccines and microbicides, thereby preventing acquisition and averting systemic infection, CD4 T-cell depletion and pathologies that otherwise rapidly ensue.

  7. Molecular Targeted Approaches to Cancer Therapy and Prevention Using Chalcones

    PubMed Central

    Jandial, Danielle D.; Blair, Christopher A.; Zhang, Saiyang; Krill, Lauren S.; Zhang, Yan-Bing; Zi, Xiaolin

    2014-01-01

    There is an emerging paradigm shift in oncology that seeks to emphasize molecularly targeted approaches for cancer prevention and therapy. Chalcones (1,3-diphenyl-2-propen-1-ones), naturally-occurring compounds with widespread distribution in spices, tea, beer, fruits and vegetables, consist of open-chain flavonoids in which the two aromatic rings are joined by a three-carbon α, β-unsaturated carbonyl system. Due to their structural diversity, relative ease of chemical manipulation and reaction of α, β-unsaturated carbonyl moiety with cysteine residues in proteins, some lead chalcones from both natural products and synthesis have been identified in a variety of screening assays for modulating important pathways or molecular targets in cancers. These pathways and targets that are affected by chalcones include MDM2/p53, tubulin, proteasome, NF-kappa B, TRIAL/death receptors and mitochondria mediated apoptotic pathways, cell cycle, STAT3, AP-1, NRF2, AR, ER, PPAR-γ and β-catenin/Wnt. Compared to current cancer targeted therapeutic drugs, chalcones have the advantages of being inexpensive, easily available and less toxic; the ease of synthesis of chalcones from substituted benzaldehydes and acetophenones also makes them an attractive drug scaffold. Therefore, this review is focused on molecular targets of chalcones and their potential implications in cancer prevention and therapy. PMID:24467530

  8. Population-level intervention strategies and examples for obesity prevention in children.

    PubMed

    Foltz, Jennifer L; May, Ashleigh L; Belay, Brook; Nihiser, Allison J; Dooyema, Carrie A; Blanck, Heidi M

    2012-08-21

    With obesity affecting approximately 12.5 million American youth, population-level interventions are indicated to help support healthy behaviors. The purpose of this review is to provide a summary of population-level intervention strategies and specific intervention examples that illustrate ways to help prevent and control obesity in children through improving nutrition and physical activity behaviors. Information is summarized within the settings where children live, learn, and play (early care and education, school, community, health care, home). Intervention strategies are activities or changes intended to promote healthful behaviors in children. They were identified from (a) systematic reviews; (b) evidence- and expert consensus-based recommendations, guidelines, or standards from nongovernmental or federal agencies; and finally (c) peer-reviewed synthesis reviews. Intervention examples illustrate how at least one of the strategies was used in a particular setting. To identify interventions examples, we considered (a) peer-reviewed literature as well as (b) additional sources with research-tested and practice-based initiatives. Researchers and practitioners may use this review as they set priorities and promote integration across settings and to find research- and practice-tested intervention examples that can be replicated in their communities for childhood obesity prevention.

  9. The role of experimental science in ICF -- examples from X-ray diagnostics and targets

    NASA Astrophysics Data System (ADS)

    Kilkenny, J. D.

    2016-10-01

    The USA Inertial Confinement Fusion (ICF) Program evolved from the Nuclear Test Program which had restricted shot opportunities for experimentalists to develop sophisticated experimental techniques. In contrast the ICF program in the US was able to increase the shot availability on its large facilities, and develop sophisticated targets and diagnostics to measure and understand the properties of the high energy density plasmas (HEDP) formed. Illustrative aspects of this evolution at Lawrence Livermore National Laboratory (LLNL), with examples of the development of diagnostics and target fabrication are described.

  10. Targeting the Epigenome with Bioactive Food Components for Cancer Prevention

    PubMed Central

    Ong, Thomas Prates; Moreno, Fernando Salvador; Ross, Sharon Ann

    2012-01-01

    Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated. PMID:22353664

  11. Targeting the epigenome with bioactive food components for cancer prevention.

    PubMed

    Ong, Thomas Prates; Moreno, Fernando Salvador; Ross, Sharon Ann

    2011-01-01

    Epigenetic processes participate in cancer development and likely influence cancer prevention. Global DNA hypomethylation, gene promoter hypermethylation and aberrant histone post-translational modifications are hallmarks of neoplastic cells which have been associated with genomic instability and altered gene expression. Because epigenetic deregulation occurs early in carcinogenesis and is potentially reversible, intervention strategies targeting the epigenome have been proposed for cancer prevention. Bioactive food components (BFCs) with anticancer potential, including folate, polyphenols, selenium, retinoids, fatty acids, isothiocyanates and allyl compounds, influence DNA methylation and histone modification processes. Such activities have been shown to affect the expression of genes involved in cell proliferation, death and differentiation that are frequently altered in cancer. Although the epigenome represents a promising target for cancer prevention with BFCs, few studies have addressed the influence of dietary components on these mechanisms in vivo, particularly on the phenotype of humans, and thus the exact mechanisms whereby diet mediates an effect on cancer prevention remains unclear. Primary factors that should be elucidated include the effective doses and dose timing of BFCs to attain epigenetic effects. Because diet-epigenome interactions are likely to occur in utero, the impact of early-life nutrition on cancer risk programming should be further investigated.

  12. [How do Prevention Projects Reach their Target Groups? Results of a Survey with Prevention Projects].

    PubMed

    Brand, T; Böttcher, S; Jahn, I

    2015-12-01

     The aim of this study was to assess methods used to access target groups in prevention projects funded within the prevention research framework by the German Federal Ministry of Education and Research.  A survey with prevention projects was conducted. Access strategies, communication channels, incentives, programme reach, and successful practical recruitment strategies were explored.  38 out of 60 projects took part in the survey. Most projects accessed their target group within structured settings (e. g., child day-care centers, schools, workplaces). Multiple communication channels and incentives were used, with written information and monetary incentives being used most frequently. Only few projects were able to report their programme reach adequately; programme reach was highest for programmes accessing the target groups in structured settings. The respondents viewed active recruitment via personal communication with the target group and key persons in the settings as the most successful strategy.  The paper provides an overview on recruitment strategies used in current preven-tion projects. More systematic research on programme reach is necessary. © Georg Thieme Verlag KG Stuttgart · New York.

  13. Methodological challenges examining subgroup differences: examples from universal school-based youth violence prevention trials.

    PubMed

    Farrell, Albert D; Henry, David B; Bettencourt, Amie

    2013-04-01

    This article reviews the literature on school-based universal violence prevention programs to illustrate key methodological challenges for investigating subgroup differences in prevention effects. The variety of potential moderating factors examined within this literature is discussed within the context of a social-ecological model. Our review of this literature identified the following methodological issues: the need for a clear a priori theoretical basis for selecting potential moderators, inflated Type I error rates that result from large numbers of comparisons, the absence of explicit tests of moderation, interpretive issues arising from a restricted range on moderator variables, the failure to report effect size estimates, the presence of potential confounding factors, and the importance of examining factors that might operate at multiple ecological levels. These points are illustrated using examples of studies, primarily within youth violence prevention research, that have identified factors within the individual, school, and community that moderate the outcomes of preventive interventions. We conclude with general recommendations for future work. These include the benefits of using the social-ecological model to provide a basis for moving from exploratory to more theory-driven confirmatory models of subgroup differences, the potential merits of qualitative research designed to identify factors that may influence the effectiveness of intervention efforts for specific subgroups of individuals, and the provision of effect size estimates and confidence intervals for effect sizes in prevention reports.

  14. Preventing the Onset of Child Sexual Abuse by Targeting Young Adolescents With Universal Prevention Programming

    PubMed Central

    Letourneau, Elizabeth J.; Schaeffer, Cindy M.; Bradshaw, Catherine P.; Feder, Kenneth A.

    2017-01-01

    Child sexual abuse (CSA) is a serious public health problem that increases risk for physical and mental health problems across the life course. Young adolescents are responsible for a substantial portion of CSA offending, yet to our knowledge, no validated prevention programs that target CSA perpetration by youth exist. Most existing efforts to address CSA rely on reactive criminal justice policies or programs that teach children to protect themselves; neither approach is well validated. Given the high rates of desistance from sexual offending following a youth’s first CSA-related adjudication, it seems plausible that many youth could be prevented from engaging in their first offense. The goal of this article is to examine how school-based universal prevention programs might be used to prevent CSA perpetrated by adolescents. We review the literature on risk and protective factors for CSA perpetration and identify several promising factors to target in an intervention. We also summarize the literature on programs that have been effective at preventing adolescent dating violence and other serious problem behaviors. Finally, we describe a new CSA prevention program under development and early evaluation and make recommendations for program design characteristics, including unambiguous messaging, parental involvement, multisession dosage, skills practice, and bystander considerations. PMID:28413921

  15. Efficient Targeting of Homelessness Prevention Services for Families

    PubMed Central

    Shinn, Marybeth; Greer, Andrew L.; Bainbridge, Jay; Kwon, Jonathan; Zuiderveen, Sara

    2013-01-01

    Objectives. We developed and evaluated a model to target homelessness prevention services to families more efficiently. Methods. We followed 11 105 families who applied for community-based services to prevent homelessness in New York City from October 1, 2004, to June 30, 2008, through administrative records, using Cox regression to predict shelter entry. Results. Over 3 years, 12.8% of applicants entered shelter. Both the complete Cox regression and a short screening model based on 15 risk factors derived from it were superior to worker judgments, with substantially higher hit rates at the same level of false alarms. We found no evidence that some families were too risky to be helped or that specific risk factors were particularly amenable to amelioration. Conclusions. Despite some limitations, an empirical risk model can increase the efficiency of homelessness prevention services. Serving the same proportion of applicants but selecting those at highest risk according to the model would have increased correct targeting of families entering shelter by 26% and reduced misses by almost two thirds. Parallel models could be developed elsewhere. PMID:24148041

  16. From protective intelligence to threat assessment: Strategies critical to preventing targeted violence and the active shooter.

    PubMed

    Doherty, Matthew

    Acts of targeted violence - including active shooter incidents - are typically over within 15 minutes, often before the first law enforcement personnel can respond to the scene. More than a third of active shooter incidents in the USA, for example, last less than five minutes. While this stark fact is often used, with unimpeachable validity, as the cornerstone of employee security awareness training and the need for each employee to make a quick decision on whether to run, hide or fight, it also underscores the importance of another critical priority: prevention. This paper focuses on several of the most effective strategies and tactics - increasingly used across the USA, but applicable all over the world - in preventing an act of targeted violence or active shooter event. It starts with a brief discussion of the common roadblocks to prevention within enterprises today as well as the warning signs that can reveal an individual's path toward an act of violence. Next, it defines targeted violence and summarises patterns that research has helped uncover with respect to attackers' backgrounds, motives and target selection. This paper also outlines the crucial role played by protective intelligence and threat assessment protocols and provides several case studies to illustrate key concepts in real-world applications. Finally, this discussion points to several emerging trends in the USA and Europe, among other regions - such as radicalisation within the workforce - that are likely to continue to mature in 2016 and the years ahead.

  17. Strategies for primary HIV prevention that target behavioral change.

    PubMed

    Safren, Steven A; Wingood, Gina; Altice, Frederick L

    2007-12-15

    In the absence of a vaccine or cure, behavioral change remains the major method to prevent transmission of the human immunodeficiency virus (HIV). Public awareness campaigns that disseminate information about the risks and routes of transmission, although important, have an insufficient influence on the behavioral changes essential to reduce the risk of HIV infection. Because of the complex interplay of cultural and psychosocial influences that guides human behavior, specific programs to decrease high-risk behavior have been developed for target populations. In this report, tested initiatives for preventing HIV infection are summarized and their success evaluated for men who have sex with men, injection drug users, and women of minority racial groups. Objective evidence of reductions in high-risk behavior in these 3 groups, which account for the majority of HIV transmissions in the United States, has critical implications for reducing the overall rate of new HIV infections.

  18. Targeting as a Mode of Science Communication: Principles, Issues and a Practical Example

    NASA Astrophysics Data System (ADS)

    Holland, G. J.; Vigh, J. L.

    2011-12-01

    Today's media landscape contains a rich and diverse range of communications opportunities. New media, such as the internet, blogosphere and social networks, are complementing, supplementing and also replacing the traditional mass media communications through print, radio and television. This diversification certainly contains pitfalls and difficulties as has been demonstrated in the Climategate affair. But there are also real opportunities for utilizing the diversity to provide targeted science communications that are framed in the context of the specific group of interest. That such targeting of audience attitudes and beliefs is an important key to effective science communications has been demonstrated by, for example, Leiserowitz, Maibach et al (2009). This approach does require an understanding of the audience and a careful framing of the message in terms familiar to the targeted group. Here many factors come into play, including: including immediacy, economics, culture, community leaders, emotional framing, and ideological filters. In this talk we shall elaborate on the principles, issues and opportunities. A practical example of working with the religious community on communicating the science of climate change will also be presented. This will include the approach adopted, progress to date and the lessons learnt.

  19. Optimal Dosing for Targeted Therapies in Oncology: Drug Development Cases Leading by Example.

    PubMed

    Sachs, Jeffrey R; Mayawala, Kapil; Gadamsetty, Satvik; Kang, Soonmo Peter; de Alwis, Dinesh P

    2016-03-15

    One of the key objectives of oncology first-in-human trials has often been to establish the maximum tolerated dose (MTD). However, targeted therapies might not exhibit dose-limiting toxicities (DLT) at doses significantly higher than sufficiently active doses, and there is frequently a limited ability to objectively quantify adverse events. Thus, while MTD-based determination of recommended phase II dose may have yielded appropriate dosing for some cytotoxics, targeted therapeutics (including monoclonal antibodies and/or immunotherapies) sometimes need alternative or complementary strategies to help identify dose ranges for a randomized dose-ranging study. One complementary strategy is to define a biologically efficacious dose (BED) using an "effect marker." An effect marker could be a target engagement, pharmacodynamic, or disease progression marker (change in tumor size for solid tumors or bone marrow blast count for some hematologic tumors). Although the concept of BED has been discussed extensively, we review specific examples in which the approach influenced oncology clinical development. Data extracted from the literature and the examples support improving dose selection strategies to benefit patients, providers, and the biopharmaceutical industry. Although the examples illustrate key contributions of effect markers in dose selection, no one-size-fits-all approach to dosing can be justified. Higher-than-optimal dosing can increase toxicity in later trials (and in clinical use), which can have a negative impact on efficacy (via lower adherence or direct sequelae of toxicities). Proper dose selection in oncology should follow a multifactorial decision process leading to a randomized, dose-ranging study instead of a single phase II dose. ©2015 American Association for Cancer Research.

  20. Targeting burn prevention in Ukraine: evaluation of base knowledge in burn prevention and first aid treatment.

    PubMed

    Gamelli, Liza; Mykychack, Iryna; Kushnir, Antin; Driscoll, Daniel N; Fuzaylov, Gennadiy

    2015-01-01

    Burn prevention has been identified by the World Health Organization (WHO) as a topic in need of further investigation and education throughout the world, with an increased need in low-income countries. It has been noted that implementing educational programs for prevention in high income countries has aided in lowering the rate of burn injuries. The purpose of this study is to evaluate the current education level of knowledge of prevention and first aid treatment of scald burns. A prevention campaign will target these educational needs as a part of an outreach program to improve burn care in Ukraine. The research team evaluated the current health structure in Ukraine and how it could benefit from the increased knowledge of burn prevention and first aid. A test was designed to assess the baseline level of knowledge with regard to first aid and scald prevention in parents, pregnant woman, and healthcare and daycare providers. A total of 14,456 tests were sent to pediatric clinics, obstetrician clinics, and daycare facilities to test respondents. A total of 6,120 completed tests were returned. Doctors presented with the highest level of knowledge averaging 77.0% on prevention and 67.5% on first aid while daycare workers presented the largest gap in knowledge at 65.0% in prevention and 54.3% in first aid. Interest in further educational materials was reported by 92% of respondents. The results of this study clearly show a lack of knowledge in first aid and prevention of scald burn injury in all the populations tested.

  1. Estrogen receptor beta as target for colorectal cancer prevention.

    PubMed

    Williams, Cecilia; DiLeo, Alfredo; Niv, Yaron; Gustafsson, Jan-Åke

    2016-03-01

    Colorectal cancer (CRC) is a leading cause of death in the United States. Despite its slow development and the capacity for early diagnosis, current preventive approaches are not sufficient. However, a role for estrogen has been demonstrated in multiple epidemiologic studies, which may benefit CRC prevention. A large body of evidence from preclinical studies indicates that expression of the estrogen receptor beta (ERβ/ESR2) demonstrates an inverse relationship with the presence of colorectal polyps and stage of tumors, and can mediate a protective response. Natural compounds, including phytoestrogens, or synthetic ERβ selective agonists, can activate or upregulate ERβ in the colon and promote apoptosis in preclinical models and in clinical experience. Importantly, this activity has been associated with a reduction in polyp formation and, in rodent models of CRC, has been shown to lower incidence of colon adenocarcinoma. Collectively, these findings indicate that targeted activation of ERβ may represent a novel clinical approach for management of colorectal adenomatous polyps and prevention of colorectal carcinoma in patients at risk for this condition. In this review, we discuss the potential of new chemopreventive or dietary approaches based on estrogen signaling.

  2. Mitosis-targeting natural products for cancer prevention and therapy.

    PubMed

    Rao, Chinthalapally V; Kurkjian, Carla D; Yamada, Hiroshi Y

    2012-12-01

    Mitosis is a complex process resulting in division of a cell into two daughter cells, and its failure often results in the death of the daughter cells (via apoptotic, necrotic, or proliferative/senescent death). Many chemicals that inhibit the mitotic process (anti-mitotic drugs) have proven effective for killing cancer cells in vitro and in clinical settings. Among the most studied anti-mitotic drugs are plant-origin natural products including taxanes (e.g. paclitaxel, docetaxel) and vinca alkaloids (e.g. vincristine, vinblastine), whose validated target is the spindle microtubules. With the success of these agents, efforts have been made to develop other spindle poisons as well as to improve efficacy of existing spindle poisons with structural modifications. Novel drugs and natural products that inhibit other proteins involved in mitosis (nonmicrotubule targets) have been sought in hopes of expanding available cancer-directed therapies. Recently, significant advances have been made in the understanding of mitotic mechanisms in tumor cells as well as in normal epithelial cells. These advances help us to identify and develop potential natural agents for the prevention and treatment of cancer. This review will focus on natural products that target mitotic process and/or proteins involved in mitotic progression.

  3. On the importance of planned health education. Prevention of ski injury as an example.

    PubMed

    Kok, G; Bouter, L M

    1990-01-01

    The planning of health education aimed at preventing sports injuries is often incomplete and not stated explicitly. In most instances, the evaluation is incomplete or nonexistent. We present a theoretical framework for planning and evaluating health education, illustrating the main points by using as an example the health education for downhill skiers. Systematic planning consists of analyzing the magnitude of the problem and the behavioral risk factors, studying behavior determinants, designing an optimal intervention, and implementing the intervention. The evaluation phase deals with the effects on these five levels (implementation, intervention, determinants, behavior, and incidence of injury). Some common pitfalls are mentioned and special attention is given to the study of determinants of behavior and to the design of the intervention. The importance of pretesting health education material and the community approach in educating sports participants is underlined. Health education, together with regulations and facilities, constitutes the health promotion strategy in the prevention of sports injuries. For most sports, there seems to be a strong need for further research on the etiology and determinants of behavior before effective prevention can be realized.

  4. Technology-Based Innovations in Child Maltreatment Prevention Programs: Examples from SafeCare®

    PubMed Central

    Cowart-Osborne, Melissa; Jackson, Matthew; Chege, Elizabeth; Baker, Evander; Whitaker, Daniel; Self-Brown, Shannon

    2014-01-01

    Each year, hundreds of thousands of children in the U.S. are victims of child maltreatment. Experts recommend behavioral, skill-based parent training programs as a strategy for the prevention of child abuse and neglect. These programs can be enhanced using innovative technology strategies. This paper presents a brief history of the use of technology in SafeCare®, a home visiting program shown to prevent child neglect and physical abuse, and highlights current work that takes a technology-based hybrid approach to SafeCare delivery. With this unique approach, the provider brings a tablet computer to each session, and the parent interacts with the software to receive psychoeducation and modeling of target skills. The provider and parent then work together to practice the targeted skills until mastery is achieved. Initial findings from ongoing research of both of these strategies indicate that they show potential for improving engagement and use of positive parenting skills for parents and ease of implementation for providers. Future directions for technology enhancements in SafeCare are also presented. PMID:25606347

  5. Small-molecule compounds exhibiting target-mediated drug disposition - A case example of ABT-384.

    PubMed

    An, Guohua; Liu, Wei; Dutta, Sandeep

    2015-10-01

    Nonlinearities are frequently encountered in pharmacokinetics, and they can occur when 1 or more processes of absorption, distribution, metabolism, and excretion are saturable. One special source of nonlinearity that has been noticed recently is the saturable binding of the drug to a high-affinity-low-capacity target, a phenomenon known as target-mediated drug disposition (TMDD). Although TMDD can occur in both small-molecule compounds and large-molecule compounds, the latter has received much more attention because of its high prevalence. With the development of more potent small-molecule drugs acting on highly specific targets and the availability of increasingly sensitive analytical techniques, small-molecule compounds exhibiting TMDD have been increasingly reported in the past several years. ABT-384 is a small-molecule drug candidate that exhibited significant nonlinear pharmacokinetics, potentially imparted by TMDD, in a first-in-human clinical trial conducted in healthy volunteers. Compared with published small-molecule compounds exhibiting TMDD, ABT-384 pharmacokinetic characteristics are more consistent with TMDD. To expand current knowledge of TMDD of small-molecule compounds and increase awareness of this interesting and clinically important phenomenon, in this review the general features of small-molecule compounds exhibiting TMDD are highlighted, with ABT-384 provided as an example. © 2015, The American College of Clinical Pharmacology.

  6. Novel Frontiers in Epilepsy Treatments: Preventing Epileptogenesis by Targeting Inflammation

    PubMed Central

    D'Ambrosio, Raimondo; Eastman, Clifford L.; Fattore, Cinzia; Perucca, Emilio

    2014-01-01

    Currently available epilepsy drugs only affect the symptoms (seizures), and there is a need for innovative treatments that target the underlying disease. Increasing evidence points to inflammation as a potentially important mechanism in epileptogenesis. In the last decade, a new generation of etiologically realistic syndrome-specific experimental models have been developed which are expected to capture the epileptogenic mechanisms operating in the corresponding patient populations, and to exhibit similar treatment-responsiveness. Recently, an intervention known have broad-ranging anti-inflammatory effects (selective brain cooling) has been found to prevent the development of spontaneously occurring seizures in an etiologically realistic rat model of post-traumatic epilepsy. Several drugs used clinically for other indications also have the potential for inhibiting inflammation, and should be investigated for anti-epileptogenic activity in these models. If results of such studies are positive, these compounds could enter rapidly Phase III trials in patients at high risk of developing epilepsy. PMID:23738999

  7. Bone Targeted Agents: Preventing skeletal complications in prostate cancer

    PubMed Central

    Morgans, Alicia K.; Smith, Matthew R.

    2013-01-01

    Summary Prostate cancer is both the most common malignancy and the most common cause of cancer death in men. In the United States, there were approximately 217,730 new prostate cancer diagnoses and more than 32,050 deaths in 2010 1. Skeletal complications occur at various points during the disease course, either due to bone metastases directly, or as an unintended consequence of androgen deprivation therapy (ADT). Up to 90% of men with metastatic castration resistant prostate cancer (CRPC) develop bone metastases2,3. Bone metastases are associated with pathologic fractures, spinal cord compression, and bone pain and can require narcotics or palliative radiation for pain relief. Additionally, ADT results in bone loss and fragility fractures. This review describes the biology of bone metastases, skeletal morbidity in men with prostate cancer, and recent advances in bone targeted therapies to prevent skeletal complications of prostate cancer. PMID:23084529

  8. Candidate Drug Targets for Prevention or Modification of Epilepsy

    PubMed Central

    Varvel, Nicholas H.; Jiang, Jianxiong; Dingledine, Raymond

    2015-01-01

    Epilepsy is a prevalent neurological disorder afflicting nearly 50 million people worldwide. The disorder is characterized clinically by recurrent spontaneous seizures attributed to abnormal synchrony of brain neurons. Despite advances in the treatment of epilepsy, nearly one-third of patients are resistant to current therapies, and the underlying mechanisms whereby a healthy brain becomes epileptic remain unresolved. Therefore, researchers have a major impetus to identify and exploit new drug targets. Here we distinguish between epileptic effectors, or proteins that set the seizure threshold, and epileptogenic mediators, which control the expression or functional state of the effector proteins. Under this framework, we then discuss attempts to regulate the mediators to control epilepsy. Further insights into the complex processes that render the brain susceptible to seizures and the identification of novel mediators of these processes will lead the way to the development of drugs to modify disease outcome and, potentially, to prevent epileptogenesis. PMID:25196047

  9. Fibrin Targeted Block Copolymers for the Prevention of Postsurgical Adhesions

    PubMed Central

    Medley, John M.; Kaplan, Eugene; Oz, Helieh S.; Sundararaj, Sharath C.; Puleo, David A.; Dziubla, Thomas D.

    2015-01-01

    Despite advances in surgical methods, postsurgical adhesions (PSA) remain a significant clinical challenge affecting millions of patients each year. These permanent fibrous connections between tissues result from the bridging of wounded internal surfaces by an extended fibrin gel matrix (FGM). Adhesion formation is a result of a systems level convergence of wound healing pathways, complicating the design of materials that could inhibit their occurrence. In this study, a systematic approach that identifies key material properties required for functional performance optimization was used to design a new fibrin-targeted PSA prevention material. A series of multifunctional polymers with varied molecular architectures was synthesized to investigate the effect of changing polymer structural parameters on the ability to disrupt the formation of an extended FGM. Initial studies in a murine adhesion model demonstrated a statistically significant reduction in the degree of PSA formation, demonstrating the potential value of this systematic approach. PMID:21695779

  10. [Communication of health risks: the example of HIV/AIDS prevention].

    PubMed

    Lehmann, H; Töppich, J

    2009-12-01

    Those seeking to educate the public about health need to communicate health risks effectively. This involves providing evidence-based information about factors and behaviors that are dangerous to people's health and making recommendations regarding how risks can be avoided or minimized. This communication usually aims to motivate people to act in a way that promotes health or prevents disease. Organized 'health education' that seeks to communicate risks is always embedded in a contextual framework that in turn influences the issues and content to be communicated and the form of communication that is chosen. The scope of available scientific knowledge is an important part of this framework as is the extent to which risks are presented in the media as being dangerous. The media's message has a strong influence on how the public and specific subgroups within it react. The article describes conditions that contribute to successful risk communication based on the example of HIV/AIDS prevention. We chose this particular case because it can serve as an example of how to deal with future epidemics that may potentially generate substantial media coverage. This field report shows how risk communication about HIV/AIDS in the mass media in Germany in the mid-1980s elicited a risk consciousness among the general public that in itself was in danger of becoming a health risk, especially for people affected by the disease, and how 'health education' responded to this challenge. It concludes by describing how these experiences with risk communication can be applied to similar types of risk communication today.

  11. BRCA1 as target for breast cancer prevention and therapy.

    PubMed

    Romagnolo, Alberto P G; Romagnolo, Donato F; Selmin, Ornella I

    2015-01-01

    The Breast Cancer 1 protein (BRCA1) is a tumor suppressor involved in basic cellular functions necessary for cell replication and DNA synthesis, but reduced expression of BRCA1, due to mutations or epigenetic inactivation, leads to impaired mammary gland differentiation and increased risk of breast cancer development. Although BRCA1 acts as a tumor suppressor and is present in all cells, where it is essential for the maintenance of the genome integrity, it is still not clear why mutations in the BRCA1 gene predispose to breast and ovarian, but not to other types of cancer. In the first part of this review, we briefly discuss the function and regulation of the BRCA1 protein, including its role associated with familial and sporadic breast cancer. The second part is an overview of the therapeutic compounds used for breast cancer treatment targeting BRCA1, and the natural food components that hold potential preventive effect against those types of breast cancer in which BRCA1 expression is either reduced or lacking. Further studies elucidating the interactions between dietary compounds and cellular pathways, involved in regulation of BRCA1expression, are necessary for the development of strategies that may successfully prevent or treat breast cancer.

  12. Strategic targeted exercise for preventing falls in elderly people.

    PubMed

    Zheng, Jiejiao; Pan, Yujian; Hua, Yinghui; Shen, Haimin; Wang, Xueqiang; Zhang, Ying; Fan, Yujing; Yu, Zhuowei

    2013-04-01

    Randomized, controlled, blinded trial to evaluate the effectiveness of strategic targeted exercise for preventing falls in elderly people. Elderly people were randomly allocated to either a control group that received conventional exercise, or a training group that received conventional exercise plus proprioception and cognitive exercises. Subjects were asked to exercise three times a week (40 min per session) for 8 weeks. In the pre- and post-training sessions, all participants were assessed using a static postural control test with eyes open and closed, the Berg Balance Scale (BBS) and the joint position sense test of the lower limbs. After 8 weeks, there were statistically significant improvements in the training group (n = 50) compared with the control group (n = 50) for mediolateral sway distance with eyes open and eyes closed, anteroposterior sway distance with eyes open but not with eyes closed, BBS scores and joint position sense test for the left but not the right knee. This study demonstrated that strategic targeted exercise could produce more beneficial effects on balance and proprioception function than conventional exercise alone, in elderly people.

  13. Bioactive food components, inflammatory targets, and cancer prevention.

    PubMed

    Kim, Young S; Young, Matthew R; Bobe, Gerd; Colburn, Nancy H; Milner, John A

    2009-03-01

    Various dietary components may modify chronic inflammatory processes at the stage of cytokine production, amplification of nuclear factor-kappaB-mediated inflammatory gene expression, and the release of anti-inflammatory cytokine, transforming growth factor-beta. This review provides a synopsis of the strengths and weaknesses of the evidence that specific bioactive food components influence inflammation-related targets linked to cancer. A target repeatedly surfacing as a site of action for several dietary components is transforming growth factor beta. Whereas the use of dietary intervention strategies offers intriguing possibilities for maintaining normal cell function by modifying a process that is essential for cancer development and progression, more information is needed to characterize the minimum quantity of the bioactive food components required to bring about a change in inflammation-mediated cancer, the ideal time for intervention, and the importance of genetics in determining the response. Unquestionably, the societal benefits of using foods and their components to prevent chronic inflammation and associated complications, including cancer, are enormous.

  14. Multi-targeted prevention and therapy of cancer by proanthocyanidins.

    PubMed

    Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K

    2008-10-08

    In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual's everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anti-carcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-kappaB, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs.

  15. Multi-targeted prevention and therapy of cancer by proanthocyanidins

    PubMed Central

    Nandakumar, Vijayalakshmi; Singh, Tripti; Katiyar, Santosh K.

    2008-01-01

    In recent years, a considerable emphasis has been focused on the importance of the naturally available botanicals that can be consumed in an individual’s everyday diet and that can also be useful as a chemopreventive or chemotherapeutic agent for certain diseases, including cancers. A wide variety of botanicals, mostly dietary flavonoids or polyphenolic substances, have been reported to possess substantial anticarcinogenic and antimutagenic activities because of their antioxidant and anti-inflammatory properties. Proanthocyanidins are considered as one of them, and are abundantly available in various parts of the plants, such as fruits, berries, bark and seeds. Their modes of action were evaluated through a number of in vitro and in vivo studies which showed their potential role as anti-carcinogenic agent. We summarize and highlight the latest developments on anti-carcinogenic activities of proanthocyanidins from different sources, specifically from grape seeds, and their molecular targets, such as NF-κB, mitogen-activated protein kinases, PI3K/Akt, caspases, cytokines, angiogenesis and cell cycle regulatory proteins and other check points, etc. Although the bioavailability and metabolism data on proanthocyanidins is still largely unavailable, certain reports indicate that at least monomers and smaller oligomeric procyanidins are absorbed in the gut. The modulation of various molecular targets by proanthocyanidins in vitro and in vivo tumor models suggests their importance, contribution and mechanism of action to the prevention of cancers of different organs. PMID:18457915

  16. DNA Methyltransferases: A Novel Target for Prevention and Therapy

    PubMed Central

    Subramaniam, Dharmalingam; Thombre, Ravi; Dhar, Animesh; Anant, Shrikant

    2013-01-01

    Cancer is the second leading cause of death in US. Despite the emergence of new, targeted agents, and the use of various therapeutic combinations, none of the available treatment options are curative in patients with advanced cancer. Epigenetic alterations are increasingly recognized as valuable targets for the development of cancer therapies. DNA methylation at the 5-position of cytosine, catalyzed by DNA methyltransferases (DNMTs), is the predominant epigenetic modification in mammals. DNMT1, the major enzyme responsible for maintenance of the DNA methylation pattern is located at the replication fork and methylates newly biosynthesized DNA. DNMT2 or TRDMT1, the smallest mammalian DNMT is believed to participate in the recognition of DNA damage, DNA recombination, and mutation repair. It is composed solely of the C-terminal domain, and does not possess the regulatory N-terminal region. The levels of DNMTs, especially those of DNMT3B, DNMT3A, and DNMT3L, are often increased in various cancer tissues and cell lines, which may partially account for the hypermethylation of promoter CpG-rich regions of tumor suppressor genes in a variety of malignancies. Moreover, it has been shown to function in self-renewal and maintenance of colon cancer stem cells and need to be studied in several cancers. Inhibition of DNMTs has demonstrated reduction in tumor formation in part through the increased expression of tumor suppressor genes. Hence, DNMTs can potentially be used as anti-cancer targets. Dietary phytochemicals also inhibit DNMTs and cancer stem cells; this represents a promising approach for the prevention and treatment of many cancers. PMID:24822169

  17. Developmental epidemiologically based preventive trials: baseline modeling of early target behaviors and depressive symptoms.

    PubMed

    Kellam, S G; Werthamer-Larsson, L; Dolan, L J; Brown, C H; Mayer, L S; Rebok, G W; Anthony, J C; Laudolff, J; Edelsohn, G

    1991-08-01

    Describes a conceptual framework for identifying and targeting developmental antecedents in early childhood that have been shown in previous work to predict delinquency and violent behavior, heavy drug use, depression, and other psychiatric symptoms and possibly disorders in late adolescence and into adulthood. Criteria are described that guided choices of targets for two epidemiologically based, randomized preventive trials carried out in 19 elementary schools in the eastern half of Baltimore, involving more than 2,400 first-grade children over the course of first and second grades. Baseline models derived from the first of two cohorts show the evolving patterns of concurrence among the target antecedents. The central role of concentration problems emerged. From Fall to Spring in first grade, concentration problems led to shy and aggressive behavior and poor achievement in both genders and to depressive symptoms among girls. There was evidence for reciprocal relationships in girls. For example, depressive symptoms led to poor achievement in both girls and boys, whereas poor achievement led to depressive symptoms in girls but not boys, at least over the first-grade year. These results provide important epidemiological data relevant to the developmental paths leading to the problem outcomes and suggest preventive trials.

  18. Targeted versus universal prevention. a resource allocation model to prioritize cardiovascular prevention.

    PubMed

    Feenstra, Talitha L; van Baal, Pieter M; Jacobs-van der Bruggen, Monique O; Hoogenveen, Rudolf T; Kommer, Geert-Jan; Baan, Caroline A

    2011-10-06

    Diabetes mellitus brings an increased risk for cardiovascular complications and patients profit from prevention. This prevention also suits the general population. The question arises what is a better strategy: target the general population or diabetes patients. A mathematical programming model was developed to calculate optimal allocations for the Dutch population of the following interventions: smoking cessation support, diet and exercise to reduce overweight, statins, and medication to reduce blood pressure. Outcomes were total lifetime health care costs and QALYs. Budget sizes were varied and the division of resources between the general population and diabetes patients was assessed. Full implementation of all interventions resulted in a gain of 560,000 QALY at a cost of €640 per capita, about €12,900 per QALY on average. The large majority of these QALY gains could be obtained at incremental costs below €20,000 per QALY. Low or high budgets (below €9 or above €100 per capita) were predominantly spent in the general population. Moderate budgets were mostly spent in diabetes patients. Major health gains can be realized efficiently by offering prevention to both the general and the diabetic population. However, a priori setting a specific distribution of resources is suboptimal. Resource allocation models allow accounting for capacity constraints and program size in addition to efficiency.

  19. The Living the Example Social Media Substance Use Prevention Program: A Pilot Evaluation

    PubMed Central

    Andrade, Elizabeth; Goldmeer, Sandra; Smith, Michelle; Snider, Jeremy; Girardo, Gunilla

    2017-01-01

    Background Adolescent substance use rates in rural areas of the United States, such as upstate New York, have risen substantially in recent years, calling for new intervention approaches in response to this trend. The Mentor Foundation USA conducts the Living the Example (LTE) campaign to engage youth in prevention using an experiential approach. As part of LTE, youth create their own prevention messages following a training curriculum in techniques for effective messaging and then share them via social media. This paper reports on a pilot evaluation of the LTE program. Objective To conduct a pilot test of LTE in two rural high schools in upstate New York. We hypothesized that positive antidrug brand representations could be promoted using social media strategies to complement the Shattering the Myths (STM) in-person, event-based approach (hypothesis 1, H1), and that youth would respond positively and engage with prevention messages disseminated by their peers. We also hypothesized that exposure to the social media prevention messages would be associated with more positive substance use avoidance attitudes and beliefs, reductions in future use intentions, and decreased substance use at posttest (hypothesis 2, H2). Methods We adapted a previously published curriculum created by the authors that focuses on branding, messaging, and social media for prevention. The curriculum consisted of five, one-hour sessions. It was delivered to participating youth in five sequential weeks after school at the two high schools in late October and early November 2016. We designed a pre- and posttest pilot implementation study to evaluate the effects of LTE on student uptake of the intervention and short-term substance use and related outcomes. Working at two high schools in upstate New York, we conducted a pilot feasibility evaluation of LTE with 9th-grade students (ie, freshmen) at these high schools. We administered a 125-item questionnaire online to capture data on media use

  20. The Living the Example Social Media Substance Use Prevention Program: A Pilot Evaluation.

    PubMed

    Evans, William; Andrade, Elizabeth; Goldmeer, Sandra; Smith, Michelle; Snider, Jeremy; Girardo, Gunilla

    2017-06-27

    Adolescent substance use rates in rural areas of the United States, such as upstate New York, have risen substantially in recent years, calling for new intervention approaches in response to this trend. The Mentor Foundation USA conducts the Living the Example (LTE) campaign to engage youth in prevention using an experiential approach. As part of LTE, youth create their own prevention messages following a training curriculum in techniques for effective messaging and then share them via social media. This paper reports on a pilot evaluation of the LTE program. To conduct a pilot test of LTE in two rural high schools in upstate New York. We hypothesized that positive antidrug brand representations could be promoted using social media strategies to complement the Shattering the Myths (STM) in-person, event-based approach (hypothesis 1, H1), and that youth would respond positively and engage with prevention messages disseminated by their peers. We also hypothesized that exposure to the social media prevention messages would be associated with more positive substance use avoidance attitudes and beliefs, reductions in future use intentions, and decreased substance use at posttest (hypothesis 2, H2). We adapted a previously published curriculum created by the authors that focuses on branding, messaging, and social media for prevention. The curriculum consisted of five, one-hour sessions. It was delivered to participating youth in five sequential weeks after school at the two high schools in late October and early November 2016. We designed a pre- and posttest pilot implementation study to evaluate the effects of LTE on student uptake of the intervention and short-term substance use and related outcomes. Working at two high schools in upstate New York, we conducted a pilot feasibility evaluation of LTE with 9th-grade students (ie, freshmen) at these high schools. We administered a 125-item questionnaire online to capture data on media use; attitudes toward social media

  1. Broad targeting of angiogenesis for cancer prevention and therapy.

    PubMed

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M; Arreola, Alexandra; Rathmell, W Kimryn; Generali, Daniele; Nagaraju, Ganji P; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I; Azmi, Asfar S; Bilsland, Alan; Keith, W Nicol; Jensen, Lasse D

    2015-12-01

    pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the "hallmarks" of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  2. Broad targeting of angiogenesis for cancer prevention and therapy

    PubMed Central

    Wang, Zongwei; Dabrosin, Charlotta; Yin, Xin; Fuster, Mark M.; Arreola, Alexandra; Rathmell, W. Kimryn; Generali, Daniele; Nagaraju, Ganji P.; El-Rayes, Bassel; Ribatti, Domenico; Chen, Yi Charlie; Honoki, Kanya; Fujii, Hiromasa; Georgakilas, Alexandros G.; Nowsheen, Somaira; Amedei, Amedeo; Niccolai, Elena; Amin, Amr; Ashraf, S. Salman; Helferich, Bill; Yang, Xujuan; Guha, Gunjan; Bhakta, Dipita; Ciriolo, Maria Rosa; Aquilano, Katia; Chen, Sophie; Halicka, Dorota; Mohammed, Sulma I.; Azmi, Asfar S.; Bilsland, Alan; Keith, W. Nicol; Jensen, Lasse D.

    2015-01-01

    angiogenesis and the pathological tumor vasculature which would be well suited as targets for anti-angiogenic therapy: (1) endothelial cell migration/tip cell formation, (2) structural abnormalities of tumor vessels, (3) hypoxia, (4) lymphangiogenesis, (5) elevated interstitial fluid pressure, (6) poor perfusion, (7) disrupted circadian rhythms, (8) tumor promoting inflammation, (9) tumor promoting fibroblasts and (10) tumor cell metabolism/acidosis. Following this analysis, we scrutinized the available literature on broadly acting anti-angiogenic natural products, with a focus on finding qualitative information on phytochemicals which could inhibit these targets and came up with 10 prototypical phytochemical compounds: (1) oleanolic acid, (2) tripterine, (3) silibinin, (4) curcumin, (5) epigallocatechin-gallate, (6) kaempferol, (7) melatonin, (8) enterolactone, (9) withaferin A and (10) resveratrol. We suggest that these plant-derived compounds could be combined to constitute a broader acting and more effective inhibitory cocktail at doses that would not be likely to cause excessive toxicity. All the targets and phytochemical approaches were further cross-validated against their effects on other essential tumorigenic pathways (based on the “hallmarks” of cancer) in order to discover possible synergies or potentially harmful interactions, and were found to generally also have positive involvement in/effects on these other aspects of tumor biology. The aim is that this discussion could lead to the selection of combinations of such anti-angiogenic compounds which could be used in potent anti-tumor cocktails, for enhanced therapeutic efficacy, reduced toxicity and circumvention of single-agent anti-angiogenic resistance, as well as for possible use in primary or secondary cancer prevention strategies. PMID:25600295

  3. Targeting 9 Risk Factors Could Prevent 1 in 3 Dementia Cases

    MedlinePlus

    ... Risk Factors Could Prevent 1 in 3 Dementia Cases: Study Reducing mid-life hearing loss might make the ... factors would possibly prevent 35 percent of dementia cases, the study findings suggested. In comparison, targeting the major genetic ...

  4. Vascular wall proteoglycan synthesis and structure as a target for the prevention of atherosclerosis

    PubMed Central

    Little, Peter J; Ballinger, Mandy L; Osman, Narin

    2007-01-01

    Atherosclerosis is the underlying pathology of most cardiovascular disease and it represents the major cause of premature death in modern societies. Current therapies target risk factors being hypertension, hypercholesterolemia, hypertriglyceridemia and hyperglycemia when diabetes is present however the maximum efficacy of these strategies is often 30% or less. Areas of vascular biology that may lead to the development of a complementary vascular wall directed therapy are: inflammation, oxidation, endothelial dysfunction, diabetes-specific factors—hyperglycemia and advanced glycation endproducts and lipid retention by vascular matrix specifically proteoglycans. The major structural features of proteoglycans that determine low-density lipoprotein (LDL) binding are the length and sulfation pattern on the glycosaminoglycan (GAG) chains. Emerging data discussed in this review indicates that these structural properties are subject to considerable regulation by vasoactive substances possibly using novel signaling pathways. For example, GAG elongation stimulated by platelet-derived growth factor is not blocked by the receptor tyrosine kinase antagonist, genistein suggesting that there may be a previously unknown signaling pathway involved in this response. Thus, modifying proteoglycan synthesis and structure may represent a prime target to prevent LDL binding and entrapment in the vessel wall and thus prevent the development and progression of atherosclerosis. PMID:17583182

  5. Patchy progress on obesity prevention: emerging examples, entrenched barriers, and new thinking.

    PubMed

    Roberto, Christina A; Swinburn, Boyd; Hawkes, Corinna; Huang, Terry T-K; Costa, Sergio A; Ashe, Marice; Zwicker, Lindsey; Cawley, John H; Brownell, Kelly D

    2015-06-13

    Despite isolated areas of improvement, no country to date has reversed its obesity epidemic. Governments, together with a broad range of stakeholders, need to act urgently to decrease the prevalence of obesity. In this Series paper, we review several regulatory and non-regulatory actions taken around the world to address obesity and discuss some of the reasons for the scarce and fitful progress. Additionally, we preview the papers in this Lancet Series, which each identify high-priority actions on key obesity issues and challenge some of the entrenched dichotomies that dominate the thinking about obesity and its solutions. Although obesity is acknowledged as a complex issue, many debates about its causes and solutions are centred around overly simple dichotomies that present seemingly competing perspectives. Examples of such dichotomies explored in this Series include personal versus collective responsibilities for actions, supply versus demand-type explanations for consumption of unhealthy food, government regulation versus industry self-regulation, top-down versus bottom-up drivers for change, treatment versus prevention priorities, and a focus on undernutrition versus overnutrition. We also explore the dichotomy of individual versus environmental drivers of obesity and conclude that people bear some personal responsibility for their health, but environmental factors can readily support or undermine the ability of people to act in their own self-interest. We propose a reframing of obesity that emphasises the reciprocal nature of the interaction between the environment and the individual. Today's food environments exploit people's biological, psychological, social, and economic vulnerabilities, making it easier for them to eat unhealthy foods. This reinforces preferences and demands for foods of poor nutritional quality, furthering the unhealthy food environments. Regulatory actions from governments and increased efforts from industry and civil society will be

  6. Preventing the aortic complications of Marfan syndrome: a case-example of translational genomic medicine

    PubMed Central

    Li-Wan-Po, Alain; Loeys, Bart; Farndon, Peter; Latham, David; Bradley, Caroline

    2011-01-01

    The translational path from pharmacological insight to effective therapy can be a long one. We aim to describe the management of Marfan syndrome as a case-example of how pharmacological and genomic insights can contribute to improved therapy. We undertook a literature search for studies of Marfan syndrome, to identify milestones in description, understanding and therapy of the syndrome. From the studies retrieved we then weaved an evidence-based description of progress. Marfan syndrome shows considerable heterogeneity in clinical presentation. It relies on defined clinical criteria with confirmation based on FBN1 mutation testing. Surgical advances have prolonged life in Marfan syndrome. First-line prophylaxis of complications with β-adrenoceptor blockers became established on the basis that reduction of aortic pressure and heart rate would help. Over-activity of proteinases, first suggested in 1980, has since been confirmed by evidence of over-expression of matrix metalloproteinases (MMP), notably MMP-2 and MMP-9. The search for MMP inhibitors led to the evaluation of doxycycline, and both animal studies and small trials, provided early evidence that this widely used antimicrobial agent was useful. Identification of the importance of TGF-β led to evaluation of angiotensin II type I receptor (AT1R) blockers with highly promising results. Combination prophylactic therapy would appear rational. Pharmacological and genomic research has provided good evidence that therapy with losartan and doxycycline would prevent the aortic complications of Marfan syndrome. If on-going well designed trials confirm their efficacy, the outlook for Marfan syndrome patients would be improved considerably. PMID:21276043

  7. Tumor Angiogenesis as a Target for Dietary Cancer Prevention

    PubMed Central

    Li, William W.; Li, Vincent W.; Hutnik, Michelle; Chiou, Albert S.

    2012-01-01

    Between 2000 and 2050, the number of new cancer patients diagnosed annually is expected to double, with an accompanying increase in treatment costs of more than $80 billion over just the next decade. Efficacious strategies for cancer prevention will therefore be vital for improving patients' quality of life and reducing healthcare costs. Judah Folkman first proposed antiangiogenesis as a strategy for preventing dormant microtumors from progressing to invasive cancer. Although antiangiogenic drugs are now available for many advanced malignancies (colorectal, lung, breast, kidney, liver, brain, thyroid, neuroendocrine, multiple myeloma, myelodysplastic syndrome), cost and toxicity considerations preclude their broad use for cancer prevention. Potent antiangiogenic molecules have now been identified in dietary sources, suggesting that a rationally designed antiangiogenic diet could provide a safe, widely available, and novel strategy for preventing cancer. This paper presents the scientific, epidemiologic, and clinical evidence supporting the role of an antiangiogenic diet for cancer prevention. PMID:21977033

  8. The influence of health disparities on targeting cancer prevention efforts.

    PubMed

    Zonderman, Alan B; Ejiogu, Ngozi; Norbeck, Jennifer; Evans, Michele K

    2014-03-01

    Despite the advances in cancer medicine and the resultant 20% decline in cancer death rates for Americans since 1991, there remain distinct cancer health disparities among African Americans, Hispanics, Native Americans, and the those living in poverty. Minorities and the poor continue to bear the disproportionate burden of cancer, especially in terms of stage at diagnosis, incidence, and mortality. Cancer health disparities are persistent reminders that state-of-the-art cancer prevention, diagnosis, and treatment are not equally effective for and accessible to all Americans. The cancer prevention model must take into account the phenotype of accelerated aging associated with health disparities as well as the important interplay of biological and sociocultural factors that lead to disparate health outcomes. The building blocks of this prevention model will include interdisciplinary prevention modalities that encourage partnerships across medical and nonmedical entities, community-based participatory research, development of ethnically and racially diverse research cohorts, and full actualization of the prevention benefits outlined in the 2010 Patient Protection and Affordable Care Act. However, the most essential facet should be a thoughtful integration of cancer prevention and screening into prevention, screening, and disease management activities for hypertension and diabetes mellitus because these chronic medical illnesses have a substantial prevalence in populations at risk for cancer disparities and cause considerable comorbidity and likely complicate effective treatment and contribute to disproportionate cancer death rates. Published by Elsevier Inc.

  9. Burn prevention in Zambia: a targeted epidemiological approach.

    PubMed

    Heard, Jason P; Latenser, Barbara A; Liao, Junlin

    2013-01-01

    The aim of this study is to assess primary burn prevention knowledge in a rural Zambian population that is disproportionately burdened by burn injuries. A 10-question survey was completed by youths, and a 15-question survey was completed by adults. The survey was available in both English and Nyanja. The surveys were designed to test their knowledge in common causes, first aid, and emergency measures regarding burn injuries. Logistic regression analysis was used to explore relationships between burn knowledge, age, school, and socioeconomic variables. A burn prevention coloring book, based on previous local epidemiological data, was also distributed to 800 school age youths. Five hundred fifty youths and 39 adults completed the survey. The most significant results show knowledge deficits in common causes of burns, first aid treatment of a burn injury, and what to do in the event of clothing catching fire. Younger children were more likely to do worse than older children. The adults performed better than the youths, but still lack fundamental burn prevention and treatment knowledge. Primary burn prevention data from the youths and adults surveyed demonstrate a clear need for burn prevention and treatment education in this population. In a country where effective and sustainable burn care is lacking, burn prevention may be a better investment to reduce burn injury than large investments in healthcare resources.

  10. A Critical Analysis of Approaches To Targeted PTSD Prevention: Current Status and Theoretically Derived Future Directions

    ERIC Educational Resources Information Center

    Feldner, Matthew T.; Monson, Candice M.; Friedman, Matthew J.

    2007-01-01

    Although efforts to prevent posttraumatic stress disorder (PTSD) have met with relatively limited success, theoretically driven preventive approaches with promising efficacy are emerging. The current article critically reviews investigations of PTSD prevention programs that target persons at risk for being exposed to a traumatic event or who have…

  11. Targeting students, teachers and parents in a wellness-based prevention program in schools.

    PubMed

    Russell-Mayhew, Shelly; Arthur, Nancy; Ewashen, Carol

    2007-01-01

    This study examines the effectiveness of a wellness-based prevention program on elementary and junior high students' body image, personal attitudes, and eating behaviors. Group differences in measures of student attitudes and eating behaviors are examined to determine the effect of targeting different participant combinations (students, parents, and teachers) in 10 groups. For elementary schools, student participants consisted of control (no intervention) (n = 36), student only (n = 81), student/parent (n = 124), student/parent/teacher (n = 103), and parent/teacher (n = 149). For junior high schools, student participants consisted of control (n = 143), student only (n=215), student/parent (n=65), student/parent/teacher (n = 14), and parent/teacher (n = 177). Overall, complete data was available for 1,095 students, 114 parents and 92 teachers. Results indicate that self-concept and eating attitudes and behaviors were positively affected by participation in the program. For example, in elementary schools posttest scores on the behavior subscale of the self-concept measure are significantly higher for the student/parent/teacher group than for the control group. Results indicate that a one-time wellness-based eating disorder prevention program with students, which have in the past shown to be minimally effective, may be more effective in changing attitudes and behaviors when teachers and parents are involved.

  12. HIV Prevention Messages Targeting Young Latino Immigrant MSM

    PubMed Central

    Solorio, Rosa; Forehand, Mark; Aguirre, Joel

    2014-01-01

    Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and for delayed diagnosis. A need exists to raise awareness about HIV prevention in this population, including the benefits of timely HIV testing. This project was developed through collaboration between University of WA researchers and Entre Hermanos, a community-based organization serving Latinos. Building from a community-based participatory research approach, the researchers developed a campaign that was executed by Activate Brands, based in Denver, Colorado. The authors (a) describe the development of HIV prevention messages through the integration of previously collected formative data; (b) describe the process of translating these messages into PSAs, including the application of a marketing strategy; (c) describe testing the PSAs within the Latino MSM community; and (c) determine a set of important factors to consider when developing HIV prevention messages for young Latino MSM who do not identify as gay. PMID:24864201

  13. HIV Prevention Messages Targeting Young Latino Immigrant MSM.

    PubMed

    Solorio, Rosa; Norton-Shelpuk, Pamela; Forehand, Mark; Martinez, Marcos; Aguirre, Joel

    2014-01-01

    Young Latino immigrant men who have sex with men (MSM) are at risk for HIV and for delayed diagnosis. A need exists to raise awareness about HIV prevention in this population, including the benefits of timely HIV testing. This project was developed through collaboration between University of WA researchers and Entre Hermanos, a community-based organization serving Latinos. Building from a community-based participatory research approach, the researchers developed a campaign that was executed by Activate Brands, based in Denver, Colorado. The authors (a) describe the development of HIV prevention messages through the integration of previously collected formative data; (b) describe the process of translating these messages into PSAs, including the application of a marketing strategy; (c) describe testing the PSAs within the Latino MSM community; and (c) determine a set of important factors to consider when developing HIV prevention messages for young Latino MSM who do not identify as gay.

  14. Targeted therapies for the prevention of lung cancer.

    PubMed

    Schachter, E Neil; Neuman, Tzvi

    2007-12-01

    Lung cancer is a leading cause of mortality and morbidity in industrialized countries and potentially one of the most preventable cancers. The major cause of this neoplasm, cigarette smoking, has been well established since the 1950s. Legislative, regulatory and educational efforts have resulted in significant reductions in the number of smokers, decreasing the percentage of individuals who initiate the smoking habit and increasing the number of persons who quit. Nevertheless, there is wide recognition of the need to address the issue of lung cancer prevention for those who are addicted to cigarettes or who are exposed to lung carcinogens in other ways. Strategies for smoking cessation now include nicotine replacement, and modulation of central nervous system addictive mechanisms through neuropharmacology. For those who have experienced prolonged carcinogen exposure a growing number of novel strategies based on epidemiologic observations as well as oncologic principles are under investigation. Many promising avenues have been proposed and while no agent is yet approved as chemopreventive for lung cancer a growing number of these agents are being tested as primary, secondary and tertiary prevention strategies. Proposed primary prevention strategies include cigarette abstinence and treatment of cigarette addiction, using appropriate cancer screening methods, decreasing environmental exposure, and possibly vaccination. Proposed secondary prevention strategies include methods for smoking cessation, lifestyle and diet modification, and modulation of molecular pathways that lead to lung cancer. Proposed tertiary prevention strategies include individually tailored therapies against certain molecular pathways as well as treatments to minimize disease metastasis and its sequelae. Currently, treatment for nicotine addiction includes nicotine replacement and medications such as bupropion and the recently approved varenicline. Attempts to modify the development of lung cancer

  15. [Validation of a measurement scale: example of a French Adverse Drug Reactions Preventability Scale].

    PubMed

    Olivier, Pascale; Caron, Jacques; Haramburu, Françoise; Imbs, Jean-Louis; Jonville-Béra, Annie-Pierre; Lagier, Georges; Sgro, Catherine; Vial, Thierry; Montastruc, Jean-Louis; Lapeyr-Mestre, Maryse

    2005-01-01

    Adverse drug reactions (ADRs) have been recognised as an important cause of hospital admission. Most of these drug-related admissions were expected ADRs and, thus, partly preventable. However, as far as we know, the assessment of the preventability of ADRs was addressed in only two studies performed in France. In contrast, several other studies have been performed, mainly in the USA, and using different methods of assessing preventability. None of these methods were clearly evaluated with regard to reproducibility, validity or relevance. The purpose of this study was to initiate the validation of a French preventability scale. Here, we propose the first two phases of validation: the content validity and reliability of the scale. A working group of pharmacovigilance experts has been specifically established for this purpose. The content validity was assessed by collecting items representative of preventability. The choice and the formulation of items and a proposal of a score (global and for each item) were adopted after the consensus of the experts. A definitive version of the ADR preventability scale was used for the assessment of reliability. During the second phase, experts independently tested the new scale from observations of ADRs (49 central nervous system haemorrhages with antivitamine K). The concordance of the experts' judgements was calculated using two statistical methods (Kappa statistic and correlation coefficient). The content validity phase was performed during several workshops where experts discussed the choice and formulation of the best items. We decided to construct a scale with a small number of items, allowing a rapid evaluation of the preventability of ADRs. On the basis of a global score, four categories of preventability of ADRs ("preventable", "potentially preventable", "unclassable", "not preventable" ADRs) were proposed. The agreement of experts regarding the global score was low, with a poor correlation coefficient value (coefficient

  16. Preventing Prostate Cancer Metastasis by Targeting Exosome Secretion

    DTIC Science & Technology

    2015-12-01

    process by a number of viruses including Biomolecules 2015, 5 1443 HIV and the hepatitis C virus [25–28]. However, the exact mechanisms by which...disorders which result from dysfunctional protein translation. These pathologies are frequently a direct consequence of mutation of an RNA binding protein...For example, mutation of the translational repressor fragile X mental retardation 1 (FMR1) results in fragile X syndrome, a developmental disorder

  17. Targeting polyamine metabolism for cancer therapy and prevention.

    PubMed

    Murray-Stewart, Tracy R; Woster, Patrick M; Casero, Robert A

    2016-10-01

    The chemically simple, biologically complex eukaryotic polyamines, spermidine and spermine, are positively charged alkylamines involved in many crucial cellular processes. Along with their diamine precursor putrescine, their normally high intracellular concentrations require fine attenuation by multiple regulatory mechanisms to keep these essential molecules within strict physiologic ranges. Since the metabolism of and requirement for polyamines are frequently dysregulated in neoplastic disease, the metabolic pathway and functions of polyamines provide rational drug targets; however, these targets have been difficult to exploit for chemotherapy. It is the goal of this article to review the latest findings in the field that demonstrate the potential utility of targeting the metabolism and function of polyamines as strategies for both chemotherapy and, possibly more importantly, chemoprevention.

  18. Drug target identification using network analysis: Taking active components in Sini decoction as an example

    NASA Astrophysics Data System (ADS)

    Chen, Si; Jiang, Hailong; Cao, Yan; Wang, Yun; Hu, Ziheng; Zhu, Zhenyu; Chai, Yifeng

    2016-04-01

    Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

  19. Drug target identification using network analysis: Taking active components in Sini decoction as an example.

    PubMed

    Chen, Si; Jiang, Hailong; Cao, Yan; Wang, Yun; Hu, Ziheng; Zhu, Zhenyu; Chai, Yifeng

    2016-04-20

    Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

  20. Drug target identification using network analysis: Taking active components in Sini decoction as an example

    PubMed Central

    Chen, Si; Jiang, Hailong; Cao, Yan; Wang, Yun; Hu, Ziheng; Zhu, Zhenyu; Chai, Yifeng

    2016-01-01

    Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound. PMID:27095146

  1. Targeting Microglia to Prevent Post-Traumatic Epilepsy

    DTIC Science & Technology

    2012-07-01

    effectiveness in preventing epileptogenesis in the LFPI model of PTE. In this first project year we have developed a high-speed video /EEG recording and analysis...served its purpose of familiarizing us with chronic video /EEG recording and analysis of spikes and seizures. However, having succeeded with this model ...explore anti-epileptogenic strategies in and animal model of post-traumatic epilepsy (PTE) using lateral fluid percussion injury (LFPI). Our focus is on

  2. A Novel Molecular Target for Breast Cancer Prevention and Treatment

    DTIC Science & Technology

    2004-06-01

    Although anti-estrogen tamoxifen shows activities in preventing development of breast cancer, there are no effective therapies for malignant estrogen...independent breast cancer, which is also often resistant to chemotherapy and g-radiation therapy . Lack of such therapies has contributed to the high...mortality for U.S. women. Novel therapies are therefore urgently needed. Retinoids, natural and synthetic vitamin A derivatives, exert profound effects on

  3. Target delamination by spallation and ejecta dragging: An example from the Ries crater's periphery

    NASA Astrophysics Data System (ADS)

    Kenkmann, Thomas; Ivanov, Boris A.

    2006-11-01

    Subhorizontal shear planes (detachments) are observed in bedded limestones in the periphery of the Ries impact crater, Germany. These detachments occur at 0.8-1.8 crater radii distance from the crater center beneath deposits of the continuous ejecta blanket. Striations on detachment planes and offsets of markers indicate top-outward shearing with radial slip vectors. Detachments were found at depths between a few meters and more than 50 m beneath the target surface. The displacements along these faults range from meters to decameters and decrease with increasing depth and distance from the crater center. With increasing crater distance, detachment horizons tend to climb to shallower levels. Cross-cutting relationships to faults associated with the crater collapse indicate that detachment faulting started prior to the collapse but continued during crater modification. Numerical modeling of the cratering process shows that near-surface deformation outside the transient crater is induced by two separate mechanisms: (i) weak spallation by interference of shock and release waves near the target surface and (ii) subsequent dragging by the deposition of the ejecta curtain. Spallation causes an upward and outward directed motion of target material that increases in magnitude toward the target surface. It leads to decoupling of the uppermost target layers in the early cratering stage without totally disintegrating the rock. The subsequent arrival of the oblique impact shower of the ejecta curtain at the target surface delivers a horizontal momentum to the uppermost target area and results in a second horizontal displacement increment by dragging. With increasing depth this effect vanishes rapidly. Spallation decoupling and subsequent ejecta dragging of near-surface rocks is probably a general cratering mechanism around craters in layered targets with weak interbeds.

  4. Current costing models: are they suitable for allocating health resources? The example of fall injury prevention in Australia.

    PubMed

    Moller, Jerry

    2005-01-01

    The example of fall injury among older people is used to define and illustrate how current Australian systems for allocation of health resources perform for funding emerging public health issues. While the examples are Australian, the allocation and priority setting methods are common in the health sector in all developed western nations. With an ageing population the number of falls injuries in Australia and the cost of treatment will rise dramatically over the next 20-50 years. Current methods of allocating funds within the health system are not well suited to meeting this coming epidemic. The information requirements for cost-benefit and cost-effectiveness measures cannot be met. Marginal approaches to health funding are likely to continue to fund already well-funded treatment or politically driven prevention processes and to miss the opportunity for new prevention initiatives in areas that do not have a high political profile. Fall injury is one of many emerging areas that struggle to make claims for funding because the critical mass of intervention and evidence of its impact is not available. The beneficiaries of allocation failure may be those who treat the disease burden that could have been easily prevented. Changes to allocation mechanisms, data systems and new initiative funding practices are required to ensure that preventative strategies are able to compete on an equal footing with treatment approaches for mainstream health funding.

  5. Community based prevention programs targeting all injuries for children

    PubMed Central

    Spinks, A; Turner, C; McClure, R; Nixon, J

    2004-01-01

    Objective: Community based models for injury prevention have become an accepted part of the overall injury control strategy. This systematic review of the scientific literature examines the evidence for their effectiveness in reducing all-cause injury in children 0–14 years of age. Methods: A comprehensive search of the literature was performed using the following study selection criteria: community based intervention study; children under 14 years; outcome measure was injury rates; and either a community control or an historical control was used in the design. Quality assessment and data abstraction were guided by a standardized procedure and performed independently by two authors. Data synthesis was in tabular and text form with meta-analysis not being possible due to the discrepancy in methods and measures between the studies. Results: Thorough electronic and library search techniques yielded only nine formally evaluated community based all-cause child injury prevention programs that have reported actual injury outcomes. Of these nine studies, seven provided high level evidence where contemporary control communities were used for comparison; the remaining two used a pre and post-design or time trend analysis where historical data from the community were used as the comparison. Only three of the seven studies with contemporary control communities found significant effect of the intervention; the two studies without controls noted significant reductions in injury rates after the intervention period. Conclusion: There is a paucity of research from which evidence regarding the effectiveness of community based childhood injury prevention programs can be obtained and hence a clear need to increase the effort on developing this evidence base. PMID:15178676

  6. [Nutrition and physical activity: two targets for cancer prevention].

    PubMed

    Thibault, Ronan; Dupertuis, Yves M; Belabed, Linda; Pichard, Claude

    2010-05-26

    The links between nutrition and cancer onset are now well established by epidemiological studies. The scientific evidence is presented in a report of the World Cancer Research Foundation (WCRF). Protective factors towards overall cancer risk are fruit and vegetable consumption and physical activity. Overweight and obesity, intakes of alcoholic beverage, fat, salt, high temperature cooked and processed red meat, increase cancer risk. In addition, beta-carotene systematic supplementation could increase lung cancer risk in smokers. As optimal controlling of these risk factors can decrease cancer mortality by 25%, nutritional counselling must be integrated in the global strategy of primary and secondary prevention of cancers.

  7. Disease prevention--should we target obesity or sedentary lifestyle?

    PubMed

    Charansonney, Olivier L; Després, Jean-Pierre

    2010-08-01

    Obesity is a major health challenge facing the modern world. Some evidence points to obesity itself as the main driver of premature mortality. We propose that this view is oversimplified. For example, high levels of physical activity and cardiorespiratory fitness are associated with lower mortality, even in those who are overweight or obese. To address this issue, we combine epidemiological and physiological evidence in a new paradigm that integrates excess calorie intake, sedentary behavior, and a maladaptive response to stress. Human physiology is optimized to allow large distances to be covered on foot every day in order to find enough food to sustain brain metabolism. Furthermore, when the body is immobilized by an injury, it triggers efficient life-saving metabolic and inflammatory responses. Both these critical adaptations are, however, confounded by a sedentary lifestyle. The implications of these issues for clinical trial design and epidemiologic data analysis are discussed in this article.

  8. The "Lugna Gatan" Project--An Example of Enterprise in Crime Prevention Work

    ERIC Educational Resources Information Center

    Roth, Niklas

    2004-01-01

    Over the course of the last decade, Stockholm has witnessed the emergence of a number of voluntary organizations that are active in the field of crime prevention. This article describes the "Lugna Gatan" project, which was initiated in Stockholm in 1994. The idea was to create an organization comprised of young adults aged between 20 and…

  9. The "Lugna Gatan" Project--An Example of Enterprise in Crime Prevention Work

    ERIC Educational Resources Information Center

    Roth, Niklas

    2004-01-01

    Over the course of the last decade, Stockholm has witnessed the emergence of a number of voluntary organizations that are active in the field of crime prevention. This article describes the "Lugna Gatan" project, which was initiated in Stockholm in 1994. The idea was to create an organization comprised of young adults aged between 20 and…

  10. Suicide Prevention Public Service Announcements (PSAs): Examples from Around the World.

    PubMed

    Ftanou, Maria; Cox, Georgina; Nicholas, Angela; Spittal, Matthew J; Machlin, Anna; Robinson, Jo; Pirkis, Jane

    2017-04-01

    Media campaigns have received increased attention as an intervention for combating suicide. Suicide prevention campaigns involving public service announcements (PSAs) have not been well described and have been subject to minimal evaluation. This study aimed to identify suicide prevention PSAs from around the world and analyze and describe their content. We searched the Internet for short, English-language PSAs that had been screened as part of suicide prevention campaigns and identified 35. Most commonly, these PSAs focused on the general population and/or people who might be at risk of suicide, and had a particular emphasis on young people. Almost 60% promoted open discussion about suicide, around 50% indicated that the life of a suicidal person was important, about 40% acknowledged the suffering associated with suicidal thoughts and feelings, about 25% stressed that suicide is preventable, and about 20% focused on the devastating impact of suicide for those left behind. Most PSAs promoted some sort of support for people at risk of suicide, usually a helpline or website. Although these messages appeared appropriate and practical there is a lack of research on the impact that they may have on people with varying degrees of suicide risk. Further work is needed to ensure that they are consistent with theories of behavior change, and that they are having their desired impacts.

  11. Beyond the scalpel: targeting hedgehog in skin cancer prevention.

    PubMed

    Rudin, Charles M

    2010-01-01

    This perspective places the article by Tang et al. in this issue of the journal (beginning on page 25) in the context of recent work defining the hedgehog signaling pathway as a central etiologic factor and as a therapeutic target in basal cell cancer. Tang et al. show that inhibition of cyclooxygenase activity, either genetically (in a relevant mouse model) or pharmacologically (in the mouse and in patients highly predisposed to develop basal cell skin cancers), may suppress basal cell carcinogenesis. This new study of cyclooxygenase inhibition, together with recent data on the efficacy of hedgehog pathway inhibition, offers new hope for patients at a high risk for basal cell cancer.

  12. Targeting memory processes with drugs to prevent or cure PTSD.

    PubMed

    Cain, Christopher K; Maynard, George D; Kehne, John H

    2012-09-01

    Post-traumatic stress disorder (PTSD) is a chronic debilitating psychiatric disorder resulting from exposure to a severe traumatic stressor and an area of great unmet medical need. Advances in pharmacological treatments beyond the currently approved SSRIs are needed. Background on PTSD, as well as the neurobiology of stress responding and fear conditioning, is provided. Clinical and preclinical data for investigational agents with diverse pharmacological mechanisms are summarized. Advances in the understanding of stress biology and mechanisms of fear conditioning plasticity provide a rationale for treatment approaches that may reduce hyperarousal and dysfunctional aversive memories in PTSD. One challenge is to determine if these components are independent or reflect a common underlying neurobiological alteration. Numerous agents reviewed have potential for reducing PTSD core symptoms or targeted symptoms in chronic PTSD. Promising early data support drug approaches that seek to disrupt dysfunctional aversive memories by interfering with consolidation soon after trauma exposure, or in chronic PTSD, by blocking reconsolidation and/or enhancing extinction. Challenges remain for achieving selectivity when attempting to alter aversive memories. Targeting the underlying traumatic memory with a combination of pharmacological therapies applied with appropriate chronicity, and in combination with psychotherapy, is expected to substantially improve PTSD treatment.

  13. Targeting memory processes with drugs to prevent or cure PTSD

    PubMed Central

    Cain, Christopher K.; Maynard, George D.; Kehne, John H.

    2015-01-01

    Introduction Post-traumatic stress disorder (PTSD) is a chronic debilitating psychiatric disorder resulting from exposure to a severe traumatic stressor and an area of great unmet medical need. Advances in pharmacological treatments beyond the currently approved SSRIs are needed. Areas covered Background on PTSD, as well as the neurobiology of stress responding and fear conditioning, is provided. Clinical and preclinical data for investigational agents with diverse pharmacological mechanisms are summarized. Expert opinion Advances in the understanding of stress biology and mechanisms of fear conditioning plasticity provide a rationale for treatment approaches that may reduce hyperarousal and dysfunctional aversive memories in PTSD. One challenge is to determine if these components are independent or reflect a common underlying neurobiological alteration. Numerous agents reviewed have potential for reducing PTSD core symptoms or targeted symptoms in chronic PTSD. Promising early data support drug approaches that seek to disrupt dysfunctional aversive memories by interfering with consolidation soon after trauma exposure, or in chronic PTSD, by blocking reconsolidation and/or enhancing extinction. Challenges remain for achieving selectivity when attempting to alter aversive memories. Targeting the underlying traumatic memory with a combination of pharmacological therapies applied with appropriate chronicity, and in combination with psychotherapy, is expected to substantially improve PTSD treatment. PMID:22834476

  14. Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design.

    PubMed

    Howe, George W; Beach, Steven R H; Brody, Gene H; Wyman, Peter A

    2015-01-01

    In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach.

  15. Translating Genetic Research into Preventive Intervention: The Baseline Target Moderated Mediator Design

    PubMed Central

    Howe, George W.; Beach, Steven R. H.; Brody, Gene H.; Wyman, Peter A.

    2016-01-01

    In this paper we present and discuss a novel research approach, the baseline target moderated mediation (BTMM) design, that holds substantial promise for advancing our understanding of how genetic research can inform prevention research. We first discuss how genetically informed research on developmental psychopathology can be used to identify potential intervention targets. We then describe the BTMM design, which employs moderated mediation within a longitudinal study to test whether baseline levels of intervention targets moderate the impact of the intervention on change in that target, and whether change in those targets mediates causal impact of preventive or treatment interventions on distal health outcomes. We next discuss how genetically informed BTMM designs can be applied to both microtrials and full-scale prevention trials. We use simulated data to illustrate a BTMM, and end with a discussion of some of the advantages and limitations of this approach. PMID:26779062

  16. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis

    PubMed Central

    Mi-ichi, Fumika; Yoshida, Hiroki; Hamano, Shinjiro

    2016-01-01

    Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by “encystation” and “excystation.” Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent. Here, we highlight studies investigating encystation using inhibitory chemicals and categorize them based on the molecules inhibited. We also present a perspective on new strategies to prevent the transmission of amebiasis. PMID:27764256

  17. Entamoeba Encystation: New Targets to Prevent the Transmission of Amebiasis.

    PubMed

    Mi-Ichi, Fumika; Yoshida, Hiroki; Hamano, Shinjiro

    2016-10-01

    Amebiasis is caused by Entamoeba histolytica infection and can produce a broad range of clinical signs, from asymptomatic cases to patients with obvious symptoms. The current epidemiological and clinical statuses of amebiasis make it a serious public health problem worldwide. The Entamoeba life cycle consists of the trophozoite, the causative agent for amebiasis, and the cyst, the form responsible for transmission. These two stages are connected by "encystation" and "excystation." Hence, developing novel strategies to control encystation and excystation will potentially lead to new measures to block the transmission of amebiasis by interrupting the life cycle of the causative agent. Here, we highlight studies investigating encystation using inhibitory chemicals and categorize them based on the molecules inhibited. We also present a perspective on new strategies to prevent the transmission of amebiasis.

  18. Simulating effects of biomarker enrichment onalzheimer's prevention trials: conceptual framework and example

    PubMed Central

    Leoutsakos, Jeannie-Marie S.; Bartlett, Alexandra L.; Forrester, Sarah N.; Lyketsos, Constantine G.

    2013-01-01

    Background We present a conceptual framework for simulations to determine the utility of biomarker enrichment to increase statistical power to detect a treatment effect in future Alzheimer prevention trials. We include a limited set of simulation results to illustrate aspects of this framework. Methods We simulated data based on the Alzheimer's Disease Anti-Inflammatory Prevention Trial, and a range of sample sizes, biomarker positive predictive values, and treatment effects. We also investigated the consequences of assuming homogeneity of parameter estimates as a function of dementia outcome. Results Use of biomarkers to increase the sample fraction that would develop AD in the absence of intervention from 0.5 to 0.8 would increase power from 0.35 to 0.69 with N=200. Ignoring sample heterogenity resulted in overestimation of power. Conclusion Biomarker enrichment can increase statistical power, but estimates of the expected increase are sensitive to a variety of assumptions outlined in the framework. PMID:23954029

  19. Constructing "Packages" of Evidence-Based Programs to Prevent Youth Violence: Processes and Illustrative Examples From the CDC's Youth Violence Prevention Centers.

    PubMed

    Kingston, Beverly; Bacallao, Martica; Smokowski, Paul; Sullivan, Terri; Sutherland, Kevin

    2016-04-01

    This paper describes the strategic efforts of six National Centers of Excellence in Youth Violence Prevention (YVPC), funded by the U.S. Centers for Disease Control and Prevention, to work in partnership with local communities to create comprehensive evidence-based program packages to prevent youth violence. Key components of a comprehensive evidence-based approach are defined and examples are provided from a variety of community settings (rural and urban) across the nation that illustrate attempts to respond to the unique needs of the communities while maintaining a focus on evidence-based programming and practices. At each YVPC site, the process of selecting prevention and intervention programs addressed the following factors: (1) community capacity, (2) researcher and community roles in selecting programs, (3) use of data in decision-making related to program selection, and (4) reach, resources, and dosage. We describe systemic barriers to these efforts, lessons learned, and opportunities for policy and practice. Although adopting an evidence-based comprehensive approach requires significant upfront resources and investment, it offers great potential for preventing youth violence and promoting the successful development of children, families and communities.

  20. Prevention of Targeted School Violence by Responding to Students' Psychosocial Crises: The NETWASS Program

    ERIC Educational Resources Information Center

    Leuschner, Vincenz; Fiedler, Nora; Schultze, Martin; Ahlig, Nadine; Göbel, Kristin; Sommer, Friederike; Scholl, Johanna; Cornell, Dewey; Scheithauer, Herbert

    2017-01-01

    The standardized, indicated school-based prevention program "Networks Against School Shootings" combines a threat assessment approach with a general model of prevention of emergency situations in schools through early intervention in student psychosocial crises and training teachers to recognize warning signs of targeted school violence.…

  1. Prevention of Targeted School Violence by Responding to Students' Psychosocial Crises: The NETWASS Program

    ERIC Educational Resources Information Center

    Leuschner, Vincenz; Fiedler, Nora; Schultze, Martin; Ahlig, Nadine; Göbel, Kristin; Sommer, Friederike; Scholl, Johanna; Cornell, Dewey; Scheithauer, Herbert

    2017-01-01

    The standardized, indicated school-based prevention program "Networks Against School Shootings" combines a threat assessment approach with a general model of prevention of emergency situations in schools through early intervention in student psychosocial crises and training teachers to recognize warning signs of targeted school violence.…

  2. Child restraint misuse: a case example and strategies for injury prevention.

    PubMed

    Beringer-Brown, Carol; Pearce, Jeanette; Rush, Carole

    2005-04-01

    Motor vehicle crashes are a leading cause of death and serious injury for children. Emergency nurses can play a key role in encouraging parents and caregivers to use child restraints consistently and correctly. This article will discuss a case scenario where a young child is seriously injured in a motor vehicle crash where his child car seat was not used correctly. Injury prevention strategies for emergency nurses will be reviewed.

  3. Using mixed methods effectively in prevention science: designs, procedures, and examples.

    PubMed

    Zhang, Wanqing; Watanabe-Galloway, Shinobu

    2014-10-01

    There is growing interest in using a combination of quantitative and qualitative methods to generate evidence about the effectiveness of health prevention, services, and intervention programs. With the emerging importance of mixed methods research across the social and health sciences, there has been an increased recognition of the value of using mixed methods for addressing research questions in different disciplines. We illustrate the mixed methods approach in prevention research, showing design procedures used in several published research articles. In this paper, we focused on two commonly used mixed methods designs: concurrent and sequential mixed methods designs. We discuss the types of mixed methods designs, the reasons for, and advantages of using a particular type of design, and the procedures of qualitative and quantitative data collection and integration. The studies reviewed in this paper show that the essence of qualitative research is to explore complex dynamic phenomena in prevention science, and the advantage of using mixed methods is that quantitative data can yield generalizable results and qualitative data can provide extensive insights. However, the emphasis of methodological rigor in a mixed methods application also requires considerable expertise in both qualitative and quantitative methods. Besides the necessary skills and effective interdisciplinary collaboration, this combined approach also requires an open-mindedness and reflection from the involved researchers.

  4. Planning cancer prevention strategies based on epidemiologic characteristics: an Egyptian example.

    PubMed

    Soliman, A S; Levin, B; El-Badawy, S; Nasser, S S; Raouf, A A; Khaled, H; El-Hattab, O H; Chamberlain, R M

    2001-01-01

    We describe the epidemiology, cancer prevention strategies, and educational messages to be learned from four characteristic cancers in Egypt: urinary bladder, liver, lung, and early-onset colorectal cancers. For bladder cancer, effective and convenient treatment of schistosomiasis, using social marketing and mass media in public and medical education has contributed dramatically to primary prevention of bladder cancer in Egypt. For liver cancer, educating hospital administrators to remove structural barriers to good practice may help the control of hepatitis transmission and related liver cancer. For lung cancer, the 50-year American experience for controlling tobacco smoking, beginning with physicians, could be very effective in Egypt and other countries with increasing smoking rates in the young so as to avert the expected epidemics of lung cancer. For colorectal cancer, more attention to physician and public education about the importance of interviewing colorectal cancer patients about a family history of cancer and the screening of at-risk families could be very effective in early detection of colorectal cancer. Countries with similar cancer epidemiology experience should make use of successful cancer prevention and education strategies that could be translated from the Egyptian experience.

  5. Targeting adenosine receptors to prevent inflammatory skin diseases.

    PubMed

    Gessi, Stefania; Merighi, Stefania; Borea, Pier Andrea

    2014-08-01

    Adenosine mediates its effects through activation of a family of four G-protein-coupled receptors, named A1 , A2A , A2B and A3 . This nucleoside plays an important role in immunity and inflammation, and the A2A adenosine receptor subtype has a key role in the inhibition of inflammatory processes besides promoting wound healing. In this issue of Experimental Dermatology, Arasa et al. show that the topical application of a selective A2A agonist, CGS 21680, to mouse skin reduced epidermal hyperplasia as well as skin inflammation, similarly to topical corticoids, without side effects like skin atrophy. Rigorously following up this work is important for the development of novel treatment strategies for chronic hyperproliferative inflammatory dermatoses, such as targeting the A2A adenosine receptor family.

  6. Non-Target Activity Detection by Post-Radioembolization Yttrium-90 PET/CT: Image Assessment Technique and Case Examples

    PubMed Central

    Kao, Yung Hsiang; Tan, Andrew E. H.; Lo, Richard H. G.; Tay, Kiang Hiong; Tan, Bien Soo; Chow, Pierce K. H.; Ng, David C. E.; Goh, Anthony S. W.

    2013-01-01

    High resolution yttrium-90 (90Y) imaging of post-radioembolization microsphere biodistribution may be achieved by conventional positron emission tomography with integrated computed tomography (PET/CT) scanners that have time-of-flight capability. However, reconstructed 90Y PET/CT images have high background noise, making non-target activity detection technically challenging. This educational article describes our image assessment technique for non-target activity detection by 90Y PET/CT, which qualitatively overcomes the problem of background noise. We present selected case examples of non-target activity in untargeted liver, stomach, gallbladder, chest wall, and kidney, supported by angiography and 90Y bremsstrahlung single-photon emission computed tomography with integrated computed tomography (SPECT/CT) or technetium-99m macroaggregated albumin SPECT/CT. PMID:24551594

  7. Angioprevention with fenretinide: targeting angiogenesis in prevention and therapeutic strategies.

    PubMed

    Sogno, Ilaria; Venè, Roberta; Ferrari, Nicoletta; De Censi, Andrea; Imperatori, Andrea; Noonan, Douglas M; Tosetti, Francesca; Albini, Adriana

    2010-07-01

    Clinical trials have revealed that N-(4-hydroxyphenyl) retinamide (4HPR; fenretinide), a synthetic retinoic acid derivative, is a highly active and promising therapeutic and chemopreventive agent. Fenretinide shows biological activity against numerous cancer types in vitro and in preclinical studies. Clinical trials have shown that fenretinide induces a significant reduction of second breast cancer in premenopausal women. Several studies on different neoplasms are ongoing, such as breast and ovarian cancer, neuroblastoma, glioblastoma, head and neck and skin cancers and others. It has minimal side effects in humans, so that trials in young women at high-risk of breast cancer and ovarian and for the prevention of other tumor types such as lung cancer could be envisaged. Here we review some ongoing clinical trials and evaluate the possible mechanisms underlying the secondary chemopreventive effects of 4HPR. In particular we report basic and translational data on the anti-angiogenic "angiopreventive" properties of fenretinide, its anti-invasive activity, its ability to induce apoptosis and to generate or enhance production of reactive oxygen species as possible molecular bases for a chemopreventive action in patients. Copyright (c) 2009 Elsevier Ireland Ltd. All rights reserved.

  8. Targeting vasculogenesis to prevent progression in multiple myeloma.

    PubMed

    Moschetta, M; Mishima, Y; Kawano, Y; Manier, S; Paiva, B; Palomera, L; Aljawai, Y; Calcinotto, A; Unitt, C; Sahin, I; Sacco, A; Glavey, S; Shi, J; Reagan, M R; Prosper, F; Bellone, M; Chesi, M; Bergsagel, L P; Vacca, A; Roccaro, A M; Ghobrial, I M

    2016-05-01

    The role of endothelial progenitor cell (EPC)-mediated vasculogenesis in hematological malignancies is not well explored. Here, we showed that EPCs are mobilized from the bone marrow (BM) to the peripheral blood at early stages of multiple myeloma (MM); and recruited to MM cell-colonized BM niches. Using EPC-defective ID1+/- ID3-/- mice, we found that MM tumor progression is dependent on EPC trafficking. By performing RNA-sequencing studies, we confirmed that endothelial cells can enhance proliferation and favor cell-cycle progression only in MM clones that are smoldering-like and have dependency on endothelial cells for tumor growth. We further confirmed that angiogenic dependency occurs early and not late during tumor progression in MM. By using a VEGFR2 antibody with anti-vasculogenic activity, we demonstrated that early targeting of EPCs delays tumor progression, while using the same agent at late stages of tumor progression is ineffective. Thus, although there is significant angiogenesis in myeloma, the dependency of the tumor cells on EPCs and vasculogenesis may actually precede this step. Manipulating vasculogenesis at an early stage of disease may be examined in clinical trials in patients with smoldering MM, and other hematological malignancies with precursor conditions.

  9. Prevention of vascular inflammation by nanoparticle targeting of adherent neutrophils

    NASA Astrophysics Data System (ADS)

    Wang, Zhenjia; Li, Jing; Cho, Jaehyung; Malik, Asrar B.

    2014-03-01

    Inflammatory diseases such as acute lung injury and ischaemic tissue injury are caused by the adhesion of a type of white blood cell--polymorphonuclear neutrophils--to the lining of the circulatory system or vascular endothelium and unchecked neutrophil transmigration. Nanoparticle-mediated targeting of activated neutrophils on vascular endothelial cells at the site of injury may be a useful means of directly inactivating neutrophil transmigration and hence mitigating vascular inflammation. Here, we report a method employing drug-loaded albumin nanoparticles, which efficiently deliver drugs into neutrophils adherent to the surface of the inflamed endothelium. Using intravital microscopy of tumour necrosis factor-α-challenged mouse cremaster post-capillary venules, we demonstrate that fluorescently tagged albumin nanoparticles are largely internalized by neutrophils adherent to the activated endothelium via cell surface Fcɣ receptors. Administration of albumin nanoparticles loaded with the spleen tyrosine kinase inhibitor, piceatannol, which blocks `outside-in' β2 integrin signalling in leukocytes, detached the adherent neutrophils and elicited their release into the circulation. Thus, internalization of drug-loaded albumin nanoparticles into neutrophils inactivates the pro-inflammatory function of activated neutrophils, thereby offering a promising approach for treating inflammatory diseases resulting from inappropriate neutrophil sequestration and activation.

  10. Efficacy and effectiveness trials: examples from smoking cessation and bullying prevention.

    PubMed

    Prochaska, James O; Evers, Kerry E; Prochaska, Janice M; Van Marter, Deborah; Johnson, Janet L

    2007-01-01

    If health psychology is to maximize impacts on health, there will need to be a shift from relying primarily on efficacy trials to increasing reliance on effectiveness trials. Efficacy trials use homogeneous, highly motivated samples with minimal complications from a single setting receiving intensive treatments delivered under highly controlled conditions. Two effectiveness trials on bullying prevention illustrate the use of a heterogeneous population from multiple sites receiving a low intensity tailored treatment delivered under highly variable conditions. In spite of considerable noise the effectiveness trials produced robust results (odds ratios of about four) that bode well for population impacts under real-world dissemination.

  11. Driving pressure and mechanical power: new targets for VILI prevention.

    PubMed

    Tonetti, Tommaso; Vasques, Francesco; Rapetti, Francesca; Maiolo, Giorgia; Collino, Francesca; Romitti, Federica; Camporota, Luigi; Cressoni, Massimo; Cadringher, Paolo; Quintel, Michael; Gattinoni, Luciano

    2017-07-01

    Several factors have been recognized as possible triggers of ventilator-induced lung injury (VILI). The first is pressure (thus the 'barotrauma'), then the volume (hence the 'volutrauma'), finally the cyclic opening-closing of the lung units ('atelectrauma'). Less attention has been paid to the respiratory rate and the flow, although both theoretical considerations and experimental evidence attribute them a significant role in the generation of VILI. The initial injury to the lung parenchyma is necessarily mechanical and it could manifest as an unphysiological distortion of the extracellular matrix and/or as micro-fractures in the hyaluronan, likely the most fragile polymer embedded in the matrix. The order of magnitude of the energy required to break a molecular bond between the hyaluronan and the associated protein is 1.12×10(-16) Joules (J), 70-90% higher than the average energy delivered by a single breath of 1L assuming a lung elastance of 10 cmH2O/L (0.5 J). With a normal statistical distribution of the bond strength some polymers will be exposed each cycle to an energy large enough to rupture. Both the extracellular matrix distortion and the polymer fractures lead to inflammatory increase of capillary permeability with edema if a pulmonary blood flow is sufficient. The mediation analysis of higher vs. lower tidal volume and PEEP studies suggests that the driving pressure, more than tidal volume, is the best predictor of VILI, as inferred by increased mortality. This is not surprising, as both tidal volume and respiratory system elastance (resulting in driving pressure) may independently contribute to the mortality. For the same elastance driving pressure is a predictor similar to plateau pressure or tidal volume. Driving pressure is one of the components of the mechanical power, which also includes respiratory rate, flow and PEEP. Finding the threshold for mechanical power would greatly simplify assessment and prevention of VILI.

  12. Targeting Innate Immunity for Type 1 Diabetes Prevention.

    PubMed

    Needell, James C; Zipris, Danny

    2017-09-27

    Despite immense research efforts, type 1 diabetes (T1D) remains an autoimmune disease without a known trigger or approved intervention. Over the last three decades, studies have primarily focused on delineating the role of the adaptive immune system in the mechanism of T1D. The discovery of Toll-like receptors in the 1990s has advanced the knowledge on the role of the innate immune system in host defense as well as mechanisms that regulate adaptive immunity including the function of autoreactive T cells. Recent investigations suggest that inflammation plays a key role in promoting a large number of autoimmune disorders including T1D. Data from the LEW1.WR1 rat model of virus-induced disease and the RIP-B7.1 mouse model of diabetes suggest that innate immune signaling plays a key role in triggering disease progression. There is also evidence that innate immunity may be involved in the course of T1D in humans; however, a small number of clinical trials have shown that interfering with the function of the innate immune system following disease onset exerts only a modest effect on β-cell function. The data implying that innate immune pathways are linked with mechanisms of islet autoimmunity hold great promise for the identification of novel disease pathways that may be harnessed for clinical intervention. Nevertheless, more work needs to be done to better understand mechanisms by which innate immunity triggers β-cell destruction and assess the therapeutic value in blocking innate immunity for diabetes prevention.

  13. IR and millimeter waves: Properties, models, and examples of ground target applications

    NASA Astrophysics Data System (ADS)

    Kjellgren, Jan

    1989-08-01

    Literature concerning these objectives was studied. The theory and the background effects are analyzed. Propagation is also addressed. Examples of models of infrared radiometry: PRISM (Physically Reasonable Infrared Signature Model), applied mostly for vehicles; SPACE (Sun, Precipitation, Atmosphere, Clouds, Earth) is used in thermal signatures for military applications. Multispectral image simulation is studied. Concerning multisensors, some applications are reviewed: a counting system for bomber aircraft, and the same for armored cars, based principally on millimeter waves. Some multisensor concepts for propagation problems, such as the identification of remote attack weapons requiring a fitting with three sensors, are given: the laser radar; an infrared sensor for heat data; a sensor of the radiometry in the millimeter wave band.

  14. Clinical Decision Support for Nurses: A Fall Risk and Prevention Example.

    PubMed

    Lytle, Kathryn S; Short, Nancy M; Richesson, Rachel L; Horvath, Monica M

    2015-12-01

    Clinical decision support tools in electronic health records have demonstrated improvement with process measures and clinician performance, predominantly for providers. Clinical decision support tools could improve patient fall risk identification and prevention plans, a common concern for nursing. This quality-improvement project used clinical decision support to improve the rate of nurse compliance with documented fall risk assessments and, for patients at high risk, fall prevention plans of care in 16 adult inpatient units. Preintervention and postintervention data were compared using quarterly audits, retrospective chart review, safety reports, and falls and falls-with-injury rates. Documentation of fall risk assessments on the 16 units improved significantly according to quarterly audit data (P = .05), whereas documentation of the plans of care did not. Retrospective chart review on two units indicated improvement for admission fall risk assessment (P = .05) and a decrease in the documentation of the shift plan of care (P = .01); one unit had a statistically significant decrease in documentation of plans of care on admission (P = .00). Examination of safety reports for patients who fell showed all patients before and after clinical decision support had fall risk assessments documented. Falls and falls with injury did not change significantly before and after clinical decision support intervention.

  15. Occupational asthma prevention and management in industry--an example of a global programme.

    PubMed

    Gannon, Paul F G; Berg, A S; Gayosso, R; Henderson, B; Sax, S E; Willems, H M J

    2005-12-01

    Isocyanates are widely used in the manufacture of polyurethane foams, plastics, coatings and adhesives, and are known to cause occupational asthma in a proportion of exposed workers. Substitution as a prevention strategy is not currently a feasible option. For this reason, health and safety professionals working together in an automotive coatings business created a proactive global programme to address the known potential effects of isocyanates on its workers. The goals of the programme are prevention, early detection and mitigation of effect of key endpoints, especially asthma and to a lesser degree dermatitis, in people who are occupationally exposed, or potentially exposed, to isocyanates and products containing isocyanates. The surveillance programme for isocyanates has several important components, which include assessment of exposure, pre-placement questionnaire and spirometry, training and education of employees, regularly administered periodic questionnaires, medical assessment for abnormal questionnaire responses, process for early reporting and investigation of symptomatic employees and incidents, group data review and management reporting. Although regional differences exist regarding availability of specialized services, we have successfully implemented this programme in parts of North America, Europe and Latin America, and are currently implementing elsewhere. These simple control measures are relatively inexpensive and can be applied in even small business settings. It is recommended that all employers who manufacture, handle or use isocyanate-containing products consider such a strategy.

  16. Simulating effects of biomarker enrichment on Alzheimer's disease prevention trials: conceptual framework and example.

    PubMed

    Leoutsakos, Jeannie-Marie S; Bartlett, Alexandra L; Forrester, Sarah N; Lyketsos, Constantine G

    2014-03-01

    We present a conceptual framework for simulations to determine the utility of biomarker enrichment to increase statistical power to detect a treatment effect in future Alzheimer's disease prevention trials. We include a limited set of simulation results to illustrate aspects of this framework. We simulated data based on the Alzheimer's Disease Anti-Inflammatory Prevention Trial, and a range of sample sizes, biomarker positive predictive values, and treatment effects. We also investigated the consequences of assuming homogeneity of parameter estimates as a function of dementia outcome. Use of biomarkers to increase the sample fraction that would develop Alzheimer's disease in the absence of intervention from 0.5 to 0.8 would increase power from 0.35 to 0.69 with n = 200. Ignoring sample heterogeneity resulted in overestimation of power. Biomarker enrichment can increase statistical power, but estimates of the expected increase are sensitive to a variety of assumptions outlined in the framework. Copyright © 2014 The Alzheimer's Association. Published by Elsevier Inc. All rights reserved.

  17. [Addictions and psoriasis: an example of the dermatologist's implication in preventive medicine ?].

    PubMed

    Meyer, N; Viraben, R; Paul, C

    2008-02-01

    Association between psoriasis and addictive disorders has been longtime suspected and several studies are supporting the association of psoriasis and alcohol, and of psoriasis and tobacco. The association of psoriasis and other addictive disorders has not yet been reported. The association of psoriasis and alcohol is not restricted to alcoholism (defined as excessive alcohol consumption with psychic and/or psychic (correction of physic) dependence). It has been suggested that psoriasis is more closely linked to alcohol misuse than it is to alcoholism. The association of psoriasis and alcohol seems not been influenced by the gender, and shows a dose-effect relation. The most striking link between cigarette smoking and psoriasis has been established in palmo-plantar pustulosis. This link also seems to exist for other forms of psoriasis, with a dose-effect relation. Cigarette smoking could be involved in the high prevalence of lung cancer and cardio vascular disorders in psoriatic patients. There are a number of difficulties in the assessment of the correlation between psoriasis, cigarette smoking, and alcohol, and even more so in establishing a causal or etiologic relationship between the three, because of several confusion factors. This must not occult the reality of this association and its impact of psoriatic patients' health and the importance of detecting and preventing them. The detection and the prevention of the complications of these addictions belong to the dermatologists.

  18. Targeting tumor-stroma crosstalk: the example of the NT157 inhibitor.

    PubMed

    Rampias, T; Favicchio, R; Stebbing, J; Giamas, G

    2016-05-19

    Recent clinical research has provided evidence that cancer progression and therapy resistance is driven not only by tumor's genetic profile but also by complex paracrine interactions within the tumor microenvironment (TME). The role of TME in modulating tumor drug sensitivity is increasingly recognized and targeting TME has been the focus of novel therapeutic approaches. Two recent reports show that a new anti-cancer drug, the inhibitor NT157 has the potential to inhibit IGF-1R and STAT3 signaling pathways in cancer cells and stroma cells of TME leading to a decrease in cancer cell survival.

  19. The Moving Target of Climate Mitigation: Examples from the Energy Sector in California

    NASA Astrophysics Data System (ADS)

    Tarroja, B.; AghaKouchak, A.; Forrest, K.; Chiang, F.; Samuelsen, S.

    2016-12-01

    In response to the concerns of climate change-induced impacts on human health, environmental integrity, and the secure operation of resource supply infrastructures, strategies to reduce greenhouse gas (GHG) emissions of major societal sectors have been in development. In the energy sector, these strategies are based in low carbon primary energy deployment, increased energy efficiency, and implementing complementary technologies for operational resilience. While these strategies are aimed at climate mitigation, a degree of climate change-induced impacts will occur by the time of their deployment, and many of these impacts can compromise the effectiveness of these climate mitigation strategies. In order to develop climate mitigation strategies that will achieve their GHG reduction and other goals, the impact that climate change-induced conditions can have on different components of climate mitigation strategies must be understood. This presentation will highlight three examples of how climate change-induced conditions affect components of climate mitigation strategies in California: through impacts on 1) hydropower generation, 2) renewable potential for geothermal and solar thermal resources to form part of the renewable resource portfolio, and 3) the magnitudes and shapes of the electric load demand that must be met sustainably. These studies are part of a larger, overarching project to understand how climate change impacts the energy system and how to develop a sustainable energy infrastructure that is resilient against these impacts.

  20. Research on regional intrusion prevention and control system based on target tracking

    NASA Astrophysics Data System (ADS)

    Liu, Yanfei; Wang, Jieling; Jiang, Ke; He, Yanhui; Wu, Zhilin

    2017-08-01

    In view of the fact that China’s border is very long and the border prevention and control measures are single, we designed a regional intrusion prevention and control system which based on target-tracking. The system consists of four parts: solar panel, radar, electro-optical equipment, unmanned aerial vehicle and intelligent tracking platform. The solar panel provides independent power for the entire system. The radar detects the target in real time and realizes the high precision positioning of suspicious targets, then through the linkage of electro-optical equipment, it can achieve full-time automatic precise tracking of targets. When the target appears within the range of detection, the drone will be launched to continue the tracking. The system is mainly to realize the full time, full coverage, whole process integration and active realtime control of the border area.

  1. Methods of defining best practice for population health approaches with obesity prevention as an example.

    PubMed

    McNeil, Deborah A; Flynn, Mary A T

    2006-11-01

    Childhood obesity has reached a crisis stage and has become a population health issue. The few traditional systematic reviews that have been done to identify best practice provide little direction for action. The concept of evidence-based practice has been adopted in health care, and in medicine in particular, to determine best practice. Evidence-based medicine has its origins in the scientific method and for many researchers this concept means strict adherence to standards determining internal validity in order to justify a practice as evidence based. Practitioners addressing population health face challenges in identifying criteria for determining evidence, in part because of the nature of population health with its goal of shifting the health of whole populations. As well, the type of evidence provided by more traditional critical appraisal schema is limiting. Expanded approaches in finding and defining evidence have been proposed that use: expert panels; broad and inclusive search and selection strategies; appraisal criteria that incorporate context and generalizability. A recent synthesis of 147 programmes addressing childhood overweight and obesity provides a concrete example of using a broader approach to identify evidence for best practice (Flynn et al. 2006). Incorporating evaluation and population health frameworks as criterion components in addition to traditional methodological rigour criteria, this synthesis has identified programmes that provide contextual information that can be used to populate what Swinburn et al. (2005) have described as the 'promise table'. Using this approach a range in 'certainty of effectiveness' and a range in 'potential for population impact' are integrated to identify promising strategies. The exercise can provide direction for agencies and practitioners in taking action to address obesity.

  2. From Target Selection to Post-Stimulation Analysis: Example of an Unconventional Faulted Reservoir

    NASA Astrophysics Data System (ADS)

    LeCalvez, J. H.; Williams, M.; Xu, W.; Stokes, J.; Moros, H.; Maxwell, S. C.; Conners, S.

    2011-12-01

    As the global balance of supply and demand forces the hydrocarbon industry toward unconventional resources, technology- and economics-driven shale oil and gas production is gaining momentum throughout many basins worldwide. Production from such unconventional plays is facilitated by massive hydraulic fracturing treatments aimed at increasing permeability and reactivating natural fractures. Large-scale faulting and fracturing partly control stress distribution, hence stimulation-derived hydraulically-induced fracture systems development. Therefore, careful integrated approaches to target selection, treatment staging, and stimulation methods need to be used to economically maximize ultimate hydrocarbon recovery. We present a case study of a multistage, multilateral stimulation project in the Fort Worth Basin, Texas. Wells had to be drilled within city limits in a commercially developing building area. Well locations and trajectories were determined in and around large-scale faults using 3D surface seismic with throws varying from seven to thirty meters. As a result, three horizontal wells were drilled in the Lower Barnett Shale section, 150 m apart with the central well landed about 25 m shallower than the outside laterals. Surface seismic indicates that the surface locations are on top of a major fault complex with the lateral sections drilling away from the major fault system and through a smaller fault. Modeling of the borehole-based microseismic monitoring options led to the selection of an optimum set of configurations given the operational restrictions faced: monitoring would mainly take place using a horizontal array to be tractored downhole and moved according to the well and stage to be monitored. Wells were completed using a perf-and-plug approach allowing for each stimulation stage to obtain a precise orientation of the various three-component accelerometers of the monitoring array as well as the calibration of the velocity model used to process the

  3. Designs for Evaluating the Community-Level Impact of Comprehensive Prevention Programs: Examples from the CDC Centers of Excellence in Youth Violence Prevention.

    PubMed

    Farrell, Albert D; Henry, David; Bradshaw, Catherine; Reischl, Thomas

    2016-04-01

    This article discusses the opportunities and challenges of developing research designs to evaluate the impact of community-level prevention efforts. To illustrate examples of evaluation designs, we describe six projects funded by the Centers for Disease Control and Prevention to evaluate multifaceted approaches to reduce youth violence in high-risk communities. Each of these projects was designed to evaluate the community-level impact of multiple intervention strategies to address individual and contextual factors that place youth at risk for violent behavior. Communities differed across projects in their setting, size, and how their boundaries were defined. Each project is using multiple approaches to compare outcomes in one or more intervention communities to those in comparison communities. Five of the projects are using comparative interrupted time-series designs to compare outcomes in an intervention community to matched comparison communities. A sixth project is using a multiple baseline design in which the order and timing of intervention activities is randomized across three communities. All six projects are also using regression point displacement designs to compare outcomes within intervention communities to those within broader sets of similar communities. Projects are using a variety of approaches to assess outcomes including archival records, surveys, and direct observations. We discuss the strengths and weaknesses of the designs of these projects and illustrate the challenges of designing high-quality evaluations of comprehensive prevention approaches implemented at the community level.

  4. A Review of Culturally Targeted/Tailored Tobacco Prevention and Cessation Interventions for Minority Adolescents

    PubMed Central

    Singh, Nisha; Krishnan-Sarin, Suchitra

    2012-01-01

    Aim: Emerging racial/ethnic disparities in tobacco use behaviors and resulting long-term health outcomes highlight the importance of developing culturally tailored/targeted tobacco prevention and cessation interventions. This manuscript describes the efficacy and the components of prevention and cessation interventions developed for minority adolescents. Methods: Thirteen studies focused on culturally tailoring and targeting tobacco prevention/cessation interventions were selected and information on intervention design (type, number of sessions), setting (school or community), theoretical constructs, culture-specific components (surface/deep structures), and treatment outcomes were extracted. Results: Of the 13 studies, 5 focused on prevention, 4 on cessation, and 4 combined prevention and cessation, and most of the studies were primarily school-based, while a few used community locations. Although diverse minority groups were targeted, a majority of the studies (n = 6) worked with Hispanic adolescents. The most common theoretical construct examined was the Social Influence Model (n = 5). The overall findings indicated that culturally tailoring cessation interventions did not appear to improve tobacco quit rates among minority adolescents, but culturally tailored prevention interventions appeared to produce lower tobacco initiation rates among minority adolescents than control conditions. Conclusions: The results of review suggest that there is a critical need to develop better interventions to reduce tobacco use among minority adolescents and that developing a better understanding of cultural issues related to both cessation and initiation of tobacco use among minority populations is a key component of this endeavor. PMID:22614548

  5. Targeted prevention of brucellosis in cattle, sheep, and goats in the Russian Federation.

    PubMed

    Sklyarov, Oleg; Shumilov, Konstantin; Klimanov, Arkadii; Denisov, Aleksander

    2010-10-01

    The article presents a brief history of the brucellosis prevention in animals in the world and in the Russian Federation. Data are taken from studies on the immunogenic activity and epizootic efficacy of vaccines against brucellosis in animals, which made it possible, in the final analysis, to regard these preparations as highly important for brucellosis prevention. The relationship between the epizootic brucellosis situation in Russia and the employment of specific agents in targeted prevention of brucellosis in cattle, sheep, and goats, and the sequence of their use, are presented briefly, substantiating the feasibility of their use and improvement.

  6. Targeting early antecedents to prevent tobacco smoking: findings from an epidemiologically based randomized field trial.

    PubMed Central

    Kellam, S G; Anthony, J C

    1998-01-01

    OBJECTIVES: This study examined whether interventions aimed at aggressive/disruptive classroom behavior and poor academic achievement would reduce the incidence of initiation of smoking. METHODS: An epidemiologically based, universal randomized preventive trial involved 2311 children in 2 classroom-based preventive interventions or controls. Each intervention was directed at 1 of the aforementioned 2 antecedents over first and second grades in 19 urban schools. RESULTS: Smoking initiation was reduced in both cohorts for boys assigned to the behavioral intervention. CONCLUSIONS: Targeting early risk antecedents such as aggressive behavior appears to be an important smoking prevention strategy. PMID:9772850

  7. [Dementia prevention: potential treatments and how to target high risk patients].

    PubMed

    Samaras, Nikolaos; Samaras, Dimitrios; Frangos, Emilia; Forster, Alexandre

    2013-05-22

    The burden related to the ever-increasing dementia prevalence in older individuals, imposes the implementation of prevention strategies. It is now known that brain lesions related to Alzheimer's disease precede the onset of the first symptoms. Consequently, prevention strategies should be implemented early, before clinically overt dementia. Blood and spine fluid tests, electroencephalogram, brain magnetic resonance and brain nuclear imaging should help physicians to better target "high-risk" patients prone to benefit from such strategies, already in a preclinical disease stage. Since no efficient pharmacological treatments exist for the time being, lifestyle factors such as nutritionand physical exercise are the cornerstones for dementia prevention.

  8. Teens on Target Violence Prevention Curriculum for Grades 6-12.

    ERIC Educational Resources Information Center

    Becker, Marla G.; Calhoun, Deane

    This curriculum is designed to help schools implement programs to prevent violence among students in grades 6-12. It is a six-session, school based curriculum intended for adolescents who are living in communities experiencing high rates of violence. It is facilitated by trained Teens on Target (TNT) members/peer educators, young people who are…

  9. Prevention-Related Research Targeting African American Alternative Education Program Students

    ERIC Educational Resources Information Center

    Carswell, Steven B.; Hanlon, Thomas E.; Watts, Amy M.; O'Grady, Kevin E.

    2014-01-01

    This article reports on a program of research that examined the background, planning, implementation, and evaluation of an after-school preventive intervention program within an ongoing urban alternative education program targeting African American students referred to the school because of their problematic behavior in regular schools. The…

  10. Teens on Target Violence Prevention Curriculum for Grades 6-12.

    ERIC Educational Resources Information Center

    Becker, Marla G.; Calhoun, Deane

    This curriculum is designed to help schools implement programs to prevent violence among students in grades 6-12. It is a six-session, school based curriculum intended for adolescents who are living in communities experiencing high rates of violence. It is facilitated by trained Teens on Target (TNT) members/peer educators, young people who are…

  11. Prevention-Related Research Targeting African American Alternative Education Program Students

    ERIC Educational Resources Information Center

    Carswell, Steven B.; Hanlon, Thomas E.; Watts, Amy M.; O'Grady, Kevin E.

    2014-01-01

    This article reports on a program of research that examined the background, planning, implementation, and evaluation of an after-school preventive intervention program within an ongoing urban alternative education program targeting African American students referred to the school because of their problematic behavior in regular schools. The…

  12. Validity of teacher ratings in selecting influential aggressive adolescents for a targeted preventive intervention.

    PubMed

    Henry, David B; Miller-Johnson, Shari; Simon, Thomas R; Schoeny, Michael E

    2006-03-01

    This study describes a method for using teacher nominations and ratings to identify socially influential, aggressive middle school students for participation in a targeted violence prevention intervention. The teacher nomination method is compared with peer nominations of aggression and influence to obtain validity evidence. Participants were urban, predominantly African American and Latino sixth-grade students who were involved in a pilot study for a large multi-site violence prevention project. Convergent validity was suggested by the high correlation of teacher ratings of peer influence and peer nominations of social influence. The teacher ratings of influence demonstrated acceptable sensitivity and specificity when predicting peer nominations of influence among the most aggressive children. Results are discussed in terms of the application of teacher nominations and ratings in large trials and full implementation of targeted prevention programs.

  13. Validity of Teacher Ratings in Selecting Influential Aggressive Adolescents for a Targeted Preventive Intervention

    PubMed Central

    Henry, David B.; Miller-Johnson, Shari; Simon, Thomas R.; Schoeny, Michael E.

    2009-01-01

    This study describes a method for using teacher nominations and ratings to identify socially influential, aggressive middle school students for participation in a targeted violence prevention intervention. The teacher nomination method is compared with peer nominations of aggression and influence to obtain validity evidence. Participants were urban, predominantly African American and Latino sixth-grade students who were involved in a pilot study for a large multi-site violence prevention project. Convergent validity was suggested by the high correlation of teacher ratings of peer influence and peer nominations of social influence. The teacher ratings of influence demonstrated acceptable sensitivity and specificity when predicting peer nominations of influence among the most aggressive children. Results are discussed m terms of the application of teacher nominations and ratings in large trials and full implementation of targeted prevention programs. PMID:16378226

  14. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    PubMed Central

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  15. Periparturient stress and immune suppression as a potential cause of retained placenta in highly productive dairy cows: examples of prevention.

    PubMed

    Mordak, Ryszard; Stewart, Peter Anthony; Anthony, Stewart Peter

    2015-12-02

    The immune system during the periparturient period is impaired. At this time the most important factor causing immune-suppression in highly productive cows is metabolic stress resulting from hormonal and metabolic fluctuations, a negative energy balance, shortage of proteins, minerals and vitamins which are required to meet the demands of the fetus as well as the onset of lactation. This stress can activate the hypothalamic-pituitary-adrenocortical axis (HPA), which results in increase plasma corticosteroids. As a result, the cortisol concentration during the periparturient period increases by several folds particularly on the day of calving. Cortisol is a powerful immune-suppressive agent. During stress, this hormone causes depression of the leukocyte proliferation and their functions. Decreased phagocytosis of neutrophils, decreased cytotoxic ability of lymphocytes, as well as depressed activity of their cytokines, make it impossible for the normal, efficient maternal immune recognition and rejection of fetal membranes (as a foreign, allogeneic tissue expressed fetal antigens-MHC class I proteins by trophoblast cells) and finally results in their retention in cows. The metabolic periparturient stress also activates production of catecholamines, especially adrenalin. Adrenalin activates adrenoreceptors of the myometrium and then causes hypotony or atony of the uterus. Thus, cortisol and adrenalin inhibit rejection and expulsion of fetal membranes and cause their retention. These mechanisms of retained placenta (RP) often have a metabolic etiology and occur in herds, where important infectious diseases causing placentitis are absent or prevented. The aim of this article is to show the fundamental mechanisms occurring during periparturient stress and the accompanied immune-suppression in cows, as well as their consequences in relation to RP. The paper also gives examples of the symptomatic prevention of RP in cows caused by metabolic and immune suppressive factors

  16. A Systematic Review of Preventive Health Educational Videos Targeting Infectious Diseases in Schoolchildren

    PubMed Central

    Bieri, Franziska A.; Gray, Darren J.; Raso, Giovanna; Li, Yue-Sheng; McManus, Donald P.

    2012-01-01

    We conducted a systematic review of preventive health educational videos targeting infectious diseases in schoolchildren to formulate recommendations for establishing an evidence base for future studies. We included studies that evaluated interventions involving video-based health education in schools to improve knowledge and attitudes and to change behavior regarding different infections. The majority of the 11 studies we reviewed concluded that videos were well received by schools, teachers, and children, and are promising and effective health education tools, having a positive impact on knowledge and attitudes. However, there is a pressing need for more standardized, high-quality studies to draw evidence-based conclusions on the value of educational videos targeting infectious diseases. Therefore, we provide a descriptive summary of the results and make recommendations for studies using preventive educational videos targeting infectious diseases in schoolchildren on the basis of our experiences gained in a video-based cluster randomized trial. PMID:23222138

  17. Promoting culturally targeted chronic disease prevention research through an adapted participatory research approach: The Qassim-Stanford Universities project.

    PubMed

    Winter, Sandra J; King, Abby C; Stafford, Randall S; Winkleby, Marilyn A; Haskell, William L; Farquhar, John W

    2011-06-01

    The Kingdom of Saudi Arabia (KSA), similar to other countries in the Eastern Mediterranean, has been experiencing a recent rapid increase in the prevalence of chronic diseases and associated risk factors. To begin to take advantage of the chronic disease prevention and health promotion (CDPHP) knowledge available from other nations, researchers at a newly established University in the Qassim Province of the KSA have partnered with Stanford University in the United States of America. To ensure that CDPHP research and interventions are culturally relevant and appropriate, a participatory research approach has been adopted where local researchers are the target "community." Contextual challenges of conducting CDPHP research in the KSA, at the individual, social/cultural, organizational and environmental/policy levels, are identified, as well as examples of CDPHP intervention strategies that may be culturally appropriate at each level.

  18. Early life programming as a target for prevention of child and adolescent mental disorders

    PubMed Central

    2014-01-01

    This paper concerns future policy development and programs of research for the prevention of mental disorders based on research emerging from fetal and early life programming. The current review offers an overview of findings on pregnancy exposures such as maternal mental health, lifestyle factors, and potential teratogenic and neurotoxic exposures on child outcomes. Outcomes of interest are common child and adolescent mental disorders including hyperactive, behavioral and emotional disorders. This literature suggests that the preconception and perinatal periods offer important opportunities for the prevention of deleterious fetal exposures. As such, the perinatal period is a critical period where future mental health prevention efforts should be focused and prevention models developed. Interventions grounded in evidence-based recommendations for the perinatal period could take the form of public health, universal and more targeted interventions. If successful, such interventions are likely to have lifelong effects on (mental) health. PMID:24559477

  19. Role of n-3 Polyunsaturated Fatty Acids and Exercise in Breast Cancer Prevention: Identifying Common Targets

    PubMed Central

    Abdelmagid, Salma A.; MacKinnon, Jessica L.; Janssen, Sarah M.; Ma, David W.L.

    2016-01-01

    Diet and exercise are recognized as important lifestyle factors that significantly influence breast cancer risk. In particular, dietary n-3 polyunsaturated fatty acids (PUFAs) have been shown to play an important role in breast cancer prevention. Growing evidence also demonstrates a role for exercise in cancer and chronic disease prevention. However, the potential synergistic effect of n-3 PUFA intake and exercise is yet to be determined. This review explores targets for breast cancer prevention that are common between n-3 PUFA intake and exercise and that may be important study outcomes for future research investigating the combined effect of n-3 PUFA intake and exercise. These lines of evidence highlight potential new avenues for research and strategies for breast cancer prevention. PMID:27812288

  20. Prevention of Child Sexual Abuse by Targeting Pre-Offenders Before First Offense.

    PubMed

    Levine, James A; Dandamudi, Krishna

    2016-10-01

    The population of potential child abuse offenders has largely been unstudied. In the current study, we examine whether a six-component model used for primary diabetes prevention could be adapted to child sexual abuse pre-offenders, whereby individuals who are prone to sexual abuse but have not yet committed an offense can be prevented from committing a first offense. The six components include: define and track the magnitude of the problem, delineate a well-established risk factor profile so that at-risk persons can be identified, define valid screening tests to correctly rule in those with the disease and rule out those without disease, test effectiveness of interventions-the Dunkelfeld Project is an example, produce and disseminate reliable outcome data so that widespread application can be justified, and establish a system for continuous improvement. By using the diabetes primary prevention model as a model, the number of victims of child sexual abuse might be diminished.

  1. The value of prevention: managing the risks associated with targeted violence and active shooters.

    PubMed

    Doherty, Matthew

    2016-01-01

    Every time we turn on the news, or open our Internet browsers, a story about an active shooter--at a school, house of worship, public place and even in our workplace--spills onto the page, the author reports. In this article he focuses on how we can prevent these incidents from occurring. What exactly is "targeted violence"--and why is what experts call "behavioral threat assessment" one of the single most effective ways to prevent the next active shooter incident in any organization?

  2. Analysing Time to Event Data in Dementia Prevention Trials: The Example of the GuidAge Study of EGb761.

    PubMed

    Scherrer, B; Andrieu, S; Ousset, P J; Berrut, G; Dartigues, J F; Dubois, B; Pasquier, F; Piette, F; Robert, P; Touchon, J; Garnier, P; Mathiex-Fortunet, H; Vellas, B

    2015-12-01

    Time-to-event analysis is frequently used in medical research to investigate potential disease-modifying treatments in neurodegenerative diseases. Potential treatment effects are generally evaluated using the logrank test, which has optimal power and sensitivity when the treatment effect (hazard ratio) is constant over time. However, there is generally no prior information as to how the hazard ratio for the event of interest actually evolves. In these cases, the logrank test is not necessarily the most appropriate to use. When the hazard ratio is expected to decrease or increase over time, alternative statistical tests such as the Fleming-Harrington test, provide a better sensitivity. An example of this comes from a large, five-year randomised, placebo-controlled prevention trial (GuidAge) in 2854 community-based subjects making spontaneous memory complaints to their family physicians, which evaluated whether treatment with EGb761 can modify the risk of developing AD. The primary outcome measure was the time to conversion from memory complaint to Alzheimer's type dementia. Although there was no significant difference in the hazard function of conversion between the two treatment groups according to the preplanned logrank test, a significant treatment-by-time interaction for the incidence of AD was observed in a protocol-specified subgroup analysis, suggesting that the hazard ratio is not constant over time. For this reason, additional post hoc analyses were performed using the Fleming-Harrington test to evaluate whether there was a signal of a late effect of EGb761. Applying the Fleming-Harrington test, the hazard function for conversion to dementia in the placebo group was significantly different from that in the EGb761 treatment group (p = 0.0054), suggesting a late effect of EGb761. Since this was a post hoc analysis, no definitive conclusions can be drawn as to the effectiveness of the treatment. This post hoc analysis illustrates the interest of performing

  3. Chatters on the Internet: a special target group for HIV prevention.

    PubMed

    Hospers, H J; Harterink, P; Van Den Hoek, K; Veenstra, J

    2002-08-01

    This study examined characteristics of men who use gay chat boxes on the Internet, including dating behaviour and sexual risk-taking with sex partners who were initially met through chatting. Men on chat boxes were asked to complete a brief questionnaire on the Internet. The questionnaire contained questions on demographics, chatting-related variables, and dating and risk-taking sexual behaviour. The results show that a large majority of the 190 respondents reported actual encounters as well as sex with men who were initially met through chatting. Almost 30% of the respondents who engaged in sex with chat dates reported inconsistent safe sexual behaviour. The level of unprotected sex increased as the number of sex partners who were met through chatting increased. These results suggest that chatters on the Internet may be a new target group for HIV prevention. Further study is needed to gain insight into the feasibility of prevention efforts for this target group.

  4. Skeletal muscle mitochondria as a target to prevent or treat type 2 diabetes mellitus.

    PubMed

    Hesselink, Matthijs K C; Schrauwen-Hinderling, Vera; Schrauwen, Patrick

    2016-11-01

    Low levels of physical activity and the presence of obesity are associated with mitochondrial dysfunction. In addition, mitochondrial dysfunction has been associated with the development of insulin resistance and type 2 diabetes mellitus (T2DM). Although the evidence for a causal relationship between mitochondrial function and insulin resistance is still weak, emerging evidence indicates that boosting mitochondrial function might be beneficial to patient health. Exercise training is probably the most recognized promoter of mitochondrial function and insulin sensitivity and hence is still regarded as the best strategy to prevent and treat T2DM. Animal data, however, have revealed several new insights into the regulation of mitochondrial metabolism, and novel targets for interventions to boost mitochondrial function have emerged. Importantly, many of these targets seem to be regulated by factors such as nutrition, ambient temperature and circadian rhythms, which provides a basis for nonpharmacological strategies to prevent or treat T2DM in humans. Here, we will review the current evidence that mitochondrial function can be targeted therapeutically to improve insulin sensitivity and to prevent T2DM, focusing mainly on human intervention studies.

  5. Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy

    PubMed Central

    Mukhopadhyay, Partha; Horváth, Béla; Zsengellér, Zsuzsanna; Zielonka, Jacek; Tanchian, Galin; Holovac, Eileen; Kechrid, Malek; Patel, Vivek; Stillman, Isaac E.; Parikh, Samir M.; Joseph, Joy; Kalyanaraman, Balaraman; Pacher, Pál

    2011-01-01

    Cisplatin is a widely used anti-neoplastic agent; however, its major limitation is the development of dose-dependent nephrotoxicity whose precise mechanisms are poorly understood. Here we show that mitochondrial dysfunction is not only a feature of cisplatin nephrotoxicity, but that targeted delivery of superoxide dismutase mimetics to mitochondria largely prevents the renal effects of cisplatin. Cisplatin induced renal oxidative stress, deterioration of mitochondrial structure and function, an intense inflammatory response, histopathological injury, and renal dysfunction. A single systemic dose of mitochondrially-targeted antioxidants, MitoQ or Mito-CP, dose-dependently prevented cisplatin-induced renal dysfunction. Mito-CP also prevented mitochondrial injury and dysfunction, renal inflammation, and tubular injury and apoptosis. Despite being broadly renoprotective against cisplatin, Mito-CP did not diminish cisplatin’s anti-neoplastic effect in a human bladder cancer cell line. Our results highlight the central role of mitochondrially generated oxidants in the pathogenesis of cisplatin nephrotoxicity. Since similar compounds appear to be safe in humans, mitochondrially-targeted antioxidants may represent a novel therapeutic approach against cisplatin nephrotoxicity. PMID:22120494

  6. Targeting the AMP-Activated Protein Kinase for Cancer Prevention and Therapy

    PubMed Central

    Kim, InYoung; He, Yu-Ying

    2013-01-01

    Despite the advances in biomedical research and clinical applications, cancer remains a leading cause of death worldwide. Given the limitations of conventional chemotherapeutics, including serious toxicities and reduced quality of life for patients, the development of safe and efficacious alternatives with known mechanism of action is much needed. Prevention of cancer through dietary intervention may hold promise and has been investigated extensively in the recent years. AMP-activated protein kinase (AMPK) is an energy sensor that plays a key role in the regulation of protein and lipid metabolism in response to changes in fuel availability. When activated, AMPK promotes energy-producing catabolic pathways while inhibiting anabolic pathways, such as cell growth and proliferation – thereby antagonizing carcinogenesis. Other anti-cancer effects of AMPK may include promoting autophagy and DNA repair upon UVB damage. In the last decade, interest in AMPK has grown extensively as it emerged as an attractive target molecule for cancer prevention and treatment. Among the latest developments is the activation of AMPK by naturally occurring dietary constituents and plant products – termed phytochemicals. Owing to their efficacy and safety, phytochemicals are considered as an alternative to the conventional harmful chemotherapy. The rising popularity of using phytochemicals for cancer prevention and therapy is supported by a substantial progress in identifying the molecular pathways involved, including AMPK. In this article, we review the recent progress in this budding field that suggests AMPK as a new molecular target in the prevention and treatment of cancer by phytochemicals. PMID:23875169

  7. Target DNA bending by the Mu transpososome promotes careful transposition and prevents its reversal

    PubMed Central

    Fuller, James R; Rice, Phoebe A

    2017-01-01

    The transposition of bacteriophage Mu serves as a model system for understanding DDE transposases and integrases. All available structures of these enzymes at the end of the transposition reaction, including Mu, exhibit significant bends in the transposition target site DNA. Here we use Mu to investigate the ramifications of target DNA bending on the transposition reaction. Enhancing the flexibility of the target DNA or prebending it increases its affinity for transpososomes by over an order of magnitude and increases the overall reaction rate. This and FRET confirm that flexibility is interrogated early during the interaction between the transposase and a potential target site, which may be how other DNA binding proteins can steer selection of advantageous target sites. We also find that the conformation of the target DNA after strand transfer is involved in preventing accidental catalysis of the reverse reaction, as conditions that destabilize this conformation also trigger reversal. DOI: http://dx.doi.org/10.7554/eLife.21777.001 PMID:28177285

  8. Being targeted: Young women's experience of being identified for a teenage pregnancy prevention programme.

    PubMed

    Sorhaindo, Annik; Bonell, Chris; Fletcher, Adam; Jessiman, Patricia; Keogh, Peter; Mitchell, Kirstin

    2016-06-01

    Research on the unintended consequences of targeting 'high-risk' young people for health interventions is limited. Using qualitative data from an evaluation of the Teens & Toddlers Pregnancy Prevention programme, we explored how young women experienced being identified as at risk for teenage pregnancy to understand the processes via which unintended consequences may occur. Schools' lack of transparency regarding the targeting strategy and criteria led to feelings of confusion and mistrust among some young women. Black and minority ethnic young women perceived that the assessment of their risk was based on stereotyping. Others felt their outgoing character was misinterpreted as signifying risk. To manage these imposed labels, stigma and reputational risks, young women responded to being targeted by adopting strategies, such as distancing, silence and refusal. To limit harmful consequences, programmes could involve prospective participants in determining their need for intervention or introduce programmes for young people at all levels of risk.

  9. The costs of HIV prevention for different target populations in Mumbai, Thane and Bangalore.

    PubMed

    Chandrashekar, Sudha; Vassall, Anna; Reddy, Bhaskar; Shetty, Govindraj; Vickerman, Peter; Alary, Michel

    2011-12-29

    Avahan, the India AIDS Initiative, delivers HIV prevention services to high-risk populations at scale. Although the broad costs of such HIV interventions are known, to-date there has been little data available on the comparative costs of reaching different target groups, including female sex workers (FSWs), replace with 'high risk men who have sex with men (HR-MSM) and trans-genders. Costs are estimated for the first three years of Avahan scale up differentiated by typology of female sex workers (brothel, street, home, lodge based, bar based), HR-MSM and transgenders in urban districts in India: Mumbai and Thane in Maharashtra and Bangalore in Karnataka. Financial and economic costs were collected prospectively from a provider perspective. Outputs were measured using data collected by the Avahan programme. Costs are presented in US$2008. Costs were found to vary substantially by target group. Non-governmental organisations (NGOs) working with transgender populations had a higher mean cost (US $116) per person reached compared to those dealing primarily with FSWs (US $75-96) and MSWs (US $90) by the end of year three of the programme in Mumbai. The mean cost of delivering the intervention to HR-MSMs (US $42) was higher than delivering it to FSWs (US $37) in Bangalore. The package of services delivered to each target group was similar, and our results suggest that cost variation is related to the target population size, the intensity of the programme (in terms of number of contacts made per year) and a number of specific issues related to each target group. Based on our data policy makers and program managers need to consider the ease of accessing high risk population when planning and budgeting for HIV prevention services for these populations and avoid funding programmes on the basis of target population size alone.

  10. The costs of HIV prevention for different target populations in Mumbai, Thane and Bangalore

    PubMed Central

    2011-01-01

    Background Avahan, the India AIDS Initiative, delivers HIV prevention services to high-risk populations at scale. Although the broad costs of such HIV interventions are known, to-date there has been little data available on the comparative costs of reaching different target groups, including female sex workers (FSWs), replace with ‘high risk men who have sex with men (HR-MSM) and trans-genders. Methods Costs are estimated for the first three years of Avahan scale up differentiated by typology of female sex workers (brothel, street, home, lodge based, bar based), HR-MSM and transgenders in urban districts in India: Mumbai and Thane in Maharashtra and Bangalore in Karnataka. Financial and economic costs were collected prospectively from a provider perspective. Outputs were measured using data collected by the Avahan programme. Costs are presented in US$2008. Results Costs were found to vary substantially by target group. Non-governmental organisations (NGOs) working with transgender populations had a higher mean cost (US $116) per person reached compared to those dealing primarily with FSWs (US $75-96) and MSWs (US $90) by the end of year three of the programme in Mumbai. The mean cost of delivering the intervention to HR-MSMs (US $42) was higher than delivering it to FSWs (US $37) in Bangalore. The package of services delivered to each target group was similar, and our results suggest that cost variation is related to the target population size, the intensity of the programme (in terms of number of contacts made per year) and a number of specific issues related to each target group. Conclusions Based on our data policy makers and program managers need to consider the ease of accessing high risk population when planning and budgeting for HIV prevention services for these populations and avoid funding programmes on the basis of target population size alone. PMID:22375837

  11. Identifying Well-Connected Opinion Leaders for Informal Health Promotion: The Example of the ASSIST Smoking Prevention Program.

    PubMed

    Holliday, Jo; Audrey, Suzanne; Campbell, Rona; Moore, Laurence

    2016-08-01

    Methods used to select opinion leaders for informal behavior change interventions vary, affecting the role they adopt and the outcomes of interventions. The development of successful identification methods requires evidence that these methods achieve their aims. This study explored whether the "whole community" nomination process used in the ASSIST smoking prevention program successfully identified "peer supporters" who were well placed within their school social networks to diffuse an antismoking message to their peers. Data were collected in the United Kingdom during A Stop Smoking in Schools Trial. Behavioral data were provided at baseline and post intervention by all students. Social network data were provided post intervention by students in four control and six intervention schools. Centrality measures calculated using UCINET demonstrate that the ASSIST nomination process successfully identified peer supporters who were more socially connected than others in their year and who had social connections across the entire year group including the program's target group. The results indicate that three simple questions can identify individuals who are held in high esteem by their year group and who also have the interpersonal networks required of opinion leaders to successfully disseminate smoke-free messages through their social networks. This approach could be used in other informal health promotion initiatives.

  12. Identifying Well-Connected Opinion Leaders for Informal Health Promotion: The Example of the ASSIST Smoking Prevention Program

    PubMed Central

    Holliday, Jo; Audrey, Suzanne; Campbell, Rona; Moore, Laurence

    2016-01-01

    ABSTRACT Methods used to select opinion leaders for informal behavior change interventions vary, affecting the role they adopt and the outcomes of interventions. The development of successful identification methods requires evidence that these methods achieve their aims. This study explored whether the “whole community” nomination process used in the ASSIST smoking prevention program successfully identified “peer supporters” who were well placed within their school social networks to diffuse an antismoking message to their peers. Data were collected in the United Kingdom during A Stop Smoking in Schools Trial. Behavioral data were provided at baseline and post intervention by all students. Social network data were provided post intervention by students in four control and six intervention schools. Centrality measures calculated using UCINET demonstrate that the ASSIST nomination process successfully identified peer supporters who were more socially connected than others in their year and who had social connections across the entire year group including the program’s target group. The results indicate that three simple questions can identify individuals who are held in high esteem by their year group and who also have the interpersonal networks required of opinion leaders to successfully disseminate smoke-free messages through their social networks. This approach could be used in other informal health promotion initiatives. PMID:26699125

  13. Targeting cholesterol crystal-induced inflammation for the secondary prevention of cardiovascular disease.

    PubMed

    Nidorf, Stefan M; Eikelboom, John W; Thompson, Peter L

    2014-01-01

    Cholesterol crystals are present in nascent and advanced atherosclerotic plaque. Under some conditions, they may enlarge and cause direct plaque trauma or trigger an inflammatory cascade that promotes the growth and instability of atherosclerotic plaque. Therapies that reduce the risk of cholesterol crystal formation or prevent the associated inflammatory response have the potential to improve the clinical outcome of patients with cardiovascular disease. Statins have pleiotropic effects that can reduce the size of the free cholesterol pool contained within atherosclerotic plaques and prevent the formation of cholesterol crystals. Colchicine prevents crystal-induced inflammation by virtue of its ability to inhibit macrophage and neutrophil function. Both statins and colchicine have been demonstrated to reduce the risk of cardiovascular events in patients with stable coronary disease. The efficacy of statins and colchicine for cardiovascular prevention supports the hypothesis that crystal-induced inflammation plays an integral role in the progression and instability of coronary disease. Inhibition of cholesterol crystal-induced inflammation offers a promising new target for the secondary prevention of cardiovascular disease.

  14. Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

    DOE PAGES

    Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; ...

    2016-01-21

    Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescentmore » detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases« less

  15. Targeted nitric oxide delivery by supramolecular nanofibers for the prevention of restenosis after arterial injury

    SciTech Connect

    Bahnson, Edward S. M.; Kassam, Hussein A.; Moyer, Tyson J.; Jiang, Wulin; Morgan, Courtney E.; Vercammen, Janet M.; Jiang, Qun; Flynn, Megan E.; Stupp, Samuel I.; Kibbe, Melina R.

    2016-01-21

    Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. Here we sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. As a result, structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. In conclusion, we successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases

  16. Targeted Nitric Oxide Delivery by Supramolecular Nanofibers for the Prevention of Restenosis After Arterial Injury

    PubMed Central

    Bahnson, Edward S.M.; Kassam, Hussein A.; Moyer, Tyson J.; Jiang, Wulin; Morgan, Courtney E.; Vercammen, Janet M.; Jiang, Qun; Flynn, Megan E.; Stupp, Samuel I.

    2016-01-01

    Abstract Aims: Cardiovascular interventions continue to fail as a result of arterial restenosis secondary to neointimal hyperplasia. We sought to develop and evaluate a systemically delivered nanostructure targeted to the site of arterial injury to prevent neointimal hyperplasia. Nanostructures were based on self-assembling biodegradable molecules known as peptide amphiphiles. The targeting motif was a collagen-binding peptide, and the therapeutic moiety was added by S-nitrosylation of cysteine residues. Results: Structure of the nanofibers was characterized by transmission electron microscopy and small-angle X-ray scattering. S-nitrosylation was confirmed by mass spectrometry, and nitric oxide (NO) release was assessed electrochemically and by chemiluminescent detection. The balloon carotid artery injury model was performed on 10-week-old male Sprague-Dawley rats. Immediately after injury, nanofibers were administered systemically via tail vein injection. S-nitrosylated (S-nitrosyl [SNO])-targeted nanofibers significantly reduced neointimal hyperplasia 2 weeks and 7 months following balloon angioplasty, with no change in inflammation. Innovation: This is the first time that an S-nitrosothiol (RSNO)-based therapeutic was shown to have targeted local effects after systemic administration. This approach, combining supramolecular nanostructures with a therapeutic NO-based payload and a targeting moiety, overcomes the limitations of delivering NO to a site of interest, avoiding undesirable systemic side effects. Conclusion: We successfully synthesized and characterized an RSNO-based therapy that when administered systemically, targets directly to the site of vascular injury. By integrating therapeutic and targeting chemistries, these targeted SNO nanofibers provided durable inhibition of neointimal hyperplasia in vivo and show great potential as a platform to treat cardiovascular diseases. Antioxid. Redox Signal. 27, 401–418. PMID:26593400

  17. Host-Targeting Agents to Prevent and Cure Hepatitis C Virus Infection.

    PubMed

    Zeisel, Mirjam B; Crouchet, Emilie; Baumert, Thomas F; Schuster, Catherine

    2015-11-02

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) which are leading indications of liver transplantation (LT). To date, there is no vaccine to prevent HCV infection and LT is invariably followed by infection of the liver graft. Within the past years, direct-acting antivirals (DAAs) have had a major impact on the management of chronic hepatitis C, which has become a curable disease in the majority of DAA-treated patients. In contrast to DAAs that target viral proteins, host-targeting agents (HTAs) interfere with cellular factors involved in the viral life cycle. By acting through a complementary mechanism of action and by exhibiting a generally higher barrier to resistance, HTAs offer a prospective option to prevent and treat viral resistance. Indeed, given their complementary mechanism of action, HTAs and DAAs can act in a synergistic manner to reduce viral loads. This review summarizes the different classes of HTAs against HCV infection that are in preclinical or clinical development and highlights their potential to prevent HCV infection, e.g., following LT, and to tailor combination treatments to cure chronic HCV infection.

  18. Host-Targeting Agents to Prevent and Cure Hepatitis C Virus Infection

    PubMed Central

    Zeisel, Mirjam B.; Crouchet, Emilie; Baumert, Thomas F.; Schuster, Catherine

    2015-01-01

    Chronic hepatitis C virus (HCV) infection is a major cause of liver cirrhosis and hepatocellular carcinoma (HCC) which are leading indications of liver transplantation (LT). To date, there is no vaccine to prevent HCV infection and LT is invariably followed by infection of the liver graft. Within the past years, direct-acting antivirals (DAAs) have had a major impact on the management of chronic hepatitis C, which has become a curable disease in the majority of DAA-treated patients. In contrast to DAAs that target viral proteins, host-targeting agents (HTAs) interfere with cellular factors involved in the viral life cycle. By acting through a complementary mechanism of action and by exhibiting a generally higher barrier to resistance, HTAs offer a prospective option to prevent and treat viral resistance. Indeed, given their complementary mechanism of action, HTAs and DAAs can act in a synergistic manner to reduce viral loads. This review summarizes the different classes of HTAs against HCV infection that are in preclinical or clinical development and highlights their potential to prevent HCV infection, e.g., following LT, and to tailor combination treatments to cure chronic HCV infection. PMID:26540069

  19. Using Process Data to Understand Outcomes in Sexual Health Promotion: An Example from a Review of School-Based Programmes to Prevent Sexually Transmitted Infections

    ERIC Educational Resources Information Center

    Shepherd, J.; Harden, A.; Barnett-Page, E.; Kavanagh, J.; Picot, J.; Frampton, G. K.; Cooper, K.; Hartwell, D.; Clegg, A.

    2014-01-01

    This article discusses how process indicators can complement outcomes as part of a comprehensive explanatory evaluation framework, using the example of skills-based behavioural interventions to prevent sexually transmitted infections and promote sexual health among young people in schools. A systematic review was conducted, yielding 12 eligible…

  20. Using Process Data to Understand Outcomes in Sexual Health Promotion: An Example from a Review of School-Based Programmes to Prevent Sexually Transmitted Infections

    ERIC Educational Resources Information Center

    Shepherd, J.; Harden, A.; Barnett-Page, E.; Kavanagh, J.; Picot, J.; Frampton, G. K.; Cooper, K.; Hartwell, D.; Clegg, A.

    2014-01-01

    This article discusses how process indicators can complement outcomes as part of a comprehensive explanatory evaluation framework, using the example of skills-based behavioural interventions to prevent sexually transmitted infections and promote sexual health among young people in schools. A systematic review was conducted, yielding 12 eligible…

  1. Co-targeting AR and HSP90 suppresses prostate cancer cell growth and prevents resistance mechanisms.

    PubMed

    Centenera, Margaret M; Carter, Sarah L; Gillis, Joanna L; Marrocco-Tallarigo, Deborah L; Grose, Randall H; Tilley, Wayne D; Butler, Lisa M

    2015-10-01

    Persistent androgen receptor (AR) signaling in castration resistant prostate cancer (CRPC) underpins the urgent need for therapeutic strategies that better target this pathway. Combining classes of agents that target different components of AR signaling has the potential to delay resistance and improve patient outcomes. Many oncoproteins, including the AR, rely on the molecular chaperone heat shock protein 90 (Hsp90) for functional maturation and stability. In this study, enhanced anti-proliferative activity of the Hsp90 inhibitors 17-allylamino-demethoxygeldanamycin (17-AAG) and AUY922 in androgen-sensitive and CRPC cells was achieved when the agents were used in combination with AR antagonists bicalutamide or enzalutamide. Moreover, significant caspase-dependent cell death was achieved using sub-optimal agent doses that individually have no effect. Expression profiling demonstrated regulation of a broadened set of AR target genes with combined 17-AAG and bicalutamide compared with the respective single agent treatments. This enhanced inhibition of AR signaling was accompanied by impaired chromatin binding and nuclear localization of the AR. Importantly, expression of the AR variant AR-V7 that is implicated in resistance to AR antagonists was not induced by combination treatment. Likewise, the heat shock response that is typically elicited with therapeutic doses of Hsp90 inhibitors, and is a potential mediator of resistance to these agents, was significantly reduced by combination treatment. In summary, the co-targeting strategy in this study more effectively inhibits AR signaling than targeting AR or HSP90 alone and prevents induction of key resistance mechanisms in prostate cancer cells. These findings merit further evaluation of this therapeutic strategy to prevent CRPC growth.

  2. Intestinal Immunity and Gut Microbiota as Therapeutic Targets for Preventing Atherosclerotic Cardiovascular Diseases.

    PubMed

    Yamashita, Tomoya; Kasahara, Kazuyuki; Emoto, Takuo; Matsumoto, Takuya; Mizoguchi, Taiji; Kitano, Naoki; Sasaki, Naoto; Hirata, Ken-Ichi

    2015-01-01

    Atherosclerosis is considered a chronic inflammatory disease and an intervention targeting the inflammatory process could be a new therapeutic strategy for preventing atherosclerotic cardiovascular diseases (CVD). We hypothesized that the intestine, which is considered the biggest immune organ in the human body, could be a therapeutic target for preventing CVD. We demonstrated that oral administration of anti-CD3 antibody or an active form of vitamin D3 reduced atherosclerosis in mice via induction of regulatory T cells and tolerogenic dendritic cells in the gut-associated lymphoid tissues. Similar to regulatory immune responses achieved by oral tolerance, our method had systemic effects that ultimately contributed towards atherosclerosis reduction. Recently, we have been interested in the gut microbiota, which have been reported as highly associated with intestinal immunity and systemic metabolic disorders, including obesity and diabetes. Notably, the guts of obese individuals are predominantly colonized by Firmicutes over Bacteroidetes. The association between atherosclerosis and microbiota has been attracting increased attention, and gut microbiota have been shown to participate in the metabolism of a proatherogenic compound called trimethylamine-N-oxide (TMAO) and aggravate CVD. Our investigation of the relationship between susceptibility to CVD and the gut microbiota revealed a characteristic flora type. Here, we discuss the evidence for the relationship between the gut microbiota and cardiometabolic diseases, and consider the gut microbiota as new potential therapeutic targets for treating CVD. (Circ J 2015; 79: 1882-1890).

  3. Intraperitoneal administration of chitosan/DsiRNA nanoparticles targeting TNFα prevents radiation-induced fibrosis.

    PubMed

    Nawroth, Isabel; Alsner, Jan; Behlke, Mark A; Besenbacher, Flemming; Overgaard, Jens; Howard, Kenneth A; Kjems, Jørgen

    2010-10-01

    One of the most common and dose-limiting long-term adverse effects of radiation therapy is radiation-induced fibrosis (RIF), which is characterized by restricted tissue flexibility, reduced compliance or strictures, pain and in severe cases, ulceration and necrosis. Several strategies have been proposed to ameliorate RIF but presently no effective one is available. Recent studies have reported that tumor necrosis factor-α (TNFα) plays a role in fibrogenesis. Male CDF1 mice were radiated with a single dose of 45 Gy. Chitosan/DsiRNA nanoparticles targeting TNFα were intraperitoneal injected and late radiation-induced fibrosis (RIF) was assessed using a modification of the leg contracture model. Additionally, the effect of these nanoparticles on tumor growth and tumor control probability in the absence of radiation was examined in a C3H mammary carcinoma model. We show in this work, that targeting TNFα in macrophages by intraperitoneal administration of chitosan/DsiRNA nanoparticles completely prevented radiation-induced fibrosis in CDF1 mice without revealing any cytotoxic side-effects after a long-term administration. Furthermore, such TNFα targeting was selective without any significant influence on tumor growth or irradiation-related tumor control probability. This nanoparticle-based RNAi approach represents a novel approach to prevent RIF with potential application to improve clinical radiation therapeutic strategies. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

  4. The opportunities for and obstacles against prevention: the example of Germany in the areas of tobacco and alcohol

    PubMed Central

    2010-01-01

    Background Recent years have seen a growing research and policy interest in prevention in many developed countries. However, the actual efforts and resources devoted to prevention appear to have lagged well behind the lip service paid to the topic. Discussion We review the evidence on the considerable existing scope for health gains from prevention as well as for greater prevention policy efforts in Germany. We also discuss the barriers to "more and better" prevention and provide modest suggestions about how some of the obstacles could be overcome. Summary In Germany, there are substantial health gains to be reaped from the implementation of evidence-based, cost-effective preventive interventions and policies. Barriers to more prevention include social, historical, political, legal and economic factors. While there is sufficient evidence to scale up prevention efforts in some public health domains in Germany, in general there is a comparative shortage of research on non-clinical preventive interventions. Some of the existing barriers in Germany are at least in principle amenable to change, provided sufficient political will exists. More research on prevention by itself is no panacea, but could help facilitate more policy action. In particular, there is an economic efficiency-based case for public funding and promotion of research on non-clinical preventive interventions, in Germany and beyond, to confront the peculiar challenges that set this research apart from its clinical counterpart. PMID:20718995

  5. Liver targeting of catalase by cationization for prevention of acute liver failure in mice.

    PubMed

    Ma, Shen-Feng; Nishikawa, Makiya; Katsumi, Hidemasa; Yamashita, Fumiyoshi; Hashida, Mitsuru

    2006-01-10

    To achieve hepatic delivery of CAT for the prevention of CCl4-induced acute liver failure in mice, two types of cationized CAT derivatives, HMD- and ED-conjugated CAT, were developed. Slight structural changes occurred during cationization and the number of increased free amino groups was 3.1 in HMD-CAT and 13.6 in ED-CAT. 111In-cationized CAT derivatives showed an increased binding to HepG2 cells, and were rapidly taken up by the liver. H2O2-induced cytotoxicity in HepG2 cells was significantly prevented by preincubation of the cells with cationized CAT derivatives. A bolus intravenous injection of the cationized CAT derivatives reduced the hepatotoxicity induced by CCl4 in mice. The ED-CAT, which showed more rapid and greater binding to the liver than the HMD-CAT, exhibited more beneficial effects as far as all the parameters examined (serum GOT, GPT, LDH and hepatic GSH) were concerned, suggesting that a high degree of cationization is effective in delivering CAT to the liver to prevent CCl4-induced hepatotoxicity. These results suggest that cationized CAT derivatives are effective in preventing acute liver failure, and ED-based cationization is a suitable method for developing liver-targetable cationized CAT derivatives, because it provides CAT with a high degree of cationization and a high remaining enzymatic activity.

  6. [Molecular targets and novel pharmacological options to prevent myocardial hypertrophic remodeling].

    PubMed

    Coppini, Raffaele; Ferrantini, Cecilia; Poggesi, Corrado; Mugelli, Alessandro; Olivotto, Iacopo

    2016-03-01

    Myocardial hypertrophic remodeling is a pathophysiological feature of several cardiac conditions and is the hallmark of hypertrophic cardiomyopathy (HCM), the most common monogenic inherited disease of the heart. In recent years, preclinical and clinical studies investigated the underlying molecular mechanisms and intracellular signaling pathways involved in pathologic cardiomyocyte hypertrophy and highlighted a number of possible molecular targets of therapy aimed at preventing its development. Early prevention of myocardial hypertrophic remodeling is particularly sought after in HCM, as current therapeutic strategies are unable to remove the primary cause of disease, i.e. the disease-causing gene mutation. Studies on transgenic animal models or human myocardial samples from patients with HCM identified intracellular calcium overload as a central mechanism driving pathological hypertrophy. In this review, we analyze recent preclinical and clinical studies on animal models and patients with HCM aimed at preventing or modifying hypertrophic myocardial remodeling. Mounting evidence shows that prevention of pathological hypertrophy is a feasible strategy in HCM and will enter the clinical practice in the near future. Considering the close mechanistic similarities between HCM and secondary hypertrophy, these studies are also relevant for the common forms of cardiac hypertrophy, such as hypertensive or valvular heart disease.

  7. Prevention of delirium in hospitalized older patients: risk factors and targeted intervention strategies.

    PubMed

    Inouye, S K

    2000-05-01

    Delirium is a common, costly, and potentially devastating condition for hospitalized older patients. Delirium is a multifactorial syndrome, involving the inter-relationship between patient vulnerability, or predisposing factors at admission, and noxious insults or precipitating factors during hospitalization. Through a series of studies, we first identified significant predisposing factors for delirium, including vision impairment, severe illness, cognitive impairment, and dehydration. Subsequently, significant precipitating factors were identified, including physical restraint use, malnutrition, adding more than three drugs, bladder catheter use, and any iatrogenic event. Through targeting preventive strategies towards six identified risk factors in a controlled clinical trial, we were successful in the primary prevention of delirium. In 852 subjects, the incidence of delirium was significantly reduced in the intervention group compared with usual care (9.9% vs 15.0%, matched odds ratio: 0.60; 95% confidence interval: 0.39-0.92). The total number of days and episodes of delirium were also significantly reduced in the intervention group. Based on this work, evidence-based recommendations for delirium prevention are proposed. While not all cases of delirium will be preventable with this approach, unifying medical and epidemiological approaches to delirium represents a key advance essential to reducing the high morbidity and mortality associated with delirium in the older population.

  8. Frequently mutated genes/pathways and genomic instability as prevention targets in liver cancer.

    PubMed

    Rao, Chinthalapally V; Asch, Adam S; Yamada, Hiroshi Y

    2017-01-01

    The incidence of liver cancer has increased in recent years. Worldwide, liver cancer is common: more than 600000 related deaths are estimated each year. In the USA, about 27170 deaths due to liver cancer are estimated for 2016. Liver cancer is highly resistant to conventional chemotherapy and radiotherapy. For all stages combined, the 5-year survival rate is 15-17%, leaving much to be desired for liver cancer prevention and therapy. Heterogeneity, which can originate from genomic instability, is one reason for poor outcome. About 80-90% of liver cancers are hepatocellular carcinoma (HCC), and recent cancer genome sequencing studies have revealed frequently mutated genes in HCC. In this review, we discuss the cause of the tumor heterogeneity based on the functions of genes that are frequently mutated in HCC. We overview the functions of the genes that are most frequently mutated (e.g. TP53, CTNNB1, AXIN1, ARID1A and WWP1) that portray major pathways leading to HCC and identify the roles of these genes in preventing genomic instability. Notably, the pathway analysis suggested that oxidative stress management may be critical to prevent accumulation of DNA damage and further mutations. We propose that both chromosome instability (CIN) and microsatellite instability (MIN) are integral to the hepatic carcinogenesis process leading to heterogeneity in HCC and that the pathways leading to heterogeneity may be targeted for prognosis, prevention and treatment.

  9. Prevention of Targeted School Violence by Responding to Students' Psychosocial Crises: The NETWASS Program.

    PubMed

    Leuschner, Vincenz; Fiedler, Nora; Schultze, Martin; Ahlig, Nadine; Göbel, Kristin; Sommer, Friederike; Scholl, Johanna; Cornell, Dewey; Scheithauer, Herbert

    2017-01-01

    The standardized, indicated school-based prevention program "Networks Against School Shootings" combines a threat assessment approach with a general model of prevention of emergency situations in schools through early intervention in student psychosocial crises and training teachers to recognize warning signs of targeted school violence. An evaluation study in 98 German schools with 3,473 school staff participants (Mage  = 46.2 years) used a quasi-experimental comparison group design with three measurement points (pre, post, and 7 months followup) with schools randomly allocated to implementation conditions. The study found increases in teachers' expertise and evaluation skills, enhanced abilities to identify students experiencing a psychosocial crisis, and positive secondary effects (e.g., teacher-student interaction, feelings of safety). © 2017 The Authors. Child Development © 2017 Society for Research in Child Development, Inc.

  10. CDK5 targeting prevents β-amyloid aggregation involving GSK3 β and phosphatases

    PubMed Central

    Castro-Alvarez, John Fredy; Uribe-Arias, Alejandro; Cardona-Gómez, Gloria Patricia

    2015-01-01

    Inappropriate activation of CDK5 due to proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles, β-amyloid aggregation and chronic neurodegeneration. At 18 months of age, 3xTg-AD mice were sacrificed after either three weeks (short-term) or one year (long-term) of CDK5 knockdown. In short-term-treated animals, CDK5 knockdown reversed β-amyloid aggregation in the hippocampi via inhibitory phosphorylation of GSK3β Ser 9 and activation of phosphatase PP2A. In long-term-treated animals, CDK5 knockdown induced a persistent reduction in CDK5 and prevented β-amyloid aggregation, but the effect on APP processing was reduced, suggesting that yearly booster therapy would be necessary. These findings further validate CDK5 as a target for preventing or blocking amyloidosis in older transgenic mice. PMID:25711385

  11. Cancer Prevention with Promising Natural Products: Mechanisms of Action and Molecular Targets

    PubMed Central

    Pratheeshkumar, Poyil; Sreekala, Chakkenchath; Zhang, Zhuo; Budhraja, Amit; Ding, Songze; Son, Young-Ok; Wang, Xin; Hitron, Andrew; Hyun-Jung, Kim; Wang, Lei; Lee, Jeong-Chae; Shi, Xianglin

    2016-01-01

    Cancer is the second leading cause of death worldwide. There is greater need for more effective and less toxic therapeutic and preventive strategies. Natural products are becoming an important research area for novel and bioactive molecules for drug discovery. Phytochemicals and dietary compounds have been used for the treatment of cancer throughout history due to their safety, low toxicity, and general availability. Many active phytochemicals are in human clinical trials. Studies have indicated that daily consumption of dietary phytochemicals have cancer protective effects against carcinogens. They can inhibit, delay, or reverse carcinogenesis by inducing detoxifying and antioxidant enzymes systems, regulating inflammatory and proliferative signaling pathways, and inducing cell cycle arrest and apoptosis. Epidemiological studies have also revealed that high dietary intakes of fruits and vegetables reduce the risk of cancer. This review discusses potential natural cancer preventive compounds, their molecular targets, and their mechanisms of actions. PMID:22583402

  12. [A population-targeted approach to connect prevention, care and welfare: visualising the trend].

    PubMed

    Lemmens, L C; Drewes, H W; Lette, M; Baan, C A

    2017-01-01

    To map initiatives in the Netherlands using a population-targeted approach to link prevention, care and welfare. Descriptive investigation, based on conversations and structured interviews. We searched for initiatives in which providers in the areas of prevention, care and welfare together with health insurers and/or local authorities attempted to provide the 'triple aim': improving the health of the population and the quality of care, and managing costs. We found potential initiatives on the basis of interviews with key figures, project databases and congress programmes. We looked for additional information on websites and via contact persons to gather additional information to determine whether the initiative met the inclusion criteria. An initiative should link prevention, care and welfare with a minimum of three players actively pursuing a population-targeted goal through multiple interventions for a non-disease specific and district-transcending population. We described the goal, organisational structure, parties involved, activities and funding on the basis of interviews conducted in the period August-December 2015 with the managers of the initiatives included. We found 19 initiatives which met the criteria where there was experimentation with organisational forms, levels of participation, interventions and funding. It was noticeable that the interventions mostly concerned medical care. There was a lack of insight into the 'triple aim', mostly because data exchange between parties is generally difficult. There is an increasing number of initiatives that follow a population-targeted approach. Although the different parties strive to connect the three domains, they are still searching for an optimal collaboration, organisational form, data exchange and financing.

  13. Molecular targets of dietary agents for prevention and therapy of cancer.

    PubMed

    Aggarwal, Bharat B; Shishodia, Shishir

    2006-05-14

    While fruits and vegetables are recommended for prevention of cancer and other diseases, their active ingredients (at the molecular level) and their mechanisms of action less well understood. Extensive research during the last half century has identified various molecular targets that can potentially be used not only for the prevention of cancer but also for treatment. However, lack of success with targeted monotherapy resulting from bypass mechanisms has forced researchers to employ either combination therapy or agents that interfere with multiple cell-signaling pathways. In this review, we present evidence that numerous agents identified from fruits and vegetables can interfere with several cell-signaling pathways. The agents include curcumin (turmeric), resveratrol (red grapes, peanuts and berries), genistein (soybean), diallyl sulfide (allium), S-allyl cysteine (allium), allicin (garlic), lycopene (tomato), capsaicin (red chilli), diosgenin (fenugreek), 6-gingerol (ginger), ellagic acid (pomegranate), ursolic acid (apple, pears, prunes), silymarin (milk thistle), anethol (anise, camphor, and fennel), catechins (green tea), eugenol (cloves), indole-3-carbinol (cruciferous vegetables), limonene (citrus fruits), beta carotene (carrots), and dietary fiber. For instance, the cell-signaling pathways inhibited by curcumin alone include NF-kappaB, AP-1, STAT3, Akt, Bcl-2, Bcl-X(L), caspases, PARP, IKK, EGFR, HER2, JNK, MAPK, COX2, and 5-LOX. The active principle identified in fruit and vegetables and the molecular targets modulated may be the basis for how these dietary agents not only prevent but also treat cancer and other diseases. This work reaffirms what Hippocrates said 25 centuries ago, let food be thy medicine and medicine be thy food.

  14. Targeting arachidonic acid pathway by natural products for cancer prevention and therapy.

    PubMed

    Yarla, Nagendra Sastry; Bishayee, Anupam; Sethi, Gautam; Reddanna, Pallu; Kalle, Arunasree M; Dhananjaya, Bhadrapura Lakkappa; Dowluru, Kaladhar S V G K; Chintala, Ramakrishna; Duddukuri, Govinda Rao

    2016-10-01

    Arachidonic acid (AA) pathway, a metabolic process, plays a key role in carcinogenesis. Hence, AA pathway metabolic enzymes phospholipase A2s (PLA2s), cyclooxygenases (COXs) and lipoxygenases (LOXs) and their metabolic products, such as prostaglandins and leukotrienes, have been considered novel preventive and therapeutic targets in cancer. Bioactive natural products are a good source for development of novel cancer preventive and therapeutic drugs, which have been widely used in clinical practice due to their safety profiles. AA pathway inhibitory natural products have been developed as chemopreventive and therapeutic agents against several cancers. Curcumin, resveratrol, apigenin, anthocyans, berberine, ellagic acid, eugenol, fisetin, ursolic acid, [6]-gingerol, guggulsteone, lycopene and genistein are well known cancer chemopreventive agents which act by targeting multiple pathways, including COX-2. Nordihydroguaiaretic acid and baicalein can be chemopreventive molecules against various cancers by inhibiting LOXs. Several PLA2s inhibitory natural products have been identified with chemopreventive and therapeutic potentials against various cancers. In this review, we critically discuss the possible utility of natural products as preventive and therapeutic agents against various oncologic diseases, including prostate, pancreatic, lung, skin, gastric, oral, blood, head and neck, colorectal, liver, cervical and breast cancers, by targeting AA pathway. Further, the current status of clinical studies evaluating AA pathway inhibitory natural products in cancer is reviewed. In addition, various emerging issues, including bioavailability, toxicity and explorability of combination therapy, for the development of AA pathway inhibitory natural products as chemopreventive and therapeutic agents against human malignancy are also discussed. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Therapeutic targeting of diabetic retinal neuropathy as a strategy in preventing diabetic retinopathy.

    PubMed

    de Moraes, Gabriela; Layton, Christopher J

    2016-12-01

    Diabetes causes a panretinal neurodegeneration herein termed diabetic retinal neuropathy, which manifests in the retina early and progresses throughout the disease. Clinical manifestations include changes in the ERG, perimetry, dark adaptation, contrast sensitivity and colour vision which correlate with laboratory findings of thinning of the retinal neuronal layers, increased apoptosis in neurons and activation of glial cells. Possible mechanisms include oxidative stress, neuronal AGE accumulation, altered balance of neurotrophic factors and loss of mitohormesis. Retinal neural damage precedes and is a biologically plausible cause of retinal vasculopathy later in diabetes, and this review suggests that strategies to target it directly could prevent diabetes induced blindness. The efficacy of fenofibrate in reducing retinopathy progression provides a possible proof of concept for this approach. Strategies which may target diabetic retinal neuropathy include reducing retinal metabolic demand, improving mitochondrial function with AMPK and Sirt1 activators or providing neurotrophic support with neurotrophic supplementation. © 2016 Royal Australian and New Zealand College of Ophthalmologists.

  16. Cost effectiveness of targeted HIV prevention interventions for female sex workers in India.

    PubMed

    Prinja, Shankar; Bahuguna, Pankaj; Rudra, Shalini; Gupta, Indrani; Kaur, Manmeet; Mehendale, S M; Chatterjee, Susmita; Panda, Samiran; Kumar, Rajesh

    2011-06-01

    To ascertain the cost effectiveness of targeted interventions for female sex workers (FSW) under the National AIDS Control Programme in India. A compartmental mathematical Markov state model was used over a 20-year time horizon (1995-2015) to estimate the cost effectiveness of FSW targeted interventions, with a health system perspective. The incremental costs and effects of FSW targeted interventions were compared against a baseline scenario of mass media for the general population alone. The incremental cost-effectiveness ratio was computed at a 3% discount rate using HIV infections averted and disability-adjusted life-years (DALY) as benefit measures. It was assumed that the transmission of the HIV virus moves from a high-risk group (FSW) to the client population and finally to the general population (partners of clients). Targeted interventions for FSW result in a reduction of 47% (1.6 million) prevalent and 36% (2.7 million) cumulative HIV cases, respectively, in 2015. Adult HIV prevalence in India, with and without (mass media only) FSW interventions, would be 0.25% and 0.48% in 2015. Indian government and development partners spend an average US $104 (INR4680) per HIV infection averted and US $10.7 (INR483) per DALY averted. Discounting at 3%, FSW targeted interventions cost US $105.5 (INR4748) and US $10.9 (INR490) per HIV case and DALY averted, respectively. At the current gross domestic product in India, targeted intervention is a cost-effective strategy for HIV prevention in India.

  17. Multicomponent targeted intervention to prevent delirium in hospitalized older patients: what is the economic value?

    PubMed

    Rizzo, J A; Bogardus, S T; Leo-Summers, L; Williams, C S; Acampora, D; Inouye, S K

    2001-07-01

    Delirium, or acute confusional state, is a common and serious occurrence among hospitalized older persons. Current estimates suggest that delirium complicates hospital stays for more than 2.3 million older persons each year, involving more than 17.5 million hospital days and accounting for more than $4 billion (1994 dollars) of Medicare expenditures. A 40% reduction was recently reported in the risk for delirium among hospitalized older persons receiving a multicomponent targeted risk factor intervention (MTI) strategy to prevent delirium, compared with subjects receiving usual hospital care.1 Before recommending that this preventive strategy be implemented in clinical practice, however, the cost implications must be thoroughly examined as well. The present analysis performs net cost evaluations of the MTI for the prevention of delirium among hospitalized patients. Hospital charge and cost-to-charge ratio data are linked to a database of 852 subjects, who were treated with MTI or usual care. Multivariable regression methods were used to help isolate the impact of MTI on hospital costs. These results were then combined with our earlier work on the impact of the MTI on delirium prevention to assess the cost effectiveness of this intervention. The MTI significantly reduced nonintervention costs among subjects at intermediate risk for developing delirium, but not among subjects at high risk. When MTI intervention costs were included, MTI had no significant effect on overall health care costs in the intermediate risk cohort, but raised overall costs in the high risk group. Because the MTI prevented delirium in the intermediate risk group without raising costs, the conclusion reached is that it is a cost effective treatment option for patients at intermediate risk for developing delirium. In contrast, the results suggest that the MTI is not cost effective for subjects at high risk.

  18. Differential Challenges in Coalition Building among HIV Prevention Coalitions Targeting Specific Youth Populations

    PubMed Central

    Robles-Schrader, Grisel M.; Harper, Gary W.; Purnell, Marjorie; Monarrez, Veronica; Ellen, Jonathan M.

    2012-01-01

    Coalitions provide the potential for merging the power, influence, and resources of fragmented individuals and institutions into one collective group that can more effectively focus its efforts on a specific community health issue. Connect to Protect® coalitions devote resources to address the HIV epidemic at a structural level. This research examines differential challenges in coalition processes that may facilitate/hinder coalition building to achieve HIV prevention through structural change. Qualitative interviews conducted with community partners participating across 10 coalitions were analyzed to compare responses of those individuals working on HIV prevention coalitions targeting adolescent and young adult gay and bisexual men versus those targeting adolescent and young adult heterosexual women. Community partner responses revealed differences across several key areas including: a) acceptability and goals in discussing sexual issues with adolescents, b) goals of sexual health promotion activities, and c) competition among collaborating agencies. Themes highlighted in this research can complement existing community intervention literature by helping community mobilizers, interventionists, and researchers understand how cultural norms affect youth-specific coalition work. PMID:24188354

  19. Mitochondrial NHE1: a newly identified target to prevent heart disease.

    PubMed

    Alvarez, Bernardo V; Villa-Abrille, María C

    2013-01-01

    Mitochondrial damage has been associated with early steps of cardiac dysfunction in heart subjected to ischemic stress, oxidative stress and hypertrophy. A common feature for the mitochondrial deterioration is the loss of the mitochondrial membrane potential (ΔΨ m) with the concomitant irreversible opening of the mitochondrial permeability transition pore (MPTP) which follows the mitochondrial Ca(2+) overload, and the subsequent mitochondrial swelling. We have recently characterized the expression of the Na(+)/H(+) exchanger 1 (mNHE1) in mitochondrial membranes. This surprising observation provided a unique target for the prevention of the Ca(2+)-induced MPTP opening, based on the inhibition of the NHE1 m. In this line, inhibition of NHE1 m activity and/or reduction of NHE1 m expression decreased the Ca(2+)-induced mitochondrial swelling and the release of reactive oxygen species (ROS) in isolated cardiac mitochondria and preserved the ΔΨ m in isolated cardiomyocytes. Mitochondrial NHE1 thus represents a novel target to prevent cardiac disease, opening new avenues for future research.

  20. Differential challenges in coalition building among HIV prevention coalitions targeting specific youth populations.

    PubMed

    Robles-Schrader, Grisel M; Harper, Gary W; Purnell, Marjorie; Monarrez, Veronica; Ellen, Jonathan M

    2012-01-01

    Coalitions provide the potential for merging the power, influence, and resources of fragmented individuals and institutions into one collective group that can more effectively focus its efforts on a specific community health issue. Connect to Protect® coalitions devote resources to address the HIV epidemic at a structural level. This study examines differential challenges in coalition processes that may hinder coalition building to achieve HIV prevention through structural change. Qualitative interviews conducted with community partners participating across 10 coalitions were analyzed to compare responses of those individuals working on HIV prevention coalitions targeting adolescent and young adult gay and bisexual men versus those targeting adolescent and young adult heterosexual women. Community partner responses revealed differences across several key areas including: (a) acceptability and goals in discussing sexual issues with adolescents, (b) goals of sexual health promotion activities, and (c) competition among collaborating agencies. Themes highlighted in this study can complement existing community intervention literature by helping community mobilizers, interventionists, and researchers understand how cultural norms affect youth-specific coalition work.

  1. Mitochondria-Targeted Antioxidant Prevents Cardiac Dysfunction Induced by Tafazzin Gene Knockdown in Cardiac Myocytes

    PubMed Central

    He, Quan; Harris, Nicole; Ren, Jun; Han, Xianlin

    2014-01-01

    Tafazzin, a mitochondrial acyltransferase, plays an important role in cardiolipin side chain remodeling. Previous studies have shown that dysfunction of tafazzin reduces cardiolipin content, impairs mitochondrial function, and causes dilated cardiomyopathy in Barth syndrome. Reactive oxygen species (ROS) have been implicated in the development of cardiomyopathy and are also the obligated byproducts of mitochondria. We hypothesized that tafazzin knockdown increases ROS production from mitochondria, and a mitochondria-targeted antioxidant prevents tafazzin knockdown induced mitochondrial and cardiac dysfunction. We employed cardiac myocytes transduced with an adenovirus containing tafazzin shRNA as a model to investigate the effects of the mitochondrial antioxidant, mito-Tempo. Knocking down tafazzin decreased steady state levels of cardiolipin and increased mitochondrial ROS. Treatment of cardiac myocytes with mito-Tempo normalized tafazzin knockdown enhanced mitochondrial ROS production and cellular ATP decline. Mito-Tempo also significantly abrogated tafazzin knockdown induced cardiac hypertrophy, contractile dysfunction, and cell death. We conclude that mitochondria-targeted antioxidant prevents cardiac dysfunction induced by tafazzin gene knockdown in cardiac myocytes and suggest mito-Tempo as a potential therapeutic for Barth syndrome and other dilated cardiomyopathies resulting from mitochondrial oxidative stress. PMID:25247053

  2. Targeting the NFκB signaling pathways for breast cancer prevention and therapy.

    PubMed

    Wang, Wei; Nag, Subhasree A; Zhang, Ruiwen

    2015-01-01

    The activation of nuclear factor-kappaB (NFκB), a proinflammatory transcription factor, is a commonly observed phenomenon in breast cancer. It facilitates the development of a hormone-independent, invasive, high-grade, and late-stage tumor phenotype. Moreover, the commonly used cancer chemotherapy and radiotherapy approaches activate NFκB, leading to the development of invasive breast cancers that show resistance to chemotherapy, radiotherapy, and endocrine therapy. Inhibition of NFκB results in an increase in the sensitivity of cancer cells to the apoptotic effects of chemotherapeutic agents and radiation and restoring hormone sensitivity, which is correlated with increased disease-free survival in patients with breast cancer. In this review article, we focus on the role of the NFκB signaling pathways in the development and progression of breast cancer and the validity of NFκB as a potential target for breast cancer prevention and therapy. We also discuss the recent findings that NFκB may have tumor suppressing activity in certain cancer types. Finally, this review also covers the state-of-the-art development of NFκB inhibitors for cancer therapy and prevention, the challenges in targeting validation, and pharmacology and toxicology evaluations of these agents from the bench to the bedside.

  3. A systematic review of universal campaigns targeting child physical abuse prevention

    PubMed Central

    Poole, Mary Kathryn; Seal, David W.; Taylor, Catherine A.

    2014-01-01

    The purpose of this review was to better understand the impact of universal campaign interventions with a media component aimed at preventing child physical abuse (CPA). The review included 17 studies featuring 15 campaigns conducted from 1989 to 2011 in five countries. Seven studies used experimental designs, but most were quasi-experimental. CPA incidence was assessed in only three studies and decreased significantly in two. Studies also found significant reductions in relevant outcomes such as dysfunctional parenting, child problem behaviors and parental anger as well as increases in parental self-efficacy and knowledge of concepts and actions relevant to preventing child abuse. The following risk factors were most frequently targeted in campaigns: lack of knowledge regarding positive parenting techniques, parental impulsivity, the stigma of asking for help, inadequate social support and inappropriate expectations for a child’s developmental stage. The evidence base for universal campaigns designed to prevent CPA remains inconclusive due to the limited availability of rigorous evaluations; however, Triple-P is a notable exception. Given the potential for such interventions to shift population norms relevant to CPA and reduce rates of CPA, there is a need to further develop and rigorously evaluate such campaigns. PMID:24711483

  4. A systematic review of universal campaigns targeting child physical abuse prevention.

    PubMed

    Poole, Mary Kathryn; Seal, David W; Taylor, Catherine A

    2014-06-01

    The purpose of this review was to better understand the impact of universal campaign interventions with a media component aimed at preventing child physical abuse (CPA). The review included 17 studies featuring 15 campaigns conducted from 1989 to 2011 in five countries. Seven studies used experimental designs, but most were quasi-experimental. CPA incidence was assessed in only three studies and decreased significantly in two. Studies also found significant reductions in relevant outcomes such as dysfunctional parenting, child problem behaviors and parental anger as well as increases in parental self-efficacy and knowledge of concepts and actions relevant to preventing child abuse. The following risk factors were most frequently targeted in campaigns: lack of knowledge regarding positive parenting techniques, parental impulsivity, the stigma of asking for help, inadequate social support and inappropriate expectations for a child's developmental stage. The evidence base for universal campaigns designed to prevent CPA remains inconclusive due to the limited availability of rigorous evaluations; however, Triple-P is a notable exception. Given the potential for such interventions to shift population norms relevant to CPA and reduce rates of CPA, there is a need to further develop and rigorously evaluate such campaigns. © The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  5. Preventive effect of dietary quercetin on disuse muscle atrophy by targeting mitochondria in denervated mice.

    PubMed

    Mukai, Rie; Matsui, Naoko; Fujikura, Yutaka; Matsumoto, Norifumi; Hou, De-Xing; Kanzaki, Noriyuki; Shibata, Hiroshi; Horikawa, Manabu; Iwasa, Keiko; Hirasaka, Katsuya; Nikawa, Takeshi; Terao, Junji

    2016-05-01

    Quercetin is a major dietary flavonoid in fruits and vegetables. We aimed to clarify the preventive effect of dietary quercetin on disuse muscle atrophy and the underlying mechanisms. We established a mouse denervation model by cutting the sciatic nerve in the right leg (SNX surgery) to lack of mobilization in hind-limb. Preintake of a quercetin-mixed diet for 14days before SNX surgery prevented loss of muscle mass and atrophy of muscle fibers in the gastrocnemius muscle (GM). Phosphorylation of Akt, a key phosphorylation pathway of suppression of protein degradation, was activated in the quercetin-mixed diet group with and without SNX surgery. Intake of a quercetin-mixed diet suppressed the generation of hydrogen peroxide originating from mitochondria and elevated mitochondrial peroxisome proliferator-activated receptor-γ coactivator 1α mRNA expression as well as NADH dehydrogenase 4 expression in the GM with SNX surgery. Quercetin and its conjugated metabolites reduced hydrogen peroxide production in the mitochondrial fraction obtained from atrophied muscle. In C2C12 myotubes, quercetin reached the mitochondrial fraction. These findings suggest that dietary quercetin can prevent disuse muscle atrophy by targeting mitochondria in skeletal muscle tissue through protecting mitochondria from decreased biogenesis and reducing mitochondrial hydrogen peroxide release, which can be related to decreased hydrogen peroxide production and/or improvements on antioxidant capacity of mitochondria. Copyright © 2016 Elsevier Inc. All rights reserved.

  6. The impact of a targeted radio campaign to prevent STIs and HIV/AIDS in Mozambique.

    PubMed

    Karlyn, A S

    2001-10-01

    In 1997 to 1998, Population Services International (PSI) carried out a targeted radio campaign in Mozambique to promote behavior change for the prevention of sexually transmitted infections (STIs) and HIV/AIDS. To evaluate the coverage and impact of the campaign, PSI designed and implemented a cross-sectional study using a two-stage random sample of "at-risk" individuals; 754 individuals between the ages of 13 and 49 were interviewed. Over half (52.4%) heard the campaign and 45.5% recalled one or more radio messages. However, recall of specific messages in specific risk groups was low. A multivariate model demonstrates that among those exposed to the radio campaign, 97.2% reported intent to change their sexual behavior compared with 62.8% of those not exposed to the campaign (p < .001). Among those who recalled campaign messages, 86.1% attempted to change their behavior compared with 58% of those who had no message recall (p <.001). Success in changing behavior is significantly higher among those with message recall (83.8%) than those without (56.8%, p < .001). This study illustrates the difficulties in using radio to target a specific group with a corresponding behavior change message. Although general recall of campaign messages was high per target group, the campaign did not succeed in ensuring exposure to the intended target group. The strategy of airing all of the spots simultaneously with different but similar messages resulted in one spot "stepping on" another. Despite the limitations in using radio to target, exposure to the radio campaign has contributed to individual intent to change sexual behavior.

  7. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorder Symptoms and Unhealthy Weight Gain among Female College Students

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2012-01-01

    Objective: Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women. Method: Female college students at high-risk for these outcomes by virtue of body image concerns (N = 398; M age = 18.4 years, SD = 0.6) were randomized to the Healthy Weight group-based 4-hr prevention program,…

  8. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorder Symptoms and Unhealthy Weight Gain among Female College Students

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2012-01-01

    Objective: Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women. Method: Female college students at high-risk for these outcomes by virtue of body image concerns (N = 398; M age = 18.4 years, SD = 0.6) were randomized to the Healthy Weight group-based 4-hr prevention program,…

  9. National survey on sports injuries in the Netherlands: target populations for sports injury prevention programs.

    PubMed

    Schmikli, Sandor L; Backx, Frank J G; Kemler, Helena J; van Mechelen, Willem

    2009-03-01

    To define target populations for sports injury prevention programs. A computer-assisted telephone survey on sports injuries and sports participation during 2000-2005 using a 3-month recall period. Data obtained from a representative sample of Dutch citizens. Fifty-eight thousand four hundred five Dutch citizens aged older than 3 years. Age, gender, and type of sports were used to distinguish subgroups with a substantial contribution to sports injuries. The absolute number of sports injuries, the incidence of sports injuries per 10,000 hours, the severity, and costs of sports injuries. Sports participation was associated with 1.5 million injuries per year and 10 injuries per 10,000 hours; of these, 50% had to be treated medically. Two-thirds of all medically treated sports injuries were associated with 9 sports (representing 18 subpopulations, all younger than 55 years): outdoor soccer (males 4-54 years and females 4-17 years), indoor soccer (males 18-34 years), tennis (males/females 35-54 years), volleyball (females 18-54 years), field hockey (males 18-34 years and females 4-17 years), running/jogging (males/females 35-54 years), gymnastics (males/females 4-17 years), skiing/snowboarding (males 4-17 years and females 18-34 years), and equestrian sports (females 18-34 years). These groups showed more than average injury rates and covered two-thirds of all direct and indirect costs (euro 400 million). The survey identified the most important (sports-, age-, and gender-specific) target populations for injury prevention programs in the Netherlands. Sports participants aged older than 55 years were excluded from these target groups because of their limited contribution to the total sports injury problem.

  10. REDD1 Is a Major Target of Testosterone Action in Preventing Dexamethasone-Induced Muscle Loss

    PubMed Central

    Wu, Yong; Zhao, Weidong; Zhao, Jingbo; Zhang, Yuanfei; Qin, Weiping; Pan, Jiangping; Bauman, William A.; Blitzer, Robert D.; Cardozo, Christopher

    2010-01-01

    Glucocorticoids are a well-recognized and common cause of muscle atrophy that can be prevented by testosterone. However, the molecular mechanisms underlying such protection have not been described. Thus, the global effects of testosterone on dexamethasone-induced changes in gene expression were evaluated in rat gastrocnemius muscle using DNA microarrays. Gene expression was analyzed after 7-d administration of dexamethasone, dexamethasone plus testosterone, or vehicle. Dexamethasone changed expression of 876 probe sets by at least 2-fold. Among these, 474 probe sets were changed by at least 2-fold in the opposite direction in the dexamethasone plus testosterone group (genes in opposition). Major biological themes represented by genes in opposition included IGF-I signaling, myogenesis and muscle development, and cell cycle progression. Testosterone completely prevented the 22-fold increase in expression of the mammalian target of rapamycin (mTOR) inhibitor regulated in development and DNA damage responses 1 (REDD1), and attenuated dexamethasone induced increased expression of eIF4E binding protein 1, Forkhead box O1, and the p85 regulatory subunit of the IGF-I receptor but prevented decreased expression of IRS-1. Testosterone attenuated increases in REDD1 protein in skeletal muscle and L6 myoblasts and prevented dephosphorylation of p70S6 kinase at the mTOR-dependent site Thr389 in L6 myoblast cells. Effects of testosterone on REDD1 mRNA levels occurred within 1 h, required the androgen receptor, were blocked by bicalutamide, and were due to inhibition of transcriptional activation of REDD1 by dexamethasone. These data suggest that testosterone blocks dexamethasone-induced changes in expression of REDD1 and other genes that collectively would otherwise down-regulate mTOR activity and hence also down-regulate protein synthesis. PMID:20032058

  11. An example of international drug politics--the development and distribution of substance prevention programs directed at adolescents.

    PubMed

    Lilja, John; Giota, Joanna; Hamilton, David; Larsson, Sam

    2007-01-01

    Many substance use prevention programs directed at adolescents exist that have been developed by researchers in the United States and are intended to be used in school settings. Some of the problems associated with such programs are reviewed, including their accessibility, ease of use, copyright status, evaluation options, program scales, and ratings, together with an overall consideration of the factors and processes posited to be associated with substance use and non-use (posited "at-risk" and "protective" mechanisms). The authors contend that there is a great need to: (a) develop substance use prevention programs which are commercially available but are not protected by copyright, (b) assess empirically each component in a program separately, and (c) encourage funding bodies to be more active in supporting the production of manuals and evaluation instruments for substance use prevention programs directed at adolescents. We need more and better process evaluations that are also sensitive to both endogenous and exogenous forces in order to know the processes by which a successful prevention program achieves its effects, is prevented from doing so and which processes are irrelevant. A social competence framework might be used as both a goal and as a theoretical base to achieve a better understanding of the processes by which substance use prevention programs reach their effects.

  12. WHO BENEFITS MOST FROM A BROADLY TARGETED PREVENTION PROGRAM? DIFFERENTIAL EFFICACY ACROSS POPULATIONS IN THE TEEN OUTREACH PROGRAM

    PubMed Central

    Allen, Joseph P.; Philliber, Susan

    2006-01-01

    This study examined a highly successful, well-documented, national program to prevent teenage pregnancy and school failure—the Teen Outreach program—to address a fundamental question: How well can a developmentally focused, broadly targeted prevention program address the needs of those students within the program who are at the highest risk of problematic behavior. The hypothesis that the developmental focus of a broadly targeted intervention would lead it to have greater program efficacy among those young people who began the program at greatest risk was examined with multisite data collected on more than 3,300 Teen Outreach and comparison group students. Results confirmed prior findings regarding the overall efficacy of the Teen Outreach program, and indicated that the program appeared most effective for those students at greatest initial risk of the problem behaviors being targeted. Implications for the targeting of the Teen Outreach program specifically and of similar primary prevention programs more generally are discussed. PMID:17235364

  13. The role of cyclic nucleotide signaling pathways in cancer: targets for prevention and treatment.

    PubMed

    Fajardo, Alexandra M; Piazza, Gary A; Tinsley, Heather N

    2014-02-26

    For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) have been recognized as important signaling molecules within cells. Under normal physiological conditions, cyclic nucleotides regulate a myriad of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide signaling has been observed in a number of pathophysiological conditions, including cancer. While the distinct molecular alterations responsible for these effects vary depending on the specific cancer type, several studies have demonstrated that activation of cyclic nucleotide signaling through one of three mechanisms-induction of cyclic nucleotide synthesis, inhibition of cyclic nucleotide degradation, or activation of cyclic nucleotide receptors-is sufficient to inhibit proliferation and activate apoptosis in many types of cancer cells. These findings suggest that targeting cyclic nucleotide signaling can provide a strategy for the discovery of novel agents for the prevention and/or treatment of selected cancers.

  14. The Role of Cyclic Nucleotide Signaling Pathways in Cancer: Targets for Prevention and Treatment

    PubMed Central

    Fajardo, Alexandra M.; Piazza, Gary A.; Tinsley, Heather N.

    2014-01-01

    For more than four decades, the cyclic nucleotides cyclic AMP (cAMP) and cyclic GMP (cGMP) have been recognized as important signaling molecules within cells. Under normal physiological conditions, cyclic nucleotides regulate a myriad of biological processes such as cell growth and adhesion, energy homeostasis, neuronal signaling, and muscle relaxation. In addition, altered cyclic nucleotide signaling has been observed in a number of pathophysiological conditions, including cancer. While the distinct molecular alterations responsible for these effects vary depending on the specific cancer type, several studies have demonstrated that activation of cyclic nucleotide signaling through one of three mechanisms—induction of cyclic nucleotide synthesis, inhibition of cyclic nucleotide degradation, or activation of cyclic nucleotide receptors—is sufficient to inhibit proliferation and activate apoptosis in many types of cancer cells. These findings suggest that targeting cyclic nucleotide signaling can provide a strategy for the discovery of novel agents for the prevention and/or treatment of selected cancers. PMID:24577242

  15. Molecular Pathways: Aspirin and Wnt Signaling—A Molecularly Targeted Approach to Cancer Prevention and Treatment

    PubMed Central

    Gala, Manish K.; Chan, Andrew T.

    2014-01-01

    The anti-inflammatory properties of aspirin have resulted in its widespread use as an analgesic, anti-pyretic, and cardioprotective agent. Beyond these applications, multiple observational studies and randomized controlled trials have demonstrated a chemopreventative role for aspirin, particularly in the development of colorectal neoplasia. Given the critical importance of Wnt dysregulation in colorectal carcinogenesis, the interplay between aspirin and canonical Wnt signaling has become a focus of investigation. These studies have illuminated our understanding of the anti-cancer mechanisms of aspirin, yielding the identification of potential biomarkers for which aspirin's chemopreventative efficacy can be safely optimized into routine clinical practice and providing leads into the discovery of novel preventive and therapeutic targets. In this review, we summarize key experimental and clinical studies of this interaction, as well as highlight future strategies to advance their clinical translation. PMID:25501125

  16. Chesapeake Bay regions of concern: Geographical targeting protocol for remediation, reduction, prevention and assessment actions

    SciTech Connect

    Batiuk, R.A.

    1994-12-31

    As a result of a two year reevaluation of a Basinwide Toxics Reduction Strategy, the Chesapeake Bay Program identified the need to more effectively direct reduction and prevention actions toward regional areas with known toxic problems as well as areas where significant potential exists for toxic impacts on living resources and habitats. Building upon the geographical targeting efforts in the Great Lakes and Puget Sound, a protocol was established for identifying and categorizing areas ranging from known toxic problems to areas with low probability for adverse effects to insufficient data. The identification protocol is based on a series of criteria which include evaluation of sediment contamination concentrations and ambient sediment toxicity. The process for development and application of the Regions of Concern protocol along with a focus on the sediment assessment criteria and how they influenced the over-all categorization of regions will be presented.

  17. Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use.

    PubMed

    Young, E J; Blouin, A M; Briggs, S B; Sillivan, S E; Lin, L; Cameron, M D; Rumbaugh, G; Miller, C A

    2016-05-01

    Memories associated with drug use increase vulnerability to relapse in substance use disorder (SUD), and there are no pharmacotherapies for the prevention of relapse. Previously, we reported a promising finding that storage of memories associated with methamphetamine (METH), but not memories for fear or food reward, is vulnerable to disruption by actin depolymerization in the basolateral amygdala complex (BLC). However, actin is not a viable therapeutic target because of its numerous functions throughout the body. Here we report the discovery of a viable therapeutic target, nonmuscle myosin IIB (NMIIB), a molecular motor that supports memory by directly driving synaptic actin polymerization. A single intra-BLC treatment with Blebbistatin (Blebb), a small-molecule inhibitor of class II myosin isoforms, including NMIIB, produced a long-lasting disruption of context-induced drug seeking (at least 30 days). Further, postconsolidation genetic knockdown of Myh10, the heavy chain of the most highly expressed NMII in the BLC, was sufficient to produce METH-associated memory loss. Blebb was found to be highly brain penetrant. A single systemic injection of the compound selectively disrupted the storage of METH-associated memory and reversed the accompanying increase in BLC spine density. This effect was specific to METH-associated memory, as it had no effect on an auditory fear memory. The effect was also independent of retrieval, as METH-associated memory was disrupted 24 h after a single systemic injection of Blebb delivered in the home cage. Together, these results argue for the further development of small-molecule inhibitors of NMII as potential therapeutics for the prevention of SUD relapse triggered by drug associations.

  18. RANK ligand as a potential target for breast cancer prevention in BRCA1-mutation carriers.

    PubMed

    Nolan, Emma; Vaillant, François; Branstetter, Daniel; Pal, Bhupinder; Giner, Göknur; Whitehead, Lachlan; Lok, Sheau W; Mann, Gregory B; Rohrbach, Kathy; Huang, Li-Ya; Soriano, Rosalia; Smyth, Gordon K; Dougall, William C; Visvader, Jane E; Lindeman, Geoffrey J

    2016-08-01

    Individuals who have mutations in the breast-cancer-susceptibility gene BRCA1 (hereafter referred to as BRCA1-mutation carriers) frequently undergo prophylactic mastectomy to minimize their risk of breast cancer. The identification of an effective prevention therapy therefore remains a 'holy grail' for the field. Precancerous BRCA1(mut/+) tissue harbors an aberrant population of luminal progenitor cells, and deregulated progesterone signaling has been implicated in BRCA1-associated oncogenesis. Coupled with the findings that tumor necrosis factor superfamily member 11 (TNFSF11; also known as RANKL) is a key paracrine effector of progesterone signaling and that RANKL and its receptor TNFRSF11A (also known as RANK) contribute to mammary tumorigenesis, we investigated a role for this pathway in the pre-neoplastic phase of BRCA1-mutation carriers. We identified two subsets of luminal progenitors (RANK(+) and RANK(-)) in histologically normal tissue of BRCA1-mutation carriers and showed that RANK(+) cells are highly proliferative, have grossly aberrant DNA repair and bear a molecular signature similar to that of basal-like breast cancer. These data suggest that RANK(+) and not RANK(-) progenitors are a key target population in these women. Inhibition of RANKL signaling by treatment with denosumab in three-dimensional breast organoids derived from pre-neoplastic BRCA1(mut/+) tissue attenuated progesterone-induced proliferation. Notably, proliferation was markedly reduced in breast biopsies from BRCA1-mutation carriers who were treated with denosumab. Furthermore, inhibition of RANKL in a Brca1-deficient mouse model substantially curtailed mammary tumorigenesis. Taken together, these findings identify a targetable pathway in a putative cell-of-origin population in BRCA1-mutation carriers and implicate RANKL blockade as a promising strategy in the prevention of breast cancer.

  19. Nonmuscle myosin IIB as a therapeutic target for the prevention of relapse to methamphetamine use

    PubMed Central

    Young, Erica J.; Blouin, Ashley M.; Briggs, Sherri B.; Sillivan, Stephanie E.; Lin, Li; Cameron, Michael D.; Rumbaugh, Gavin; Miller, Courtney A.

    2015-01-01

    Memories associated with drug use increase vulnerability to relapse in substance use disorder (SUD) and there are no pharmacotherapies for the prevention of relapse. Previously, we reported a promising finding that storage of memories associated with methamphetamine (METH), but not memories for fear or food reward, is vulnerable to disruption by actin depolymerization in the basolateral amygdala complex (BLC). However, actin is not a viable therapeutic target because of its numerous functions throughout the body. Here we report the discovery of a viable therapeutic target, nonmuscle myosin II (NMIIB), a molecular motor that supports memory by directly driving synaptic actin polymerization. A single intra-BLC treatment with Blebbistatin, a small molecule inhibitor of class II myosin isoforms, including NMIIB, produced a long-lasting disruption of context-induced drug seeking (at least 30 days). Further, post-consolidation genetic knockdown of Myh10, the heavy chain of the most highly expressed NMII in the BLC, was sufficient to produce METH-associated memory loss. Blebbistatin was found to be highly brain penetrant. A single systemic injection of the compound selectively disrupted the storage of METH-associated memory and reversed the accompanying increase in BLC spine density. This effect was specific to METH-associated memory, as it had no effect on an auditory fear memory. The effect was also independent of retrieval, as METH-associated memory was disrupted twenty-four hours after a single systemic injection of Blebbistatin delivered in the home cage. Together, these results argue for the further development of small molecule inhibitors of nonmuscle myosin II as potential therapeutics for the prevention of SUD relapse triggered by drug associations. PMID:26239291

  20. Effectiveness of programmes as part of primary prevention demonstrated on the example of cardiovascular diseases and the metabolic syndrome.

    PubMed

    Korczak, Dieter; Dietl, Markus; Steinhauser, Gerlinde

    2011-04-01

    The HTA-report (HTA = Health Technology Assessment) deals with the primary prevention of cardiovascular diseases and diabetes mellitus type 2. In 2009 approximately 356,000 people died in Germany due to cardiovascular diseases. According to estimations about 6.3 million people are suffering from diabetes mellitus type 2. The interventions that are subsidized by the public health insurance are mainly focused on sufficient physical activities, healthy nutrition, stress management and the reduction of the consumption of addictive drugs and luxury food. Which lifestyle-related measures and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are effective? To what extent will the health status be improved by these offers? To what extent will existing health resources and skills be strengthened by these offers? Are there any differences regarding the effectiveness among the interventions with respect to different settings or subgroups? Which lifestyle-related interventions and/or programmes for primary prevention of cardiovascular diseases and of the metabolic syndrome are sustainable and cost-effective? Which outcome parameters are in the view of the contributors decisive for the evaluation of the effectiveness? In the view of the contributor are there different values between the outcome parameters? In the view of the payers and other actors are there different values between the outcome parameters? Which ethical and juridical factors have to be considered? Which social and/or socio-economic parameters influence the use of the services and effectiveness? A systematic literature research is done in 35 databases. For the period 2005 to 2010, reviews, epidemiological and clinical studies as well as economical evaluations which deal with primary prevention programmes regarding cardiovascular diseases or the metabolic syndrome are included. 44 publications meet the inclusion criteria. These studies confirm the effectiveness of the

  1. Could targeted exercise programmes prevent lower limb injury in community Australian football?

    PubMed

    Andrew, Nadine; Gabbe, Belinda J; Cook, Jill; Lloyd, David G; Donnelly, Cyril J; Nash, Clare; Finch, Caroline F

    2013-08-01

    related to tendon injury and four were hip or groin injury related. Another 12 papers targeted general lower limb injuries. Most (n = 27 [57%]) were observational studies, investigating injury risk factors. Twenty reported the results of intervention trials. Of these, 15 were efficacy trials reporting the effects of an intervention in reducing injury rates, four were biomechanical interventions in which the impact of the intervention on a known injury risk factor was assessed and one reported changes in injury risk factors as well as injury rates. The strength of the evidence base for exercise programmes for lower limb injury prevention was found to be limited, primarily due to the research methods employed, low adherence to interventions by the study participants and a lack of statistical power. Limited evidence obtained from a small number of RCTs suggests that balance and control exercises might be efficacious in preventing ankle ligament injuries and a programme involving a combination of balance and control exercises, eccentric hamstring, plyometrics and strength exercises could be efficacious in preventing all lower limb injuries. Overall, the evidence for exercise programmes as an efficacious lower limb injury prevention strategy is predominantly restricted to studies addressing injury aetiology and mechanisms. The findings of this review highlight the need to develop and test interventions in well designed population-based trials with an emphasis on promoting intervention uptake and adherence and, hence, intervention effectiveness. The results of this review can inform the development of the components of a future lower limb injury prevention exercise protocol for community-level Australian football.

  2. Integrated strategies for combination HIV prevention: principles and examples for men who have sex with men in the Americas and heterosexual African populations.

    PubMed

    Celum, Connie; Baeten, Jared M; Hughes, James P; Barnabas, Ruanne; Liu, Albert; Van Rooyen, Heidi; Buchbinder, Susan

    2013-07-01

    Combination HIV prevention is of high priority for increasing the impact of partially efficacious HIV prevention interventions for specific populations and settings. Developing the package requires critical review of local epidemiology of HIV infection regarding most-impacted populations and those at high risk of HIV transmission and acquisition, drivers of HIV infection, and available interventions to address these risk factors. Interventions should be considered in terms of the evidence basis for efficacy, potential synergies, and feasibility of delivery at scale, which is important to achieve high coverage and impact, coupled with high acceptability to populations, which will impact uptake, adherence, and retention. Evaluation requires process measures of uptake, adherence, retention, and outcome measures of reduction in HIV infectiousness and acquisition. Three examples of combination prevention concepts are summarized for men who have sex with men in the Americas, young women in sub-Saharan Africa, and HIV serodiscordant couples.

  3. Methylphenidate and μ opioid receptor interactions: a pharmacological target for prevention of stimulant abuse.

    PubMed

    Zhu, Jinmin; Spencer, Thomas J; Liu-Chen, Lee-Yuan; Biederman, Joseph; Bhide, Pradeep G

    2011-01-01

    Methylphenidate (MPH) is one of the most commonly used and highly effective treatments for attention deficit hyperactivity disorder (ADHD) in children and adults. As the therapeutic use of MPH has increased, so has its abuse and illicit street-use. Yet, the mechanisms associated with development of MPH-associated abuse and dependence are not well understood making it difficult to develop methods to help its mitigation. As a result, many ADHD patients especially children and youth, that could benefit from MPH treatment do not receive it and risk lifelong disabilities associated with untreated ADHD. Therefore, understanding the mechanisms associated with development of MPH addiction and designing methods to prevent it assume high public health significance. Using a mouse model we show that supra-therapeutic doses of MPH produce rewarding effects (surrogate measure for addiction in humans) in a conditioned place preference paradigm and upregulate μ opioid receptor (MOPR) activity in the striatum and nucleus accumbens, brain regions associated with reward circuitry. Co-administration of naltrexone, a non-selective opioid receptor antagonist, prevents MPH-induced MOPR activation and the rewarding effects. The MPH-induced MOPR activation and rewarding effect require activation of the dopamine D1 but not the D2-receptor. These findings identify the MOPR as a potential target for attenuating rewarding effects of MPH and suggest that a formulation that combines naltrexone with MPH could be a useful pharmaceutical approach to alleviate abuse potential of MPH and other stimulants.

  4. Sphingosine Kinase: A Novel Putative Target for the Prevention of Infection-Triggered Preterm Birth

    PubMed Central

    Vyas, Vibhuti; Ashby, Charles R.; Reznik, Sandra E.

    2013-01-01

    Preterm birth is defined as any delivery before 37 complete weeks of gestation. It is a universal challenge in the field of obstetrics owing to its high rate of mortality, long-term morbidity, associated human suffering and economic burden. In the United States, about 12.18% deliveries in 2009 were preterm, producing an exorbitant cost of $5.8 billion. Infection-associated premature rupture of membranes (PROM) accounts for 40% of extremely preterm births (<28 weeks of gestation). Major research efforts are directed towards improving the understanding of the pathophysiology of preterm birth and ways to prevent or at least postpone delivery. Endothelin-1 (ET-1) is a potent vasoconstrictor that plays a significant role in infection-triggered preterm birth. Its involvement in a number of pathological mechanisms and its elevation in preterm delivered amniotic fluid samples implicate it in preterm birth. Sphingosine kinase (SphK) is a ubiquitous enzyme responsible for the production of sphingosine-1-phosphate (S1P). S1P acts as second messenger in a number of cell proliferation and survival pathways. SphK is found to play a key role in ET-1 mediated myometrial contraction. This review highlights SphK as a prospective target with great potential to prevent preterm birth. PMID:23818902

  5. Anxiety Sensitivity Amelioration Training (ASAT): a longitudinal primary prevention program targeting cognitive vulnerability.

    PubMed

    Schmidt, Norman B; Eggleston, A Meade; Woolaway-Bickel, Kelly; Fitzpatrick, Kathleen Kara; Vasey, Michael W; Richey, J Anthony

    2007-01-01

    Fear of arousal symptoms, often referred to as anxiety sensitivity (AS) appears to be associated with risk for anxiety pathology and other Axis I conditions. Findings from a longitudinal prevention program targeting AS are reported. Participants (n=404) scoring high on the Anxiety Sensitivity Index (ASI) were randomly assigned to receive a brief intervention designed to reduce AS (Anxiety Sensitivity Amelioration Training (ASAT)) or a control condition. Participants were followed for up to 24 months. Findings indicate that ASAT produced greater reductions in ASI levels compared with the control condition. Moreover, reductions were specific to anxiety sensitivity relative to related cognitive risk factors for anxiety. ASAT also produced decreased subjective fear responding to a 20% CO(2) challenge delivered postintervention. Data from the follow-up period show a lower incidence of Axis I diagnoses in the treated condition though the overall group difference was not statistically different at all follow-up intervals. Overall, findings are promising for the preventative efficacy of a brief, computer-based intervention designed to decrease anxiety sensitivity.

  6. Development of a Targeted Smoking Relapse-Prevention Intervention for Cancer Patients.

    PubMed

    Meltzer, Lauren R; Meade, Cathy D; Diaz, Diana B; Carrington, Monica S; Brandon, Thomas H; Jacobsen, Paul B; McCaffrey, Judith C; Haura, Eric B; Simmons, Vani N

    2016-08-01

    We describe the series of iterative steps used to develop a smoking relapse-prevention intervention customized to the needs of cancer patients. Informed by relevant literature and a series of preliminary studies, an educational tool (DVD) was developed to target the unique smoking relapse risk factors among cancer patients. Learner verification interviews were conducted with 10 cancer patients who recently quit smoking to elicit feedback and inform the development of the DVD. The DVD was then refined using iterative processes and feedback from the learner verification interviews. Major changes focused on visual appeal, and the inclusion of additional testimonials and graphics to increase comprehension of key points and further emphasize the message that the patient is in control of their ability to maintain their smoking abstinence. Together, these steps resulted in the creation of a DVD titled Surviving Smokefree®, which represents the first smoking relapse-prevention intervention for cancer patients. If found effective, the Surviving Smokefree® DVD is an easily disseminable and low-cost portable intervention which can assist cancer patients in maintaining smoking abstinence.

  7. Nuclear receptors and epigenetic regulation: opportunities for nutritional targeting and disease prevention.

    PubMed

    Romagnolo, Donato F; Zempleni, Janos; Selmin, Ornella I

    2014-07-01

    Posttranslational modifications of histones, alterations in the recruitment and functions of non-histone proteins, DNA methylation, and changes in expression of noncoding RNAs contribute to current models of epigenetic regulation. Nuclear receptors (NRs) are a group of transcription factors that, through ligand-binding, act as sensors to changes in nutritional, environmental, developmental, pathophysiologic, and endocrine conditions and drive adaptive responses via gene regulation. One mechanism through which NRs direct gene expression is the assembly of transcription complexes with cofactors and coregulators that possess chromatin-modifying properties. Chromatin modifications can be transient or become part of the cellular "memory" and contribute to genomic imprinting. Because many food components bind to NRs, they can ultimately influence transcription of genes associated with biologic processes, such as inflammation, proliferation, apoptosis, and hormonal response, and alter the susceptibility to chronic diseases (e.g., cancer, diabetes, obesity). The objective of this review is to highlight how NRs influence epigenetic regulation and the relevance of dietary compound-NR interactions in human nutrition and for disease prevention and treatment. Identifying gene targets of unliganded and bound NRs may assist in the development of epigenetic maps for food components and dietary patterns. Progress in these areas may lead to the formulation of disease-prevention models based on epigenetic control by individual or associations of food ligands of NRs.

  8. Bone targeted therapies for the prevention of skeletal morbidity in men with prostate cancer.

    PubMed

    Saylor, Philip J

    2014-01-01

    Men with prostate cancer suffer substantially from bone-related complications. Androgen deprivation therapy itself is a cause of loss of bone mineral density and is associated with an increased incidence of osteoporotic fractures. In advanced disease, bone is by far the most common site of metastasis. Complications of bone metastases prominently include pain and the potential for skeletal events such as spinal cord compression and pathologic fractures. Elevated osteoclast activity is an important aspect of the pathophysiology of both treatment-related osteoporosis and skeletal complications due to metastases. The osteoclast is therefore a therapeutic target. Denosumab is a fully human monoclonal antibody to receptor activator of nuclear factor-κ-B ligand that was designed to potently inhibit osteoclast activity and is the central focus of this review. Bisphosphonates, radiopharmaceuticals and systemically-active hormonal agents such as abiraterone acetate and enzalutamide have each been shown to improve skeletal morbidity in specific clinical situations. Denosumab is the only agent that has been shown to prevent osteoporotic fractures in men receiving androgen deprivation therapy and at elevated risk for fracture. It has also demonstrated superiority to the potent bisphosphonate zoledronic acid for the prevention of skeletal-related events in men with castration-resistant prostate cancer metastatic to bone. Efficacy and toxicity data will be discussed.

  9. [The role of medical university in modern prevention of cardiovascular diseases. Examples from Medical University of Gdańsk].

    PubMed

    Zdrojewski, Tomasz; Wierucki, Lukasz; Ignaszewska-Wyrzykowska, Agata; Zarzeczna-Baran, Marzena; Wojdak-Haasa, Ewa; Mogilnaya, Irina; Narkiewicz, Krzysztof; Szczech, Radosław; Rutkowski, Marcin; Bandosz, Piotr; Januszko, Wiktor; Krupa-Wojciechowska, Barbara; Wyrzykowski, Bogdan

    2005-01-01

    Constant worsening of epidemiological situation in cardiovascular diseases in Poland in the 70's and 80's called for intensive measures in the field of preventive cardiology. Thus in 90's, in order to change this situation, among others, team from Department of Hypertension and Diabetology from Medical University of Gdańsk started, in cooperation with other medical universities, important regional and national research programs and preventive interventions. The aim of the educational program carried out in years 1999-2001 for Members of the Polish Parliament, opinion leaders and decision makers was to increase knowledge of the Polish elites about epidemic of cardiovascular diseases in our country. These actions made possible receiving greater support from the government for new epidemiological and preventive programs in this field. Thanks to NATPOL PLUS project, carried out on the representative sample of adults in 2002, we determined for the first time the prevalence and control of main cardiovascular risk factors in Poland. Results of this program helped planning preventive tasks in the National Cardiovascular Diseases Prevention and Treatment Program POLKARD 2003-2005. The aim of the preventive programmes: SOPKARD and Polish Four-Cities Project was to work out standards of modern, comprehensive interventions. They permitted planning and introduction of the largest preventive program: the Polish 400 Cities Project (PP400M). The PP400M is addressed to citizens of all small towns (to 8000 citizens) and surrounding villages in the whole country. All these accomplishments in the field of quickly expanded clinical epidemiology and cardiovascular prevention are directed mainly to Pomeranian and Polish citizens, especially those who are not aware of high risk of myocardial infarction or stroke. The main principle of our strategy is the role of university as an expert in preparation and supervision of the programs, which were carried out by the specialized organizations

  10. Molecular mechanisms of diabetic retinopathy, general preventive strategies, and novel therapeutic targets.

    PubMed

    Safi, Sher Zaman; Qvist, Rajes; Kumar, Selva; Batumalaie, Kalaivani; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors.

  11. A genetic strategy to identify targets for the development of drugs that prevent bacterial persistence.

    PubMed

    Kim, Jee-Hyun; O'Brien, Kathryn M; Sharma, Ritu; Boshoff, Helena I M; Rehren, German; Chakraborty, Sumit; Wallach, Joshua B; Monteleone, Mercedes; Wilson, Daniel J; Aldrich, Courtney C; Barry, Clifton E; Rhee, Kyu Y; Ehrt, Sabine; Schnappinger, Dirk

    2013-11-19

    Antibacterial drug development suffers from a paucity of targets whose inhibition kills replicating and nonreplicating bacteria. The latter include phenotypically dormant cells, known as persisters, which are tolerant to many antibiotics and often contribute to failure in the treatment of chronic infections. This is nowhere more apparent than in tuberculosis caused by Mycobacterium tuberculosis, a pathogen that tolerates many antibiotics once it ceases to replicate. We developed a strategy to identify proteins that Mycobacterium tuberculosis requires to both grow and persist and whose inhibition has the potential to prevent drug tolerance and persister formation. This strategy is based on a tunable dual-control genetic switch that provides a regulatory range spanning three orders of magnitude, quickly depletes proteins in both replicating and nonreplicating mycobacteria, and exhibits increased robustness to phenotypic reversion. Using this switch, we demonstrated that depletion of the nicotinamide adenine dinucleotide synthetase (NadE) rapidly killed Mycobacterium tuberculosis under conditions of standard growth and nonreplicative persistence induced by oxygen and nutrient limitation as well as during the acute and chronic phases of infection in mice. These findings establish the dual-control switch as a robust tool with which to probe the essentiality of Mycobacterium tuberculosis proteins under different conditions, including those that induce antibiotic tolerance, and NadE as a target with the potential to shorten current tuberculosis chemotherapies.

  12. Molecular Mechanisms of Diabetic Retinopathy, General Preventive Strategies, and Novel Therapeutic Targets

    PubMed Central

    Safi, Sher Zaman; Kumar, Selva; Ismail, Ikram Shah Bin

    2014-01-01

    The growing number of people with diabetes worldwide suggests that diabetic retinopathy (DR) and diabetic macular edema (DME) will continue to be sight threatening factors. The pathogenesis of diabetic retinopathy is a widespread cause of visual impairment in the world and a range of hyperglycemia-linked pathways have been implicated in the initiation and progression of this condition. Despite understanding the polyol pathway flux, activation of protein kinase C (KPC) isoforms, increased hexosamine pathway flux, and increased advanced glycation end-product (AGE) formation, pathogenic mechanisms underlying diabetes induced vision loss are not fully understood. The purpose of this paper is to review molecular mechanisms that regulate cell survival and apoptosis of retinal cells and discuss new and exciting therapeutic targets with comparison to the old and inefficient preventive strategies. This review highlights the recent advancements in understanding hyperglycemia-induced biochemical and molecular alterations, systemic metabolic factors, and aberrant activation of signaling cascades that ultimately lead to activation of a number of transcription factors causing functional and structural damage to retinal cells. It also reviews the established interventions and emerging molecular targets to avert diabetic retinopathy and its associated risk factors. PMID:25105142

  13. Bone targeted therapy for preventing skeletal-related events in metastatic breast cancer.

    PubMed

    Irelli, Azzurra; Cocciolone, Valentina; Cannita, Katia; Zugaro, Luigi; Di Staso, Mario; Lanfiuti Baldi, Paola; Paradisi, Stefania; Sidoni, Tina; Ricevuto, Enrico; Ficorella, Corrado

    2016-06-01

    Cancer cells can alter physiological mechanisms within bone resulting in high bone turnover, and consequently in skeletal-related events (SREs), causing severe morbidity in affected patients. The goals of bone targeted therapy, as bisphosphonates and denosumab, are the reduction of incidence and the delay in occurrence of the SREs, to improve quality of life and pain control. The toxicity profile is similar between bisphosphonates and denosumab, even if pyrexia, bone pain, arthralgia, renal failure and hypercalcemia are more common with bisphosphonates, while hypocalcemia and toothache are more frequently reported with denosumab. Osteonecrosis of the jaw (ONJ) occurred infrequently without statistically significant difference. The present review aims to provide an assessment on bone targeted therapies for preventing the occurrence of SREs in bone metastatic breast cancer patients, critically analyzing the evidence available so far on their effectiveness, in light of the different mechanisms of action. Thus, we try to provide tools for the most fitting treatment of bone metastatic breast cancer patients. We also provide an overview on the usefulness of bone turnover markers in clinical practice and new molecules currently under study for the treatment of bone metastatic disease. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Target-Derived Neurotrophins Coordinate Transcription and Transport of Bclw to Prevent Axonal Degeneration

    PubMed Central

    Cosker, Katharina E.; Pazyra-Murphy, Maria F.; Fenstermacher, Sara J.

    2013-01-01

    Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit. PMID:23516285

  15. Target-derived neurotrophins coordinate transcription and transport of bclw to prevent axonal degeneration.

    PubMed

    Cosker, Katharina E; Pazyra-Murphy, Maria F; Fenstermacher, Sara J; Segal, Rosalind A

    2013-03-20

    Establishment of neuronal circuitry depends on both formation and refinement of neural connections. During this process, target-derived neurotrophins regulate both transcription and translation to enable selective axon survival or elimination. However, it is not known whether retrograde signaling pathways that control transcription are coordinated with neurotrophin-regulated actions that transpire in the axon. Here we report that target-derived neurotrophins coordinate transcription of the antiapoptotic gene bclw with transport of bclw mRNA to the axon, and thereby prevent axonal degeneration in rat and mouse sensory neurons. We show that neurotrophin stimulation of nerve terminals elicits new bclw transcripts that are immediately transported to the axons and translated into protein. Bclw interacts with Bax and suppresses the caspase6 apoptotic cascade that fosters axonal degeneration. The scope of bclw regulation at the levels of transcription, transport, and translation provides a mechanism whereby sustained neurotrophin stimulation can be integrated over time, so that axonal survival is restricted to neurons connected within a stable circuit.

  16. Mechanism of One-to-Many Molecular Recognition Accompanying Target-Dependent Structure Formation: For the Tumor Suppressor p53 Protein as an Example.

    PubMed

    Hayashi, Tomohiko; Oshima, Hiraku; Yasuda, Satoshi; Kinoshita, Masahiro

    2015-11-05

    The new type of molecular recognition, in which an intrinsically disordered region (IDR) of a protein binds to many different target proteins with target-dependent structure formation, is indispensable to the expression of life phenomena and also implicated in a number of diseases. According to the prevailing view, the physicochemical factors responsible for the binding are also target dependent. Here we consider an IDR of the tumor suppressor p53 protein, p53CTD, as an important example related to carcinogenesis and analyze its binding to four targets accompanying the formation of target-dependent structures (i.e., helix, sheet, and two different coils) using our statistical-mechanical method combined with molecular models for water. We find that all of the seemingly different binding processes are driven by a large gain of the translational, configurational entropy of water in the system. The gain originates from sufficiently high shape complementarity on the atomic level within the p53CTD-target interface. It is also required that the electrostatic complementarity be ensured as much as possible to compensate for the dehydration. Such complementarities are achieved in harmony with the portion of the target to which p53CTD binds, leading to a large diversity of structures of p53CTD formed upon binding: If they are not achievable, the binding does not occur. This finding is made possible only by calculating the changes in thermodynamic quantities upon binding and decomposing them into physically insightful components.

  17. Targeting cellular senescence prevents age-related bone loss in mice.

    PubMed

    Farr, Joshua N; Xu, Ming; Weivoda, Megan M; Monroe, David G; Fraser, Daniel G; Onken, Jennifer L; Negley, Brittany A; Sfeir, Jad G; Ogrodnik, Mikolaj B; Hachfeld, Christine M; LeBrasseur, Nathan K; Drake, Matthew T; Pignolo, Robert J; Pirtskhalava, Tamar; Tchkonia, Tamara; Oursler, Merry Jo; Kirkland, James L; Khosla, Sundeep

    2017-09-01

    Aging is associated with increased cellular senescence, which is hypothesized to drive the eventual development of multiple comorbidities. Here we investigate a role for senescent cells in age-related bone loss through multiple approaches. In particular, we used either genetic (i.e., the INK-ATTAC 'suicide' transgene encoding an inducible caspase 8 expressed specifically in senescent cells) or pharmacological (i.e., 'senolytic' compounds) means to eliminate senescent cells. We also inhibited the production of the proinflammatory secretome of senescent cells using a JAK inhibitor (JAKi). In aged (20- to 22-month-old) mice with established bone loss, activation of the INK-ATTAC caspase 8 in senescent cells or treatment with senolytics or the JAKi for 2-4 months resulted in higher bone mass and strength and better bone microarchitecture than in vehicle-treated mice. The beneficial effects of targeting senescent cells were due to lower bone resorption with either maintained (trabecular) or higher (cortical) bone formation as compared to vehicle-treated mice. In vitro studies demonstrated that senescent-cell conditioned medium impaired osteoblast mineralization and enhanced osteoclast-progenitor survival, leading to increased osteoclastogenesis. Collectively, these data establish a causal role for senescent cells in bone loss with aging, and demonstrate that targeting these cells has both anti-resorptive and anabolic effects on bone. Given that eliminating senescent cells and/or inhibiting their proinflammatory secretome also improves cardiovascular function, enhances insulin sensitivity, and reduces frailty, targeting this fundamental mechanism to prevent age-related bone loss suggests a novel treatment strategy not only for osteoporosis, but also for multiple age-related comorbidities.

  18. A systematic review of suicide prevention interventions targeting indigenous peoples in Australia, United States, Canada and New Zealand

    PubMed Central

    2013-01-01

    Background Indigenous peoples of Australia, Canada, United States and New Zealand experience disproportionately high rates of suicide. As such, the methodological quality of evaluations of suicide prevention interventions targeting these Indigenous populations should be rigorously examined, in order to determine the extent to which they are effective for reducing rates of Indigenous suicide and suicidal behaviours. This systematic review aims to: 1) identify published evaluations of suicide prevention interventions targeting Indigenous peoples in Australia, Canada, United States and New Zealand; 2) critique their methodological quality; and 3) describe their main characteristics. Methods A systematic search of 17 electronic databases and 13 websites for the period 1981–2012 (inclusive) was undertaken. The reference lists of reviews of suicide prevention interventions were hand-searched for additional relevant studies not identified by the electronic and web search. The methodological quality of evaluations of suicide prevention interventions was assessed using a standardised assessment tool. Results Nine evaluations of suicide prevention interventions were identified: five targeting Native Americans; three targeting Aboriginal Australians; and one First Nation Canadians. The main intervention strategies employed included: Community Prevention, Gatekeeper Training, and Education. Only three of the nine evaluations measured changes in rates of suicide or suicidal behaviour, all of which reported significant improvements. The methodological quality of evaluations was variable. Particular problems included weak study designs, reliance on self-report measures, highly variable consent and follow-up rates, and the absence of economic or cost analyses. Conclusions There is an urgent need for an increase in the number of evaluations of preventive interventions targeting reductions in Indigenous suicide using methodologically rigorous study designs across geographically

  19. Estimating the cost-effectiveness of lifestyle intervention programmes to prevent diabetes based on an example from Germany: Markov modelling.

    PubMed

    Neumann, Anne; Schwarz, Peter; Lindholm, Lars

    2011-11-18

    Type 2 diabetes mellitus (T2D) poses a large worldwide burden for health care systems. One possible tool to decrease this burden is primary prevention. As it is unethical to wait until perfect data are available to conclude whether T2D primary prevention intervention programmes are cost-effective, we need a model that simulates the effect of prevention initiatives. Thus, the aim of this study is to investigate the long-term cost-effectiveness of lifestyle intervention programmes for the prevention of T2D using a Markov model. As decision makers often face difficulties in applying health economic results, we visualise our results with health economic tools. We use four-state Markov modelling with a probabilistic cohort analysis to calculate the cost per quality-adjusted life year (QALY) gained. A one-year cycle length and a lifetime time horizon are applied. Best available evidence supplies the model with data on transition probabilities between glycaemic states, mortality risks, utility weights, and disease costs. The costs are calculated from a societal perspective. A 3% discount rate is used for costs and QALYs. Cost-effectiveness acceptability curves are presented to assist decision makers. The model indicates that diabetes prevention interventions have the potential to be cost-effective, but the outcome reveals a high level of uncertainty. Incremental cost-effectiveness ratios (ICERs) were negative for the intervention, ie, the intervention leads to a cost reduction for men and women aged 30 or 50 years at initiation of the intervention. For men and women aged 70 at initiation of the intervention, the ICER was EUR27,546/QALY gained and EUR19,433/QALY gained, respectively. In all cases, the QALYs gained were low. Cost-effectiveness acceptability curves show that the higher the willingness-to-pay threshold value, the higher the probability that the intervention is cost-effective. Nonetheless, all curves are flat. The threshold value of EUR50,000/QALY gained has a

  20. 'Atypical' CAR T cells: NKG2D and Erb-B as examples of natural receptor/ligands to target recalcitrant solid tumors.

    PubMed

    Gilham, David E; Maher, John

    2017-08-01

    Chimeric antigen receptor (CAR) T-cell therapy has recently been recommended for approval for certain B-cell malignancies bringing the approach closer to mainstream cancer treatment. This rapid rise to prominence has been driven by impressive clinical results and the means to successfully commercialize the approach now being actively pursued. The current success of CAR T cells in B-cell malignancies relies upon the absolute lineage specificity of the CD19 antigen. CARs can also be targeted using non-antibody approaches, including the use of receptors and ligands to provide target specificity that have different specificities and binding kinetics. The specific examples of NKG2D and Erb-B are used that provide different characteristics and target profiles for CAR T-cell therapy of cancer.

  1. Targeted delivery of geranylgeranylacetone to mitochondria by triphenylphosphonium modified nanoparticles: a promising strategy to prevent aminoglycoside-induced hearing loss.

    PubMed

    Wang, Zhenjie; Kuang, Xiao; Shi, Jia; Guo, Weiling; Liu, Hongzhuo

    2017-08-22

    Prevention of hair cell death is an important target for the prevention of hearing loss. Here, we report the engineering of biodegradable poly(lactic-co-glycolic acid) nanoparticles (PLGA NPs) decorated with triphenylphosphonium (TPP) cations as a robust mitochondrial delivery platform, with the aim of preserving mitochondrial integrity and shutting off the initiation of cell death. Geranylgeranylacetone (GGA), a 70 kDa heat shock protein (HSP70) inducer, was used as a therapeutic molecule to attenuate gentamicin (Gen) induced hearing loss. The diameter of the mitochondria-targeting NPs is 145 nm and the encapsulation efficiency is 80.6%. Lysosomal escape and mitochondrial targeting studies indicated the promising therapeutic potential of TPP modified NPs. Finally, the zebrafish lateral line model was applied to verify the efficacy of the GGA loaded targeting NPs for preventing gentamicin-induced death hair cell. The results showed that the prepared targeted NPs provided significant protection: the survival of hair cells increased from 36% to 69% under acute exposure and from 20% to 62% under chronic exposure. In addition, targeted NPs exhibited significantly improved efficiency in alleviating gentamicin-induced hair cell damage compared with free drugs and untargeted NPs, supporting the hypothesis of mitochondrial targeting delivery in the treatment of aminoglycoside-induced hearing loss. These TPP modified NPs demonstrated promise for the treatment of mitochondrial dysfunction.

  2. Guidance for a personal target value of F(E)NO in allergic asthma: case report and theoretical example.

    PubMed

    Högman, Marieann; Meriläinen, Pekka

    2013-03-01

    In clinically stable asthma the exhaled NO values (F(E)NO) are generally higher than in control subjects. Therefore, reference values are of limited importance in clinical practice. This is demonstrated in this case report, but it is also shown that NO parameters from non-linear modelling do have a clinical value. A subject with asthma was treated with inhaled corticosteroids for 1 week. The non-linear NO model was used to measure the response to treatment. The NO parameters from subjects with atopic rhinitis and asthma were fed into a computer program to generate theoretical F(E)NO₀.₀₅ values, i.e. target values. There was a dramatic decrease in F(E)NO₀.₀₅ due to treatment, from 82 to 34 ppb, but it remained higher than in healthy controls. This is due to the elevated diffusion rate of NO, unchanged by treatment. When the NO parameters are known, a personal best value of F(E)NO₀.₀₅ (fractional concentration of exhaled NO in the gas phase, 0.05 L/s) can be calculated, which can be the target value when only F(E)NO₀.₀₅ can be monitored. In conclusion, reference values for NO parameters are shown to be clinically useful. It is essential that every patient receives his/her target value of F(E)NO₀.₀₅, when only a single NO measurement is available. In our opinion, this is the reason why there are few successful studies of trying to target the NO value with inhaled corticosteroids.

  3. Bridging the gap between research and practice: review of a targeted hospital inpatient fall prevention programme.

    PubMed

    Barker, A; Kamar, J; Morton, A; Berlowitz, D

    2009-12-01

    Falls among older inpatients are frequent and have negative consequences. In this study, the effectiveness of a fall prevention programme in reducing falls and fall injuries in an acute hospital was studied. Retrospective audit. The Northern Hospital, an acute, metropolitan, hospital in Australia. A multi-factorial fall prevention programme that included establishment of a multidisciplinary committee, risk assessment of all patients on "high-risk" wards and targeted interventions for patients identified as high risk. Fall and fall injury rates per 1000 occupied bed-days were analysed using generalised additive models (GAM) and, because of the presence of autocorrelation, generalised additive mixed models (GAMM), respectively. During the 9-year observation of 271 095 patients, there were 2910 falls and 843 fall injuries. The GAM predicted rate of falls was stable in the 3 years after the programme was implemented, increased in 2006, then decreased between October 2006 and December 2007 from 4.13 (95% CI 3.65 to 4.67) to 2.83 (95% CI 2.24 to 3.59; p = 0.005). The GAMM predicted rate of fall injuries reduced from 1.66 (95% CI 1.24 to 2.21) to 0.61 (95% CI 0.43 to 0.88) after programme implementation (p<0.001). The falls rate varied throughout the observation period, and no significant change in the rate from preprogramme to postprogramme implementation was observed. The finding of no reduction in falls during the observation period may be explained by improved reporting throughout the observation period. The reduction in fall injuries was substantial and sustained. Identification of a local problem, use of a fall risk assessment to guide the delivery of simple interventions, integration of processes into daily clinical practice and creating systems that demand accountability of staff are factors that appear to have contributed to the programme's success.

  4. Targeting the Overproduction of Peroxynitrite for the Prevention and Reversal of Paclitaxel-Induced Neuropathic Pain

    PubMed Central

    Doyle, Timothy; Chen, Zhoumou; Muscoli, Carolina; Bryant, Leesa; Esposito, Emanuela; Cuzzocrea, Salvatore; Dagostino, Concetta; Ryerse, Jan; Rausaria, Smita; Kamadulski, Andrew; Neumann, William L.

    2012-01-01

    Chemotherapy-induced peripheral neuropathy (CIPN) accompanied by chronic neuropathic pain is a major dose-limiting side effect of a large number of antitumoral agents including paclitaxel (Taxol). Thus, CIPN is one of most common causes of dose reduction and discontinuation of what is otherwise a life-saving therapy. Neuropathological changes in spinal cord are linked to CIPN, but the causative mediators and mechanisms remain poorly understood. We report that formation of peroxynitrite (PN) in response to activation of nitric oxide synthases and NADPH oxidase in spinal cord contributes to neuropathological changes through two mechanisms. The first involves modulation of neuroexcitatory and proinflammatory (TNF-α and IL-1β) and anti-inflammatory (IL-10 and IL-4) cytokines in favor of the former. The second involves post-translational nitration and modification of glia-derived proteins known to be involved in glutamatergic neurotransmission (astrocyte-restricted glutamate transporters and glutamine synthetase). Targeting PN with PN decomposition catalysts (PNDCs) not only blocked the development of paclitaxel-induced neuropathic pain without interfering with antitumor effects, but also reversed it once established. Herein, we describe our mechanistic study on the role(s) of PN and the prevention of neuropathic pain in rats using known PNDCs (FeTMPyP5+ and MnTE-2-PyP5+). We also demonstrate the prevention of CIPN with our two new orally active PNDCs, SRI6 and SRI110. The improved chemical design of SRI6 and SRI110 also affords selectivity for PN over other reactive oxygen species (such as superoxide). Our findings identify PN as a critical determinant of CIPN, while providing the rationale toward development of superoxide-sparing and “PN-targeted” therapeutics. PMID:22553021

  5. Targeting Sleep, Food, and Activity in Infants for Obesity Prevention: An RCT.

    PubMed

    Taylor, Barry J; Gray, Andrew R; Galland, Barbara C; Heath, Anne-Louise M; Lawrence, Julie; Sayers, Rachel M; Cameron, Sonya; Hanna, Maha; Dale, Kelly; Coppell, Kirsten J; Taylor, Rachael W

    2017-03-01

    The few existing early-life obesity prevention initiatives have concentrated on nutrition and physical activity, with little examination of sleep. This community-based, randomized controlled trial allocated 802 pregnant women (≥16 years, <34 weeks' gestation) to: control, FAB (food, activity, and breastfeeding), sleep, or combination (both interventions) groups. All groups received standard well-child care. FAB participants received additional support (8 contacts) promoting breastfeeding, healthy eating, and physical activity (antenatal-18 months). Sleep participants received 2 sessions (antenatal, 3 weeks) targeting prevention of sleep problems, as well as a sleep treatment program if requested (6-24 months). Combination participants received both interventions (9 contacts). BMI was measured at 24 months by researchers blinded to group allocation, and secondary outcomes (diet, physical activity, sleep) were assessed by using a questionnaire or accelerometry at multiple time points. At 2 years, 686 women remained in the study (86%). No significant intervention effect was observed for BMI at 24 months (P = .086), but there was an overall group effect for the prevalence of obesity (P = .027). Exploratory analyses found a protective effect for obesity among those receiving the "sleep intervention" (sleep and combination compared with FAB and control: odds ratio, 0.54 [95% confidence interval, 0.35-0.82]). No effect was observed for the "FAB intervention" (FAB and combination compared with sleep and control: odds ratio, 1.20 [95% confidence interval, 0.80-1.81]). A well-developed food and activity intervention did not seem to affect children's weight status. However, further research on more intensive or longer running sleep interventions is warranted. Copyright © 2017 by the American Academy of Pediatrics.

  6. Preventing tuberculosis transmission at a maternity hospital by targeted screening radiography of migrants.

    PubMed

    Schechner, V; Lessing, J B; Grisaru-Soen, G; Braun, T; Abu-Hanna, J; Carmeli, Y; Aviram, G

    2015-07-01

    Israel has been the destination of large numbers of illegal migrants from East African countries in recent years. Despite efforts to detect and treat active tuberculosis (TB) at the border, 75% of all active TB cases diagnosed in our hospital were illegal migrants. In 2012, there was a large-scale TB exposure in our maternity ward, neonatal, and paediatric intensive care units following the admission of an infectious but apparently asymptomatic migrant who was in labour. A hospital-wide screening programme was subsequently implemented to prevent exposure of patients and staff to TB. To report the results of the first year of this intervention in the maternity hospital. All illegal migrants from countries where TB is highly prevalent were screened by chest radiography (CR) upon admission to the maternity hospital. The results were immediately categorized by a radiologist as either 'suggestive of active pulmonary TB' or 'non-suggestive'. Patients with CR suggestive of TB were placed in airborne isolation and underwent further evaluation. Four hundred and thirty-one apparently asymptomatic migrant women underwent CR screening. Most (363, 84%) presented in labour. Eleven women (2.6%) had a CR suggestive of active pulmonary TB which was confirmed in three (0.7% of screened women). No TB cases were missed by the CRs. Neither patients nor hospital staff were exposed to TB. Targeted CR screening for TB among high-risk women upon their admission to a maternity hospital had a high yield and was an effective strategy to prevent in-hospital transmission of TB. Copyright © 2015 The Healthcare Infection Society. Published by Elsevier Ltd. All rights reserved.

  7. Grafting of a new target prevents synapse loss in abducens internuclear neurons induced by axotomy.

    PubMed

    Benítez-Temiño, B; de la Cruz, R R; Pastor, A M

    2003-01-01

    The loss of afferent synaptic boutons is a prominent alteration induced by axotomy on adult central neurons. In this work we attempted to prove whether synapse loss could be reverted by reconnection with a new target. We severed the medial longitudinal fascicle of adult cats and then transplanted embryonic cerebellar primordia at the lesion site immediately after lesion. As previously shown, the transected axons from abducens internuclear neurons penetrate and reinnervate the graft [J Comp Neurol 444 (2002) 324]. By immunocytochemistry and electron microscopy we studied the synaptology of abducens internuclear neurons under three conditions: control, axotomy and transplant (2 months of survival time). Semithin sections of the abducens nucleus were immunostained against calretinin, to identify abducens internuclear neurons, and either synaptophysin (SF), to label synaptic terminals, or glial fibrillary acidic protein (GFAP) to detect the astrocytic reaction. Optical and linear density of SF and GFAP immunostaining were measured. Data revealed a significant decrease in the density of SF-labeled terminals with a parallel increase in GFAP-immunoreactive elements after axotomy. On the contrary, in the transplant group, the density of SF-labeled terminals was found similar to control, and the astrocytic reaction induced by lesion was significantly reduced. At the ultrastructural level, synaptic coverage and linear density of boutons were measured around the somata of abducens internuclear neurons. Whereas a significant reduction in both parameters was found after axotomy, cells of the transplant group received a normal density of synaptic endings. The ratio between F- and S-type boutons was found similar in the three groups. Therefore, these findings indicate that the grafting of a new target can prevent the loss of afferent synaptic boutons produced by the axotomy.

  8. Keap1-Nrf2 Signaling: A Target for Cancer Prevention by Sulforaphane

    PubMed Central

    Kensler, Thomas W; Egner, Patricia A; Agyeman, Abena S.; Visvanathan, Kala; Groopman, John D; Chen, Jian-Guo; Chen, Tao-Yang; Fahey, Jed W; Talalay, Paul

    2013-01-01

    Sulforaphane is a promising agent under preclinical evaluation in many models of disease prevention. This bioactive phytochemical affects many molecular targets in cellular and animal models; however, amongst the most sensitive is Keap1, a key sensor for the adaptive stress response system regulated through the transcription factor Nrf2. Keap1 is a sulfhydryl-rich protein that represses Nrf2 signaling by facilitating the poly ubiquitination of Nrf2 thereby enabling its subsequent proteasomal degradation. Interaction of sulforaphane with Keap1 disrupts this function and allows for nuclear accumulation of Nrf2 and activation of its transcriptional program. Enhanced transcription of Nrf2 target genes provokes a strong cytoprotective response that enhances resistance to carcinogenesis and other diseases mediated by exposures to electrophiles and oxidants. Clinical evaluation of sulforaphane has been largely conducted by utilizing preparations of broccoli or broccoli sprouts rich in either sulforaphane or its precursor form in plants, a stable β-thioglucose conjugate termed glucoraphanin. We have conducted a series of clinical trials in Qidong, China, a region where exposures to food- and air-borne carcinogens has been considerable, to evaluate the suitability of broccoli sprout beverages, rich in either glucoraphanin (GRR) or sulforaphane SFR or both for their bioavailability, tolerability and pharmacodynamic action in population-based interventions. Results from these clinical trials indicate that interventions with well characterized preparations of broccoli sprouts may enhance the detoxication of aflatoxins and air-borne toxins, which may in turn attenuate their associated health risks, including cancer, in exposed individuals. PMID:22752583

  9. PREVENTION OF COLITIS-ASSOCIATED CANCER: NATURAL COMPOUNDS THAT TARGET THE IL-6 SOLUBLE RECEPTOR

    PubMed Central

    Moriasi, Cate; Subramaniam, Dharmalingam; Awasthi, Shanjana; Anant, Shrikant; Ramalingam, Satish

    2014-01-01

    The risk of developing colorectal cancer increases in patients with inflammatory bowel disease (IBD) and a growing body of evidence shows the critical role of interleukin (IL-6) in this process. IL-6 is both a pro- and anti-inflammatory cytokine whose effects are mediated through activation of STAT3. Recent studies have also demonstrated that IL-6 trans-signaling through its soluble receptor occurs in IBD and cancer. IL-6 trans-signaling therefore is emerging as an attractive approach to diminish the inflammatory signals in conditions of chronic inflammation. The purpose of cancer chemoprevention is to either delay the onset or progression from precancerous lesions. Natural compounds because of their low toxicity render themselves excellent candidates that can be administered over the lifetime of an individual. With the focus of managing IBD over a long time and preventing onset of colitis-associated cancer, we believe that there should be increased research focus on identifying chemopreventive compounds that can render themselves to long term use possibly for the lifetime of predisposed individuals. Here, we review the role of IL-6 signaling in IBD and colitis-associated cancer and underscore the importance of searching for natural compounds that would target the IL-6 trans-signaling pathway as a way to diminish chronic inflammatory conditions in the gastrointestinal tract and possibly hamper the progression to colon cancer. We propose that effective screening and identification of natural chemopreventive compounds that target IL-6 trans-signaling has important implications for the development of optimal strategies against cancer development triggered by inflammation. PMID:22583410

  10. Participatory workshops are not enough to prevent policy implementation failures: an example of a policy development process concerning the drug interferon-beta for multiple sclerosis.

    PubMed

    Moret-Hartman, Margriet; Reuzel, Rob; Grin, John; van der Wilt, Gert Jan

    2008-06-01

    A possible explanation for policy implementation failure is that the views of the policy's target groups are insufficiently taken into account during policy development. It has been argued that involving these groups in an interactive process of policy development could improve this. We analysed a project in which several target populations participated in workshops aimed to optimise the utilisation of an expensive novel drug (interferon beta) for patients with Multiple Sclerosis. All participants seemed to agree on the appropriateness of establishing a central registry of Multiple Sclerosis patients and developing guidelines. Nevertheless, these policy measures were not implemented. Possible explanations include (1) the subject no longer had high priority when the costs appeared lower than expected, (2) the organisers had paid insufficient attention to the perceived problems of parties involved, and (3) changes within the socio-political context. The workshops in which representatives of the policy's target populations participated did not provide enough interactivity to prevent policy implementation failure.

  11. Brief Report: Clinical Trials Aiming to Prevent Rheumatoid Arthritis Cannot Detect Prevention Without Adequate Risk Stratification: A Trial of Methotrexate Versus Placebo in Undifferentiated Arthritis as an Example.

    PubMed

    Burgers, Leonie E; Allaart, Cornelia F; Huizinga, Tom W J; van der Helm-van Mil, Annette H M

    2017-05-01

    Prevention of rheumatoid arthritis (RA) was the aim of several trials in undifferentiated arthritis (UA), with overall negative results. As preparatory work has revealed that only ∼30% of UA patients progress to having RA, we hypothesized that inclusion of patients without imminent RA could lead to false-negative results. We undertook this study to evaluate this hypothesis by reinvestigating the Probable Rheumatoid Arthritis: Methotrexate versus Placebo Treatment (PROMPT) trial (a 1-year course of methotrexate [MTX] versus placebo in UA) after excluding patients without a high risk of developing RA. A validated prediction model was used to determine the risk of RA in all patients included in the PROMPT trial. Patients with a prediction score of ≥8 (positive predictive value of ≥84% for developing RA) were considered to have a high risk of developing RA. The effect of a 1-year course of MTX during 5 years of follow-up was reinvestigated in these patients. Twenty-two of the 110 patients in the PROMPT trial had a high risk of RA at baseline. In the MTX arm, 6 of 11 patients (55%) developed RA, compared to 11 of 11 patients (100%) in the placebo arm (P = 0.011). Time to RA development was longer in the MTX arm than in the placebo arm (median 22.5 months versus 3 months; P < 0.001). Drug-free remission was achieved by 4 of 11 patients (36%) in the MTX arm compared to 0 of 11 patients (0%) in the placebo arm (P = 0.031). These beneficial effects of MTX were observed both in anti-citrullinated protein antibody (ACPA)-positive and in ACPA-negative UA patients with a high risk of RA, but not in UA patients without a high risk of RA. In retrospect, 43 of 110 patients fulfilled the American College of Rheumatology/European League Against Rheumatism 2010 classification criteria for RA at baseline. In addition, beneficial effects were observed only in patients with a high prediction score. A 1-year course of MTX delayed and prevented RA development in high

  12. Qualitative investigation of targets for and barriers to interventions to prevent psychosis relapse

    PubMed Central

    2014-01-01

    Background Early signs based relapse prevention interventions for psychosis show promise. In order to examine how they might be improved we sought to better understand the early relapse process, service users’ abilities to identify early signs, and any potential facilitators and barriers to early signs interventions. Methods Data from in-depth interviews with a convenience sample of service users with psychosis varying in gender, age, duration of mental health problems, and time since last relapse were analysed using a thematic approach. Interview transcripts were coded inductively and relationships between emerging themes were examined by the research team to provide a thorough synthesis of the data. Results Three central themes emerged from the analysis: 1) recognising risk factors (how risk factors were identified and linked to relapse, and reactions to such risk factors); 2) identifying early signs (issues related to both recognising and recalling signs of relapse); 3) reacting to deterioration (participants’ thoughts and feelings in response to early signs, including help seeking and its challenges). Conclusions There was considerable variation in the attention participants had paid to pre-relapse signs, the ease with which they were able to recall them, and their reactions to them. For many, there were substantial barriers to help seeking from services. A family or friend confidant was an important means of assistance, although the supportive presence of significant others was not always available. Based on these results, a number of recommendations about facilitating service users’ recognition of early signs and targeting potential accelerants of relapse are made. PMID:25030092

  13. Staphylococcus aureus Clumping Factor A Remains a Viable Vaccine Target for Prevention of S. aureus Infection.

    PubMed

    Anderson, Annaliesa S; Scully, Ingrid L; Buurman, Ed T; Eiden, Joseph; Jansen, Kathrin U

    2016-03-08

    In a recent article, X. Li et al. [mBio 7(1):e02232-15, 2016, http://dx.doi.org/10.1128/mBio.02232-15] investigate the utility of a vaccine composed of the Staphylococcus aureus protein clumping factor A (ClfA) in protecting mice from S. aureus infection. ClfA, one of the first proteins to be identified as a potential vaccine antigen for S. aureus prophylaxis, is currently a component of several investigational vaccines. The authors conclude that ClfA may not be effective for S. aureus prophylaxis. In contrast, previously published papers reporting positive data suggested that ClfA was potentially an important vaccine target to prevent invasive S. aureus disease. This commentary addresses the observed differences between the findings of Li et al. and those from other publications, highlighting the importance for preclinical vaccine antigen assessments to reflect the biological role of said antigen in virulence and, consequently, the importance of choosing appropriate preclinical disease models to test such antigens.

  14. Chronic mechanistic target of rapamycin inhibition: preventing cancer to delay aging, or vice versa?.

    PubMed

    Sharp, Zelton Dave; Curiel, Tyler Jay; Livi, Carolina Becker

    2013-01-01

    Cancer and aging appear to be inexorably linked, yet approaches to ameliorate them in concert are lacking. Although not (easily) feasible in humans, years of preclinical research show that diet and growth factor restriction each successfully address cancer and aging together. Chronic treatment of genetically heterogeneous mice with an enteric formulation of rapamycin (eRapa) extended maximum lifespan of both genders when started in mid or late life. In part, cancer amelioration in treated mice suggested that long-term eRapa, like diet restriction, could be a pharmacological approach feasible for use in the clinic. We review the current understanding of the role of the mechanistic target of rapamycin (mTOR) in cancer and aging. We also discuss the tumor immune surveillance system, and the need for a better understanding of its responses to mTOR inhibitors. We also address the issue of the misperception that rapamycin is a potent immunosuppressant. Finally, we review the current state of mTOR inhibitors in the cancer clinic. Because of the burgeoning elderly population most at risk for cancer, there is a great need for our eRapa findings to be a proof of concept for the development of new and more comprehensive approaches to cancer prevention that are safe and also mitigate other deleterious effects of aging. Copyright © 2013 S. Karger AG, Basel.

  15. A Preliminary Study of a Spanish Graphic Novella Targeting Hearing Loss Prevention.

    PubMed

    Guiberson, Mark; Wakefield, Emily

    2017-09-18

    This preliminary study developed a digital graphic novella targeting hearing protection beliefs of Spanish-speaking agricultural workers. Researchers used pretest-posttest interview surveys to establish if the novella had an immediate influence on the participants' beliefs about noise-induced hearing loss and usage of hearing protection devices. Researchers developed a digital graphic novella directed to increase knowledge about noise-induced hearing loss and increase the proper use of hearing protection devices. The novella was tailored to meet the specific linguistic and literacy needs of Spanish-speaking agricultural workers. Thirty-one Spanish-speaking farmworkers of Mexican nationality participated. This study included an interview survey with specific questions on noise-induced hearing loss, myths, and hearing protection device usage. A pretest-posttest design was applied to measure the graphic novella's immediate influence on workers. The posttest scores on Hearing Protection Beliefs statements were significantly better than pretest scores, with a large effect size observed. Digital media may be an effective way to overcome language and literacy barriers with Spanish-speaking workers when providing health education and prevention efforts.

  16. Dietary phytochemicals for possible preventive and therapeutic option of uterine fibroids: Signaling pathways as target.

    PubMed

    Islam, Md Soriful; Segars, James H; Castellucci, Mario; Ciarmela, Pasquapina

    2017-02-01

    A growing interest has emerged on dietary phytochemicals to control diverse pathological conditions. Unfortunately, dietary phytochemical research in uterine fibroids is still under construction. Uterine fibroids/leiomyomas are benign tumors developing from the myometrium of the uterus in premenopausal women. They may occur in more than 70% of women, and approximately 25% of women show clinically significant symptoms. These include heavy and prolonged menstrual bleeding, pelvic pressure (urinary frequency, incontinence, and difficulty with urination), pelvic pain, pelvic mass, infertility, and reproductive dysfunction. Due to lack of medical treatments surgery has been definitive choice for fibroid management. Moreover, surgery negatively affects women's quality of life, and its associated cost appears to be expensive. The molecular mechanism of fibroids development and growth is not fully elucidated. However, accumulated evidence shows that several signaling pathways, including Smad 2/3, PI3K/AKT/mTOR, ERK 1/2 and β-catenin are involved in the leiomyoma pathogenesis, indicating that they could serve as targets for prevention and/or treatment of this tumor. Therefore, in this review, we discuss the involvement of signaling pathways in leiomyoma development and growth, and introduce some potential dietary phytochemicals that could modulate those signaling pathways.

  17. Specific Targeting of Akt Kinase Isoforms: Taking the Precise Path for Prevention and Treatment of Cancer.

    PubMed

    Roy, Nand Kishor; Bordoloi, Devivasha; Monisha, Javadi; Padmavathi, Ganesan; Kotoky, Jibon; Golla, Ramesh; Kunnumakkara, Ajaikumar B

    2017-01-01

    Akt kinase is a serine threonine kinase that exists in three isoforms, located in different chromosomes and has distinct sites of expression which orchestrates diverse cellular processes required for normal functioning of the cell. Though, these Akt isoforms have some overlapping actions, but they also have specific roles and interestingly, sometimes they even perform contrasting functions. There are various alterations such as amplification, overexpression, mutation, etc. associated with these isoforms which have great implications in the development of cancer. Moreover, these alterations also induce chemo and radio resistance in cancer cells that impede the existing treatment modules. Furthermore, many reports have shown their potential as efficient prognostic biomarkers. Although, many studies have discussed the implications of Akt kinase proteins in different cancers but in-depth analysis of isoform- specific involvement is least examined and hence demands more attention. This review discusses the divergent roles of Akt isoforms comprehensively in different cancers and finding their immense prospects as potential targets for cancer prevention and treatment. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  18. Factor XII: a novel target for safe prevention of thrombosis and inflammation.

    PubMed

    Kenne, E; Nickel, K F; Long, A T; Fuchs, T A; Stavrou, E X; Stahl, F R; Renné, T

    2015-12-01

    Plasma protein factor XII (FXII) activates the procoagulant and proinflammatory contact system that drives both the kallikrein-kinin system and the intrinsic pathway of coagulation. When zymogen FXII comes into contact with negatively charged surfaces, it auto-activates to the serine proteaseactivated FXII (FXIIa). Recently, various in vivo activators of FXII have been identified including heparin, misfolded protein aggregates, polyphosphate and nucleic acids. Murine models have established a central role of FXII in arterial and venous thrombosis. Despite its central function in thrombosis, deficiency in FXII does not impair haemostasis in animals and humans. In a preclinical cardiopulmonary bypass system in large animals, the FXIIa-blocking antibody 3F7 prevented thrombosis; however, in contrast to traditional anticoagulants, bleeding was not increased. In addition to its function in thrombosis, FXIIa initiates formation of the inflammatory mediator bradykinin. This mediator increases vascular leak, causes vasodilation, and induces chemotaxis with implications for septic, anaphylactic and allergic disease states. Therefore, targeting FXIIa appears to be a promising strategy for thromboprotection without associated bleeding risks but with anti-inflammatory properties.

  19. Staphylococcus aureus Clumping Factor A Remains a Viable Vaccine Target for Prevention of S. aureus Infection

    PubMed Central

    Scully, Ingrid L.; Buurman, Ed T.; Eiden, Joseph; Jansen, Kathrin U.

    2016-01-01

    ABSTRACT In a recent article, X. Li et al. [mBio 7(1):e02232-15, 2016, http://dx.doi.org/10.1128/mBio.02232-15] investigate the utility of a vaccine composed of the Staphylococcus aureus protein clumping factor A (ClfA) in protecting mice from S. aureus infection. ClfA, one of the first proteins to be identified as a potential vaccine antigen for S. aureus prophylaxis, is currently a component of several investigational vaccines. The authors conclude that ClfA may not be effective for S. aureus prophylaxis. In contrast, previously published papers reporting positive data suggested that ClfA was potentially an important vaccine target to prevent invasive S. aureus disease. This commentary addresses the observed differences between the findings of Li et al. and those from other publications, highlighting the importance for preclinical vaccine antigen assessments to reflect the biological role of said antigen in virulence and, consequently, the importance of choosing appropriate preclinical disease models to test such antigens. PMID:26956591

  20. The prevention of preterm labour -- corticotropin releasing hormone type 1 receptors as a target for drug design and development.

    PubMed

    Keller, P A; Kirkwood, K; Morgan, J; Westcott, S; McCluskey, A

    2003-06-01

    The role of the corticotropin releasing hormone in the onset of labour and the subsequent medicinal chemistry implications of CRH antagonists for the prevention of premature birth, and identification of the CRH type 1 receptor as the target for this drug design, are reviewed here.

  1. Prevention

    MedlinePlus

    ... Error processing SSI file About Heart Disease & Stroke Prevention Heart disease and stroke are an epidemic in ... secondhand smoke. Barriers to Effective Heart Disease & Stroke Prevention Many people with key risk factors for heart ...

  2. Confounding by indication in non-experimental evaluation of vaccine effectiveness: the example of prevention of influenza complications

    PubMed Central

    Hak, E; Verheij, T.; Grobbee, D; Nichol, K; Hoes, A

    2002-01-01

    Randomised allocation of vaccine or placebo is the preferred method to assess the effects of the vaccine on clinical outcomes relevant to the individual patient. In the absence of phase 3 trials using clinical end points, notably post-influenza complications, alternative non-experimental designs to evaluate vaccine effects or safety are often used. The application of these designs may, however, lead to invalid estimates of vaccine effectiveness or safety. As patients with poor prognosis are more likely to be immunised, selection for vaccination is confounded by patient factors that are also related to clinical end points. This paper describes several design and analytical methods aimed at limiting or preventing this confounding by indication in non-experimental studies. In short, comparison of study groups with similar prognosis, restriction of the study population, and statistical adjustment for dissimilarities in prognosis are important tools and should be considered. Only if the investigator is able to show that confounding by indication is sufficiently controlled for, results of a non-experimental study may be of use to direct an evidence based vaccine policy. PMID:12461118

  3. Effectiveness of a selective alcohol prevention program targeting personality risk factors: Results of interaction analyses.

    PubMed

    Lammers, Jeroen; Goossens, Ferry; Conrod, Patricia; Engels, Rutger; Wiers, Reinout W; Kleinjan, Marloes

    2017-08-01

    To explore whether specific groups of adolescents (i.e., scoring high on personality risk traits, having a lower education level, or being male) benefit more from the Preventure intervention with regard to curbing their drinking behaviour. A clustered randomized controlled trial, with participants randomly assigned to a 2-session coping skills intervention or a control no-intervention condition. Fifteen secondary schools throughout The Netherlands; 7 schools in the intervention and 8 schools in the control condition. 699 adolescents aged 13-15; 343 allocated to the intervention and 356 to the control condition; with drinking experience and elevated scores in either negative thinking, anxiety sensitivity, impulsivity or sensation seeking. Differential effectiveness of the Preventure program was examined for the personality traits group, education level and gender on past-month binge drinking (main outcome), binge frequency, alcohol use, alcohol frequency and problem drinking, at 12months post-intervention. Preventure is a selective school-based alcohol prevention programme targeting personality risk factors. The comparator was a no-intervention control. Intervention effects were moderated by the personality traits group and by education level. More specifically, significant intervention effects were found on reducing alcohol use within the anxiety sensitivity group (OR=2.14, CI=1.40, 3.29) and reducing binge drinking (OR=1.76, CI=1.38, 2.24) and binge drinking frequency (β=0.24, p=0.04) within the sensation seeking group at 12months post-intervention. Also, lower educated young adolescents reduced binge drinking (OR=1.47, CI=1.14, 1.88), binge drinking frequency (β=0.25, p=0.04), alcohol use (OR=1.32, CI=1.06, 1.65) and alcohol use frequency (β=0.47, p=0.01), but not those in the higher education group. Post hoc latent-growth analyses revealed significant effects on the development of binge drinking (β=-0.19, p=0.02) and binge drinking frequency (β=-0.10, p=0

  4. Entamoeba histolytica: identification of thioredoxin-targeted proteins and analysis of serine acetyltransferase-1 as a prototype example.

    PubMed

    Schlosser, Sarah; Leitsch, David; Duchêne, Michael

    2013-04-15

    Entamoeba histolytica, the causative agent of amoebiasis, possesses the dithiol-containing redox proteins Trx (thioredoxin) and TrxR (Trx reductase). Both proteins were found to be covalently modified and inactivated by metronidazole, a 5-nitroimidazole drug that is commonly used to treat infections with microaerophilic protozoan parasites in humans. Currently, very little is known about enzymes and other proteins participating in the Trx-dependent redox network of the parasite that could be indirectly affected by metronidazole treatment. On the basis of the disulfide/dithiol-exchange mechanism we constructed an active-site mutant of Trx, capable of binding interacting proteins as a stable mixed disulfide intermediate to screen the target proteome of Trx in E. histolytica. By applying Trx affinity chromatography, two-dimensional gel electrophoresis and MS, peroxiredoxin and 15 further potentially redox-regulated proteins were identified. Among them, EhSat1 (E. histolytica serine acetyltransferase-1), an enzyme involved in the L-cysteine biosynthetic pathway, was selected for detailed analysis. Binding of Trx to EhSat1 was verified by Far-Western blot analysis. Trx was able to restore the activity of the oxidatively damaged EhSat1 suggesting that the TrxR/Trx system protects sensitive proteins against oxidative stress in E. histolytica. Furthermore, the activity of peroxiredoxin, which is dependent on a functioning TrxR/Trx system, was strongly reduced in metronidazole-treated parasites.

  5. Targeting attention on local vulnerabilities using an integrated index approach: the example of the climate vulnerability index.

    PubMed

    Sullivan, C; Meigh, J

    2005-01-01

    It is known that climate impacts can have significant effects on the environment, societies and economies. For human populations, climate change impacts can be devastating, giving rise to economic disruption and mass migration as agricultural systems fail, either through drought or floods. Such events impact significantly, not only where they happen, but also in the neighbouring areas. Vulnerability to the impacts of climate change needs to be assessed, so that adaptation strategies can be developed and populations can be protected. In this paper, we address the issue of vulnerability assessment through the use of an indicator approach, the climate vulnerability index (CVI). We show how this can overcome some of the difficulties of incommensurability associated with the combination of different types of data, and how the approach can be applied at a variety of scales. Through the development of nested index values, more reliable and robust coverage of large areas can be achieved, and we provide an indication of how this could be done. While further work is required to improve the methodology through wider application and component refinement, it seems likely that this approach will have useful application in the assessment of climate vulnerability. Through its application at sub-national and community scales, the CVI can help to identify those human populations most at risk from climate change impacts, and as a result, resources can be targeted towards those most in need.

  6. A target enrichment method for gathering phylogenetic information from hundreds of loci: An example from the Compositae1

    PubMed Central

    Mandel, Jennifer R.; Dikow, Rebecca B.; Funk, Vicki A.; Masalia, Rishi R.; Staton, S. Evan; Kozik, Alex; Michelmore, Richard W.; Rieseberg, Loren H.; Burke, John M.

    2014-01-01

    • Premise of the study: The Compositae (Asteraceae) are a large and diverse family of plants, and the most comprehensive phylogeny to date is a meta-tree based on 10 chloroplast loci that has several major unresolved nodes. We describe the development of an approach that enables the rapid sequencing of large numbers of orthologous nuclear loci to facilitate efficient phylogenomic analyses. • Methods and Results: We designed a set of sequence capture probes that target conserved orthologous sequences in the Compositae. We also developed a bioinformatic and phylogenetic workflow for processing and analyzing the resulting data. Application of our approach to 15 species from across the Compositae resulted in the production of phylogenetically informative sequence data from 763 loci and the successful reconstruction of known phylogenetic relationships across the family. • Conclusions: These methods should be of great use to members of the broader Compositae community, and the general approach should also be of use to researchers studying other families. PMID:25202605

  7. Impulsive delayed reward discounting as a genetically-influenced target for drug abuse prevention: a critical evaluation

    PubMed Central

    Gray, Joshua C.; MacKillop, James

    2015-01-01

    This review evaluates the viability of delayed reward discounting (DRD), an index of how much an individual devalues a future reward based on its delay in time, for genetically-informed drug abuse prevention. A review of the literature suggests that impulsive DRD is robustly associated with drug addiction and meets most of the criteria for being an endophenotype, albeit with mixed findings for specific molecular genetic influences. Several modes of experimental manipulation have been demonstrated to reduce DRD acutely. These include behavioral strategies, such as mindfulness, reward bundling, and episodic future thinking; pharmacological interventions, including noradrenergic agonists, adrenergic agonists, and multiple monoamine agonists; and neuromodulatory interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation. However, the generalization of these interventions to positive clinical outcomes remains unclear and no studies to date have examined interventions on DRD in the context of prevention. Collectively, these findings suggest it would be premature to target DRD for genetically-informed prevention. Indeed, given the evidence of environmental contributions to impulsive DRD, whether genetically-informed secondary prevention would ever be warranted is debatable. Progress in identifying polymorphisms associated with DRD profiles could further clarify the underlying biological systems for pharmacological and neuromodulatory interventions, and, as a qualitatively different risk factor from existing prevention programs, impulsive DRD is worthy of investigation at a more general level as a novel and promising drug abuse prevention target. PMID:26388788

  8. Using target population specification, effect size, and reach to estimate and compare the population impact of two PTSD preventive interventions.

    PubMed

    Zatzick, Douglas F; Koepsell, Thomas; Rivara, Frederick P

    2009-01-01

    The population impact of a preventive intervention depends on two factors: what proportion of the full population at risk receives the intervention and how large a reduction in risk occurs among those who receive it. We sought to illustrate how information from a cognitive behavioral psychotherapy (CBT) trial and stepped collaborative care (CC) trial could be used to estimate the population impact of two contrasting approaches to PTSD prevention. We first specified trauma center target populations represented by participants in each trial. Patient characteristics were compared, as were effect size and reach indices and population-level reductions in PTSD incidence. The CBT trial demonstrated a larger effect size (50% PTSD prevention), but minimal reach (27/10,000), while the CC trial demonstrated a smaller effect size (7% PTSD prevention) but greater reach (1762/10,000). Modeling of the population impact suggested that a 9.5-fold greater cumulative reduction in the incidence of PTSD would result from the dissemination of the CC broad reach prevention strategy. A reciprocal relationship between effect size and reach was evident in these two trials. By specifying a target population, effect size and reach could be combined to project the overall population impact of each PTSD prevention approach.

  9. Impulsive delayed reward discounting as a genetically-influenced target for drug abuse prevention: a critical evaluation.

    PubMed

    Gray, Joshua C; MacKillop, James

    2015-01-01

    This review evaluates the viability of delayed reward discounting (DRD), an index of how much an individual devalues a future reward based on its delay in time, for genetically-informed drug abuse prevention. A review of the literature suggests that impulsive DRD is robustly associated with drug addiction and meets most of the criteria for being an endophenotype, albeit with mixed findings for specific molecular genetic influences. Several modes of experimental manipulation have been demonstrated to reduce DRD acutely. These include behavioral strategies, such as mindfulness, reward bundling, and episodic future thinking; pharmacological interventions, including noradrenergic agonists, adrenergic agonists, and multiple monoamine agonists; and neuromodulatory interventions, such as transcranial magnetic stimulation and transcranial direct current stimulation. However, the generalization of these interventions to positive clinical outcomes remains unclear and no studies to date have examined interventions on DRD in the context of prevention. Collectively, these findings suggest it would be premature to target DRD for genetically-informed prevention. Indeed, given the evidence of environmental contributions to impulsive DRD, whether genetically-informed secondary prevention would ever be warranted is debatable. Progress in identifying polymorphisms associated with DRD profiles could further clarify the underlying biological systems for pharmacological and neuromodulatory interventions, and, as a qualitatively different risk factor from existing prevention programs, impulsive DRD is worthy of investigation at a more general level as a novel and promising drug abuse prevention target.

  10. Estimating the Time to Benefit for Preventive Drugs with the Statistical Process Control Method: An Example with Alendronate.

    PubMed

    van de Glind, Esther M M; Willems, Hanna C; Eslami, Saeid; Abu-Hanna, Ameen; Lems, Willem F; Hooft, Lotty; de Rooij, Sophia E; Black, Dennis M; van Munster, Barbara C

    2016-05-01

    For physicians dealing with patients with a limited life expectancy, knowing the time to benefit (TTB) of preventive medication is essential to support treatment decisions. The aim of this study was to investigate the usefulness of statistical process control (SPC) for determining the TTB in relation to fracture risk with alendronate versus placebo in postmenopausal women. We performed a post hoc analysis of the Fracture Intervention Trial (FIT), a randomized, controlled trial that investigated the effect of alendronate versus placebo on fracture risk in postmenopausal women. We used SPC, a statistical method used for monitoring processes for quality control, to determine if and when the intervention group benefited significantly more than the control group. SPC discriminated between the normal variations over time in the numbers of fractures in both groups and the variations that were attributable to alendronate. The TTB was defined as the time point from which the cumulative difference in the number of clinical fractures remained greater than the upper control limit on the SPC chart. For the total group, the TTB was defined as 11 months. For patients aged ≥70 years, the TTB was 8 months [absolute risk reduction (ARR) = 1.4%]; for patients aged <70 years, it was 19 months (ARR = 0.7%). SPC is a clear and understandable graphical method to determine the TTB. Its main advantage is that there is no need to define a prespecified time point, as is the case in traditional survival analyses. Prescribing alendronate to patients who are aged ≥70 years is useful because the TTB shows that they will benefit after 8 months. Investigators should report the TTB to simplify clinical decision making.

  11. Heat shock protein 90 (Hsp90) inhibition targets canonical TGF-β signalling to prevent fibrosis.

    PubMed

    Tomcik, Michal; Zerr, Pawel; Pitkowski, Jana; Palumbo-Zerr, Katrin; Avouac, Jérôme; Distler, Oliver; Becvar, Radim; Senolt, Ladislav; Schett, Georg; Distler, Jörg H

    2014-06-01

    Targeted therapies for systemic sclerosis (SSc) and other fibrotic diseases are not yet available. We evaluated the efficacy of heat shock protein 90 (Hsp90) inhibition as a novel approach to inhibition of aberrant transforming growth factor (TGF)-β signalling and for the treatment of fibrosis in preclinical models of SSc. Expression of Hsp90 was quantified by quantitative PCR, western blot and immunohistochemistry. The effects of Hsp90 inhibition were analysed in cultured fibroblasts, in bleomycin-induced dermal fibrosis, in tight-skin (Tsk-1) mice and in mice overexpressing a constitutively active TGF-β receptor I (TβRI). Expression of Hsp90β was increased in SSc skin and in murine models of SSc in a TGF-β-dependent manner. Inhibition of Hsp90 by 17-dimethylaminoethylamino-17-demethoxy-geldanamycin (17-DMAG) inhibited canonical TGF-β signalling and completely prevented the stimulatory effects of TGF-β on collagen synthesis and myofibroblast differentiation. Treatment with 17-DMAG decreased the activation of canonical TGF-β signalling in murine models of SSc and exerted potent antifibrotic effects in bleomycin-induced dermal fibrosis, in Tsk-1 mice and in mice overexpressing a constitutively active TβRI. Dermal thickness, number of myofibroblasts and hydroxyproline content were all significantly reduced on treatment with 17-DMAG. No toxic effects were observed with 17-DMAG at antifibrotic doses. Hsp90 is upregulated in SSc and is critical for TGF-β signalling. Pharmacological inhibition of Hsp90 effectively blocks the profibrotic effects of TGF-β in cultured fibroblasts and in different preclinical models of SSc. These results have translational implications, as several Hsp90 inhibitors are in clinical trials for other indications.

  12. A cost-effectiveness analysis of alcohol prevention targeting licensed premises.

    PubMed

    Månsdotter, Anna M; Rydberg, Malin K; Wallin, Eva; Lindholm, Lars A; Andréasson, Sven

    2007-12-01

    A multi-component alcohol prevention programme targeting licensed premises has been ongoing in Stockholm since 1996. An earlier study has established that this led to a 29% reduction in police-reported violence. The objective of the present study is to calculate the programme's cost-effectiveness from a societal perspective; the cost of implementation, the savings made as a result of fewer assaults, unlawful threats and violence towards officials, and the health gains in terms of quality-adjusted life-years (QALYs). The costs included administration, studies of alcohol serving practices, community mobilization, responsible beverage service training and stricter alcohol law enforcement. For the purpose of estimating how the decrease in violence affected savings and health gains, a survey among victims of violence (N=604) was performed. The cost of the programme was estimated at Euro 796,000. The average cost of a violent crime was estimated at Euro 19,049, which implies overall savings of Euro 31.314 million related to the judicial system (78%), production losses (15%), health care issues (5%) and other damages (2%). Accordingly, the base case cost-saving ratio was 1:39. The average loss of health state weighting among the victims at 0.09 translates into 236 gained QALYs for society as a whole, which should be compared with the modest proportion of savings in the health sector. The most significant concern is the low response rate (35%), and caution needs to be exercised when interpreting our results. Yet, a reasonable conclusion is that the monetary and human benefits have been considerable.

  13. Generating political priority for regulatory interventions targeting obesity prevention: an Australian case study.

    PubMed

    Baker, Phillip; Gill, Timothy; Friel, Sharon; Carey, Gemma; Kay, Adrian

    2017-03-01

    Effective obesity prevention requires a synergistic mix of population-level interventions including a strong role for government and the regulation of the marketing, labelling, content and pricing of energy-dense foods and beverages. In this paper we adopt the agenda of the Australian Federal Government (AFG) as a case study to understand the factors generating or hindering political priority for such 'regulatory interventions' between 1990 and 2011. Using a theoretically-guided process tracing method we undertook documentary analysis and conducted 27 interviews with a diversity of actors involved in obesity politics. The analysis was structured by a theoretical framework comprising four dimensions: the power of actors involved; the ideas the actors deploy to interpret and portray the issue; the institutional and political context; and issue characteristics. Despite two periods of sustained political attention, political priority for regulatory interventions did not emerge and was hindered by factors from all four dimensions. Within the public health community, limited cohesion among experts and advocacy groups hampered technical responses and collective action efforts. An initial focus on children (child obesity), framing the determinants of obesity as 'obesogenic environments', and the deployment of 'protecting kids', 'industry demonization' and 'economic costs' frames generated political attention. Institutional norms within government effectively selected out regulatory interventions from consideration. The 'productive power' and activities of the food and advertising industries presented formidable barriers, buttressed by a libertarian/neolibertarian rhetoric emphasizing individual responsibility, a negative view of freedom (as free from 'nanny-state' intervention) and the idea that regulation imposes an unacceptable cost on business. Issue complexity, the absence of a supportive evidence base and a strict 'evidence-based' policy-making approach were used as

  14. Predictors of Success in Implementing HIV Prevention in Rural America: A State-Level Structural Factor Analysis of HIV Prevention Targeting Men who have Sex with Men

    PubMed Central

    Horvath, Keith J.

    2013-01-01

    Relatively few studies have examined the impact of modifying structural factors on HIV prevention efforts in the United States despite their high potential for lowering HIV prevalence rates. The aim of this study was to identify state-level characteristics of successful HIV prevention implementation. Structured interviews with 73 key informants in 13 rural states identified ‘more successful’ and ‘less successful’ states in HIV prevention. States were compared on demographic, religious, gay community, and funding variables. The 7 more successful states had both a wider variety and more MSM-targeted interventions. Overall funding, degree of epidemic, and “ruralness” were not significantly associated with success. Rather, successful states had less religious and Evangelical Protestant adherents and more ‘gay community’ infrastructure. They also spent a greater proportion of funds contracting community-based organizations and on MSMtargeted programming. Success in HIV prevention varies across rural states. Key demographic, social and economic indicators distinguish success in HIV prevention. PMID:17440806

  15. Clinical Efficacy of a Specifically Targeted Antimicrobial Peptide Mouth Rinse: Targeted Elimination of Streptococcus mutans and Prevention of Demineralization

    PubMed Central

    Sullivan, R.; Santarpia, P.; Lavender, S.; Gittins, E.; Liu, Z.; Anderson, M.H.; He, J.; Shi, W.; Eckert, R.

    2011-01-01

    Background/Aims Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective ‘targeting region’ comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a ‘killing region’ consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. Methods In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. Results and Conclusions C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic. PMID:21860239

  16. Clinical efficacy of a specifically targeted antimicrobial peptide mouth rinse: targeted elimination of Streptococcus mutans and prevention of demineralization.

    PubMed

    Sullivan, R; Santarpia, P; Lavender, S; Gittins, E; Liu, Z; Anderson, M H; He, J; Shi, W; Eckert, R

    2011-01-01

    Streptococcus mutans, the major etiological agent of dental caries, has a measurable impact on domestic and global health care costs. Though persistent in the oral cavity despite conventional oral hygiene, S. mutans can be excluded from intact oral biofilms through competitive exclusion by other microorganisms. This suggests that therapies capable of selectively eliminating S. mutans while limiting the damage to the normal oral flora might be effective long-term interventions to fight cariogenesis. To meet this challenge, we designed C16G2, a novel synthetic specifically targeted antimicrobial peptide with specificity for S. mutans. C16G2 consists of a S. mutans-selective 'targeting region' comprised of a fragment from S. mutans competence stimulation peptide (CSP) conjoined to a 'killing region' consisting of a broad-spectrum antimicrobial peptide (G2). In vitro studies have indicated that C16G2 has robust efficacy and selectivity for S. mutans, and not other oral bacteria, and affects targeted bacteria within seconds of contact. In the present study, we evaluated C16G2 for clinical utility in vitro, followed by a pilot efficacy study to examine the impact of a 0.04% (w/v) C16G2 rinse in an intra-oral remineralization/demineralization model. C16G2 rinse usage was associated with reductions in plaque and salivary S. mutans, lactic acid production, and enamel demineralization. The impact on total plaque bacteria was minimal. These results suggest that C16G2 is effective against S. mutans in vivo and should be evaluated further in the clinic. Copyright © 2011 S. Karger AG, Basel.

  17. AMPK as a New Attractive Therapeutic Target for Disease Prevention: The Role of Dietary Compounds AMPK and Disease Prevention.

    PubMed

    Gasparrini, Massimiliano; Giampieri, Francesca; Alvarez Suarez, Josè; Mazzoni, Luca; Y Forbes Hernandez, Tamara; Quiles, Josè L; Bullon, Pedro; Battino, Maurizio

    2016-01-01

    AMPK is a serine/threonine protein kinase that has the function of maintaining the balance between ATP production and consumption in most eukaryotic cells. It plays a relevant role in regulating cellular metabolism, preserving cellular energy homeostasis, and is involved in many other cellular processes as well as metabolic ones, including cell cycle regulation and endothelial and vascular relaxation. Recently, the effects of naturally occurring compounds able to prevent and treat diseases through AMPK activation have attracted the attention of many researchers. Among such compounds, flavonoids found in natural sources, like quercetin, genistein, epigallocatechins, resveratrol, have been proposed as AMPK activators. This review summarizes and updates the most recent findings concerning the mechanisms through which different dietary compounds, from plant foods, affect the AMPK pathway in healthy and pathological in vitro and in vivo models, paying particular attention to molecular mechanisms involved in diabetes, obesity, metabolic syndrome, cardiovascular disease and cancer.

  18. Small Molecule Targeting Malaria Merozoite Surface Protein-1 (MSP-1) Prevents Host Invasion of Divergent Plasmodial Species

    PubMed Central

    Chandramohanadas, Rajesh; Basappa; Russell, Bruce; Liew, Kingsley; Yau, Yin Hoe; Chong, Alvin; Liu, Min; Gunalan, Karthigayan; Raman, Rahul; Renia, Laurent; Nosten, Francois; Shochat, Susana Geifman; Dao, Ming; Sasisekharan, Ram; Suresh, Subra; Preiser, Peter

    2014-01-01

    Malaria causes nearly 1 million deaths annually. Recent emergence of multidrug resistance highlights the need to develop novel therapeutic interventions against human malaria. Given the involvement of sugar binding plasmodial proteins in host invasion, we set out to identify such proteins as targets of small glycans. Combining multidisciplinary approaches, we report the discovery of a small molecule inhibitor, NIC, capable of inhibiting host invasion through interacting with a major invasion-related protein, merozoite surface protein-1 (MSP-1). This interaction was validated through computational, biochemical, and biophysical tools. Importantly, treatment with NIC prevented host invasion by Plasmodium falciparum and Plasmodium vivax—major causative organisms of human malaria. MSP-1, an indispensable antigen critical for invasion and suitably localized in abundance on the merozoite surface represents an ideal target for antimalarial development. The ability to target merozoite invasion proteins with specific small inhibitors opens up a new avenue to target this important pathogen. PMID:24864124

  19. Targeting activator protein 1 signaling pathway by bioactive natural agents: Possible therapeutic strategy for cancer prevention and intervention.

    PubMed

    Tewari, Devesh; Nabavi, Seyed Fazel; Nabavi, Seyed Mohammad; Sureda, Antoni; Farooqi, Ammad Ahmad; Atanasov, Atanas G; Vacca, Rosa Anna; Sethi, Gautam; Bishayee, Anupam

    2017-09-23

    Activator protein 1 (AP-1) is a key transcription factor in the control of several cellular processes responsible for cell survival proliferation and differentiation. Dysfunctional AP-1 expression and activity are involved in several severe diseases, especially inflammatory disorders and cancer. Therefore, targeting AP-1 has recently emerged as an attractive therapeutic strategy for cancer prevention and therapy. This review summarizes our current understanding of AP-1 biology and function as well as explores and discusses several natural bioactive compounds modulating AP-1-associated signaling pathways for cancer prevention and intervention. Current limitations, challenges, and future directions of research are also critically discussed. Copyright © 2017 Elsevier Ltd. All rights reserved.

  20. An exploratory review of HIV prevention mass media campaigns targeting men who have sex with men

    PubMed Central

    2014-01-01

    Background Men who have sex with men (MSM) are at increased risk of HIV infection in both high- and low-income settings. Mass media campaigns have been used as a means of communicating HIV health promotion messages to large audiences of MSM. There is no consensus on which designs are most appropriate to evaluate the process and outcomes of such interventions. Methods An exploratory review was conducted to assess research examining awareness, acceptability, effects on HIV testing, disclosure and sexual risk, and cost-effectiveness of HIV mass media campaigns targeting MSM. We searched for quantitative and qualitative studies published between 1990 and May 2011 via the Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, Psych Info, ISI Web of Science, OpenGrey and COPAC, and contacting experts. No exclusions were made on the basis of study design or methods because our primary aim was to map evidence. We appraised study quality and present a narrative synthesis of findings. Results Sixteen reports from 12 studies were included. All were from high-income countries and most examined multi-media interventions. Half of the studies were single cross-sectional surveys. Three repeat cross-sectional studies collected data pre and post the campaign launch. The remaining three studies monitored routine data. Three studies included a nested qualitative component. Campaign coverage was the most commonly reported outcome (9 studies). Imagery, tone of language, content and relevance were identified in the qualitative research as factors influencing campaign acceptability. HIV testing rates (or intention to test) were reported by five studies. Two studies reported that testing rates were higher among men who had seen the campaigns compared to men who had not, but this may reflect confounding. Findings were less consistent regarding reductions in sexual risk behaviours (4 studies). None of the studies examined cost-effectiveness. Conclusions Campaigns aim to provide MSM

  1. Prevention

    Treesearch

    Kerry Britton; Barbara Illman; Gary Man

    2010-01-01

    Prevention is considered the most cost-effective element of the Forest Service Invasive Species Strategy (USDA Forest Service 2004). What makes prevention difficult is the desire to maximize free trade and the resulting benefits to society while, at the same time, protecting natural resources. The role of science is to first identify which commodities pose an...

  2. Framework for Optimal Global Vaccine Stockpile Design for Vaccine-Preventable Diseases: Application to Measles and Cholera Vaccines as Contrasting Examples.

    PubMed

    Thompson, Kimberly M; Duintjer Tebbens, Radboud J

    2016-07-01

    Managing the dynamics of vaccine supply and demand represents a significant challenge with very high stakes. Insufficient vaccine supplies can necessitate rationing, lead to preventable adverse health outcomes, delay the achievements of elimination or eradication goals, and/or pose reputation risks for public health authorities and/or manufacturers. This article explores the dynamics of global vaccine supply and demand to consider the opportunities to develop and maintain optimal global vaccine stockpiles for universal vaccines, characterized by large global demand (for which we use measles vaccines as an example), and nonuniversal (including new and niche) vaccines (for which we use oral cholera vaccine as an example). We contrast our approach with other vaccine stockpile optimization frameworks previously developed for the United States pediatric vaccine stockpile to address disruptions in supply and global emergency response vaccine stockpiles to provide on-demand vaccines for use in outbreaks. For measles vaccine, we explore the complexity that arises due to different formulations and presentations of vaccines, consideration of rubella, and the context of regional elimination goals. We conclude that global health policy leaders and stakeholders should procure and maintain appropriate global vaccine rotating stocks for measles and rubella vaccine now to support current regional elimination goals, and should probably also do so for other vaccines to help prevent and control endemic or epidemic diseases. This work suggests the need to better model global vaccine supplies to improve efficiency in the vaccine supply chain, ensure adequate supplies to support elimination and eradication initiatives, and support progress toward the goals of the Global Vaccine Action Plan.

  3. Use of surveillance data to identify target populations for Staphylococcus aureus vaccines and prevent surgical site infections: A pilot study

    PubMed Central

    Gustin, Marie-Paule; Giard, Marine; Bénet, Thomas; Vanhems, Philippe

    2015-01-01

    The development of anti-staphylococcal vaccines is nowadays a priority to prevent surgical site infections (SSI). The objective of the present study was to identify a potential target population by assessing surveillance data on surgery patients for possible anti-staphylococcal vaccine administration. Individuals at high risk of SSI by Staphylococcus aureus (SA) were targeted by the French SSI Surveillance Network in south-eastern France between 2008 and 2011. Among 238,470 patients, those undergoing primary total hip replacement appeared to be an interesting and healthy enough population for anti-staphylococcal vaccine testing. These male patients, subjected to multiple procedures and with American Society of Anesthesiologists score >2, had a probability of SA SSI about 21 times higher than females with no severe systemic disease and no multiple procedures. Our study indicates that surveillance data on SSI might be an interesting epidemiological source for planning vaccine trials to prevent nosocomial infections. PMID:25668663

  4. Targeting Type 2: Linguistic Agency Assignment in Diabetes Prevention Policy Messaging.

    PubMed

    Glowacki, Elizabeth M; McGlone, Matthew S; Bell, Robert A

    2016-01-01

    We explored the effects of linguistic agency assignment on the persuasive impact of a fictitious medical journal editorial about Type 2 diabetes. Participants (N = 422) read 1 of 4 versions of an editorial that differed in the language used to describe the health threat posed by the disease (threat agency) and to outline a program for preventing it (prevention agency). Threat agency was assigned either to the disease (e.g., diabetes puts individuals' lives at risk) or to humans (e.g., individuals who acquire diabetes put their lives at risk). Prevention agency was assigned either to the recommended prevention behaviors (e.g., a healthy diet and regular exercise protect children from Type 2) or to humans (e.g., children who eat a healthy diet and exercise regularly protect themselves from Type 2). Respondents' perceptions of disease severity were higher when threat agency was assigned to diabetes rather than humans. However, attitudes toward the proposed prevention program were higher when prevention agency was assigned to humans rather than to the recommended behaviors. The latter finding contrasts with agency effects observed in previous research on a viral threat, suggesting that the optimal pattern of agency assignment in prevention messaging may be different for acute and chronic lifestyle diseases.

  5. Level of Response to Alcohol as a Factor for Targeted Prevention in College Students

    PubMed Central

    Savage, Jeanne E.; Neale, Zoe; Cho, Seung Bin; Hancock, Linda; Kalmijn, Jelger A.; Smith, Tom L.; Schuckit, Marc A.; Donovan, Kristen Kidd; Dick, Danielle M.

    2015-01-01

    Background Heavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Though current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large scale evaluation (Schuckit et al., 2012; 2015) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state of the art (SOTA) standard prevention program for individuals with the low LR risk factor. Methods The present study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of four weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a six-month period. Results Individuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between level of response and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g. maximum drinks, frequency of heavy drinking) than high LR individuals. Conclusions These results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions

  6. Level of response to alcohol as a factor for targeted prevention in college students.

    PubMed

    Savage, Jeanne E; Neale, Zoe; Cho, Seung Bin; Hancock, Linda; Kalmijn, Jelger A; Smith, Tom L; Schuckit, Marc A; Donovan, Kristen Kidd; Dick, Danielle M

    2015-11-01

    Heavy alcohol consumption and alcohol problems among college students are widespread and associated with negative outcomes for individuals and communities. Although current methods for prevention and intervention programming have some demonstrated efficacy, heavy drinking remains a problem. A previous pilot study and a recent large-scale evaluation (Schuckit et al., , ) found that a tailored prevention program based on a risk factor for heavy drinking, low level of response (low LR) to alcohol, was more effective at reducing heavy drinking than a state-of-the-art (SOTA) standard prevention program for individuals with the low LR risk factor. This study enrolled 231 first-semester college freshmen with either high or low LR into the same level of response-based (LRB) or SOTA online prevention programs as in the previous reports (consisting of 4 weeks of video modules), as well as a group of matched controls not receiving alcohol prevention, and compared changes in alcohol use between these groups across a 6-month period. Individuals in alcohol prevention programs had a greater reduction in maximum drinks per occasion and alcohol use disorder symptoms than controls. There was limited evidence for interactions between LR and prevention group in predicting change in alcohol use behaviors; only among participants with strict adherence to the program was there an interaction between LR and program in predicting maximum drinks per occasion. However, overall, low LR individuals showed greater decreases in drinking behaviors, especially risky behaviors (e.g., maximum drinks, frequency of heavy drinking) than high LR individuals. These results indicate that prevention programs, including brief and relatively inexpensive web-based programs, may be effective for persons at highest risk for heavier drinking, such as those with a low LR. Tailored programs may provide incremental benefits under some conditions. Long-term follow-ups and further investigations of tailored

  7. The National Cancer Institute's PREVENT Cancer Preclinical Drug Development Program: overview, current projects, animal models, agent development strategies, and molecular targets.

    PubMed

    Shoemaker, Robert H; Suen, Chen S; Holmes, Cathy A; Fay, Judith R; Steele, Vernon E

    2016-02-01

    The PREVENT Cancer Preclinical Drug Development Program (PREVENT) is a National Cancer Institute, Division of Cancer Prevention (NCI, DCP)-supported program whose primary goal is to bring new cancer preventive interventions (small molecules and vaccines) and biomarkers through preclinical development towards clinical trials by creating partnerships between the public sector (eg, academia, industry) and DCP. PREVENT has a formalized structure for moving interventions forward in the prevention pipeline using a stage-gate process with go/no go decision points along the critical path for development. This review describes the structure of the program, its focus areas, and provides examples of projects currently in the pipeline.

  8. Acceptability of Sexually Explicit Images in HIV Prevention Messages Targeting Men Who Have Sex With Men.

    PubMed

    Iantaffi, Alex; Wilkerson, J Michael; Grey, Jeremy A; Rosser, B R Simon

    2015-01-01

    Sexually explicit media (SEM) have been used in HIV-prevention advertisements to engage men who have sex with men (MSM) and to communicate content. These advertisements exist within larger discourses, including a dominant heteronormative culture and a growing homonormative culture. Cognizant of these hegemonic cultures, this analysis examined the acceptable level of sexual explicitness in prevention advertisements. Seventy-nine MSM participated in 13 online focus groups, which were part of a larger study of SEM. Three macro themes-audience, location, and community representation-emerged from the analysis, as did the influence of homonormativity on the acceptability of SEM in HIV-prevention messages.

  9. Acceptability of Sexually Explicit Images in HIV Prevention Messages Targeting Men Who Have Sex with Men

    PubMed Central

    Iantaffi, Alex; Wilkerson, J. Michael; Grey, Jeremy A.; Rosser, B. R. Simon

    2014-01-01

    Sexually explicit media (SEM) have been used in HIV-prevention advertisements to engage men who have sex with men (MSM), and to communicate content. These advertisements exist within larger discourses, including a dominant heternormative culture, and a growing homonormative culture. Cognizant of these hegemonic cultures, this analysis examined the acceptable level of sexual explicitness in prevention advertisements. 79 MSM participated in 13 online focus groups, which were part of a larger study of SEM. Three macro-themes—audience, location and community representation—emerged from the analysis, as did the influence of homonormativity on the acceptability of SEM in HIV-prevention messages. PMID:26075485

  10. CD44 targeting reduces tumour growth and prevents post-chemotherapy relapse of human breast cancers xenografts

    PubMed Central

    Marangoni, E; Lecomte, N; Durand, L; de Pinieux, G; Decaudin, D; Chomienne, C; Smadja-Joffe, F; Poupon, M-F

    2009-01-01

    CD44 is a marker of tumour-initiating cells and is upregulated in invasive breast carcinoma; however, its role in the cancer progression is unknown. Here, we show that antibody-mediated CD44-targeting in human breast cancer xenografts (HBCx) significantly reduces tumour growth and that this effect is associated to induction of growth-inhibiting factors. Moreover, treatment with this antibody prevents tumour relapse after chemotherapy-induced remission in a basal-like HBCx. PMID:19240712

  11. [School shootings in Germany: current trends in the prevention of severe, targeted violence in German schools].

    PubMed

    Bondü, Rebecca; Scheithauer, Herbert

    2009-01-01

    In March and September 2009 the school shootings in Winnenden and Ansbach once again demonstrated the need for preventive approaches in order to prevent further offences in Germany. Due to the low frequency of such offences and the low specificity of relevant risk factors known so far, prediction and prevention seems difficult though. None the less, several preventive approaches are currently discussed. The present article highlights these approaches and their specific advantages and disadvantages. As school shootings are multicausally determined, approaches focussing only on single aspects (i.e. prohibiting violent computer games or further strengthening gun laws) do not meet requirements. Other measures such as installing technical safety devices or optimizing actions of police and school attendants are supposed to reduce harm in case of emergency. Instead, scientifically founded and promising preventive approaches focus on secondary prevention and for this purpose employ the threat assessment approach, which is widespread within the USA. In this framework, responsible occupational groups such as teachers, school psychologists and police officers are to be trained in identifying students' warning signs, judging danger of these students for self and others in a systematic process and initiating suitable interventions.

  12. Targeted prevention of childhood anxiety: engaging parents in an underserved community.

    PubMed

    Mian, Nicholas D; Eisenhower, Abbey S; Carter, Alice S

    2015-03-01

    Selective prevention programs hold the promise of alleviating child anxiety symptoms, decreasing the risk for emotional problems across the lifespan. Such programs have particular public health import for young children of poor, underserved communities. Identifying factors related to parent engagement, and methods to improve engagement, are paramount in the effort to develop anxiety-focused, community prevention programs. This feasibility study investigated the effect of an enhanced recruitment strategy to maximize parent engagement, as well as factors related to attendance in a single session focused on anxiety prevention. Participants were poor, ethnic minority parents of children aged 11-71 months (n = 256) who completed a survey that assessed anxiety risk according to trauma exposure, child anxiety, or parent anxiety, as well as preferences for preventive services (phase 1). Those meeting risk criteria (n = 101) were invited to a preventive group session (phase 2). Half of parents received enhanced recruitment (ER), which included personalized outreach, matching parent preferences, and community endorsement. Other parents were invited by mail. Chi square analyses indicated that ER was associated with planning to attend (49 vs. 6% of control). Parents receiving ER were 3.5 times more likely to attend. Higher sociodemographic risk was correlated with higher child anxiety symptoms but not attendance. Results highlight the need for improved strategies for engaging parents in preventive, community-based interventions.

  13. In vivo prevention of arterial restenosis with paclitaxel-encapsulated targeted lipid–polymeric nanoparticles

    PubMed Central

    Chan, Juliana M.; Drum, Chester L.; Bronson, Roderick T.; Golomb, Gershon; Langer, Robert; Farokhzad, Omid C.

    2011-01-01

    Following recent successes with percutaneous coronary intervention (PCI) for treating coronary artery disease (CAD), many challenges remain. In particular, mechanical injury from the procedure results in extensive endothelial denudation, exposing the underlying collagen IV-rich basal lamina, which promotes both intravascular thrombosis and smooth muscle proliferation. Previously, we reported the engineering of collagen IV-targeting nanoparticles (NPs) and demonstrated their preferential localization to sites of arterial injury. Here, we develop a systemically administered, targeted NP system to deliver an antiproliferative agent to injured vasculature. Approximately 60-nm lipid–polymeric NPs were surface functionalized with collagen IV-targeting peptides and loaded with paclitaxel. In safety studies, the targeted NPs showed no signs of toxicity and a ≥3.5-fold improved maximum tolerated dose versus paclitaxel. In efficacy studies using a rat carotid injury model, paclitaxel (0.3 mg/kg or 1 mg/kg) was i.v. administered postprocedure on days 0 and 5. The targeted NP group resulted in lower neointima-to-media (N/M) scores at 2 wk versus control groups of saline, paclitaxel, or nontargeted NPs. Compared with sham-injury groups, an ∼50% reduction in arterial stenosis was observed with targeted NP treatment. The combination of improved tolerability, sustained release, and vascular targeting could potentially provide a safe and efficacious option in the management of CAD. PMID:22087004

  14. [Family Caregivers as a Target Group for Health Promotion and Prevention].

    PubMed

    Budnick, A; Dräger, D; Blüher, S; Kummer, K

    2015-09-01

    Family caregivers are a target group for health promotion, due to the various burdens. Against this background an assessment (ARR) was developed, implemented, and validated in the project "Health Promotion for Elderly Family Caregiver". On the basis of the ARR, family caregivers received an individual, need-oriented, and specific offer for health promotion. In order to reach the target group optimally, a national health insurance company was used.

  15. Increasing the Yield in Targeted Next-Generation Sequencing by Implicating CNV Analysis, Non-Coding Exons and the Overall Variant Load: The Example of Retinal Dystrophies

    PubMed Central

    Eisenberger, Tobias; Neuhaus, Christine; Khan, Arif O.; Decker, Christian; Preising, Markus N.; Friedburg, Christoph; Bieg, Anika; Gliem, Martin; Issa, Peter Charbel; Holz, Frank G.; Baig, Shahid M.; Hellenbroich, Yorck; Galvez, Alberto; Platzer, Konrad; Wollnik, Bernd; Laddach, Nadja; Ghaffari, Saeed Reza; Rafati, Maryam; Botzenhart, Elke; Tinschert, Sigrid; Börger, Doris; Bohring, Axel; Schreml, Julia; Körtge-Jung, Stefani; Schell-Apacik, Chayim; Bakur, Khadijah; Al-Aama, Jumana Y.; Neuhann, Teresa; Herkenrath, Peter; Nürnberg, Gudrun; Nürnberg, Peter; Davis, John S.; Gal, Andreas; Bergmann, Carsten; Lorenz, Birgit; Bolz, Hanno J.

    2013-01-01

    Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover “hidden mutations” such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5′ exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of EYS revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in RP1, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5′-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even

  16. Increasing the yield in targeted next-generation sequencing by implicating CNV analysis, non-coding exons and the overall variant load: the example of retinal dystrophies.

    PubMed

    Eisenberger, Tobias; Neuhaus, Christine; Khan, Arif O; Decker, Christian; Preising, Markus N; Friedburg, Christoph; Bieg, Anika; Gliem, Martin; Charbel Issa, Peter; Holz, Frank G; Baig, Shahid M; Hellenbroich, Yorck; Galvez, Alberto; Platzer, Konrad; Wollnik, Bernd; Laddach, Nadja; Ghaffari, Saeed Reza; Rafati, Maryam; Botzenhart, Elke; Tinschert, Sigrid; Börger, Doris; Bohring, Axel; Schreml, Julia; Körtge-Jung, Stefani; Schell-Apacik, Chayim; Bakur, Khadijah; Al-Aama, Jumana Y; Neuhann, Teresa; Herkenrath, Peter; Nürnberg, Gudrun; Nürnberg, Peter; Davis, John S; Gal, Andreas; Bergmann, Carsten; Lorenz, Birgit; Bolz, Hanno J

    2013-01-01

    Retinitis pigmentosa (RP) and Leber congenital amaurosis (LCA) are major causes of blindness. They result from mutations in many genes which has long hampered comprehensive genetic analysis. Recently, targeted next-generation sequencing (NGS) has proven useful to overcome this limitation. To uncover "hidden mutations" such as copy number variations (CNVs) and mutations in non-coding regions, we extended the use of NGS data by quantitative readout for the exons of 55 RP and LCA genes in 126 patients, and by including non-coding 5' exons. We detected several causative CNVs which were key to the diagnosis in hitherto unsolved constellations, e.g. hemizygous point mutations in consanguineous families, and CNVs complemented apparently monoallelic recessive alleles. Mutations of non-coding exon 1 of EYS revealed its contribution to disease. In view of the high carrier frequency for retinal disease gene mutations in the general population, we considered the overall variant load in each patient to assess if a mutation was causative or reflected accidental carriership in patients with mutations in several genes or with single recessive alleles. For example, truncating mutations in RP1, a gene implicated in both recessive and dominant RP, were causative in biallelic constellations, unrelated to disease when heterozygous on a biallelic mutation background of another gene, or even non-pathogenic if close to the C-terminus. Patients with mutations in several loci were common, but without evidence for di- or oligogenic inheritance. Although the number of targeted genes was low compared to previous studies, the mutation detection rate was highest (70%) which likely results from completeness and depth of coverage, and quantitative data analysis. CNV analysis should routinely be applied in targeted NGS, and mutations in non-coding exons give reason to systematically include 5'-UTRs in disease gene or exome panels. Consideration of all variants is indispensable because even

  17. Endothelial microparticle uptake in target cells is annexin I/phosphatidylserine receptor dependent and prevents apoptosis.

    PubMed

    Jansen, Felix; Yang, Xiaoyan; Hoyer, Friedrich Felix; Paul, Kathrin; Heiermann, Nadine; Becher, Marc Ulrich; Abu Hussein, Nebal; Kebschull, Moritz; Bedorf, Jörg; Franklin, Bernardo S; Latz, Eicke; Nickenig, Georg; Werner, Nikos

    2012-08-01

    Endothelial microparticles (EMP) are released from activated or apoptotic cells, but their effect on target cells and the exact way of incorporation are largely unknown. We sought to determine the uptake mechanism and the biological effect of EMP on endothelial and endothelial-regenerating cells. EMP were generated from starved endothelial cells and isolated by ultracentrifugation. Caspase 3 activity assay and terminal deoxynucleotidyl transferase dUTP nick end labeling assay showed that EMP protect target endothelial cells against apoptosis in a dose-dependent manner. Proteomic analysis was performed to identify molecules contained in EMP, which might be involved in EMP uptake. Expression of annexin I in EMP was found and confirmed by Western blot, whereas the corresponding receptor phosphatidylserine receptor was present on endothelial target cells. Silencing either annexin I on EMP or phosphatidylserine receptor on target cells using small interfering RNA showed that the uptake of EMP by human coronary artery endothelial cells is annexin I/phosphatidylserine receptor dependent. Annexin I-downregulated EMP abrogated the EMP-mediated protection against apoptosis of endothelial target cells. p38 activation was found to mediate camptothecin-induced apoptosis. Finally, human coronary artery endothelial cells pretreated with EMP inhibited camptothecin-induced p38 activation. EMP are incorporated by endothelial cells in an annexin I/phosphatidylserine receptor-dependent manner and protect target cells against apoptosis. Inhibition of p38 activity is involved in EMP-mediated protection against apoptosis.

  18. Universality properties of school-based preventive intervention targeted at cannabis use.

    PubMed

    Miovský, Michal; Voňková, Hana; Gabrhelík, Roman; Šťastná, Lenka

    2015-02-01

    This study aims to examine the effect of school-based preventive intervention on cannabis use in Czech adolescents with different levels of risk factors and provide evidence of its universality. A randomized controlled prevention trial with six waves was conducted over a period of 33 months. We used a two-level logistic random-intercept model for panel data; we first looked at the statistical significance of the effect of the intervention on cannabis use, controlling for the characteristics of the children and time dummies. Then we analyzed the effects of the interactions between the intervention and the characteristics of the children on cannabis use and related it to the definition of universal preventive interventions. The setting for the study was in basic schools in the Czech Republic in the years 2007-2010. A total of 1,874 sixth-graders (mean age 11.82 years) who completed the baseline testing. According to our results, the prevention intervention was effective. We found all the selected characteristics of the children to be relevant in relation to cannabis use, except their relationships with their friends. We showed empirically that the intervention is universal in two dimensions for the selected characteristics of the children. First, all adolescents who undergo the intervention are expected to benefit. Second, with respect to the effect of the intervention on cannabis use, the total level of individual risk of cannabis use is superior to the composition of the risk factors in the individual risk profile. We present indicative evidence that the drug prevention intervention may be considered a true universal preventive intervention.

  19. New targets in the search for preventive and therapeutic agents for botulism.

    PubMed

    Anniballi, Fabrizio; Lonati, Davide; Fiore, Alfonsina; Auricchio, Bruna; De Medici, Dario; Locatelli, Carlo Alessandro

    2014-09-01

    Botulism is a severe neuroparalytic disease resulting from exposure to one of the most poisonous toxins to humans. Because of this high potency and the use of toxins as biological weapons, botulism is a public health concern and each case represents an emergency. Current therapy involves respiratory supportive care and anti-toxins administration. As a preventive measure, vaccination against toxins represents an effective strategy but is undesirable due the rarity of botulism and the effectiveness of toxins in treating several neuromuscular disorders. This paper summarizes the current issues in botulism treatment and prevention, highlighting the challenge for future researches.

  20. Primary and secondary coronary heart disease prevention using statins: is targeting Adam or Eve equally effective?

    PubMed

    Kakafika, Anna I; Athyros, Vasilios G; Tziomalos, Konstantinos; Karagiannis, Asterios; Mikhailidis, Dimitri P

    2008-06-01

    Women differ from men in terms of their cardiovascular disease risk. The existing data suggest that primary cardiovascular disease prevention treatment with a statin could be cost effective for women and men with a high cardiovascular disease risk. In secondary cardiovascular disease prevention both men and women seem to benefit equally from statin treatment. However, the relatively small number of women included in several statin trials has limited the evidence available. With regard to the question of whether Eve is becoming Adam, the answer is not yet: we need more evidence!

  1. A Systematic Review of Universal Campaigns Targeting Child Physical Abuse Prevention

    ERIC Educational Resources Information Center

    Poole, Mary Kathryn; Seal, David W.; Taylor, Catherine A.

    2014-01-01

    The purpose of this review was to better understand the impact of universal campaign interventions with a media component aimed at preventing child physical abuse (CPA). The review included 17 studies featuring 15 campaigns conducted from 1989 to 2011 in five countries. Seven studies used experimental designs, but most were quasi-experimental. CPA…

  2. Incorporating Health and Behavioral Consequences of Child Abuse in Prevention Programs Targeting Female Adolescents.

    ERIC Educational Resources Information Center

    Buzi, Ruth S.; Weinman, Maxine L.; Smith, Peggy B.

    1998-01-01

    Examined the health and behavioral consequences of child abuse, comparing parenting and never-pregnant teens. Both groups identified major consequences of suicide, prostitution, school drop-out, crime, and substance abuse. Parenting teens expressed interest in prevention programs that would address these consequences. Recommendations for child…

  3. Building Evidence for a Prevention-Focused Education Program Targeting Parents of Infants and Toddlers

    ERIC Educational Resources Information Center

    Mendel, Whitney E.; Tomasello, Nicole M.; Nochajski, Thomas H.

    2012-01-01

    A lack of parenting skills puts young children at greater risk of maltreatment, and impedes healthy child development. Using a combination of a pre-post and post-only design, a prevention-focused parenting education workshop series was assessed to determine its influence on parenting knowledge and self-efficacy. Outcome measures indicated that…

  4. Straight Talking for Targeted Pre-Schoolers: A Substance Abuse Prevention Manual.

    ERIC Educational Resources Information Center

    Heggins, Martha Jean; And Others

    This manual provides a substance abuse prevention curriculum for preschoolers that includes numerous activities that can be used in traditional learning centers. Unit One helps caregivers examine their style of interacting with young children and identify strategies that will facilitate children's problem solving, critical thinking, and decision…

  5. Incorporating Health and Behavioral Consequences of Child Abuse in Prevention Programs Targeting Female Adolescents.

    ERIC Educational Resources Information Center

    Buzi, Ruth S.; Weinman, Maxine L.; Smith, Peggy B.

    1998-01-01

    Examined the health and behavioral consequences of child abuse, comparing parenting and never-pregnant teens. Both groups identified major consequences of suicide, prostitution, school drop-out, crime, and substance abuse. Parenting teens expressed interest in prevention programs that would address these consequences. Recommendations for child…

  6. Early Life Viral Infections and the Development of Asthma – A Target for Asthma Prevention?

    PubMed Central

    Jackson, Daniel J.

    2014-01-01

    Purpose of the Review To discuss recent insights into the relationships between viral respiratory infections and asthma inception in the context of a long-term goal of moving towards prevention strategies for childhood asthma. Recent Findings There is strong evidence for respiratory syncytial virus (RSV) and human rhinovirus (RV) wheezing illnesses as important risk factors for asthma inception. The mechanisms underlying these relationships have been an intense area of study. Novel approaches for the prevention of virus infections and/or lessening the severity of associated illnesses are at various stages of development, and are important potential tools in efforts aimed at primary and secondary prevention of asthma. Summary Viral respiratory infections in early life are a major source of morbidity and critical in the development of asthma. Mechanisms by which these infections lead to asthma inception in susceptible individuals are emerging. Further, there are promising potential interventions currently available that should be tested in clinical trials. The goal of prevention of disease inception is clearly on the horizon. PMID:24569522

  7. A Systematic Review of Universal Campaigns Targeting Child Physical Abuse Prevention

    ERIC Educational Resources Information Center

    Poole, Mary Kathryn; Seal, David W.; Taylor, Catherine A.

    2014-01-01

    The purpose of this review was to better understand the impact of universal campaign interventions with a media component aimed at preventing child physical abuse (CPA). The review included 17 studies featuring 15 campaigns conducted from 1989 to 2011 in five countries. Seven studies used experimental designs, but most were quasi-experimental. CPA…

  8. Building Evidence for a Prevention-Focused Education Program Targeting Parents of Infants and Toddlers

    ERIC Educational Resources Information Center

    Mendel, Whitney E.; Tomasello, Nicole M.; Nochajski, Thomas H.

    2012-01-01

    A lack of parenting skills puts young children at greater risk of maltreatment, and impedes healthy child development. Using a combination of a pre-post and post-only design, a prevention-focused parenting education workshop series was assessed to determine its influence on parenting knowledge and self-efficacy. Outcome measures indicated that…

  9. Outcomes of a pilot obesity prevention plus intervention targeting children and parenting practices

    USDA-ARS?s Scientific Manuscript database

    Prevention-Plus interventions for primary care offer a venue to intervene with both children and parents for child obesity treatment. Such interventions can promote effective parenting practices that encourage healthy eating, physical activity (PA), and lower TV use among children. Test for feasibil...

  10. An evidence-based method for targeting an abusive head trauma prevention media campaign and its evaluation.

    PubMed

    Stewart, Tanya Charyk; Gilliland, Jason; Parry, Neil G; Fraser, Douglas D

    2015-11-01

    A triple-dose abusive head trauma (AHT) prevention program (Period of PURPLE Crying) was implemented. The third dose consisted of an education media campaign. The study objectives were to describe the qualitative and spatial methods developed to target AHT prevention and to evaluate this campaign. A questionnaire on the level of importance of factors, rated on a 7-point Likert scale, was distributed to a panel of experts to determine the best advertising locations. Ranked factors were used to create weights for statistical modeling and mapping within a Geographic Information Systems to determine optimal ad locations. The media campaign was evaluated via a telephone survey of randomly selected households. The survey found locations of new families, high population density, and high percentage of lone parents to be the most important factors for selecting billboard sites. Spatial analysis revealed six areas that ranked highest in our factors. Five billboards, four media posters, and six transit shelters were selected for our advertisements. A population-based telephone survey revealed that 23% of respondents knew the campaign. Nearly half (42%) heard the radio public service announcements, and 9% saw billboards. Extending primary prevention efforts to the public helps to create a cultural change in the way inconsolable crying, the trigger for AHT, is viewed. With the use of ranked factors and Geographic Information Systems, geographic locations with high visibility and specific risk factors for AHT were identified for targeting the campaign, facilitating the likelihood that our message was reaching the population in greatest need.

  11. An E3 ubiquitin ligase prevents ectopic localization of the centromeric histone H3 variant via the centromere targeting domain

    PubMed Central

    Ranjitkar, Prerana; Press, Maximilian O.; Yi, Xianhua; Baker, Richard; MacCoss, Michael J.; Biggins, Sue

    2010-01-01

    Summary Proper centromere function is critical to maintain genomic stability and to prevent aneuploidy, a hallmark of tumors and birth defects. A conserved feature of all eukaryotic centromeres is an essential histone H3 variant called CENP-A that requires a centromere targeting domain (CATD) for its localization. Although proteolysis prevents CENP-A from mislocalizing to euchromatin, regulatory factors have not been identified. Here, we identify an E3 ubiquitin ligase called Psh1 that leads to the degradation of Cse4, the budding yeast CENP-A homolog. Cse4 overexpression is toxic to psh1Δ cells and results in euchromatic localization. Strikingly, the Cse4 centromere targeting domain is a key regulator of its stability and helps Psh1 discriminate Cse4 from histone H3. Taken together, we propose that the CATD has a previously unknown role in maintaining the exclusive localization of Cse4 by preventing its mislocalization to euchromatin via Psh1-mediated degradation. PMID:21070971

  12. Universal school-based substance abuse prevention programs: Modeling targeted mediators and outcomes for adolescent cigarette, alcohol and marijuana use.

    PubMed

    Stephens, Peggy C; Sloboda, Zili; Stephens, Richard C; Teasdale, Brent; Grey, Scott F; Hawthorne, Richard D; Williams, Joseph

    2009-06-01

    We examined the relationships among targeted constructs of social influences and competence enhancement prevention curricula and cigarette, alcohol and marijuana use outcomes in a diverse sample of high school students. We tested the causal relationships of normative beliefs, perceptions of harm, attitudes toward use of these substances and refusal, communication, and decision-making skills predicting the self-reported use of each substance. In addition, we modeled the meditation of these constructs through the intentions to use each substance and tested the moderating effects of the skills variables on the relationships between intentions to use and self-reported use of each of these substances. Logistic regression path models were constructed for each of the drug use outcomes. Models were run using the Mplus 5.0 statistical application using the complex sample function to control for the sampling design of students nested within schools; full information maximum likelihood estimates (FIML) were utilized to address missing data. Relationships among targeted constructs and outcomes differed for each of the drugs with communication skills having a potentially iatrogenic effect on alcohol use. Program targets were mediated through the intentions to use these substances. Finally, we found evidence of a moderating effect of decision-making skills on perceptions of harm and attitudes toward use, depending upon the outcome. Prevention curricula may need to target specific drugs. In addition to normative beliefs, perceptions of harm, and refusal and decision-making skills, programs should directly target constructs proximal to behavioral outcomes such as attitudes and intentions. Finally, more research on the effects of communication skills on adolescent substance use should be examined.

  13. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles

    PubMed Central

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C.; Langer, Robert

    2016-01-01

    The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. PMID:27140638

  14. Targeted nanoparticles encapsulating (‑)-epigallocatechin-3-gallate for prostate cancer prevention and therapy

    NASA Astrophysics Data System (ADS)

    Sanna, Vanna; Singh, Chandra K.; Jashari, Rahime; Adhami, Vaqar M.; Chamcheu, Jean Christopher; Rady, Islam; Sechi, Mario; Mukhtar, Hasan; Siddiqui, Imtiaz A.

    2017-02-01

    Earlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.

  15. Targeted nanoparticles encapsulating (−)-epigallocatechin-3-gallate for prostate cancer prevention and therapy

    PubMed Central

    Sanna, Vanna; Singh, Chandra K.; Jashari, Rahime; Adhami, Vaqar M.; Chamcheu, Jean Christopher; Rady, Islam; Sechi, Mario; Mukhtar, Hasan; Siddiqui, Imtiaz A.

    2017-01-01

    Earlier we introduced the concept of ‘nanochemoprevention’ i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome. PMID:28145499

  16. Targeted nanoparticles encapsulating (-)-epigallocatechin-3-gallate for prostate cancer prevention and therapy.

    PubMed

    Sanna, Vanna; Singh, Chandra K; Jashari, Rahime; Adhami, Vaqar M; Chamcheu, Jean Christopher; Rady, Islam; Sechi, Mario; Mukhtar, Hasan; Siddiqui, Imtiaz A

    2017-02-01

    Earlier we introduced the concept of 'nanochemoprevention' i.e. the use of nanotechnology to improve the outcome of cancer chemoprevention. Here, we extended our work and developed polymeric EGCG-encapsulated nanoparticles (NPs) targeted with small molecular entities, able to bind to prostate specific membrane antigen (PSMA), a transmembrane protein that is overexpressed in prostate cancer (PCa), and evaluated their efficacy in preclinical studies. First, we performed a molecular recognition of DCL- and AG-PEGylation on ligand binding on PSMA active site. Next, the biocompatible polymers PLGA-PEG-A were synthesized and used as base to conjugate DCL or AG to obtain the respective copolymers, needed for the preparation of targeted NPs. The resulting EGCG encapsulating NPs led to an enhanced anti-proliferative activity in PCa cell lines compared to the free EGCG. The behavior of EGCG encapsulated in NPs in modulating apoptosis and cell-cycle, was also determined. Then, in vivo experiments, in mouse xenograft model of prostatic tumor, using EGCG-loaded NPs, with a model of targeted nanosystems, were conducted. The obtained data supported our hypothesis of target-specific enhanced bioavailability and limited unwanted toxicity, thus leading to a significant potential for probable clinical outcome.

  17. Targeting Inflammatory Pathways by Triterpenoids for Prevention and Treatment of Cancer

    PubMed Central

    Yadav, Vivek R.; Prasad, Sahdeo; Sung, Bokyung; Kannappan, Ramaswamy; Aggarwal, Bharat B.

    2010-01-01

    Traditional medicine and diet has served mankind through the ages for prevention and treatment of most chronic diseases. Mounting evidence suggests that chronic inflammation mediates most chronic diseases, including cancer. More than other transcription factors, nuclear factor-kappaB (NF-κB) and STAT3 have emerged as major regulators of inflammation, cellular transformation, and tumor cell survival, proliferation, invasion, angiogenesis, and metastasis. Thus, agents that can inhibit NF-κB and STAT3 activation pathways have the potential to both prevent and treat cancer. In this review, we examine the potential of one group of compounds called triterpenes, derived from traditional medicine and diet for their ability to suppress inflammatory pathways linked to tumorigenesis. These triterpenes include avicins, betulinic acid, boswellic acid, celastrol, diosgenin, madecassic acid, maslinic acid, momordin, saikosaponins, platycodon, pristimerin, ursolic acid, and withanolide. This review thus supports the famous adage of Hippocrates, “Let food be thy medicine and medicine be thy food”. PMID:22069560

  18. Using process data to understand outcomes in sexual health promotion: an example from a review of school-based programmes to prevent sexually transmitted infections.

    PubMed

    Shepherd, J; Harden, A; Barnett-Page, E; Kavanagh, J; Picot, J; Frampton, G K; Cooper, K; Hartwell, D; Clegg, A

    2014-08-01

    This article discusses how process indicators can complement outcomes as part of a comprehensive explanatory evaluation framework, using the example of skills-based behavioural interventions to prevent sexually transmitted infections and promote sexual health among young people in schools. A systematic review was conducted, yielding 12 eligible outcome evaluations, 9 of which included a process evaluation. There were few statistically significant effects in terms of changes in sexual behaviour outcomes, but statistically significant effects were more common for knowledge and self-efficacy. Synthesis of the findings of the process evaluations identified a range of factors that might explain outcomes, and these were organized into two overarching categories: the implementation of interventions, and student engagement and intervention acceptability. Factors which supported implementation and engagement and acceptability included good quality teacher training, involvement and motivation of key school stakeholders and relevance and appeal to young people. Factors which had a negative impact included teachers' failure to comprehend the theoretical basis for behaviour change, school logistical problems and omission of topics that young people considered important. It is recommended that process indicators such as these be assessed in future evaluations of school-based sexual health behavioural interventions, as part of a logic model.

  19. Targeted Prevention or Treatment of Bacterial Biofilm Infections of Severe Burns and Wounds

    DTIC Science & Technology

    2011-04-01

    highly predictable settings, thus lending it to preventive strategies. References Cited 1. Church, D ., S. Elsayed, O. Reid, B. Winston, and R. Lindsay...2006. Burn wound infections. Clin Microbiol Rev 19(2):403-34. 2. Suber, F., M. C. Carroll, and F. D . Moore, Jr. 2007. Innate response to self...12 neutrophils. Infect Immun 73(6): 3693 -701. 4. Moskowitz, S. M., J. M. Foster, J. Emerson, and J. L. Burns. 2004. Clinically feasible biofilm

  20. Targeted Prevention or Treatment of Bacterial Biofilm Infections of Severe Burns and Wounds

    DTIC Science & Technology

    2010-10-01

    to preventive strategies. 9 References Cited 1. Church, D ., S. Elsayed, O. Reid, B. Winston, and R. Lindsay. 2006. Burn wound infections. Clin...Microbiol Rev 19(2):403-34. 2. Suber, F., M. C. Carroll, and F. D . Moore, Jr. 2007. Innate response to self-antigen significantly exacerbates burn wound...M. L. Vasil, and J. A. Nick. 2005. Enhanced Pseudomonas aeruginosa biofilm development mediated by human neutrophils. Infect Immun 73(6): 3693 -701. 4

  1. Targeted preventive care may be needed for adults with congenital spine anomalies.

    PubMed

    Wilson, Richard; Lewis, Steven A; Dicianno, Brad E

    2011-08-01

    To compare hospitalizations caused by spina bifida-sensitive conditions, ambulatory care-sensitive conditions in adults with spina bifida and in the general population, our aim was to provide information about whether preventive health efforts already underway in the hospitalized general population are adequate for preventive care in spina bifida and congenital spine anomalies. Retrospective secondary data analysis. Records of hospitalized individuals who were 18 years of age and older. Comparison between individuals hospitalized with spina bifida and the general population using data from the California State Inpatient Database from the Healthcare Cost and Utilization Project for 2004 of adults. Prevalence of spina bifida-sensitive conditions and ambulatory care-sensitive conditions as reason for hospitalization and 30-day readmission. As compared with the general population, persons with spina bifida who were hospitalized in 2004 had a significantly greater number of hospitalizations, number of hospitalizations associated with both spina bifida-sensitive conditions and ambulatory care-sensitive conditions, and number of 30-day readmissions. Stratification by age shows that the admissions for spina bifida sensitive conditions were greater in persons with spina bifida than in the general population for all age groups. In contrast, only in the youngest age group did those with spina bifida experience greater hospitalizations for ambulatory care-sensitive conditions. This study provides further evidence that persons with spina bifida have hospitalizations that are beyond what the general population experiences. These conditions may be potentially preventable with appropriate ambulatory care. This group also had a greater risk for readmission within 30 days of discharge from their last hospitalization. More research is needed on the efficacy of programs aimed at prevention of these conditions. Copyright © 2011 American Academy of Physical Medicine and Rehabilitation

  2. Prioritizing multipurpose prevention technology development and investments using a target product profile.

    PubMed

    Romano, Joe; Manning, Judy; Hemmerling, Anke; McGrory, Elizabeth; Holt, Bethany Young

    2013-12-01

    Multipurpose prevention technologies (MPTs) represent a powerful opportunity to address the unmet sexual and reproductive health needs of women in at-risk populations around the world in an efficient and cost-effective manner. The development of MPT products for the combination prevention of pregnancy and sexually transmitted infections (including HIV) is a high-risk/high-gain, expensive process. The associated challenges are compounded by limitations in available resources for the development, evaluation, and delivery of such products. Consequently, an objective process for identifying MPT products with the highest public health impact potential is necessary to serve as the basis of coordinated investment of supporting agencies in the development of such products. Moreover, this process would serve as a framework for product development organizations, guiding their product development strategies. The Scientific Agenda Working Group of the Initiative for Multipurpose Prevention Technologies conducted an MPT pipeline evaluation exercise for the purpose of defining specific MPT product priorities, and to identify MPT technology gaps which need to be addressed in order to achieve development of optimal products. Through a formal and objective process, a set of MPT priority product recommendations emerged, along with several priority MPT gaps. Further, specific MPT development process priorities were identified. The detailed process and summary findings of this exercise are presented here. This article is based on a presentation at the "Product Development Workshop 2013: HIV and Multipurpose Prevention Technologies," held in Arlington, Virginia on February 21-22, 2013. It forms part of a special supplement to Antiviral Research. Copyright © 2013 Elsevier B.V. All rights reserved.

  3. Enhancing prevention in primary care: are interventions targeted towards consumers’ and providers’ perceived needs?

    PubMed Central

    Beaulieu, Marie‐Dominique; Talbot, Yves; Jadad, Alejandro R.; Xhignesse, Marianne

    2001-01-01

    Objective To explore perceived barriers to the implementation of prevention guidelines, with a particular interest to perceived information needs from the point of view of health professionals and consumers. Study Design Focus group. Setting and Participants Eight focus groups were held in three Canadian cities: three with consumer, three with family physician, and two with primary care nurses. Analysis Inductive analysis based on transcribed interviews. The material was analysed by two of the investigators. Agreement on interpretation was checked independently by three other researchers on 10% of the material. Results Lack of motivation, discontinuity of care and lack of adequate remuneration were perceived as the strongest barriers to prevention implementation. Computerized information management systems were not perceived by physicians and nurses as strong facilitating factors. Consumers expressed strongly a need for information on non‐traditional preventive interventions. Physicians and nurses expressed a need for patient education material more than for practice guidelines. Research evidence was not considered as the first criteria to judge the value of preventive information. Conclusions Evidence‐based medicine has triggered a massive effort to develop technologies to support the dissemination of evidence‐based information on the assumption that poor access to such information is an important barrier to implementation of effective practices. Our results suggest that such an assumption may not be correct. Providing only evidence‐based information from the realm of traditional medicine will appear restrictive to most users, particularly to consumers, and may not be as valued as anticipated considering the expressed scepticism toward research evidence. PMID:11281936

  4. Heart disease education and prevention program targeting immigrant Latinos: using focus group responses to develop effective interventions.

    PubMed

    Moreno, C; Alvarado, M; Balcazar, H; Lane, C; Newman, E; Ortiz, G; Forrest, M

    1997-12-01

    Although research has provided considerable knowledge concerning the positive effects of behavioral change on morbidity and mortality from heart disease and related risk factors, some segments of the population have not benefited equitably from this information. In April 1995, the National Heart, Lung, and Blood Institute (NHLBI) conducted seven focus groups to determine knowledge and attitudes about heart disease and associated risk factors, identify media usage and preferences, and assess publications usage and preferences among Spanish-speaking Latino immigrants residing in the Washington, D.C., metropolitan area. This information was gathered to assist in the development of key messages and strategies for the NHLBI Latino Community Cardiovascular Disease Prevention and Outreach Initiative, Salud para su Corazón--a heart disease prevention and education campaign. Findings from these focus groups indicate that Latinos may not benefit from heart disease prevention messages developed for the general population because of language and cultural differences. The researchers concluded that health education and disease prevention programs targeting the Latino community should develop educational materials and interventions that address language preferences and cultural values. Furthermore, to be effective, these programs should show people how to make positive behavioral changes based on their current circumstances, while remaining sensitive to the fact that Latino immigrants face major life adjustments and many are still greatly influenced by their country of origin.

  5. Docosahexaenoic acid prevents cognitive deficits in human apolipoprotein E epsilon 4-targeted replacement mice.

    PubMed

    Chouinard-Watkins, Raphaël; Vandal, Milène; Léveillé, Pauline; Pinçon, Anthony; Calon, Frédéric; Plourde, Mélanie

    2017-09-01

    At a population level, dietary consumption of fish rich in docosahexaenoic acid (DHA) is associated with prevention of cognitive decline but this association is not clear in carriers of the apolipoprotein E epsilon 4 allele (E4). Plasma and liver DHA concentrations show significant alterations in E4 carriers, in part corrected by DHA supplementation. However, whether DHA sufficiency in E4 carriers has consequences on cognition is unknown. Mice expressing human E4 or apolipoprotein E epsilon 3 allele (E3) were fed either a control diet or a diet containing DHA for 8 months and cognitive performance was tested using the object recognition test and the Barnes maze test. In E4 mice fed the control diet, impaired memory was detected and arachidonic acid concentrations were elevated in the hippocampus compared to E3 mice fed the control diet. DHA consumption prevented memory decline and restored arachidonic acid concentrations in the hippocampus of E4 mice. Our results suggest that long-term high-dose DHA intake may prevent cognitive decline in E4 carriers. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Tanning, Skin Cancer Risk, and Prevention: A Content Analysis of Eight Popular Magazines that Target Female Readers, 1997–2006

    PubMed Central

    Cho, Hyunyi; Hall, Jennifer G.; Kosmoski, Carin; Fox, Rebekah L.; Mastin, Teresa

    2008-01-01

    The majority of tanning bed users in the U.S. are women. Previous health communication research frequently focused on the risk of skin cancer, but few studies assessed the mediated communication environment that may surround women’s beliefs and behaviors relevant to tanning. A content analysis of articles in eight magazines targeting girls, young women, older women, and women who are interested in fitness during the ten-year period of 1997–2006 was conducted. The amount of coverage of tanning bed use consequences was less than 50% of the coverage of tanning benefits. About 40% of the tanning benefits coverage touted looking healthy. The coverage of prevention methods focused on sunscreen use (55%), while the more important methods (e.g., protective clothing use) were rarely featured. Longitudinally, the coverage of the risk and prevention relevant issues increased between 1997 and 2006. The data indicate that the coverage of tanning benefits also increased during the same period. PMID:20228954

  7. Cyclin-Dependent kinase 5 targeting prevents β-Amyloid aggregation involving glycogen synthase kinase 3β and phosphatases.

    PubMed

    Castro-Alvarez, John Fredy; Uribe-Arias, Alejandro; Cardona-Gómez, Gloria Patricia

    2015-08-01

    Inappropriate activation of cyclin-dependent kinase 5 (CDK5) resulting from proteolytic release of the activator fragment p25 from the membrane contributes to the formation of neurofibrillary tangles, β-amyloid (βA) aggregation, and chronic neurodegeneration. At 18 months of age, 3× Tg-AD mice were sacrificed after either 3 weeks (short term) or 1 year (long term) of CDK5 knockdown. In short-term-treated animals, CDK5 knockdown reversed βA aggregation in the hippocampi via inhibitory phosphorylation of glycogen synthase kinase 3β Ser9 and activation of phosphatase PP2A. In long-term-treated animals, CDK5 knockdown induced a persistent reduction in CDK5 and prevented βA aggregation, but the effect on amyloid precursor protein processing was reduced, suggesting that yearly booster therapy would be required. These findings further validate CDK5 as a target for preventing or blocking amyloidosis in older transgenic mice.

  8. Which population groups should be targeted for cardiovascular prevention? A modelling study based on the Norwegian Hordaland Health Study (HUSK).

    PubMed

    Brekke, Mette; Rekdal, Magne; Straand, Jørund

    2007-06-01

    To assess level of cardiovascular risk factors in a non-selected, middle-aged population. To estimate the proportion target for risk intervention according to present guidelines and according to different cut-off levels for two risk algorithms. Population survey, modelling study. The Norwegian Hordaland Health Study (HUSK) 1997-99. A total of 22 289 persons born in 1950-57. Own and relatives' cardiovascular morbidity, antihypertensive and lipid-lowering treatment, smoking, blood pressure, cholesterol. Framingham and Systematic Coronary Risk Evaluation (SCORE) algorithms. The European guidelines on CVD prevention in clinical practice were applied to estimate size of risk groups. Some 9.7% of men and 7.6% of women had CVD, diabetes mellitus, a high level of one specific risk factor, or received lipid-lowering or antihypertensive treatment. Applying a SCORE (60 years) cut-off level at 5% to the rest of the population selected 52.4% of men and 0.8% of women into a primary prevention group, while a cut-off level at 8% included 22.0% and 0.06% respectively. A cut-off level for the Framingham score (60 years) of 20% selected 43.6% of men and 4.7% of women, while a cut-off level of 25% selected 25.6% of men and 1.8% of women. The findings illustrate how choices regarding risk estimation highly affect the size of the target population. Modelling studies are important when preparing guidelines, to address implications for resource allocation and risk of medicalization. The population share to be targeted for primary prevention ought to be estimated, including the impact of various cut-off points for risk algorithms on the size of the risk population.

  9. Triennial Growth Symposium: a review of science leading to host-targeted antibody strategies for preventing growth depression due to microbial colonization.

    PubMed

    Cook, M E

    2011-07-01

    In this review, the science used to develop host-targeted therapies for improving animal growth and feed efficiency is presented. In contrast to targeting the microbiota of the host, endogenous host proteins are targeted to regulate an overactive inflammatory response in the host. Activation of the immune/inflammatory systems of an animal is costly in terms of growth and feed efficiency. For example, reduced rates of BW gain and poorer feed efficiency in vaccinated animals compared with nonvaccinated animals have been well documented. Also, the growth rate and feed efficiency of animals colonized by microorganisms is only 80 to 90% of their germ-free counterparts. Further evidence of a cost associated with immune activation is that strategies that enhance the immune capability of an animal can reduce animal growth and feed efficiency. Research now indicates that the growth-promoting effects of antibiotics are indirect, and more likely the result of reduced immune activation due to decreased microbial exposure. Studies of mechanisms by which immune/inflammatory activation reduces animal growth and feed efficiency have shown that cytokines of the acute inflammatory response (i.e., IL-1 and tumor necrosis factor α) are key triggers for host muscle wasting. Cytokine-induced muscle wasting is linked to PG signaling pathways, and it has been proposed that regulation of the PG signaling pathways provide host targets for preventing an overreactive or unwarranted inflammatory event. Intestinal secretory phospholipase A(2) (sPLA(2)) has been found to be a useful and accessible (i.e., found in the intestinal lumen) host target for the regulation of an overreactive inflammatory response to conventional environments. This review presents the science and strategy for the regulation of intestinal sPLA(2) using orally administered egg yolk antibody against the enzyme. Clinically healthy animals fed egg antibodies to sPLA(2) had improved growth and feed efficiency. Literature

  10. Prevention of alcohol abuse-related birth effects--II. Targeting and pricing.

    PubMed

    Abel, E L

    1998-01-01

    Current public health measures to reduce the occurrence of fetal alcohol abuse syndrome (FAAS) and alcohol abuse-related birth effects (AARBEs) have been ineffective, because they target alcohol consumption, rather than alcohol abuse. The present discussion contends that the most effective public health strategy for reducing FAAS and AARBEs is a combination of more specific public health messages that target alcohol abuse, coupled with higher taxes on alcohol beverages. Although alcohol consumption by alcohol abusers has been thought to be inelastic to price changes, recent studies have found that both heavy drinking and binge drinking are sensitive to alcohol price changes, and price elasticities are relatively high for heavy drinkers who are aware of the consequences of their drinking. Although price increases may have a disproportionate impact on lower socioeconomic groups, this article concludes that they are justifiable from both a utilitarian and a categorical imperative perspective.

  11. Targeted Delivery of Shear Stress-Inducible Micrornas by Nanoparticles to Prevent Vulnerable Atherosclerotic Lesions

    PubMed Central

    Wong, Wing Tak; Ma, Shuangtao; Tian, Xiao Yu; Gonzalez, Andrea Banuet; Ebong, Eno E.; Shen, Haifa

    2016-01-01

    Atherosclerosis is a chronic inflammatory vascular wall disease, and endothelial cell dysfunction plays an important role in its development and progression. Under the influence of laminar shear stress, however, the endothelium releases homeostatic factors such as nitric oxide and expresses of vasoprotective microRNAs that are resistant to atherosclerosis. Adhesion molecules such as E-selectin, exhibited on the endothelial surface, recruit monocytes that enter the vessel wall to form foam cells. Accumulation of these foam cells form fatty streaks that may progress to atherosclerotic plaques in the blood vessel wall. Interestingly, E-selectin may also serve as an affinity moiety for targeted drug delivery against atherosclerosis. We have recently developed an E-selectin-targeted platform that enriches therapeutic microRNAs in the inflamed endothelium to inhibit formation of vulnerable atherosclerotic plaques. PMID:27826369

  12. Targeting TGF-β Mediated SMAD Signaling for the Prevention of Fibrosis

    PubMed Central

    Walton, Kelly L.; Johnson, Katharine E.; Harrison, Craig A.

    2017-01-01

    Fibrosis occurs when there is an imbalance in extracellular matrix (ECM) deposition and degradation. Excessive ECM deposition results in scarring and thickening of the affected tissue, and interferes with tissue and organ homeostasis – mimicking an exaggerated “wound healing” response. Many transforming growth factor-β (TGF-β) ligands are potent drivers of ECM deposition, and additionally, have a natural affinity for the ECM, creating a concentrated pool of pro-fibrotic factors at the site of injury. Consequently, TGF-β ligands are upregulated in many human fibrotic conditions and, as such, are attractive targets for fibrosis therapy. Here, we will discuss the contribution of TGF-β proteins in the pathogenesis of fibrosis, and promising anti-fibrotic approaches that target TGF-β ligands. PMID:28769795

  13. A Novel Theranostic Platform for Targeted Cancer Therapy and Treatment Monitoring | Division of Cancer Prevention

    Cancer.gov

    DESCRIPTION (provided by applicant): Cancer treatment currently relies heavily upon administration of cytotoxic drugs that attack both cancerous and healthy cells due to limited selectivity of drugs. Therapeutic efficacy and systemic toxicity can be improved by employing a multifunctional drug delivery system that allows targeted drug delivery, controlled drug release and therapeutic effect monitoring. The integration of therapeutic and diagnostic treatments has created a new genre in patient care and personalized medicine termed theranostics. |

  14. Early detection of ovarian cancer by serum marker and targeted ultrasound imaging | Division of Cancer Prevention

    Cancer.gov

    ABSTRACT We propose to test the validity and specificity of our targeted ultrasound imaging probes in detecting early stage ovarian cancer (OVCA) by transvaginal ultrasound imaging (TVUS). We then test the predictive validity of these probes in a longitudinal study using the laying hen ? the only widely available animal model of spontaneous OVCA. OVCA is a fatal gynecological malignancy of women. An effective early detection test could reduce high mortality rate due to OVCA and morbidity associated with exploratory surgeries significantly. |

  15. Estrogen-Induced Depurination of DNA: A Novel Target for Breast Cancer Prevention

    DTIC Science & Technology

    2007-05-01

    tissue can synthesize E2 in situ suggests that much more E2 is present in target tissues than would be predicted fromplasma concentrations [61]. A...filled by DNA synthesis. Therefore, errors in BER would generate mutations in the newly- synthesized strand, i.e., mismatched heteroduplexes. A.T to G.C...A spiking procedure with synthesized DNA adduct-standards and absorption spectroscopy was used to identify the biomarkers of interest. In Fig. 8

  16. CFTR chloride channel is a molecular target of the natural cancer preventive agent resveratrol.

    PubMed

    Yang, Shuang; Yu, B O; Sui, Yujie; Zhang, Yaofang; Wang, Xue; Hou, Shuguang; Ma, Tonghui; Yang, Hong

    2013-09-01

    The naturally occurring polyphenol compound resveratrol (RES) has been receiving wide attention because of its variety of health benefits and favourable biological activities. Previous studies have shown that RES could induce intestinal chloride secretion in mouse jejunum and stimulate cAMP-dependent Cl- secretion in T84, primary cultured murine nasal septal and human sinonasal epithelial cells, but the precise molecular target is not clear. We therefore tested the hypothesis that RES may stimulate the activity of cystic fibrosis transmembrane conductance regulator (CFTR) chloride channel. Using cell-based fluorescent assays, transepithelial short-circuit current measurements and excised inside-out patch-clamp analysis; we found that RES dose-dependently potentiate CFTR Cl- channel activities, which was reversed by CFTR inhibitors CFTR(inh)-172 and GlyH101. Transepithelial Cl- secretion by CFTR-expressing FRT cells was stimulated by RES with half maximal concentration -80 microM. Intracellular cAMP content was not elevated by RES in FRT cells. Excised inside-out patch-clamp analysis indicated that RES significantly increased the chloride currents of CFTR. In ex vivo studies, RES stimulated the transmucosal chloride current of rat colon by short-circuit current assay. These data suggested that CFTR is a molecular target of RES. Our findings add a new molecular target to RES, and RES may represent a novel class of therapeutic lead compounds in treating CFTR-related diseases including CF and habitual constipation.

  17. Comparative Effectiveness of Targeted vs Empirical Antibiotic Prophylaxis to Prevent Sepsis from Transrectal Prostate Biopsy: A Retrospective Analysis.

    PubMed

    Liss, Michael A; Kim, William; Moskowitz, Dena; Szabo, Richard J

    2015-08-01

    We compared the effectiveness of targeted prophylaxis to the effectiveness of empirical prophylaxis for preventing sepsis after transrectal prostate biopsy using a retrospective multicenter quality improvement study. A total of 13 Kaiser Permanente urology departments participated in a 1-year retrospective analysis of a quality improvement study. In the targeted prophylaxis group rectal cultures were performed before transrectal prostate biopsy and antibiotic sensitivities of Escherichia coli were used to guide the selection of a single agent antibiotic for prophylaxis. Cultures were plated on 10 μg/ml ciprofloxacin infused MacConkey agar at a central laboratory. Urologists using empirical prophylaxis continued the usual regimen of ciprofloxacin monotherapy prophylaxis but sometimes added an additional prophylactic antibiotic. The primary outcome of post-biopsy sepsis was compiled by a search of the electronic medical record for the appropriate ICD-9 codes. A total of 5,355 prostate biopsy procedures were performed between May 1, 2013 and April 30, 2014. Targeted prophylaxis was used in 1,802 procedures (34%) and empirical prophylaxis was used in 3,553 (66%). The overall incidence of post-biopsy sepsis was 0.52% (28 of 5,355 cases). The incidence of sepsis was 0.44% (8 of 1,802 cases) in the targeted prophylaxis group and 0.56% (20 of 3,553) in the empirical prophylaxis group (p = 0.568). The prevalence of ciprofloxacin resistant E. coli on rectal culture was 25% (444 of 1,802 cases). Seven of the 8 patients (88%) on targeted prophylaxis in whom sepsis developed used a prophylactic antibiotic to which the bacteria causing post-biopsy sepsis were sensitive. The targeted prophylaxis protocol enabled physicians to avoid using more than 1 broad-spectrum empirical antibiotic while simultaneously achieving an overall rate of sepsis similar to the rate seen with empirical prophylaxis. Copyright © 2015 American Urological Association Education and Research, Inc

  18. Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation.

    PubMed

    Lawrence, Helen; Mawdesley, Amy Elizabeth; Holland, James Patrick; Kirby, John Andrew; Deehan, David John; Tyson-Capper, Alison Jane

    2016-02-16

    Cobalt-chrome alloy is a widely used biomaterial in joint replacements, dental implants and spinal rods. Although it is an effective and biocompatible material, adverse reactions to metal debris (ARMD) have arisen in a minority of patients, particularly in those with metal-on-metal bearing hip replacements. There is currently no treatment for ARMD and once progressive, early revision surgery of the implant is necessary. Therapeutic agents to prevent, halt or reverse ARMD would therefore be advantageous. Cobalt ions activate Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to bacterial lipopolysaccharide (LPS) resulting in the production of pro-inflammatory cytokines and chemokines. We hypothesised that anti-TLR4 neutralising antibodies, reported to inhibit TLR4-mediated inflammation, could prevent the inflammatory response to cobalt ions in an in vitro macrophage cell culture model. This study shows that a monoclonal anti-TLR4 antibody inhibited cobalt-mediated increases in pro-inflammatory IL8, CCL20 and IL1A expression, as well as IL-8 secretion. In contrast, a polyclonal antibody did not prevent the effect of cobalt ions on either IL-8 or IL1A expression, although it did have a small effect on the CCL20 response. Interestingly, both antibodies inhibited cobalt-mediated neutrophil migration although the greater effect was observed with the monoclonal antibody. In summary our data shows that a monoclonal anti-TLR4 antibody can inhibit cobalt-mediated inflammatory responses while a polyclonal antibody only inhibits the effect of specific cytokines. Anti-TLR4 antibodies have therapeutic potential in ARMD although careful antibody design is required to ensure that the LPS response is preserved.

  19. Targeting Toll-like receptor 4 prevents cobalt-mediated inflammation

    PubMed Central

    Lawrence, Helen; Mawdesley, Amy Elizabeth; Holland, James Patrick; Kirby, John Andrew; Deehan, David John; Tyson-Capper, Alison Jane

    2016-01-01

    Cobalt-chrome alloy is a widely used biomaterial in joint replacements, dental implants and spinal rods. Although it is an effective and biocompatible material, adverse reactions to metal debris (ARMD) have arisen in a minority of patients, particularly in those with metal-on-metal bearing hip replacements. There is currently no treatment for ARMD and once progressive, early revision surgery of the implant is necessary. Therapeutic agents to prevent, halt or reverse ARMD would therefore be advantageous. Cobalt ions activate Toll-like receptor 4 (TLR4), an innate immune receptor responsible for inflammatory responses to bacterial lipopolysaccharide (LPS) resulting in the production of pro-inflammatory cytokines and chemokines. We hypothesised that anti-TLR4 neutralising antibodies, reported to inhibit TLR4-mediated inflammation, could prevent the inflammatory response to cobalt ions in an in vitro macrophagecell culture model. This study shows that a monoclonal anti-TLR4 antibody inhibited cobalt-mediated increases in pro-inflammatory IL8, CCL20 and IL1A expression, as well as IL-8 secretion. In contrast, a polyclonal antibody did not prevent the effect of cobalt ions on either IL-8 or IL1A expression, although it did have a small effect on the CCL20 response. Interestingly, both antibodies inhibited cobalt-mediated neutrophil migration although the greater effect was observed with the monoclonal antibody. In summary our data shows that a monoclonal anti-TLR4 antibody can inhibit cobalt-mediated inflammatory responses while a polyclonal antibody only inhibits the effect of specific cytokines. Anti-TLR4 antibodies have therapeutic potential in ARMD although careful antibody design is required to ensure that the LPS response is preserved. PMID:26840091

  20. Preclinical sporadic Alzheimer's disease: target for personalized diagnosis and preventive intervention.

    PubMed

    Vanitallie, Theodore B

    2013-01-01

    The most opportune time for preventive intervention in sporadic Alzheimer's disease (spAD) is early in its preclinical stage (pcAD), when the odds of preventing or minimizing later disabling neurodegeneration are most favorable. The efficacy of promising preventive interventions should be assessed in patients in the earliest discernible phase of pcAD. This will require application of personalized medicine techniques, with use of suitable biomarkers to detect pcAD in individuals believed to be spAD-prone. This review focuses on the genetic biomarker, apolipoprotein E (apoE) ε4, and on certain neuroimaging biomarkers, such as structural MRI (sMRI), fluorodeoxyglucose-positron emission tomography (FDG-PET), and PET-amyloid tracers capable of delineating the extent and distribution of amyloid-beta (Aβ) deposits in the brain, that can be useful in identifying cognitively normal people who are at enhanced risk of developing spAD. Many years before AD symptoms appear, such neuroimaging procedures can disclose signature abnormalities of brain structure, function, and amyloid levels in cognitively normal apoE ε4 allele carriers and/or individuals with a family history of spAD. Although no effective treatment for spAD is yet available, there is evidence that, by taking a proactive personalized-medicine approach, the practicing physician may be able to reduce risk in AD-prone patients by attending to such modifiable AD risk factors as hypertension, obesity, type 2 diabetes, insulin resistance, hypercholesterolemia, sedentary lifestyle, and current cigarette smoking. Young patients who are ε4 positive should be advised to avoid participation in contact sports or other activities that expose them to risk of traumatic brain injury. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Evidence-based recommendations for the development of obesity prevention programs targeted at preschool children.

    PubMed

    Summerbell, C D; Moore, H J; Vögele, C; Kreichauf, S; Wildgruber, A; Manios, Y; Douthwaite, W; Nixon, C A; Gibson, E L

    2012-03-01

    The ToyBox intervention was developed using an evidence-based approach, using the findings of four reviews. These reviews included three critical and narrative reviews of educational strategies and psychological approaches explaining young children's acquisition and formation of energy-balance related behaviours, and the management of these behaviours, and also a systematic review of behavioural models underpinning school-based interventions in preschool and school settings for the prevention of obesity in children aged 4-6 years. This paper summarises and translates the findings from these reviews into practical evidence based recommendations for researchers and policy-makers to consider when developing and implementing interventions for the prevention of overweight and obesity in young (aged 4-6 years) children. The recommendations focus on two behaviours, physical activity and sedentary behaviour, and healthy eating, and include general recommendations, intervention approaches, interventions content, and simple messages. The review also briefly examines the role that the commercial sector plays in hindering or facilitating attempts to create healthy food environments for children. This paper also recognises that childhood obesity is not an issue for the education sector alone; it needs to be tackled at a multi sectoral level, recognizing the particularly important role of local governments, nongovernment organizations and the media.

  2. Trapping of growth factors by catechins: a possible therapeutical target for prevention of proliferative diseases.

    PubMed

    Doss, Michael Xavier; Potta, Shiva Prasad; Hescheler, Jürgen; Sachinidis, Agapios

    2005-05-01

    The prevention of cancer through dietary intervention is currently receiving considerable attention. Several epidemiological studies substantiate that green tea has a protective effect against a variety of malignant proliferative disorders such as lung cancer, breast cancer and prostate cancer. This preventive potential of green tea against cancer is attributed to the biologically active flavonoids called catechins. Epigallocatechin 3-o-gallate, the major catechin found in green tea, mediates diverse physiological and pharmacological actions in bringing about the regression of the tumors and also lowers the risk of nonmalignant cardiovascular proliferative diseases. Much of the current research is being focused on how these catechins specifically bring about the regression of the experimentally induced tumors both in vitro and in vivo. These catechins exert diverse physiological effects against proliferative diseases by several mechanisms, most of which are not completely characterized. This review summarizes the mechanisms by which these catechins play an essential role in regulating the process of carcinogenesis, with a special emphasis on how these catechins antagonize the growth factor-induced proliferative disorders.

  3. Local microRNA delivery targets Palladin and prevents metastatic breast cancer

    PubMed Central

    Gilam, Avital; Conde, João; Weissglas-Volkov, Daphna; Oliva, Nuria; Friedman, Eitan; Artzi, Natalie; Shomron, Noam

    2016-01-01

    Metastasis is the primary cause for mortality in breast cancer. MicroRNAs, gene expression master regulators, constitute an attractive candidate to control metastasis. Here we show that breast cancer metastasis can be prevented by miR-96 or miR-182 treatment, and decipher the mechanism of action. We found that miR-96/miR-182 downregulate Palladin protein levels, thereby reducing breast cancer cell migration and invasion. A common SNP, rs1071738, at the miR-96/miR-182-binding site within the Palladin 3′-UTR abolishes miRNA:mRNA binding, thus diminishing Palladin regulation by these miRNAs. Regulation is successfully restored by applying complimentary miRNAs. A hydrogel-embedded, gold-nanoparticle-based delivery vehicle provides efficient local, selective, and sustained release of miR-96/miR-182, markedly suppressing metastasis in a breast cancer mouse model. Combined delivery of the miRNAs with a chemotherapy drug, cisplatin, enables significant primary tumour shrinkage and metastasis prevention. Our data corroborate the role of miRNAs in metastasis, and suggest miR-96/miR-182 delivery as a potential anti-metastatic drug. PMID:27641360

  4. Empirical development of brief smoking prevention videotapes which target African-American adolescents.

    PubMed

    Sussman, S; Parker, V C; Lopes, C; Crippens, D L; Elder, P; Scholl, D

    1995-07-01

    Two studies are described which provide evaluations for two brief videotapes developed as supplemental materials in the prevention of tobacco use among African-American adolescents. One videotape (the "soap opera") provides a more general audience-oriented presentation of prevention material and it was filmed primarily at a shopping mall, whereas the other videotape (the "rap") provides a "hip-hop generation" presentation, and it was filmed primarily at an outdoor hangout. The first study compared the two videotapes against each other. The second study compared the two videotapes combined in the same presentation, controlling for order of presentation, against a discussion group control. The results of the two studies indicated few differences in receptivity to the two videotapes among primarily African-American and Latino young adolescents. The rap videotape was rated as more accurate in its depiction of the African-American lifestyle, although both videotapes were equally liked. When shown together, the videotapes were not found to be superior in decreasing behavioral intention to smoke compared to a discussion group control. No change in trial of smoking was observed within or across conditions measured over a pre-post summer interval. These data suggest that "culturally sensitive" videotapes have no more of a short-term effect on youth than do other types of brief interventions which involve minority implementers.

  5. The cell cycle: A critical therapeutic target to prevent vascular proliferative disease

    PubMed Central

    Charron, Thierry; Nili, Nafiseh; Strauss, Bradley H

    2006-01-01

    Percutaneous coronary intervention is the preferred revascularization approach for most patients with coronary artery disease. However, this strategy is limited by renarrowing of the vessel by neointimal hyperplasia within the stent lumen (in-stent restenosis). Vascular smooth muscle cell proliferation is a major component in this healing process. This process is mediated by multiple cytokines and growth factors, which share a common pathway in inducing cell proliferation: the cell cycle. The cell cycle is highly regulated by numerous mechanisms ensuring orderly and coordinated cell division. The present review discusses current concepts related to regulation of the cell cycle and new therapeutic options that target aspects of the cell cycle. PMID:16498512

  6. Efficacy trial of a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain among female college students.

    PubMed

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C Nathan

    2012-02-01

    Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women. Female college students at high-risk for these outcomes by virtue of body image concerns (N = 398; M age = 18.4 years, SD = 0.6) were randomized to the Healthy Weight group-based 4-hr prevention program, which promotes gradual lasting healthy improvements to dietary intake and physical activity, or an educational brochure control condition. Compared to controls, intervention participants showed significantly greater reductions in body dissatisfaction and eating disorder symptoms, and greater increases in physical activity, at posttest and significantly greater reductions in body mass index (BMI) and self-reported dieting at 6-month follow-up. Moderator analyses revealed significantly greater reductions in eating disorder symptoms for those with initially elevated symptoms and pressure to be thin and significantly greater reductions in BMI for those with initially elevated eating disorder symptoms. Results indicate that this intervention reduced both eating disorder symptoms and unhealthy weight gain, but suggest it should be improved to produce stronger and more persistent effects, and that it may be useful to target young women with both body image and eating disturbances. (PsycINFO Database Record (c) 2012 APA, all rights reserved).

  7. Molecular approaches toward targeted cancer prevention with some food plants and their products: inflammatory and other signal pathways.

    PubMed

    Khuda-Bukhsh, Anisur Rahman; Das, Sreemanti; Saha, Santu Kumar

    2014-01-01

    In recent years, there has been growing interest in cancer prevention by food plants and their products. Although several plant parts have potentials for chemoprevention and other therapeutic use, their molecular mechanisms of action are not always well understood. Extensive research has identified several molecular targets that can potentially be used for the prevention and/or treatment of cancer. In this review, we accumulate evidences of modulating abilities of some dietary plants and their products on several signaling pathways, including the inflammatory and apoptotic ones, which may be targeted for cancer therapy. We have mainly focused on several phytochemicals like resveratrol (red grapes and peanuts), allicin (garlic), lycopene (tomato), indole-3-carbinol (cruciferous vegetables), vitamin C (citrus fruits), [6]-gingerol (ginger), emodin (aloe), natural antioxidant mixture (spinach), beta carotenoids (carrots), sulphoraphane (mustard), ellagic acid (pomegranate), myrecitin (cranberry), carnosol (rosemary), vanillin (vanilla) and eugenol (cloves). They act through one or more signaling pathways like nuclear factor kappa B, cyclooxygenase-2, signal transducer and activator of transcription 3, Akt, mitogen activated protein kinase/extracellular regulated kinase, Bcl-2, caspases, poly (ADP-ribose) polymerase, matrix metalloproteinase 2/9, and cyclin D1. Critical knowledge on these compounds and their signaling pathways may help in formulation of effective anticancer drugs.

  8. The Keap1-Nrf2-ARE Pathway As a Potential Preventive and Therapeutic Target: An Update.

    PubMed

    Lu, Meng-Chen; Ji, Jian-Ai; Jiang, Zheng-Yu; You, Qi-Dong

    2016-09-01

    The Keap1-Nrf2-ARE ((Kelch-like ECH-Associating protein 1) nuclear factor erythroid 2 related factor 2-antioxidant response element) pathway is one of the most important defense mechanisms against oxidative and/or electrophilic stresses, and it is closely associated with inflammatory diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, and aging. In recent years, progress has been made in strategies aimed at modulating the Keap1-Nrf2-ARE pathway. The Nrf2 activator DMF (Dimethylfumarates) has been approved by the FDA as a new first-line oral drug to treat patients with relapsing forms of multiple sclerosis, while a phase 3 study of another promising candidate, CDDO-Me, was terminated for safety reasons. Directly inhibiting Keap1-Nrf2 protein-protein interactions as a novel Nrf2-modulating strategy has many advantages over using electrophilic Nrf2 activators. The development of Keap1-Nrf2 protein-protein interaction inhibitors has become a topic of intense research, and potent inhibitors of this target have been identified. In addition, inhibiting Nrf2 activity has attracted an increasing amount of attention because it may provide an alternative cancer therapy. This review summarizes the molecular mechanisms and biological functions of the Keap1-Nrf2-ARE system. The main focus of this review is on recent progress in studies of agents that target the Keap1-Nrf2-ARE pathway and the therapeutic applications of such agents.

  9. Taxi Drivers: A Target Population for the Prevention of Transmissible Disease?

    PubMed

    Limper, Heather M; Burns, Jennifer L; Alexander, Kenneth A

    2016-04-01

    We set out to assess the feasibility and uptake of an on-site influenza vaccination campaign targeting taxi drivers in airport taxicab lots in Chicago, Illinois. Influenza vaccine was provided by the Chicago Department of Public Health as this event aligned with ongoing efforts to provide influenza vaccinations throughout the city. Clinicians and clinic support staff were volunteers recruited from the University of Chicago Medicine and incorporated nursing staff, physicians, physician residents, and administrative support. Together, this allowed for a cost-effective approach to provide free influenza vaccines to the primarily uninsured taxi driver population. During these events, 545 taxi drivers received influenza vaccine in 2012 while 354 drivers were immunized in 2013. Nearly all drivers reported uninsured or under-insured status. The ability to use volunteers and healthcare organization's desires to meet the needs of the community, in collaboration with often under-staffed but highly dedicated local health departments have the potential to offer valuable public health services to underserved members of the community. Educational initiatives targeting vaccine hesitancy and misinformation may be necessary to improve immunization coverage among this population.

  10. shRNA targeting α-synuclein prevents neurodegeneration in a Parkinson’s disease model

    PubMed Central

    Zharikov, Alevtina D.; Cannon, Jason R.; Tapias, Victor; Bai, Qing; Horowitz, Max P.; Shah, Vipul; El Ayadi, Amina; Hastings, Teresa G.; Greenamyre, J. Timothy; Burton, Edward A.

    2015-01-01

    Multiple convergent lines of evidence implicate both α-synuclein (encoded by SCNA) and mitochondrial dysfunction in the pathogenesis of sporadic Parkinson’s disease (PD). Occupational exposure to the mitochondrial complex I inhibitor rotenone increases PD risk; rotenone-exposed rats show systemic mitochondrial defects but develop specific neuropathology, including α-synuclein aggregation and degeneration of substantia nigra dopaminergic neurons. Here, we inhibited expression of endogenous α-synuclein in the adult rat substantia nigra by adeno-associated virus–mediated delivery of a short hairpin RNA (shRNA) targeting the endogenous rat Snca transcript. Knockdown of α-synuclein by ~35% did not affect motor function or cause degeneration of nigral dopaminergic neurons in control rats. However, in rotenone-exposed rats, progressive motor deficits were substantially attenuated contralateral to α-synuclein knockdown. Correspondingly, rotenone-induced degeneration of nigral dopaminergic neurons, their dendrites, and their striatal terminals was decreased ipsilateral to α-synuclein knockdown. These data show that α-synuclein knockdown is neuroprotective in the rotenone model of PD and indicate that endogenous α-synuclein contributes to the specific vulnerability of dopaminergic neurons to systemic mitochondrial inhibition. Our findings are consistent with a model in which genetic variants influencing α-synuclein expression modulate cellular susceptibility to environmental exposures in PD patients. shRNA targeting the SNCA transcript should be further evaluated as a possible neuroprotective therapy in PD. PMID:26075822

  11. PERIPARTUM DEPRESSION AND ANXIETY AS AN INTEGRATIVE CROSS DOMAIN TARGET FOR PSYCHIATRIC PREVENTATIVE MEASURES

    PubMed Central

    Babb, Jessica A.; Deligiannidis, Kristina M.; Murgatroyd, Christopher A.

    2014-01-01

    Exposure to high levels of early life stress has been identified as a potent risk factor for neurodevelopmental delays in infants, behavioral problems and autism in children, but also for several psychiatric illnesses in adulthood, such as depression, anxiety, autism, and posttraumatic stress disorder. Despite having robust adverse effects on both mother and infant, the pathophysiology of peripartum depression and anxiety are poorly understood. The objective of this review is to highlight the advantages of using an integrated approach addressing several behavioral domains in both animal and clinical studies of peripartum depression and anxiety. It is postulated that a greater focus on integrated cross domain studies will lead to advances in treatments and preventative measures for several disorders associated with peripartum depression and anxiety. PMID:24709228

  12. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression

    PubMed Central

    Gucalp, Ayca; Iyengar, Neil M.; Hudis, Clifford A.; Dannenberg, Andrew J.

    2016-01-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. PMID:26970134

  13. Targeting obesity-related adipose tissue dysfunction to prevent cancer development and progression.

    PubMed

    Gucalp, Ayca; Iyengar, Neil M; Hudis, Clifford A; Dannenberg, Andrew J

    2016-02-01

    The incidence of obesity, a leading modifiable risk factor for common solid tumors, is increasing. Effective interventions are needed to minimize the public health implications of obesity. Although the mechanisms linking increased adiposity to malignancy are incompletely understood, growing evidence points to complex interactions among multiple systemic and tissue-specific pathways including inflamed white adipose tissue. The metabolic and inflammatory consequences of white adipose tissue dysfunction collectively provide a plausible explanation for the link between overweight/obesity and carcinogenesis. Gaining a better understanding of these underlying molecular pathways and developing risk assessment tools that identify at-risk populations will be critical in implementing effective and novel cancer prevention and management strategies. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Neuroscience of alcohol for addiction medicine: Neurobiological targets for prevention and intervention in adolescents.

    PubMed

    Cservenka, Anita; Nagel, Bonnie J

    2016-01-01

    Structural and functional neuroimaging studies indicate that heavy alcohol use during adolescence may be neurotoxic to the brain. This chapter reviews the neuroimaging findings in cross-sectional and longitudinal studies of adolescent heavy alcohol users. These youth exhibit reductions in prefrontal, hippocampal, and cerebellar brain volume, decreased frontoparietal, and increased frontolimbic white matter integrity, as well as alterations in blood oxygen level-dependent response during working memory, inhibitory control, verbal encoding, decision making, and reward processing-some of which appear to differ between males and females. Although some exist, additional longitudinal studies will significantly advance addiction medicine by aiding prevention scientists and treatment providers to develop neurobiologically informed ways of strengthening neural networks prior to and after the onset of heavy alcohol use, thereby promoting healthy cognitive functioning across the adolescent period. © 2016 Elsevier B.V. All rights reserved.

  15. Are the neurotrophic factors a suitable therapeutic target for the prevention of epileptogenesis?

    PubMed

    Simonato, Michele; Zucchini, Silvia

    2010-07-01

    Neurotrophic factors are involved in the survival of neurons as well as in the proliferation and differentiation of neuronal precursors. Therefore, modulating their levels in lesion areas may exert favorable effects on seizure-induced damage. However, it is unclear if damage limitation or repair may prevent epileptogenesis; it is also uncertain which neurotrophic factor should be administered for limiting or repairing damage while avoiding possible proepileptic effects. We used viral vectors to locally supplement fibroblast growth factor-2 (FGF-2) and brain-derived neurotrophic factor (BDNF), when an epileptogenic damage was already in place. These vectors were tested in the pilocarpine model of status epilepticus-induced neurodegeneration and epileptogenesis. FGF-2/BDNF expressing vectors increased neuronogenesis, limited neuronal damage, and reduced the occurrence of spontaneous seizures. These findings are discussed with consideration of the hurdles that will have to be overcome before clinical application.

  16. Application of the multiphase optimization strategy to a pilot study: an empirical example targeting obesity among children of low-income mothers.

    PubMed

    Kugler, Kari C; Balantekin, Katherine N; Birch, Leann L; Savage, Jennifer S

    2016-11-22

    Emerging approaches to building more efficient and effective behavioral interventions are becoming more widely available. The current paper provides an empirical example of the use of the engineering-inspired multiphase optimization strategy (MOST) to build a remotely delivered responsive parenting intervention to prevent obesity among children of low-income mothers with and without depressive symptoms. Participants were 107 mothers with (n = 45) and without (n = 62) depressive symptoms who had a child aged 12 to 42 months participating in the Women, Infants and Children program. Participants were randomized to one of sixteen experimental conditions using a factorial design that included a combination of the following eight remotely delivered intervention components: responsive feeding curriculum (given to all participants), parenting curriculum, portion size guidance, obesogenic risk assessment, personalized feedback on mealtime routines, feeding curriculum counseling, goal setting, mobile messaging, and social support. This design enabled efficient identification of components with low feasibility and acceptability. Completion rates were high (85%) and did not statistically differ by depressive symptoms. However, mothers with depressive symptoms who received obesogenic risk assessment and personalized feedback on mealtime routines components had lower completion rates than mothers without depressive symptoms. All intervention components were feasible to implement except the social support component. Regardless of experimental condition, most participants reported that the program increased their awareness of what, when, and how to feed their children. MOST provided an efficient way to assess the feasibility of components prior to testing them with a fully powered experiment. This framework helped identify potentially challenging combinations of remotely delivered intervention components. Consideration of how these results can inform future studies

  17. The strategic framework of tuberculosis control and prevention in the elderly: a scoping review towards End TB targets.

    PubMed

    Li, Jun; Chung, Pui-Hong; Leung, Cyrus L K; Nishikiori, Nobuyuki; Chan, Emily Y Y; Yeoh, Eng-Kiong

    2017-06-01

    With the rapid pace of population ageing, tuberculosis (TB) in the elderly increasingly becomes a public health challenge. Despite the increasing burden and high risks for TB in the elderly, targeted strategy has not been well understood and evaluated. We undertook a scoping review to identify current TB strategies, research and policy gaps in the elderly and summarized the results within a strategic framework towards End TB targets. Databases of Embase, MEDLINE, Global health and EBM reviews were searched for original studies, review articles, and policy papers published in English between January 1990 and December 2015. Articles examining TB strategy, program, guideline or intervention in the elderly from public health perspective were included.Nineteen articles met the inclusion criteria. Most of them were qualitative studies, issued in high- and middle-income countries and after 2000. To break the chain of TB transmission and reactivation in the elderly, infection control, interventions of avoiding delay in diagnosis and containment are essential for preventing transmission, especially in elderly institutions and aged immigrants; screening of latent TB infection and preventive therapy had effective impacts on reducing the risk of reactivation and should be used less reluctantly in older people; optimizing early case-finding with a high index of suspicion, systematic screening for prioritized high-risk groups, initial empirical and adequate follow-up treatment with close monitoring and evaluation, as well as enhanced programmatic management are fundamental pillars for active TB elimination. Evaluation of TB epidemiology, risk factors, impacts and cost-effectiveness of interventions, adopting accurate and rapid diagnostic tools, shorter and less toxic preventive therapy, are critical issues for developing strategy in the elderly towards End TB targets.TB control strategies in the elderly were comprehensively mapped in a causal link pathway. The framework and

  18. Internet based HIV prevention research targeting rural MSM: feasibility, acceptability, and preliminary efficacy

    PubMed Central

    Williams, M. L.; Daniel, C. M.; Clayton, S.

    2008-01-01

    Internet delivered primary prevention interventions for HIV risk reduction present significant challenges. Changing lifestyle behaviors, such as beginning to use condoms, is difficult and men seeking dates on line may want to avoid thinking about HIV risk which may lead to low initiation and high dropout rates. Many Internet delivered HIV risk reduction programs have mimicked face-to-face outreach programs, failing to take advantage of the Internet’s capabilities or did not conduct evaluation. This study focuses on examining the feasibility, acceptability, and efficacy of an Internet delivered HIV risk reduction program for rural men who have sex with men (MSM). The program included online recruiting, three intervention modules, each with two sessions, online questionnaires. The intervention was developed based on iterative research and the Information-Motivation-Behavioral skills model. Participants (N = 475) were randomly assigned to one of six module orders and data were collected automatically at pre-test and after each module. Data supports the feasibility and acceptability of the program as demonstrated by good retention and rapid program completion. Knowledge, self-efficacy, outcome expectancies and motivation increase in a dose response fashion. Post-intervention behavior changes included reduced anal sex and significant increases in condom use. Limitations include a short follow-up period, a predominantly young white rural sample, and the lack of an attention control. Overall the results of the study provide support for the efficacy of Internet-based interventions to reduce risk of HIV infection. Results also support traditional research methods to evaluate HIV prevention programs delivered exclusively through the Internet. PMID:18770021

  19. Internet based HIV prevention research targeting rural MSM: feasibility, acceptability, and preliminary efficacy.

    PubMed

    Bowen, A M; Williams, M L; Daniel, C M; Clayton, S

    2008-12-01

    Internet delivered primary prevention interventions for HIV risk reduction present significant challenges. Changing lifestyle behaviors, such as beginning to use condoms, is difficult and men seeking dates on line may want to avoid thinking about HIV risk which may lead to low initiation and high dropout rates. Many Internet delivered HIV risk reduction programs have mimicked face-to-face outreach programs, failing to take advantage of the Internet's capabilities or did not conduct evaluation. This study focuses on examining the feasibility, acceptability, and efficacy of an Internet delivered HIV risk reduction program for rural men who have sex with men (MSM). The program included online recruiting, three intervention modules, each with two sessions, online questionnaires. The intervention was developed based on iterative research and the Information-Motivation-Behavioral skills model. Participants (N = 475) were randomly assigned to one of six module orders and data were collected automatically at pre-test and after each module. Data supports the feasibility and acceptability of the program as demonstrated by good retention and rapid program completion. Knowledge, self-efficacy, outcome expectancies and motivation increase in a dose response fashion. Post-intervention behavior changes included reduced anal sex and significant increases in condom use. Limitations include a short follow-up period, a predominantly young white rural sample, and the lack of an attention control. Overall the results of the study provide support for the efficacy of Internet-based interventions to reduce risk of HIV infection. Results also support traditional research methods to evaluate HIV prevention programs delivered exclusively through the Internet.

  20. Targeting obesity for the prevention of chronic cardiovascular disease through gut microbiota-herb interactions: An opportunity for traditional herbs.

    PubMed

    Chen, Feng; Jiang, Jun; Tian, Dan-Dan; Wen, Qi; Li, Yong-Hui; Zhang, Jun-Qing; Cheng, Chen; Wang, Tengfei

    2016-10-14

    Cardiovascular disease still remains the primary cause of death worldwide and the obesity is becoming recognized as one of the most critical contributing risk factors. The increased prevalence of obesity casts a cloud over the global health and the whole societies will still be burdened in the future. Therefore, prevention and therapy of obesity is a beneficial strategy for the prevention of chronic cardiovascular disease. Numerous studies have demonstrated that gut microbiota takes part in human health and disease including obesity. Traditional herbs hold great potential to improve people's health and wellness, particularly in the area of chronic inflammatory diseases although the mechanisms of action remain poorly understood. Emerging explorations of gut microbiota-herb interactions provide a potential to revolutionize the way we view herbal therapeutics. This review summarizes the experimental studies performed on animals and humans regarding the gut microbiota-herb interactions targeting obesity. This review also discusses the opportunity of herbs with potent activities but low oral bioavailability conundrum for prevention and therapy for obesity and related cardiovascular disease.

  1. Dual CD19 and CD123 targeting prevents antigen-loss relapses after CD19-directed immunotherapies

    PubMed Central

    Barrett, David M.; Shestova, Olga; Hofmann, Ted J.; Perazzelli, Jessica; Klichinsky, Michael; Aikawa, Vania; Nazimuddin, Farzana; Kozlowski, Miroslaw; Scholler, John; Lacey, Simon F.; Melenhorst, Jan J.; Morrissette, Jennifer J.D.; Christian, David A.; Hunter, Christopher A.; Kalos, Michael; Porter, David L.; June, Carl H.; Grupp, Stephan A.

    2016-01-01

    Potent CD19-directed immunotherapies, such as chimeric antigen receptor T cells (CART) and blinatumomab, have drastically changed the outcome of patients with relapsed/refractory B cell acute lymphoblastic leukemia (B-ALL). However, CD19-negative relapses have emerged as a major problem that is observed in approximately 30% of treated patients. Developing approaches to preventing and treating antigen-loss escapes would therefore represent a vertical advance in the field. Here, we found that in primary patient samples, the IL-3 receptor α chain CD123 was highly expressed on leukemia-initiating cells and CD19-negative blasts in bulk B-ALL at baseline and at relapse after CART19 administration. Using intravital imaging in an antigen-loss CD19-negative relapse xenograft model, we determined that CART123, but not CART19, recognized leukemic blasts, established protracted synapses, and eradicated CD19-negative leukemia, leading to prolonged survival. Furthermore, combining CART19 and CART123 prevented antigen-loss relapses in xenograft models. Finally, we devised a dual CAR-expressing construct that combined CD19- and CD123-mediated T cell activation and demonstrated that it provides superior in vivo activity against B-ALL compared with single-expressing CART or pooled combination CART. In conclusion, these findings indicate that targeting CD19 and CD123 on leukemic blasts represents an effective strategy for treating and preventing antigen-loss relapses occurring after CD19-directed therapies PMID:27571406

  2. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorders and Obesity among Female College Students: 1- and 2-Year Follow-Up Effects

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2013-01-01

    Objective: Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups. Method: Female college students at risk for these outcomes because of body image concerns (N = 398) were randomized to the "Healthy Weight 2" group-based 4-hr prevention program, which promotes lasting healthy…

  3. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorders and Obesity among Female College Students: 1- and 2-Year Follow-Up Effects

    ERIC Educational Resources Information Center

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2013-01-01

    Objective: Evaluate the effects of a prevention program targeting both eating disorders and obesity at 1- and 2-year follow-ups. Method: Female college students at risk for these outcomes because of body image concerns (N = 398) were randomized to the "Healthy Weight 2" group-based 4-hr prevention program, which promotes lasting healthy…

  4. Protein arginylation targets alpha synuclein, facilitates normal brain health, and prevents neurodegeneration.

    PubMed

    Wang, Junling; Han, Xuemei; Leu, Nicolae Adrian; Sterling, Stephanie; Kurosaka, Satoshi; Fina, Marie; Lee, Virginia M; Dong, Dawei W; Yates, John R; Kashina, Anna

    2017-09-12

    Alpha synuclein (α-syn) is a central player in neurodegeneration, but the mechanisms triggering its pathology are not fully understood. Here we found that α-syn is a highly efficient substrate for arginyltransferase ATE1 and is arginylated in vivo by a novel mid-chain mechanism that targets the acidic side chains of E46 and E83. Lack of arginylation leads to increased α-syn aggregation and causes the formation of larger pathological aggregates in neurons, accompanied by impairments in its ability to be cleared via normal degradation pathways. In the mouse brain, lack of arginylation leads to an increase in α-syn's insoluble fraction, accompanied by behavioral changes characteristic for neurodegenerative pathology. Our data show that lack of arginylation in the brain leads to neurodegeneration, and suggests that α-syn arginylation can be a previously unknown factor that facilitates normal α-syn folding and function in vivo.

  5. Mertk on tumor macrophages is a therapeutic target to prevent tumor recurrence following radiation therapy

    PubMed Central

    Crittenden, Marka R.; Baird, Jason; Friedman, David; Savage, Talicia; Uhde, Lauren; Alice, Alejandro; Cottam, Benjamin; Young, Kristina; Newell, Pippa; Nguyen, Cynthia; Bambina, Shelly; Kramer, Gwen; Akporiaye, Emmanuel; Malecka, Anna; Jackson, Andrew; Gough, Michael J.

    2016-01-01

    Radiation therapy provides a means to kill large numbers of cancer cells in a controlled location resulting in the release of tumor-specific antigens and endogenous adjuvants. However, by activating pathways involved in apoptotic cell recognition and phagocytosis, irradiated cancer cells engender suppressive phenotypes in macrophages. We demonstrate that the macrophage-specific phagocytic receptor, Mertk is upregulated in macrophages in the tumor following radiation therapy. Ligation of Mertk on macrophages results in anti-inflammatory cytokine responses via NF-kB p50 upregulation, which in turn limits tumor control following radiation therapy. We demonstrate that in immunogenic tumors, loss of Mertk is sufficient to permit tumor cure following radiation therapy. However, in poorly immunogenic tumors, TGFb inhibition is also required to result in tumor cure following radiation therapy. These data demonstrate that Mertk is a highly specific target whose absence permits tumor control in combination with radiation therapy. PMID:27602953

  6. Reservoir Targeted Vaccine Against Borrelia burgdorferi: A New Strategy to Prevent Lyme Disease Transmission

    PubMed Central

    Richer, Luciana Meirelles; Brisson, Dustin; Melo, Rita; Ostfeld, Richard S.; Zeidner, Nordin; Gomes-Solecki, Maria

    2014-01-01

    A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A–specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease. PMID:24523510

  7. Targeted complement inhibition as a promising strategy for preventing inflammatory complications in hemodialysis

    PubMed Central

    DeAngelis, Robert A.; Reis, Edimara S.; Ricklin, Daniel; Lambris, John D.

    2012-01-01

    Hemodialysis is the most common method used to remove waste and hazardous products of metabolism in patients suffering from renal failure. Hundreds of thousands of people with end-stage renal disease undergo hemodialysis treatment in the United States each year. Strikingly, the 5-year survival rate for all dialysis patients is only 35%. Most of the patients succumb to cardiovascular disease that is exacerbated by the chronic induction of inflammation caused by contact of the blood with the dialysis membrane. The complement system, a strong mediator of pro-inflammatory networks, is a key contributor to such biomaterial-induced inflammation. Though only evaluated in experimental ex vivo settings, specific targeting of complement activation during hemodialysis has uncovered valuable information that points towards the therapeutic use of complement inhibitors as means to control the unwelcomed inflammatory responses and consequent pathologies in hemodialysis patients. PMID:22964235

  8. Inhibition of metabolism of diethylene glycol prevents target organ toxicity in rats.

    PubMed

    Besenhofer, Lauren M; Adegboyega, Patrick A; Bartels, Michael; Filary, Mark J; Perala, Adam W; McLaren, Marie C; McMartin, Kenneth E

    2010-09-01

    Diethylene glycol (DEG) is an industrial chemical, the misuse of which has led to numerous epidemic poisonings worldwide. The mechanism of its toxicity has not been defined as to the precise relationship between the metabolism of DEG and target organ toxicity. The purpose of this study was to investigate the mechanism for the acute toxicity of DEG, and the effect of the alcohol dehydrogenase inhibitor 4-methylpyrazole (fomepizole), by determining the relationship between accumulation of DEG or its metabolites and the resulting kidney and liver toxicity. Rats were treated by oral gavage with water, 2 g/kg DEG (low dose), 10 g/kg DEG (high dose), or 10 g/kg DEG + fomepizole, and blood and urine were collected over 48 h. Rats treated with high-dose DEG had metabolic acidosis, increased BUN and creatinine, and marked kidney necrosis, noted by histopathology. A minor degree of liver damage was noted at the high dose. After low and high doses of DEG, 2-hydroxyethoxyacetic acid (HEAA) was the primary metabolite in the urine, with only minor amounts of urinary diglycolic acid (DGA). Small amounts of ethylene glycol (EG), but not oxalate or glycolate, were observed in the urine. Treatment with fomepizole blocked the formation of HEAA and DGA and the development of metabolic acidosis and the kidney and liver toxicity. These results indicate that the mechanism for the target organ toxicity results from metabolites of DEG, and not DEG itself nor formation of EG from DEG, and that fomepizole may be a useful antidote for treating DEG poisoning.

  9. Targeting educational campaigns for prevention of malaria and dengue fever: an assessment in Thailand.

    PubMed

    Brusich, Macy; Grieco, John; Penney, Naomi; Tisgratog, Rungarun; Ritthison, Wanapa; Chareonviriyaphap, Theeraphap; Achee, Nicole

    2015-01-23

    The current study assessed the knowledge, attitudes, and practices (KAP) of at-risk populations for malaria and/or dengue fever in relation to mosquito exposure and household mosquito control practices. Specific objectives included comparison of individual and household level health practices between a rural and urban setting in Thailand. Findings are intended to guide Thailand Ministry of Health educational campaigns targeting arthropod-borne disease. A mixed method design was employed using a forced choice and open-ended questionnaire to assess KAP of participants seeking point-of-care treatment for malaria and/or dengue fever at government health-care facilities. Following informed consent, household construction characterization (percent eave gap, floor, wall, and roof material) and mosquito collections both indoors (using aspiration) and outside (using traps) were conducted at a subsample of participant homes. All mosquitoes were identified to genus and anopheline and aedine samples processed for potential pathogen infection. A total of 64 participants were recruited from both study sites; 62 categorized as malaria symptomology and 2 categorized as dengue across all study healthcare facilities. Significant associations between study site and household construction were indicated. Trends also identified household level practices and both occupation and household construction regarding type of mosquito control products purchased and the abundance of mosquitoes in sampled homes. Overall, Ministry of Health information from education campaigns regarding malaria and dengue fever strategies is reaching the intended target populations at the study sites. Participants are aware of the presence of mosquitoes and that they serve as the potential vector for transmitting malaria and dengue fever diseases. However, specific knowledge gaps were also identified in each study site that may influence exposure to infected mosquitoes. Findings from this study are intended to

  10. siRNA Targeting the 2Apro Genomic Region Prevents Enterovirus 71 Replication In Vitro

    PubMed Central

    Kong, Zhenzhen; Shao, Qixiang; Su, Zhaoliang; Wang, Shengjun; Chen, Jianguo

    2016-01-01

    Enterovirus 71 (EV71) is the most important etiological agent of hand, foot, and mouth disease (HFMD) in young children, which is associated with severe neurological complications and has caused significant mortalities in recent HFMD outbreaks in Asia. However, there is no effective antiviral therapy against EV71. In this study, RNA interference (RNAi) was used as an antiviral strategy to inhibit EV71 replication. Three small interfering RNAs (siRNAs) targeting the 2Apro region of the EV71 genome were designed and synthesized. All the siRNAs were transfected individually into rhabdomyosarcoma (RD) cells, which were then infected with strain EV71-2006-52-9. The cytopathic effects (CPEs) in the infected RD cells, cell viability, viral titer, and viral RNA and protein expression were examined to evaluate the specific viral inhibition by the siRNAs. The results of cytopathogenicity and MTT tests indicated that the RD cells transfected with the three siRNAs showed slight CPEs and significantly high viability. The 50% tissue culture infective dose (TCID50) values demonstrated that the viral titer of the groups treated with three siRNAs were lower than those of the control groups. qRT–PCR and western blotting revealed that the levels of viral RNA and protein in the RD cells treated with the three siRNAs were lower than those in the controls. When RD cells transfected with siRNAs were also infected with strain EV71-2008-43-16, the expression of the VP1 protein was significantly inhibited. The levels of interferon α (IFN-α) and IFN-β did not differ significantly in any group. These results suggest that siRNAs targeting the 2Apro region of the EV71 genome exerted antiviral effects in vitro. PMID:26886455

  11. Targeting mTOR Signaling Can Prevent the Progression of FSGS.

    PubMed

    Zschiedrich, Stefan; Bork, Tillmann; Liang, Wei; Wanner, Nicola; Eulenbruch, Kristina; Munder, Stefan; Hartleben, Björn; Kretz, Oliver; Gerber, Simon; Simons, Matias; Viau, Amandine; Burtin, Martine; Wei, Changli; Reiser, Jochen; Herbach, Nadja; Rastaldi, Maria-Pia; Cohen, Clemens D; Tharaux, Pierre-Louis; Terzi, Fabiola; Walz, Gerd; Gödel, Markus; Huber, Tobias B

    2017-07-01

    Mammalian target of rapamycin (mTOR) signaling is involved in a variety of kidney diseases. Clinical trials administering mTOR inhibitors to patients with FSGS, a prototypic podocyte disease, led to conflicting results, ranging from remission to deterioration of kidney function. Here, we combined complex genetic titration of mTOR complex 1 (mTORC1) levels in murine glomerular disease models, pharmacologic studies, and human studies to precisely delineate the role of mTOR in FSGS. mTORC1 target genes were significantly induced in microdissected glomeruli from both patients with FSGS and a murine FSGS model. Furthermore, a mouse model with constitutive mTORC1 activation closely recapitulated human FSGS. Notably, the complete knockout of mTORC1 by induced deletion of both Raptor alleles accelerated the progression of murine FSGS models. However, lowering mTORC1 signaling by deleting just one Raptor allele ameliorated the progression of glomerulosclerosis. Similarly, low-dose treatment with the mTORC1 inhibitor rapamycin efficiently diminished disease progression. Mechanistically, complete pharmacologic inhibition of mTOR in immortalized podocytes shifted the cellular energy metabolism toward reduced rates of oxidative phosphorylation and anaerobic glycolysis, which correlated with increased production of reactive oxygen species. Together, these data suggest that podocyte injury and loss is commonly followed by adaptive mTOR activation. Prolonged mTOR activation, however, results in a metabolic podocyte reprogramming leading to increased cellular stress and dedifferentiation, thus offering a treatment rationale for incomplete mTOR inhibition. Copyright © 2017 by the American Society of Nephrology.

  12. Prevention of viral hepatitis C: assessment of a comic strip-based information campaign targeting adolescents.

    PubMed

    Ingrand, Isabelle; Verneau, Alain; Silvain, Christine; Beauchant, Michel

    2004-06-01

    The risk of exposure to hepatitis C virus increases markedly in adolescence, and students are thus a preferential target for information campaigns. The aim of this study was to evaluate the results of a hepatitis C information campaign targeting secondary-school students. The study was done in 52 classes of 11 general and vocational secondary schools. Before the information meetings and two months afterwards, the students received an anonymous questionnaire to test their knowledge of hepatitis C. The information session was backed up by a comic strip depicting scenarios involving hepatitis C. The students were aged from 14 to 24 years (mean 15.9 years, SD 0.9 years). Respectively 1509 and 1419 questionnaires were completed before and after the information session. Answers to the first questionnaire showed that the students' knowledge of hepatitis C was poor. Scores improved significantly after the information session, from an overall mean of 6.2 (SD 2.0) to 8.5 (SD 1.7) (p<0.001). The largest score improvement concerned transmission due to illicit drug use, the potential severity of the disease, and lack of a vaccine. The improvement was significantly larger among pupils who said they read the comic strip than among those who did not (p=0.02). General and vocational secondary school students in France have mediocre knowledge of hepatitis C, particularly its modes of transmission and the lack of a vaccine. Knowledge improved significantly when measured two months after an information session, suggesting that subsequent at-risk behaviours might be reduced.

  13. Combination Therapy for Ulcerative Colitis: Orally Targeted Nanoparticles Prevent Mucosal Damage and Relieve Inflammation

    PubMed Central

    Xiao, Bo; Zhang, Zhan; Viennois, Emilie; Kang, Yuejun; Zhang, Mingzhen; Han, Moon Kwon; Chen, Jiucun; Merlin, Didier

    2016-01-01

    Combination therapy is an emerging strategy that is under intensive preclinical investigation for the treatment of various diseases. CD98 is highly overexpressed on the surfaces of epithelial cells and macrophages in the colon tissue with ulcerative colitis (UC), which is usually associated with mucosal damage and inflammation. We previously proved that CD98 siRNA (siCD98)-induced down-regulation of CD98 in colitis tissue decreased the severity of UC to a certain extent. In an effort to further improve the therapeutic efficacy, we aim to simultaneously deliver siCD98 in combination with a potent anti-inflammatory agent, curcumin (CUR), using hyaluronic acid (HA)-functionalized polymeric nanoparticles (NPs). The resultant spherical HA-siCD98/CUR-NPs are featured by a desirable particle size (∼246 nm) and slightly negative zeta potential (∼-14 mV). The NPs functionalized with HA are able to guide the co-delivery of drugs to the targeted cells related to UC therapy (colonic epithelial cells and macrophages). Compared to either siCD98- or CUR-based monotherapy, co-delivery of siCD98 and CUR by HA-functionalized NPs can exert combinational effects against UC by protecting the mucosal layer and alleviating inflammation both in vitro and in vivo. This study shows the promising capability of the co-delivered siCD98 and CUR for boosting the conventional monotherapy via this novel nanotherapeutic agent, which offers a structurally simple platform for orally administered delivery of drugs to target cells in UC therapy. PMID:27924161

  14. Targeting of Fn14 Prevents Cancer-Induced Cachexia and Prolongs Survival.

    PubMed

    Johnston, Amelia J; Murphy, Kate T; Jenkinson, Laura; Laine, David; Emmrich, Kerstin; Faou, Pierre; Weston, Ross; Jayatilleke, Krishnath M; Schloegel, Jessie; Talbo, Gert; Casey, Joanne L; Levina, Vita; Wong, W Wei-Lynn; Dillon, Helen; Sahay, Tushar; Hoogenraad, Joan; Anderton, Holly; Hall, Cathrine; Schneider, Pascal; Tanzer, Maria; Foley, Michael; Scott, Andrew M; Gregorevic, Paul; Liu, Spring Yingchun; Burkly, Linda C; Lynch, Gordon S; Silke, John; Hoogenraad, Nicholas J

    2015-09-10

    The cytokine TWEAK and its cognate receptor Fn14 are members of the TNF/TNFR superfamily and are upregulated in tumors. We found that Fn14, when expressed in tumors, causes cachexia and that antibodies against Fn14 dramatically extended lifespan by inhibiting tumor-induced weight loss although having only moderate inhibitory effects on tumor growth. Anti-Fn14 antibodies prevented tumor-induced inflammation and loss of fat and muscle mass. Fn14 signaling in the tumor, rather than host, is responsible for inducing this cachexia because tumors in Fn14- and TWEAK-deficient hosts developed cachexia that was comparable to that of wild-type mice. These results extend the role of Fn14 in wound repair and muscle development to involvement in the etiology of cachexia and indicate that Fn14 antibodies may be a promising approach to treat cachexia, thereby extending lifespan and improving quality of life for cancer patients. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. Cognitive frailty, a novel target for the prevention of elderly dependency.

    PubMed

    Ruan, Qingwei; Yu, Zhuowei; Chen, Ma; Bao, Zhijun; Li, Jin; He, Wei

    2015-03-01

    Frailty is a complex and heterogeneous clinical syndrome. Cognitive frailty has been considered as a subtype of frailty. In this study, we refine the definition of cognitive frailty based on existing reports about frailty and the latest progress in cognition research. We obtain evidence from the literature regarding the role of pre-physical frailty in pathological aging. We propose that cognitive impairment of cognitive frailty results from physical or pre-physical frailty and comprises two subtypes: the reversible and the potentially reversible. Reversible cognitive impairment is indicated by subjective cognitive decline (SCD) and/or positive fluid and imaging biomarkers of amyloid-β accumulation and neurodegeneration. Potentially reversible cognitive impairment is MCI (CDR=0.5). Based on the severity of cognitive impairment, it is possible to determine the primary and secondary preventative measures for cognitive frailty. We further determine whether SCD is a component of pre-clinical AD or the early stage of other neurodegenerative diseases, which is required for guiding personal clinical intervention.

  16. Estrogen activity as a preventive and therapeutic target in thyroid cancer.

    PubMed

    Rajoria, Shilpi; Suriano, Robert; George, Andrea L; Shanmugam, Arulkumaran; Jussim, Casey; Shin, Edward J; Moscatello, Augustine L; Geliebter, Jan; Carpi, Angelo; Tiwari, Raj K

    2012-03-01

    Thyroid cancer is the most common endocrine-related cancer with increasing incidences during the last five years. Interestingly, according to the American Thyroid Association, the incidences of thyroid proliferative diseases occur four to five times more in women than in men with the risk of developing thyroid disorders being one in every eight females. Several epidemiological studies have suggested a possible correlation between incidences of thyroid malignancies and hormones but the precise contribution of estrogen in thyroid proliferative disease initiation, and progression is not well understood. This review is an attempt to define the phenotypic and genotypic modulatory effects of estrogen on thyroid proliferative diseases. The significance and relevance of expression of estrogen receptors, α and β, in normal and malignant thyroid tissues and their effects on different molecular pathways involved in growth and function of the thyroid gland are discussed. These novel findings open up areas of developing alternative therapeutic treatments and preventive approaches which employ the use of antiestrogen to treat thyroid malignancies. Copyright © 2012 Elsevier Masson SAS. All rights reserved.

  17. Targeting epithelial-mesenchymal transition: Metal organic network nano-complexes for preventing tumor metastasis.

    PubMed

    Fan, Jin-Xuan; Zheng, Di-Wei; Rong, Lei; Zhu, Jing-Yi; Hong, Sheng; Li, Cao; Xu, Zu-Shun; Cheng, Si-Xue; Zhang, Xian-Zheng

    2017-09-01

    Tumor metastasis is the leading cause of death in cancer patients, and epithelial-mesenchymal transition (EMT) is an essential step in tumor metastasis. Unfortunately, during the chemotherapy, EMT could be induced under the selective pressure of clinical cytotoxic drugs. Here, to solve this problem, we have synthesized multi-functional epigallocatechin gallate/iron nano-complexes (EIN) as a versatile coating material to improve conventional therapies. In vitro studies showed that this strategy could eliminate EMT-type cancer cells. Mechanism studies also revealed that EIN was able to down-regulate the downstream expression of metastasis-associated factors, decrease the migration ability of cancer cells and prevent cancer cells from gaining drug resistance. In vivo investigation revealed that EIN had superior ability to enhance the therapeutic effect of conventional nanomedicines and inhibit the EMT process. Our study indicates the promising use of EIN to make up for the deficiencies of chemotherapy may provide insights into systematic cancer therapy to overcome tumor metastasis and drug resistance. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Most at-risk populations: contextualising HIV prevention programmes targeting marginalised groups in Zanzibar, Tanzania.

    PubMed

    Ahmed, Naheed

    2014-09-01

    According to a 2009 UNAIDS report the HIV/AIDS prevalence rate in Zanzibar, Tanzania, is low in the general population (0.6%), but high among vulnerable groups, specifically sex workers (10.8%), injecting drug users (15.1%), and men who have sex with men (12.3%). In response to this concentrated epidemic, the Government of Zanzibar, international and local non-profit organisations have focused their prevention activities on these marginal populations. Although these efforts are beneficial in terms of disseminating information about HIV/AIDS and referring clients to health clinics, they fail to address how the socio-economic status of these groups places them at a greater risk for contracting and dying from the virus. Furthermore, there is an absence of qualitative research on these populations which is needed to understand the challenges these groups face and to improve the effectiveness of interventions. Through interviews with employees of government agencies and non-profit organisations, medical professionals, vulnerable populations and HIV/AIDS patients, this paper used a political economy of health and syndemic framework to examine how local realities inform and challenge HIV/AIDS programmes in Zanzibar.

  19. Public education for the prevention of hemoglobinopathies: a study targeting Kocaeli University students.

    PubMed

    Gülleroğlu, Kaan Savaş; Sarper, Nazan; Gökalp, Ayşe Sevim

    2007-12-05

    In addition to premarital screening programs, education of the general population is important in preventing hemoglobinopathies. The aim of the present study was the education of university students. Short questionnaires were applied before and after a prepared lecture. A 20-minute audiovisual education was provided including the clinical characteristics and inheritance of thalassemia and sickle cell anemia (SCA) as well as the importance of carrier screening. The attendance to 42 lectures was low (n= 1348 = 5%). Seventy-four percent of the students had heard of thalassemia. The percentage of the students who had some accurate knowledge was 25% for thalassemia and 11.7% for SCA. Following the lecture, these numbers increased to 86.2% and 72.1% for thalassemia and SCA, respectively. Only 13.6% of the students were aware of the risk of being carriers, but this increased to 78.6% following the lecture; 92.4% learned that these hemoglobinopathies were inherited and 78.8% learned that consanguineous marriages would increase the risk. Education on hemoglobinopathies must be integrated into the curricula of middle schools and high schools.

  20. The MAPK/JNK signalling pathway offers potential therapeutic targets for the prevention of acquired deafness.

    PubMed

    Zine, A; van de Water, T R

    2004-08-01

    The c-Jun N-terminal kinases (JNKs) are also called stress activated protein kinases (SAPKs) and are members of the family of mitogen activated protein kinases (MAPKs). While the functions of the JNKs under physiological conditions are diverse and not completely understood, there is increasing evidence that JNKs are potent effectors of apoptosis of oxidative stress-damaged cells in both the brain and the mammalian inner ear following a trauma. The activation of the inducible transcription factor c-Jun by N-terminal phosphorylation is a central event in JNK-mediated apoptosis of oxidative stress-damaged auditory hair cells following exposure to either acoustic trauma or a toxic level of an aminoglycoside antibiotic and also the apoptosis of auditory neurons as a consequence of a loss of the trophic support provided by the auditory hair cells. In this review, we summarise what is known about the expression and activation of G-proteins, JNKs, c-Jun and c-Fos under oxidative stress conditions within the mammalian cochlea. A particular focus is put on a new peptide conjugate that is a promising protective agent(s) and pharmacological strategies for preventing cochlear damage induced by both acoustic trauma and aminoglycoside ototoxic damage.

  1. What are the key food groups to target for preventing obesity and improving nutrition in schools?

    PubMed

    Bell, A C; Swinburn, B A

    2004-02-01

    To determine differences in the contribution of foods and beverages to energy consumed in and out of school, and to compare consumption patterns between school canteen users and noncanteen users. Cross-sectional National Nutrition Survey, 1995. Australia. SUBJECTS ON SCHOOL DAYS: A total of 1656 children aged 5-15 y who had weekday 24-h dietary recall data. An average of 37% of total energy intake was consumed at school. Energy-dense foods and beverages such as fat spreads, packaged snacks, biscuits and fruit/cordial drinks made a greater contribution to energy intake at school compared to out of school (P< or =0.01). Fast foods and soft drinks contributed 11 and 3% of total energy intake; however, these food groups were mostly consumed out of school. Fruit intake was low and consumption was greater in school. In all, 14% of children purchased food from the canteen and they obtained more energy from fast food, packaged snacks, desserts, milk and confectionary (P< or =0.05) than noncanteen users. : Energy-dense foods and beverages are over-represented in the Australian school environment. To help prevent obesity and improve nutrition in schools, biscuits, snack bars and fruit/cordial drinks brought from home and fast food, packaged snacks, and confectionary sold at canteens should be replaced with fruit and water.

  2. Alcohol prevention targeting licensed premises: a study of effects on violence.

    PubMed

    Wallin, Eva; Norström, Thor; Andréasson, Sven

    2003-03-01

    This research studied the effects of a community alcohol prevention program on violent crimes. Starting in 1996, a 10-year multicomponent program based on community mobilization, training in responsible beverage service for servers and stricter enforcement of existing alcohol laws has been conducted in Stockholm, Sweden. The project has been led by an action group consisting of members from the hospitality industry and the authorities. We used a time-series quasi-experimental design that included a control area. Data on police-reported violence during the period of January 1994 to September 2000 were analyzed through ARIMA modeling. During the intervention period, violent crimes decreased significantly by 29% in the intervention area, controlled for the development in the control area. The intervention seems to have been successful in reducing violent crimes. This effect is most likely due to a combination of various policy changes initiated by the project. The findings support the notion that community action projects working on a local basis can be effective in decreasing alcohol-related problems at licensed premises.

  3. Pharmacological targeting of peptidylarginine deiminase 4 prevents cancer-associated kidney injury in mice.

    PubMed

    Cedervall, Jessica; Dragomir, Anca; Saupe, Falk; Zhang, Yanyu; Ärnlöv, Johan; Larsson, Erik; Dimberg, Anna; Larsson, Anders; Olsson, Anna-Karin

    2017-01-01

    Renal insufficiency is a frequent cancer-associated problem affecting more than half of all cancer patients at the time of diagnosis. To minimize nephrotoxic effects the dosage of anticancer drugs are reduced in these patients, leading to sub-optimal treatment efficacy. Despite the severity of this cancer-associated pathology, the molecular mechanisms, as well as therapeutic options, are still largely lacking. We here show that formation of intravascular tumor-induced neutrophil extracellular traps (NETs) is a cause of kidney injury in tumor-bearing mice. Analysis of clinical biomarkers for kidney function revealed impaired creatinine clearance and elevated total protein levels in urine from tumor-bearing mice. Electron microscopy analysis of the kidneys from mice with cancer showed reversible pathological signs such as mesangial hypercellularity, while permanent damage such as fibrosis or necrosis was not observed. Removal of NETs by treatment with DNase I, or pharmacological inhibition of the enzyme peptidylarginine deiminase 4 (PAD4), was sufficient to restore renal function in mice with cancer. Tumor-induced systemic inflammation and impaired perfusion of peripheral vessels could be reverted by the PAD4 inhibitor. In conclusion, the current study identifies NETosis as a previously unknown cause of cancer-associated renal dysfunction and describes a novel promising approach to prevent renal failure in individuals with cancer.

  4. Mammalian target of rapamycin inhibition prevents glomerular hypertrophy in a model of renal mass reduction.

    PubMed

    Rovira, Jordi; Arellano, Edgar M; Carreras, Joaquim; Campos, Begoña; Vodenik, Barbara; Bañón-Maneus, Elisenda; Ramírez-Bajo, María José; Moya-Rull, Daniel; Solé-González, Amanda; Hernández, Astrid; Revuelta, Ignacio; Quintana, Luis F; Howat, William J; Campistol, Josep M; Diekmann, Fritz

    2009-09-15

    Sirolimus (SRL) is a potent and specific immunosuppressive drug used in organ transplantation, as basic therapy or in combination with calcineurin inhibitors. Although SRL is a nonnephrotoxic drug, many reports have related its use with the development of proteinuria, especially after conversion. Therefore, the aim of this study was to elucidate the interrelation between early and late SRL administration on the development of glomerular hypertrophy and proteinuria in a model of renal mass reduction (RMR). Rats underwent 2/3 cryoablation of the left kidney and subsequent right nephrectomy (n=42) or sham operations (n=29). Two weeks before (early study) or 12 weeks after (late study) surgery, SRL or vehicle was administered three times weekly. Creatinine clearance and proteinuria were determined throughout the study, and a complete histologic analysis was performed at the end of the study. Treatment with SRL had no effect on creatinine clearance, independently of the administration time. Four weeks after RMR, a significant increase in proteinuria was observed. Proteinuria was stabilized after early and late SRL administration, whereas vehicle-treated animals showed a further increase in proteinuria. Glomerular hypertrophy was strongly associated with proteinuria, and early SRL introduction prevented glomerular enlargement. The histologic analysis showed less structural damage in the two groups of animals treated with SRL than in the control group. Although early SRL introduction blocked glomerular hypertrophy, SRL treatment revealed the potential to halt progression of proteinuria and histologic damage at any time of administration in a model of RMR.

  5. Tomato as a Source of Carotenoids and Polyphenols Targeted to Cancer Prevention

    PubMed Central

    Martí, Raúl; Roselló, Salvador; Cebolla-Cornejo, Jaime

    2016-01-01

    A diet rich in vegetables has been associated with a reduced risk of many diseases related to aging and modern lifestyle. Over the past several decades, many researches have pointed out the direct relation between the intake of bioactive compounds present in tomato and a reduced risk of suffering different types of cancer. These bioactive constituents comprise phytochemicals such as carotenoids and polyphenols. The direct intake of these chemoprotective molecules seems to show higher efficiencies when they are ingested in its natural biological matrix than when they are ingested isolated or in dietary supplements. Consequently, there is a growing trend for improvement of the contents of these bioactive compounds in foods. The control of growing environment and processing conditions can ensure the maximum potential accumulation or moderate the loss of bioactive compounds, but the best results are obtained developing new varieties via plant breeding. The modification of single steps of metabolic pathways or their regulation via conventional breeding or genetic engineering has offered excellent results in crops such as tomato. In this review, we analyse the potential of tomato as source of the bioactive constituents with cancer-preventive properties and the result of modern breeding programs as a strategy to increase the levels of these compounds in the diet. PMID:27331820

  6. Small-area analysis: targeting high-risk areas for adolescent pregnancy prevention programs.

    PubMed

    Gould, J B; Herrchen, B; Pham, T; Bera, S; Brindis, C

    1998-01-01

    Traditional methods of identifying areas in need of adolescent pregnancy prevention programs may overlook small localities with high levels of adolescent childbearing in communities and counties where this is not a universal problem. The present study assessed the potential of a "geomapping" approach based on measurement of the number of births occurring to teens 15-17 years old in each California (US) zip code in 1992-94. A total of 415 zip codes with teen birth rates in excess of the state's 75th percentile cut-off point (62.8 births/1000) were identified. 210 of these zip codes, accounting for 96% of all births to 15-17 year olds in the 75th-percentile zip codes, differed significantly (p 0.01) from the state average of 44.5 births/1000 15-17 year olds. 178 (85%) of these 210 "hot spots" also included birth rates exceeding the third quartile among teens 10-14 and/or 18-19 years old. Panels of local experts reviewed these "hot spots" for accuracy and grouped them into 82 potential project areas on the basis of demographics, geography, and political infrastructure. Although there was substantial variation, localities with the highest teen birth rates tended to be characterized by minority overrepresentation, poverty, and poor prenatal care coverage. In addition to identifying areas with unmet need, this approach encourages community participation in program development.

  7. Pilot evaluation of a media literacy program for tobacco prevention targeting early adolescents shows mixed results.

    PubMed

    Kaestle, Christine E; Chen, Yvonnes; Estabrooks, Paul A; Zoellner, Jamie; Bigby, Brandon

    2013-01-01

    The purpose of this pilot study was to assess the impact of media literacy for tobacco prevention for youth delivered through a community site. A randomized pretest-posttest evaluation design with matched-contact treatment and control conditions. The pilot study was delivered through the YMCA in a lower-income suburban and rural area of Southwest Virginia, a region long tied, both economically and culturally, to the tobacco industry. Children ages 8 to 14 (76% white, 58% female) participated in the study (n = 38). The intervention was an antismoking media literacy program (five 1-hour lessons) compared with a matched-contact creative writing control program. General media literacy, three domains of tobacco-specific media literacy ("authors and audiences," "messages and meanings," and "representation and reality"), tobacco attitudes, and future expectations were assessed. Multiple regression modeling assessed the impact of the intervention, controlling for pretest measures, age, and sex. General media literacy and tobacco-specific "authors and audiences" media literacy improved significantly for treatment compared with control (p < .05); results for other tobacco-specific media literacy measures and for tobacco attitudes were not significant. Future expectations of smoking increased significantly for treatment participants ages 10 and younger (p < .05). Mixed results indicated that improvements in media literacy are accompanied by an increase in future expectations to smoke for younger children.

  8. Animal Models and “Omics” Technologies for Identification of Novel Biomarkers and Drug Targets to Prevent Heart Failure

    PubMed Central

    Hou, Yunlong; Adrian-Segarra, Juan M.; Richter, Manfred; Kubin, Natalia; Shin, Jaeyoung; Werner, Isabella; Walther, Thomas; Schönburg, Markus; Pöling, Jochen; Warnecke, Henning; Braun, Thomas; Kostin, Sawa; Kubin, Thomas

    2015-01-01

    It is now accepted that heart failure (HF) is a complex multifunctional disease rather than simply a hemodynamic dysfunction. Despite its complexity, stressed cardiomyocytes often follow conserved patterns of structural remodelling in order to adapt, survive, and regenerate. When cardiac adaptations cannot cope with mechanical, ischemic, and metabolic loads efficiently or become chronically activated, as, for example, after infection, then the ongoing structural remodelling and dedifferentiation often lead to compromised pump function and patient death. It is, therefore, of major importance to understand key events in the progression from a compensatory left ventricular (LV) systolic dysfunction to a decompensatory LV systolic dysfunction and HF. To achieve this, various animal models in combination with an “omics” toolbox can be used. These approaches will ultimately lead to the identification of an arsenal of biomarkers and therapeutic targets which have the potential to shape the medicine of the future. PMID:26236717

  9. Preterm Birth Prevention Post-Conization: A Model of Cervical Length Screening with Targeted Cerclage

    PubMed Central

    Kindinger, Lindsay M.; MacIntyre, David A.; Cacciatore, Stefano; Yulia, Angela; Cook, Joanna; Terzidou, Vasso; Teoh, T. G.; Bennett, Phillip R.

    2016-01-01

    Women with a history of excisional treatment (conization) for cervical intra-epithelial neoplasia (CIN) are at increased risk of preterm birth, perinatal morbidity and mortality in subsequent pregnancy. We aimed to develop a screening model to effectively differentiate pregnancies post-conization into low- and high-risk for preterm birth, and to evaluate the impact of suture material on the efficacy of ultrasound indicated cervical cerclage. We analysed longitudinal cervical length (CL) data from 725 pregnant women post-conization attending preterm surveillance clinics at three London university Hospitals over a ten year period (2004–2014). Rates of preterm birth <37 weeks after targeted cerclage for CL<25mm were compared with local and national background rates and expected rates for this cohort. Rates for cerclage using monofilament or braided suture material were also compared. Of 725 women post-conization 13.5% (98/725) received an ultrasound indicated cerclage and 9.7% (70/725) delivered prematurely, <37weeks; 24.5% (24/98) of these despite insertion of cerclage. The preterm birth rate was lower for those that had monofilament (9/60, 15%) versus braided (15/38, 40%) cerclage (RR 0.7, 95% CI 0.54 to 0.94, P = 0.008). Accuracy parameters of interval reduction in CL between longitudinal second trimester screenings were calculated to identify women at low risk of preterm birth, who could safely discontinue surveillance. A reduction of CL <10% between screening timepoints predicts term birth, >37weeks. Our triage model enables timely discharge of low risk women, eliminating 36% of unnecessary follow-up CL scans. We demonstrate that preterm birth in women post-conization may be reduced by targeted cervical cerclage. Cerclage efficacy is however suture material-dependant: monofilament is preferable to braided suture. The introduction of triage prediction models has the potential to reduce the number of unnecessary CL scan for women at low risk of preterm birth

  10. Targeting Activation of Specific NF-κB Subunits Prevents Stress-Dependent Atherothrombotic Gene Expression

    PubMed Central

    Djuric, Zdenka; Kashif, Muhammed; Fleming, Thomas; Muhammad, Sajjad; Piel, David; von Bauer, Rüdiger; Bea, Florian; Herzig, Stephan; Zeier, Martin; Pizzi, Marina; Isermann, Berend; Hecker, Markus; Schwaninger, Markus; Bierhaus, Angelika; Nawroth, Peter P

    2012-01-01

    Psychosocial stress has been shown to be a contributing factor in the development of atherosclerosis. Although the underlying mechanisms have not been elucidated entirely, it has been shown previously that the transcription factor nuclear factor-κB (NF-κB) is an important component of stress-activated signaling pathway. In this study, we aimed to decipher the mechanisms of stress-induced NF-κB-mediated gene expression, using an in vitro and in vivo model of psychosocial stress. Induction of stress led to NF-κB-dependent expression of proinflammatory (tissue factor, intracellular adhesive molecule 1 [ICAM-1]) and protective genes (manganese superoxide dismutase [MnSOD]) via p50, p65 or cRel. Selective inhibition of the different subunits and the respective kinases showed that inhibition of cRel leads to the reduction of atherosclerotic lesions in apolipoprotein−/− (ApoE−/−) mice via suppression of proinflammatory gene expression. This observation may therefore provide a possible explanation for ineffectiveness of antioxidant therapies and suggests that selective targeting of cRel activation may provide a novel approach for the treatment of stress-related inflammatory vascular disease. PMID:23114885

  11. Reservoir targeted vaccine against Borrelia burgdorferi: a new strategy to prevent Lyme disease transmission.

    PubMed

    Richer, Luciana Meirelles; Brisson, Dustin; Melo, Rita; Ostfeld, Richard S; Zeidner, Nordin; Gomes-Solecki, Maria

    2014-06-15

    A high prevalence of infection with Borrelia burgdorferi in ixodid ticks is correlated with a high incidence of Lyme disease. The transmission of B. burgdorferi to humans can be disrupted by targeting 2 key elements in its enzootic cycle: the reservoir host and the tick vector. In a prospective 5-year field trial, we show that oral vaccination of wild white-footed mice resulted in outer surface protein A-specific seropositivity that led to reductions of 23% and 76% in the nymphal infection prevalence in a cumulative, time-dependent manner (2 and 5 years, respectively), whereas the proportion of infected ticks recovered from control plots varied randomly over time. Significant decreases in tick infection prevalence were observed within 3 years of vaccine deployment. Implementation of such a long-term public health measure could substantially reduce the risk of human exposure to Lyme disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  12. Molecular Targeting of ERKs/RSK2 Signaling Axis in Cancer Prevention

    PubMed Central

    Yoo, Sun-Mi; Cho, Sung Jun; Cho, Yong-Yeon

    2015-01-01

    RSK2 is a downstream signaling protein of ERK1 and ERK2 and plays a key role in physiological homeostasis. For this reason, RSK2 is a highly conserved protein among the p90RSK family members. In its location in the signaling pathway, RSK2 is a kinase just upstream of transcription and epigenetic factors, and a few kinases involved in cell cycle regulation and protein synthesis. Moreover, activation of RSK2 by growth factors is directly involved in cell proliferation, anchorage-independent cell transformation and cancer development. Direct evidences regarding the etiological roles of RSK2 in cancer development in humans have been published by our research group illustrating that elevated total- and phospho-RSK2 protein levels mediated by ERK1 and ERK2 are higher in skin cancer tissues compared to normal skin tissues. Notably, it has been shown that RSK2 ectopic expression in JB6 Cl41 cells induces cell proliferation and anchorage- independent cell transformation. Importantly, knockdown of RSK2 suppresses Ras-mediated foci formation and anchorage-independent colony growth of cancer cells. Kaempferol is a one of the natural compounds showing selectivity in inhibiting RSK2 activity in epidermal growth factor-induced G1/S cell cycle transition and cell transformation. Thus, ERKs/RSK2 signaling axis is an important target signaling molecule in chemoprevention. PMID:26473154

  13. Cholera cases cluster in time and space in Matlab, Bangladesh: implications for targeted preventive interventions.

    PubMed

    Debes, Amanda K; Ali, Mohammad; Azman, Andrew S; Yunus, Mohammad; Sack, David A

    2016-12-01

    : Cholera remains a serious public health threat in Asia, Africa and in parts of the Americas. Three World health Organization (WHO) pre-qualified oral cholera vaccines are now available but their supply is limited, so current supplies must be administered strategically. This requires an improved understanding of disease transmission and control strategies. : We used demographics and disease surveillance data collected from 1991 to 2000 in Matlab, Bangladesh, to estimate the spatial and temporal extent of the zone of increased risk around cholera cases. Specifically, we compare the cholera incidence among individuals living close to cholera cases with that among individuals living close to those without medically-attended cholera in this rural endemic setting. : Those living within 50 m of a confirmed cholera case had 36 times (95% confidence interval: 23-56) the risk of becoming a cholera case in the first 3 days (after case presentation) compared with risk elsewhere in the community. The relative risk gradually declined in space and time, but remained significantly high up to 450 me away within 3 days of case presentation, and up to 150 m away within 23 days from the date of presentation of the case. : These findings suggest that, if conducted rapidly, vaccinating individuals living close to a case (ring vaccination) could be an efficient and effective strategy to target vaccine to a high-risk population in an endemic setting.

  14. Myeloperoxidase targets oxidative host attacks to Salmonella and prevents collateral tissue damage.

    PubMed

    Schürmann, Nura; Forrer, Pascal; Casse, Olivier; Li, Jiagui; Felmy, Boas; Burgener, Anne-Valérie; Ehrenfeuchter, Nikolaus; Hardt, Wolf-Dietrich; Recher, Mike; Hess, Christoph; Tschan-Plessl, Astrid; Khanna, Nina; Bumann, Dirk

    2017-01-23

    Host control of infections crucially depends on the capability to kill pathogens with reactive oxygen species (ROS). However, these toxic molecules can also readily damage host components and cause severe immunopathology. Here, we show that neutrophils use their most abundant granule protein, myeloperoxidase, to target ROS specifically to pathogens while minimizing collateral tissue damage. A computational model predicted that myeloperoxidase efficiently scavenges diffusible H2O2 at the surface of phagosomal Salmonella and converts it into highly reactive HOCl (bleach), which rapidly damages biomolecules within a radius of less than 0.1 μm. Myeloperoxidase-deficient neutrophils were predicted to accumulate large quantities of H2O2 that still effectively kill Salmonella, but most H2O2 would leak from the phagosome. Salmonella stimulation of neutrophils from normal and myeloperoxidase-deficient human donors experimentally confirmed an inverse relationship between myeloperoxidase activity and extracellular H2O2 release. Myeloperoxidase-deficient mice infected with Salmonella had elevated hydrogen peroxide tissue levels and exacerbated oxidative damage of host lipids and DNA, despite almost normal Salmonella control. These data show that myeloperoxidase has a major function in mitigating collateral tissue damage during antimicrobial oxidative bursts, by converting diffusible long-lived H2O2 into highly reactive, microbicidal and locally confined HOCl at pathogen surfaces.

  15. A Modified R-Type Bacteriocin Specifically Targeting Clostridium difficile Prevents Colonization of Mice without Affecting Gut Microbiota Diversity

    PubMed Central

    Gebhart, Dana; Lok, Stephen; Clare, Simon; Tomas, Myreen; Stares, Mark; Scholl, Dean; Donskey, Curtis J.; Lawley, Trevor D.

    2015-01-01

    ABSTRACT Clostridium difficile is a leading cause of nosocomial infections worldwide and has become an urgent public health threat requiring immediate attention. Epidemic lineages of the BI/NAP1/027 strain type have emerged and spread through health care systems across the globe over the past decade. Limiting person-to-person transmission and eradicating C. difficile, especially the BI/NAP1/027 strain type, from health care facilities are difficult due to the abundant shedding of spores that are impervious to most interventions. Effective prophylaxis for C. difficile infection (CDI) is lacking. We have genetically modified a contractile R-type bacteriocin (“diffocin”) from C. difficile strain CD4 to kill BI/NAP1/027-type strains for this purpose. The natural receptor binding protein (RBP) responsible for diffocin targeting was replaced with a newly discovered RBP identified within a prophage of a BI/NAP1/027-type target strain by genome mining. The resulting modified diffocins (a.k.a. Avidocin-CDs), Av-CD291.1 and Av-CD291.2, were stable and killed all 16 tested BI/NAP1/027-type strains. Av-CD291.2 administered in drinking water survived passage through the mouse gastrointestinal (GI) tract, did not detectably alter the mouse gut microbiota or disrupt natural colonization resistance to C. difficile or the vancomycin-resistant Enterococcus faecium (VREF), and prevented antibiotic-induced colonization of mice inoculated with BI/NAP1/027-type spores. Given the high incidence and virulence of the pathogen, preventing colonization by BI/NAP1/027-type strains and limiting their transmission could significantly reduce the occurrence of the most severe CDIs. This modified diffocin represents a prototype of an Avidocin-CD platform capable of producing targetable, precision anti-C. difficile agents that can prevent and potentially treat CDIs without disrupting protective indigenous microbiota. PMID:25805733

  16. Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services.

    PubMed

    Bellis, Mark A; Leckenby, Nicola; Hughes, Karen; Luke, Chris; Wyke, Sacha; Quigg, Zara

    2012-09-06

    Emergency department (ED) data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172) over a three-year period (31st March 2008 to 30th March 2011) to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P < 0.001); with male:female ratios increasing on more violent nights. Risks peak at age 18 years. Deprived individuals have greater risks of presenting across all ages (AOR 3.87, 95% CIs 3.82-3.92; P < 0.001). Proportions of assaults from deprived communities increase midweek. Female presentations in affluent areas peak aged 20 years. By age 13, females from deprived communities exceed this peak. Presentations peak on Friday and Saturday nights and the eves of public holidays; the largest peak is on New Year's Eve. Assaults increase over summer with a nadir in January. Impacts of annual celebrations without holidays vary. Some (Halloween, Guy Fawkes and St Patrick's nights) see increased assaults while others (St George's and Valentine's Day nights) do not. Home nation World Cup football matches are associated with nearly a three times increase in midweek assault presentation. Other football and rugby events examined show no impact. The 2008 Olympics saw assaults fall. The overall calendar model strongly predicts observed presentations (R2 = 0.918; P < 0.001). To date, the role of ED data

  17. Nighttime assaults: using a national emergency department monitoring system to predict occurrence, target prevention and plan services

    PubMed Central

    2012-01-01

    Background Emergency department (ED) data have the potential to provide critical intelligence on when violence is most likely to occur and the characteristics of those who suffer the greatest health impacts. We use a national experimental ED monitoring system to examine how it could target violence prevention interventions towards at risk communities and optimise acute responses to calendar, holiday and other celebration-related changes in nighttime assaults. Methods A cross-sectional examination of nighttime assault presentations (6.01 pm to 6.00 am; n = 330,172) over a three-year period (31st March 2008 to 30th March 2011) to English EDs analysing changes by weekday, month, holidays, major sporting events, and demographics of those presenting. Results Males are at greater risk of assault presentation (adjusted odds ratio [AOR] 3.14, 95% confidence intervals [CIs] 3.11-3.16; P < 0.001); with male:female ratios increasing on more violent nights. Risks peak at age 18 years. Deprived individuals have greater risks of presenting across all ages (AOR 3.87, 95% CIs 3.82-3.92; P < 0.001). Proportions of assaults from deprived communities increase midweek. Female presentations in affluent areas peak aged 20 years. By age 13, females from deprived communities exceed this peak. Presentations peak on Friday and Saturday nights and the eves of public holidays; the largest peak is on New Year’s Eve. Assaults increase over summer with a nadir in January. Impacts of annual celebrations without holidays vary. Some (Halloween, Guy Fawkes and St Patrick’s nights) see increased assaults while others (St George’s and Valentine’s Day nights) do not. Home nation World Cup football matches are associated with nearly a three times increase in midweek assault presentation. Other football and rugby events examined show no impact. The 2008 Olympics saw assaults fall. The overall calendar model strongly predicts observed presentations (R2 = 0.918; P < 0

  18. The receptor EP3 to PGE2: A rational target to prevent atherothrombosis without inducing bleeding.

    PubMed

    Mawhin, Marie-Anne; Tilly, Peggy; Fabre, Jean-Etienne

    2015-09-01

    The prostanoid E2 (PGE2) is known to modulate the aggregative response of platelets to their conventional agonists such as ADP, TXA2, thrombin or collagen. Through the activation of its receptor EP3, PGE2 sensitizes platelets to their agonists but also inhibits them through its two other receptors, EP2 and EP4. In mice, the net result of these opposed actions is the EP3-mediated potentiation of platelet aggregation and the in vivo aggravation of murine atherothrombosis. Since the pathway PGE2/EP3 is not involved in murine hemostasis, we propose a "platelet EP3 paradigm" to describe this apparently paradoxical association between the facilitating impact on atherothrombosis and the unaltered hemostasis. Consistent with this paradigm, a drug blocking EP3 dramatically decreased atherothrombosis without inducing bleeding in mice. In humans, several studies did not agree on the effect of PGE2 on platelets. Reinterpreting these data with the notion of "potentiation window" and taking the platelet initial cAMP level into account reconciled these inconsistent results. Thereby, the in vitro potentiating effect of PGE2 on human platelets becomes clear. In addition, the EP3 blocking drug DG-041 abrogated the potentiating effect of PGE2 in whole human blood but did not prolong bleeding times in volunteers. Thus, the murine "platelet EP3 paradigm" would apply to humans if the aggravating role of PGE2 on atherothrombosis is shown in patients. Therefore, testing an EP3 blocker in a phase III trial would be of high interest to fulfill the unmet medical need which is to control atherothrombosis without impacting hemostasis and thus to improve the prevention of myocardial infarction. Copyright © 2015 Elsevier Inc. All rights reserved.

  19. Targeting the CaMKII/ERK Interaction in the Heart Prevents Cardiac Hypertrophy.

    PubMed

    Cipolletta, Ersilia; Rusciano, Maria Rosaria; Maione, Angela Serena; Santulli, Gaetano; Sorriento, Daniela; Del Giudice, Carmine; Ciccarelli, Michele; Franco, Antonietta; Crola, Catherine; Campiglia, Pietro; Sala, Marina; Gomez-Monterrey, Isabel; De Luca, Nicola; Trimarco, Bruno; Iaccarino, Guido; Illario, Maddalena

    2015-01-01

    Activation of Ca2+/Calmodulin protein kinase II (CaMKII) is an important step in signaling of cardiac hypertrophy. The molecular mechanisms by which CaMKII integrates with other pathways in the heart are incompletely understood. We hypothesize that CaMKII association with extracellular regulated kinase (ERK), promotes cardiac hypertrophy through ERK nuclear localization. In H9C2 cardiomyoblasts, the selective CaMKII peptide inhibitor AntCaNtide, its penetratin conjugated minimal inhibitory sequence analog tat-CN17β, and the MEK/ERK inhibitor UO126 all reduce phenylephrine (PE)-mediated ERK and CaMKII activation and their interaction. Moreover, AntCaNtide or tat-CN17β pretreatment prevented PE induced CaMKII and ERK nuclear accumulation in H9C2s and reduced the hypertrophy responses. To determine the role of CaMKII in cardiac hypertrophy in vivo, spontaneously hypertensive rats were subjected to intramyocardial injections of AntCaNtide or tat-CN17β. Left ventricular hypertrophy was evaluated weekly for 3 weeks by cardiac ultrasounds. We observed that the treatment with CaMKII inhibitors induced similar but significant reduction of cardiac size, left ventricular mass, and thickness of cardiac wall. The treatment with CaMKII inhibitors caused a significant reduction of CaMKII and ERK phosphorylation levels and their nuclear localization in the heart. These results indicate that CaMKII and ERK interact to promote activation in hypertrophy; the inhibition of CaMKII-ERK interaction offers a novel therapeutic approach to limit cardiac hypertrophy.

  20. Predictors of Depression Stigma in Medical Students: Potential Targets for Prevention and Education.

    PubMed

    Wimsatt, Leslie A; Schwenk, Thomas L; Sen, Ananda

    2015-11-01

    Suicide rates are higher among U.S. physicians than the general population. Untreated depression is a major risk factor, yet depression stigma presents a barrier to treatment. This study aims to identify early career indications of stigma among physicians-in-training and to inform the design of stigma-reduction programs. A cross-sectional student survey administered at a large, Midwestern medical school in fall 2009 included measures of depression symptoms, attitudes toward mental health, and potential sources of depression stigma. Principal components factor analysis and linear regression were used to examine stigma factors associated with depression in medical students. The response rate was 65.7%, with 14.7% students reporting a previous depression diagnosis. Most students indicated that, if depressed, they would feel embarrassed if classmates knew. Many believed that revealing depression could negatively affect professional advancement. Factor analyses revealed three underlying stigma constructs: personal weakness, public devaluation, and social/professional discrimination. Students associating personal weakness with depression perceived medication as less efficacious and the academic environment as more competitive. Those endorsing public stigma viewed medication and counseling as less efficacious and associated depression with an inability to cope. Race, gender, and diagnosis of past/current depression also related to beliefs about stigma. Depression measures most strongly predicted stigma associated with personal weakness and social/professional discrimination. Recommendations for decreasing stigma among physicians-in-training include consideration of workplace perceptions, depression etiology, treatment efficacy, and personal attributes in the design of stigma reduction programs that could facilitate help-seeking behavior among physicians throughout their career. Copyright © 2015 American Journal of Preventive Medicine. Published by Elsevier Inc. All

  1. Glycogen synthase kinase-3: a potential preventive target for prostate cancer management.

    PubMed

    Li, Benyi; Thrasher, James Brantley; Terranova, Paul

    2015-11-01

    Prostate cancers are the frequently diagnosed cancers in men, and patients with metastatic disease only have 28% chance for 5-year survival. Patients with low-risk tumors are subjected to active surveillance, whereas high-risk cases are actively treated. Unfortunately, there is no cure for patients with late-stage disease. Glycogen synthase kinase-3 (GSK-3, α and β) is a protein serine/threonine kinase and has diverse cellular functions and numerous substrates. We sought to summarize all the studies done with GSK-3 in prostate cancers and to provide a prospective direction for future work. A comprehensive search of the literature on the electronic databases PubMed was conducted for the subject terms of GSK-3 and prostate cancer. Gene mutation and expression information was extracted from Oncomine and COSMIC databases. Case reports were not included. Accumulating evidence indicates that GSK-3α is mainly expressed in low-risk prostate cancers and is related to hormone-dependent androgen receptor (AR)-mediated gene expression, whereas GSK-3β is mainly expressed in high-risk prostate cancers and is related to hormone-independent AR-mediated gene expression. GSK-3 has been demonstrated as a positive regulator in AR transactivation and prostate cancer growth independent of the Wnt/β-catenin pathway. Different types of GSK-3inhibitors including lithium show promising results in suppressing tumor growth in different animal models of prostate cancer. Importantly, clinical use of lithium is associated with reduced cancer incidence in psychiatric patients. Taken together, GSK-3 inhibition might be implicated in prostate cancer management as a preventive treatment. Copyright © 2015 Elsevier Inc. All rights reserved.

  2. Sedentary behaviour as a new behavioural target in the prevention and treatment of type 2 diabetes.

    PubMed

    Henson, Joseph; Dunstan, David W; Davies, Melanie J; Yates, Thomas

    2016-01-01

    Our modern day society encompasses an ecological niche in which sedentary behaviour, labour-saving devices and energy dense foods have become the new reference of living. We now spend more time sedentary, defined as sitting, than in all other activities combined. It has recently been confirmed that the consequences of our modern chair dependency are substantial and a direct contributing factor to the ever increasing epidemic of chronic diseases witnessed within industrialized environments. Epidemiological evidence--from both cross-sectional and prospective observational studies--has indicated that the time spent in sedentary behaviour is a distinct risk factor for several health outcomes, including type 2 diabetes mellitus, insulin resistance, all-cause and cardiovascular disease mortality, depression and some types of cancer. Importantly, these detrimental associations remain even after accounting for time spent in moderate-to-vigorous physical activity, with the strongest and most persistent associations seen between sedentary time and type 2 diabetes mellitus. Importantly, experimental studies have started to confirm the observational associations, with mounting evidence showing that breaking prolonged sitting time with light ambulation is an effective strategy for improving postprandial glucose regulation. Indeed, there is even emerging evidence showing that simply substituting sitting for standing regularly throughout the day may be of sufficient stimulus to improve glucose regulation. We highlight some of the key definitions, issues and evidence underpinning the link between sedentary behaviour and chronic disease in order to better inform clinicians and patients about the importance of incorporating reduced sitting time into type 2 diabetes mellitus management and prevention pathways. Copyright © 2016 John Wiley & Sons, Ltd.

  3. The actin cytoskeleton as a therapeutic target for the prevention of relapse to methamphetamine use

    PubMed Central

    Young, Erica J.; Briggs, Sherri B.; Miller, Courtney A.

    2015-01-01

    A high rate of relapse is a defining characteristic of substance use disorder for which few treatments are available. Exposure to environmental cues associated with previous drug use can elicit relapse by causing the involuntary retrieval of deeply engrained associative memories that trigger a strong motivation to seek out drugs. Our lab is focused on identifying and disrupting mechanisms that support these powerful consolidated memories, with the goal of developing therapeutics. A particularly promising mechanism is regulation of synaptic dynamics by actin polymerization within dendritic spines. Emerging evidence indicates that memory is supported by structural and functional plasticity dendritic spines, for which actin polymerization is critical, and that prior drug use increases both spine and actin dynamics. Indeed we have found that inhibiting amygdala (AMY) actin polymerization immediately or twenty-four hours prior to testing disrupted methamphetamine (METH)-associated memories, but not food reward or fear memories. Furthermore, METH training increased AMY spine density which was reversed by actin depolymerization treatment. Actin dynamics were also shifted to a more dynamic state by METH training. While promising, actin polymerization inhibitors are not a viable therapeutic, as a multitude of peripheral process (e.g. cardiac function) rely on dynamic actin. For this reason, we have shifted our focus upstream of actin polymerization to nonmuscle myosin II. We and others have demonstrated that myosin IIb imparts a mechanical force that triggers spine actin polymerization in response to synaptic stimulation. Similar to an actin depolymerizing compound, pre-test inhibition of myosin II ATPase activity in the AMY produced a rapid and lasting disruption of drug-seeking behavior. While many questions remain, these findings indicate that myosin II represents a potential therapeutic avenue to target the actin cytoskeleton and disrupt the powerful, extinction

  4. Novel potential targets for prevention of arterial restenosis: insights from the pre-clinical research.

    PubMed

    Forte, Amalia; Rinaldi, Barbara; Berrino, Liberato; Rossi, Francesco; Galderisi, Umberto; Cipollaro, Marilena

    2014-12-01

    Restenosis is the pathophysiological process occurring in 10-15% of patients submitted to revascularization procedures of coronary, carotid and peripheral arteries. It can be considered as an excessive healing reaction of the vascular wall subjected to arterial/venous bypass graft interposition, endarterectomy or angioplasty. The advent of bare metal stents, drug-eluting stents and of the more recent drug-eluting balloons, have significantly reduced, but not eliminated, the incidence of restenosis, which remains a clinically relevant problem. Biomedical research in pre-clinical animal models of (re)stenosis, despite its limitations, has contributed enormously to the identification of processes involved in restenosis progression, going well beyond the initial dogma of a primarily proliferative disease. Although the main molecular and cellular mechanisms underlying restenosis have been well described, new signalling molecules and cell types controlling the progress of restenosis are continuously being discovered. In particular, microRNAs and vascular progenitor cells have recently been shown to play a key role in this pathophysiological process. In addition, the advanced highly sensitive high-throughput analyses of molecular alterations at the transcriptome, proteome and metabolome levels occurring in injured vessels in animal models of disease and in human specimens serve as a basis to identify novel potential therapeutic targets for restenosis. Molecular analyses are also contributing to the identification of reliable circulating biomarkers predictive of post-interventional restenosis in patients, which could be potentially helpful in the establishment of an early diagnosis and therapy. The present review summarizes the most recent and promising therapeutic strategies identified in experimental models of (re)stenosis and potentially translatable to patients subjected to revascularization procedures.

  5. Targeted overexpression of mitochondrial catalase prevents radiation-induced cognitive dysfunction.

    PubMed

    Parihar, Vipan K; Allen, Barrett D; Tran, Katherine K; Chmielewski, Nicole N; Craver, Brianna M; Martirosian, Vahan; Morganti, Josh M; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M; Nelson, Gregory A; Allen, Antiño R; Limoli, Charles L

    2015-01-01

    Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain.

  6. Targeted Overexpression of Mitochondrial Catalase Prevents Radiation-Induced Cognitive Dysfunction

    PubMed Central

    Parihar, Vipan K.; Allen, Barrett D.; Tran, Katherine K.; Chmielewski, Nicole N.; Craver, Brianna M.; Martirosian, Vahan; Morganti, Josh M.; Rosi, Susanna; Vlkolinsky, Roman; Acharya, Munjal M.; Nelson, Gregory A.; Allen, Antiño R.

    2015-01-01

    Abstract Aims: Radiation-induced disruption of mitochondrial function can elevate oxidative stress and contribute to the metabolic perturbations believed to compromise the functionality of the central nervous system. To clarify the role of mitochondrial oxidative stress in mediating the adverse effects of radiation in the brain, we analyzed transgenic (mitochondrial catalase [MCAT]) mice that overexpress human catalase localized to the mitochondria. Results: Compared with wild-type (WT) controls, overexpression of the MCAT transgene significantly decreased cognitive dysfunction after proton irradiation. Significant improvements in behavioral performance found on novel object recognition and object recognition in place tasks were associated with a preservation of neuronal morphology. While the architecture of hippocampal CA1 neurons was significantly compromised in irradiated WT mice, the same neurons in MCAT mice did not exhibit extensive and significant radiation-induced reductions in dendritic complexity. Irradiated neurons from MCAT mice maintained dendritic branching and length compared with WT mice. Protected neuronal morphology in irradiated MCAT mice was also associated with a stabilization of radiation-induced variations in long-term potentiation. Stabilized synaptic activity in MCAT mice coincided with an altered composition of the synaptic AMPA receptor subunits GluR1/2. Innovation: Our findings provide the first evidence that neurocognitive sequelae associated with radiation exposure can be reduced by overexpression of MCAT, operating through a mechanism involving the preservation of neuronal morphology. Conclusion: Our article documents the neuroprotective properties of reducing mitochondrial reactive oxygen species through the targeted overexpression of catalase and how this ameliorates the adverse effects of proton irradiation in the brain. Antioxid. Redox Signal. 22, 78–91. PMID:24949841

  7. Do pharmacological approaches that prevent opioid tolerance target different elements in the same regulatory machinery?

    PubMed

    Garzón, Javier; Rodríguez-Muñoz, María; Sánchez-Blázquez, Pilar

    2008-06-01

    In the nervous system, the interaction of opioids like heroin and morphine with the G protein-coupled Mu-opioid receptor (MOR) provokes the development of tolerance to these opioids, as well as physical dependence. Tolerance implies that higher doses of these drugs must be consumed in order to obtain an equivalent sensation, a situation that contributes notably to the social problems surrounding recreational opioid abuse. The mechanisms that promote opioid tolerance involve a series of adaptive changes in the MOR and in the post-receptor signalling elements. Pharmacological studies have consistently identified a number of signalling proteins relevant to morphine-induced tolerance, including the delta-opioid receptor (DOR), protein kinase C (PKC), protein kinase A (PKA), calcium/calmodulin-dependent kinase II (CaMKII), nitric oxide synthase (NOS), N-methyl-D-aspartate acid glutamate receptors (NMDAR), and regulators of G-signalling (RGS) proteins. Thus, it is feasible that these treatments which diminish morphine tolerance target distinct elements within the same regulatory machinery. In this scheme, the signals originated at the agonist-activated MORs would be recognised by elements such as the NMDARs, which in turn exert a negative feedback on MOR-evoked signalling. This process involves DOR regulation of MORs, MOR-induced activation of NMDARs (probably via the regulation of Src, recruiting PKC and Galpha subunits) and the NMDAR-mediated activation of CaMKII. The active CaMKII promotes the sequestering of morphine-activated Gbetagamma dimers by phosducin-like proteins (PhLP) and of Galpha subunits by RGS proteins and tolerance to opioids like morphine develops. Future efforts to study these phenomena should focus on fitting additional pieces into this puzzle in order to fully define the mechanism underlying the desensitization of MORs in neural cells.

  8. The Actin Cytoskeleton as a Therapeutic Target for the Prevention of Relapse to Methamphetamine Use.

    PubMed

    Young, Erica J; Briggs, Sherri B; Miller, Courtney A

    2015-01-01

    A high rate of relapse is a defining characteristic of substance use disorder for which few treatments are available. Exposure to environmental cues associated with previous drug use can elicit relapse by causing the involuntary retrieval of deeply engrained associative memories that trigger a strong motivation to seek out drugs. Our lab is focused on identifying and disrupting mechanisms that support these powerful consolidated memories, with the goal of developing therapeutics. A particularly promising mechanism is regulation of synaptic dynamics by actin polymerization within dendritic spines. Emerging evidence indicates that memory is supported by structural and functional plasticity dendritic spines, for which actin polymerization is critical, and that prior drug use increases both spine and actin dynamics. Indeed we have found that inhibiting amygdala (AMY) actin polymerization immediately or twenty-four hours prior to testing disrupted methamphetamine (METH)-associated memories, but not food reward or fear memories. Furthermore, METH training increased AMY spine density which was reversed by actin depolymerization treatment. Actin dynamics were also shifted to a more dynamic state by METH training. While promising, actin polymerization inhibitors are not a viable therapeutic, as a multitude of peripheral process (e.g. cardiac function) rely on dynamic actin. For this reason, we have shifted our focus upstream of actin polymerization to nonmuscle myosin II. We and others have demonstrated that myosin IIb imparts a mechanical force that triggers spine actin polymerization in response to synaptic stimulation. Similar to an actin depolymerizing compound, pre-test inhibition of myosin II ATPase activity in the AMY produced a rapid and lasting disruption of drug-seeking behavior. While many questions remain, these findings indicate that myosin II represents a potential therapeutic avenue to target the actin cytoskeleton and disrupt the powerful, extinction

  9. Weight Gain Prevention: Identifying Theory-Based Targets for Health Behavior Change in Young Adults

    PubMed Central

    Strong, Kathryn A.; Parks, Serena L.; Anderson, Eileen; Winett, Richard; Davy, Brenda M.

    2008-01-01

    Young adults attending college are more vulnerable to weight gain than the general population. We sought to identify health behavior change targets related to weight management in college students. Based on the social cognitive theory model for health behavior change, we investigated the health-related lifestyle behaviors and physiological characteristics of this population. Forty-three college students (18.3±0.1 years) completed a series of quantitative assessments (body weight and composition, cardiorespiratory fitness, diet and activity habits) and structured qualitative assessments (structured interview or focus group). Participants were predominantly normal-weight (mean BMI=22.2±0.4 kg/m2) and fit (VO2max = 50.5±1.5 ml/kg/min). However, healthy eating and physical activity were not considered high priorities, despite having ample free time, high exercise self-efficacy, positive outcome expectations for exercise, and a desire to exercise more. Participants reported that regularly engaging in exercise was difficult. This may have been due to poor planning/time management, satisfaction with body image, lack of accountability and feelings of laziness. Dietary patterns generally met recommendations but were low in fruits, vegetables and whole grains. Social support for exercise and healthy dietary habits were important factors associated with health behaviors. Students reported a decline in exercise and dietary habits relative to high school, which may contribute to college weight gain. Our results suggest that this population may not have adequate self-regulatory skills, such as planning and self-monitoring, to maintain healthy behaviors in the college environment. Dietitians working with young adults attending college may use these findings to guide the behavioral therapy component of their weight management medical nutrition therapy goals and outcomes. PMID:18926139

  10. Spatiotemporal mapping of cervical cancer incidence highlights need for targeted prevention in Songkhla province, Thailand.

    PubMed

    Zhao, Jun; Virani, Shama; Sriplung, Hutcha

    2017-04-01

    The national cervical cancer screening program in Thailand has been successful in reducing overall burden from this disease. However, evaluation on spatial and temporal scales is needed to assess the efficacy of this program in smaller regions. Here, we geographically assess incidence in a province with a uniquely heterogeneous distribution of lifestyle factors associated with religiosity. Cervical cancer cases were extracted from the provincial cancer registry from 1989 to 2013. Age-adjusted incidence rates were calculated using population statistics from the census bureau and adjusted to the Segi world standard population. Bayesian hierarchical modelling was employed to spatiotemporally map cervical cancer incidence trends in Songkhla province in 5-year period. Overall, the incidence of cervical cancer decreased in Songkhla province. The three districts with a Muslim population of greater than 70% had consistently lower cervical cancer rates from 1989 to 2013 compared with the rest of the predominantly Buddhist districts. Hotspots of incidence were identified in Sadao, Hat Yai and the juncture of Mueang Songkhla and Singhanakhon in each 5-year period. Distinct cervical cancer incidence trends by religion over time indicate differences in sexual habits, lifestyle and religion-associated culture between Muslims and Buddhists, and suggest divergent risk factor profiles for these groups. The high incidence rates in Sadao and Hat Yai is likely explained by the main road to Malaysia, which runs across these two areas and has frequent commercial sex trade. Female sex workers should be targeted as a vulnerable population for screening efforts to address this continuing burden of cervical cancer.

  11. A geranyl acetophenone targeting cysteinyl leukotriene synthesis prevents allergic airway inflammation in ovalbumin-sensitized mice

    SciTech Connect

    Ismail, Norazren; Jambari, Nuzul Nurahya; Zareen, Seema; Akhtar, Mohamad Nadeem; Shaari, Khozirah; Zamri-Saad, Mohamad; Tham, Chau Ling; Sulaiman, Mohd Roslan; Lajis, Nordin Hj; Israf, Daud Ahmad

    2012-03-01

    Asthma is associated with increased pulmonary inflammation and airway hyperresponsiveness. The current use of corticosteroids in the management of asthma has recently raised issues regarding safety and lack of responsiveness in 5–10% of asthmatic individuals. The aim of the present study was to investigate the therapeutic effect of a non-steroidal small molecule that has cysteinyl leukotriene (cysLT) inhibitory activity, upon attenuation of allergic lung inflammation in an acute murine model. Mice were sensitized with ovalbumin (OVA) and treated with several intraperitoneal doses (100, 20, 2 and 0.2 mg/kg) of 2,4,6,-trihydroxy-3-geranylacetophenone (tHGA). Bronchoalveolar lavage was performed, blood and lung samples were obtained and respiratory function was measured. OVA sensitization increased pulmonary inflammation and pulmonary allergic inflammation was significantly reduced at doses of 100, 20 and 2 mg/kg with no effect at the lowest dose of 0.2 mg/kg. The beneficial effects in the lung were associated with reduced eosinophilic infiltration and reduced secretion of Th2 cytokines and cysLTs. Peripheral blood reduction of total IgE was also a prominent feature. Treatment with tHGA significantly attenuated altered airway hyperresponsiveness as measured by the enhanced pause (Penh) response to incremental doses of methacholine. These data demonstrate that tHGA, a synthetic non-steroidal small molecule, can prevent acute allergic inflammation. This proof of concept opens further avenues of research and development of tHGA as an additional option to the current armamentarium of anti-asthma therapeutics. -- Highlights: ► Safer and effective anti-asthmatic drugs are in great demand. ► tHGA is a new 5-LO/cysLT inhibitor that inhibits allergic asthma in mice. ► tHGA is a natural compound that can be synthesized. ► Doses as low as 2 mg/kg alleviate lung pathology in experimental asthma. ► tHGA is a potential drug lead for the treatment of allergic asthma.

  12. Voluntary Medical Male Circumcision for HIV Prevention in Swaziland: Modeling the Impact of Age Targeting.

    PubMed

    Kripke, Katharine; Okello, Velephi; Maziya, Vusi; Benzerga, Wendy; Mirira, Munamato; Gold, Elizabeth; Schnure, Melissa; Sgaier, Sema; Castor, Delivette; Reed, Jason; Njeuhmeli, Emmanuel

    2016-01-01

    Voluntary medical male circumcision (VMMC) for HIV prevention has been a priority for Swaziland since 2009. Initially focusing on men ages 15-49, the Ministry of Health reduced the minimum age for VMMC from 15 to 10 years in 2012, given the existing demand among 10- to 15-year-olds. To understand the implications of focusing VMMC service delivery on specific age groups, the MOH undertook a modeling exercise to inform policy and implementation in 2013-2014. The impact and cost of circumcising specific age groups were assessed using the Decision Makers' Program Planning Tool, Version 2.0 (DMPPT 2.0), a simple compartmental model. We used age-specific HIV incidence from the Swaziland HIV Incidence Measurement Survey (SHIMS). Population, mortality, births, and HIV prevalence were imported from a national Spectrum/Goals model recently updated in consultation with country stakeholders. Baseline male circumcision prevalence was derived from the most recent Swaziland Demographic and Health Survey. The lowest numbers of VMMCs per HIV infection averted are achieved when males ages 15-19, 20-24, 25-29, and 30-34 are circumcised, although the uncertainty bounds for the estimates overlap. Circumcising males ages 25-29 and 20-24 provides the most immediate reduction in HIV incidence. Circumcising males ages 15-19, 20-24, and 25-29 provides the greatest magnitude incidence reduction within 15 years. The lowest cost per HIV infection averted is achieved by circumcising males ages 15-34: $870 U.S. dollars (USD). The potential impact, cost, and cost-effectiveness of VMMC scale-up in Swaziland are not uniform. They vary by the age group of males circumcised. Based on the results of this modeling exercise, the Ministry of Health's Swaziland Male Circumcision Strategic and Operational Plan 2014-2018 adopted an implementation strategy that calls for circumcision to be scaled up to 50% coverage for neonates, 80% among males ages 10-29, and 55% among males ages 30-34.

  13. Curcumin―The Paradigm of a Multi-Target Natural Compound with Applications in Cancer Prevention and Treatment

    PubMed Central

    Teiten, Marie-Hélène; Eifes, Serge; Dicato, Mario; Diederich, Marc

    2010-01-01

    As cancer is a multifactor disease, it may require treatment with compounds able to target multiple intracellular components. We summarize here how curcumin is able to modulate many components of intracellular signaling pathways implicated in inflammation, cell proliferation and invasion and to induce genetic modulations eventually leading to tumor cell death. Clinical applications of this natural compound were initially limited by its low solubility and bioavailability in both plasma and tissues but combination with adjuvant and delivery vehicles was reported to largely improve bio-availability of curcumin. Moreover, curcumin was reported to act in synergism with several natural compounds or synthetic agents commonly used in chemotherapy. Based on this, curcumin could thus be considered as a good candidate for cancer prevention and treatment when used alone or in combination with other conventional treatments. PMID:22069551

  14. Targeting angiogenesis as a therapeutic means to reinforce osteocyte survival and prevent nonunions in the aftermath of radiotherapy

    PubMed Central

    Donneys, Alexis; Nelson, Noah S.; Page, Erin E.; Deshpande, Sagar S.; Felice, Peter A.; Tchanque–Fossuo, Catherine N.; Spiegel, Joshua P.; Buchman, Steven R.

    2016-01-01

    Background Radiotherapy (XRT) exerts detrimental collateral effects on bone tissue through mechanisms of vascular damage and impediments to osteocytes, ultimately predisposing patients to the debilitating problems of late pathologic fractures and nonunions. We posit that angiogenic therapy will reverse these pathologic effects in a rat model of radiated fracture healing. Methods Three groups of rats underwent mandibular osteotomy. Radiated groups received a fractionated 35 Gy dose before surgery. The deferoxamine (DFO) group received local injections postoperatively. A 40-day healing period was allowed before histology. Analysis of variance (ANOVA; p < .05) was used for group comparisons. Results Radiated fractures revealed a significantly decreased osteocyte count and corresponding increase in empty lacunae when compared to nonradiated fractures (p = .001). With the addition of DFO, these differences were not appreciated. Further, a 42% increase in bony unions was observed after DFO therapy. Conclusion Targeting angiogenesis is a useful means for promoting osteocyte survival and preventing bone pathology after XRT. PMID:24801669

  15. A modified R-type bacteriocin specifically targeting Clostridium difficile prevents colonization of mice without affecting gut microbiota diversity.

    PubMed

    Gebhart, Dana; Lok, Stephen; Clare, Simon; Tomas, Myreen; Stares, Mark; Scholl, Dean; Donskey, Curtis J; Lawley, Trevor D; Govoni, Gregory R

    2015-03-24

    Clostridium difficile is a leading cause of nosocomial infections worldwide and has become an urgent public health threat requiring immediate attention. Epidemic lineages of the BI/NAP1/027 strain type have emerged and spread through health care systems across the globe over the past decade. Limiting person-to-person transmission and eradicating C. difficile, especially the BI/NAP1/027 strain type, from health care facilities are difficult due to the abundant shedding of spores that are impervious to most interventions. Effective prophylaxis for C. difficile infection (CDI) is lacking. We have genetically modified a contractile R-type bacteriocin ("diffocin") from C. difficile strain CD4 to kill BI/NAP1/027-type strains for this purpose. The natural receptor binding protein (RBP) responsible for diffocin targeting was replaced with a newly discovered RBP identified within a prophage of a BI/NAP1/027-type target strain by genome mining. The resulting modified diffocins (a.k.a. Avidocin-CDs), Av-CD291.1 and Av-CD291.2, were stable and killed all 16 tested BI/NAP1/027-type strains. Av-CD291.2 administered in drinking water survived passage through the mouse gastrointestinal (GI) tract, did not detectably alter the mouse gut microbiota or disrupt natural colonization resistance to C. difficile or the vancomycin-resistant Enterococcus faecium (VREF), and prevented antibiotic-induced colonization of mice inoculated with BI/NAP1/027-type spores. Given the high incidence and virulence of the pathogen, preventing colonization by BI/NAP1/027-type strains and limiting their transmission could significantly reduce the occurrence of the most severe CDIs. This modified diffocin represents a prototype of an Avidocin-CD platform capable of producing targetable, precision anti-C. difficile agents that can prevent and potentially treat CDIs without disrupting protective indigenous microbiota. Treatment and prevention strategies for bacterial diseases rely heavily on traditional

  16. A Targeted Infection Prevention Intervention in Nursing Home Residents With Indwelling Devices

    PubMed Central

    Mody, Lona; Krein, Sarah L.; Saint, Sanjay K.; Min, Lillian C.; Montoya, Ana; Lansing, Bonnie; McNamara, Sara E.; Symons, Kathleen; Fisch, Jay; Koo, Evonne; Rye, Ruth Anne; Galecki, Andrzej; Kabeto, Mohammed U.; Fitzgerald, James T.; Olmsted, Russell N.; Kauffman, Carol A.; Bradley, Suzanne F.

    2015-01-01

    IMPORTANCE Indwelling devices (eg, urinary catheters and feeding tubes) are often used in nursing homes (NHs). Inadequate care of residents with these devices contributes to high rates of multidrug-resistant organisms (MDROs) and device-related infections in NHs. OBJECTIVE To test whether a multimodal targeted infection program (TIP) reduces the prevalence of MDROs and incident device-related infections. DESIGN, SETTING, AND PARTICIPANTS Randomized clinical trial at 12 community-based NHs from May 2010 to April 2013. Participants were high-risk NH residents with urinary catheters, feeding tubes, or both. INTERVENTIONS Multimodal, including preemptive barrier precautions, active surveillance for MDROs and infections, and NH staff education. MAIN OUTCOMES AND MEASURES The primary outcome was the prevalence density rate of MDROs, defined as the total number of MDROs isolated per visit averaged over the duration of a resident's participation. Secondary outcomes included new MDRO acquisitions and new clinically defined device-associated infections. Data were analyzed using a mixed-effects multilevel Poisson regression model (primary outcome) and a Cox proportional hazards model (secondary outcome), adjusting for facility-level clustering and resident-level variables. RESULTS In total, 418 NH residents with indwelling devices were enrolled, with 34 174 device-days and 6557 anatomic sites sampled. Intervention NHs had a decrease in the overall MDRO prevalence density (rate ratio, 0.77; 95% CI, 0.62–0.94). The rate of new methicillin-resistant Staphylococcus aureus acquisitions was lower in the intervention group than in the control group (rate ratio, 0.78; 95% CI, 0.64–0.96). Hazard ratios for the first and all (including recurrent) clinically defined catheter-associated urinary tract infections were 0.54 (95% CI, 0.30–0.97) and 0.69 (95% CI, 0.49–0.99), respectively, in the intervention group and the control group. There were no reductions in new vancomycin

  17. A targeted infection prevention intervention in nursing home residents with indwelling devices: a randomized clinical trial.

    PubMed

    Mody, Lona; Krein, Sarah L; Saint, Sanjay; Min, Lillian C; Montoya, Ana; Lansing, Bonnie; McNamara, Sara E; Symons, Kathleen; Fisch, Jay; Koo, Evonne; Rye, Ruth Anne; Galecki, Andrzej; Kabeto, Mohammed U; Fitzgerald, James T; Olmsted, Russell N; Kauffman, Carol A; Bradley, Suzanne F

    2015-05-01

    Indwelling devices (eg, urinary catheters and feeding tubes) are often used in nursing homes (NHs). Inadequate care of residents with these devices contributes to high rates of multidrug-resistant organisms (MDROs) and device-related infections in NHs. To test whether a multimodal targeted infection program (TIP) reduces the prevalence of MDROs and incident device-related infections. Randomized clinical trial at 12 community-based NHs from May 2010 to April 2013. Participants were high-risk NH residents with urinary catheters, feeding tubes, or both. Multimodal, including preemptive barrier precautions, active surveillance for MDROs and infections, and NH staff education. The primary outcome was the prevalence density rate of MDROs, defined as the total number of MDROs isolated per visit averaged over the duration of a resident's participation. Secondary outcomes included new MDRO acquisitions and new clinically defined device-associated infections. Data were analyzed using a mixed-effects multilevel Poisson regression model (primary outcome) and a Cox proportional hazards model (secondary outcome), adjusting for facility-level clustering and resident-level variables. In total, 418 NH residents with indwelling devices were enrolled, with 34,174 device-days and 6557 anatomic sites sampled. Intervention NHs had a decrease in the overall MDRO prevalence density (rate ratio, 0.77; 95% CI, 0.62-0.94). The rate of new methicillin-resistant Staphylococcus aureus acquisitions was lower in the intervention group than in the control group (rate ratio, 0.78; 95% CI, 0.64-0.96). Hazard ratios for the first and all (including recurrent) clinically defined catheter-associated urinary tract infections were 0.54 (95% CI, 0.30-0.97) and 0.69 (95% CI, 0.49-0.99), respectively, in the intervention group and the control group. There were no reductions in new vancomycin-resistant enterococci or resistant gram-negative bacilli acquisitions or in new feeding tube-associated pneumonias or

  18. Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions

    PubMed Central

    Chu, Sao-Yu; Wang, Chun-Han; Lin, I-Ya

    2017-01-01

    Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry. PMID:28448523

  19. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer's-like pathology.

    PubMed

    Olmos-Alonso, Adrian; Schetters, Sjoerd T T; Sri, Sarmi; Askew, Katharine; Mancuso, Renzo; Vargas-Caballero, Mariana; Holscher, Christian; Perry, V Hugh; Gomez-Nicola, Diego

    2016-03-01

    The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer's disease. However, the study of microglial proliferation in Alzheimer's disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported. In this study we found increased proliferation of microglial cells in human Alzheimer's disease, in line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with disease severity. Using a transgenic model of Alzheimer's-like pathology (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proliferation, in the proximity of amyloid-β plaques. Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine kinase inhibitor (GW2580) resulted in the blockade of microglial proliferation and the shifting of the microglial inflammatory profile to an anti-inflammatory phenotype. Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performance in memory and behavioural tasks and a prevention of synaptic degeneration, although these changes were not correlated with a change in the number of amyloid-β plaques. Our results provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer's disease, and validate the application of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle microglial activation and the progression of Alzheimer's disease. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain.

  20. Pharmacological targeting of CSF1R inhibits microglial proliferation and prevents the progression of Alzheimer’s-like pathology

    PubMed Central

    Olmos-Alonso, Adrian; Schetters, Sjoerd T. T.; Sri, Sarmi; Askew, Katharine; Mancuso, Renzo; Vargas-Caballero, Mariana; Holscher, Christian; Perry, V. Hugh

    2016-01-01

    The proliferation and activation of microglial cells is a hallmark of several neurodegenerative conditions. This mechanism is regulated by the activation of the colony-stimulating factor 1 receptor (CSF1R), thus providing a target that may prevent the progression of conditions such as Alzheimer’s disease. However, the study of microglial proliferation in Alzheimer’s disease and validation of the efficacy of CSF1R-inhibiting strategies have not yet been reported. In this study we found increased proliferation of microglial cells in human Alzheimer’s disease, in line with an increased upregulation of the CSF1R-dependent pro-mitogenic cascade, correlating with disease severity. Using a transgenic model of Alzheimer’s-like pathology (APPswe, PSEN1dE9; APP/PS1 mice) we define a CSF1R-dependent progressive increase in microglial proliferation, in the proximity of amyloid-β plaques. Prolonged inhibition of CSF1R in APP/PS1 mice by an orally available tyrosine kinase inhibitor (GW2580) resulted in the blockade of microglial proliferation and the shifting of the microglial inflammatory profile to an anti-inflammatory phenotype. Pharmacological targeting of CSF1R in APP/PS1 mice resulted in an improved performance in memory and behavioural tasks and a prevention of synaptic degeneration, although these changes were not correlated with a change in the number of amyloid-β plaques. Our results provide the first proof of the efficacy of CSF1R inhibition in models of Alzheimer’s disease, and validate the application of a therapeutic strategy aimed at modifying CSF1R activation as a promising approach to tackle microglial activation and the progression of Alzheimer’s disease. PMID:26747862

  1. Semaphorin-1a prevents Drosophila olfactory projection neuron dendrites from mis-targeting into select antennal lobe regions.

    PubMed

    Shen, Hung-Chang; Chu, Sao-Yu; Hsu, Tsai-Chi; Wang, Chun-Han; Lin, I-Ya; Yu, Hung-Hsiang

    2017-04-01

    Elucidating how appropriate neurite patterns are generated in neurons of the olfactory system is crucial for comprehending the construction of the olfactory map. In the Drosophila olfactory system, projection neurons (PNs), primarily derived from four neural stem cells (called neuroblasts), populate their cell bodies surrounding to and distribute their dendrites in distinct but overlapping patterns within the primary olfactory center of the brain, the antennal lobe (AL). However, it remains unclear whether the same molecular mechanisms are employed to generate the appropriate dendritic patterns in discrete AL glomeruli among PNs produced from different neuroblasts. Here, by examining a previously explored transmembrane protein Semaphorin-1a (Sema-1a) which was proposed to globally control initial PN dendritic targeting along the dorsolateral-to-ventromedial axis of the AL, we discover a new role for Sema-1a in preventing dendrites of both uni-glomerular and poly-glomerular PNs from aberrant invasion into select AL regions and, intriguingly, this Sema-1a-deficient dendritic mis-targeting phenotype seems to associate with the origins of PNs from which they are derived. Further, ectopic expression of Sema-1a resulted in PN dendritic mis-projection from a select AL region into adjacent glomeruli, strengthening the idea that Sema-1a plays an essential role in preventing abnormal dendritic accumulation in select AL regions. Taken together, these results demonstrate that Sema-1a repulsion keeps dendrites of different types of PNs away from each other, enabling the same types of PN dendrites to be sorted into destined AL glomeruli and permitting for functional assembly of olfactory circuitry.

  2. Injury prevention target groups in soccer: injury characteristics and incidence rates in male junior and senior players.

    PubMed

    Schmikli, Sandor L; de Vries, Wouter R; Inklaar, Han; Backx, Frank J G

    2011-05-01

    To identify target groups for injury prevention in male amateur soccer players under 35 years of age. A computer-assisted telephone survey with a 12-month recall period for injuries in a representative sample of Dutch citizens from the Injuries and Physical Activity Netherlands (IPAN)-database. A comparison of the volume of soccer injuries, the incidence and the need for medical attention per level of exposure and age category. The incidence in seniors was twice that of juniors (17.5% versus 8.1%; odds ratio (OR=2.4). In juniors the overall incidence was lowest in the category with the least amount of soccer exposure time (0-3 h: 2.9%; 3-5 h: 13.0%; 5+ h: 12.3%). A comparable result was found in seniors: (0-3 h: 12.0%; 3-5 h: 21.6%; 5+ h: 21.5%). Within each level of soccer exposure, a different incidence was found in juniors and seniors (0-3 h: OR=4.6; 3-5 h: OR=1.8; 5+ h: OR=1.9). Ankle, knee and upper leg injuries were most common (59.9%). Contusions, strains and sprains dominated (78.1%). Body region and type of injuries were similar in both age categories. Medical treatment for injuries was equally necessary in both age groups. Senior male amateur soccer players and particularly the more skilled seniors (involved in soccer at least 3 h per week), should be primarily targeted for studies on injury risk factors and prevention programs.

  3. Interventions among male clients of female sex workers in Benin, West Africa: an essential component of targeted HIV preventive interventions

    PubMed Central

    Lowndes, C M; Alary, M; Labbé, A‐C; Gnintoungbè, C; Belleau, M; Mukenge, L; Meda, H; Ndour, M; Anagonou, S; Gbaguidi, A

    2007-01-01

    Objectives To assess the impact of interventions targeted towards female sex workers (FSWs) and their male clients on client HIV/STI prevalence and sexual behaviour. Methods From 1993 to 2006, an HIV/STI preventive intervention focusing on condom promotion and STI care was implemented among FSWs in Cotonou, Benin, and then expanded to cover their male sexual partners in 2000. The interventions were scaled up to five other cities of Benin in 2001–2002. Serial cross‐sectional surveys of HIV/STI prevalence and sexual behaviour were carried out among clients in Cotonou in 1998, 2002 and 2005; and in the five other cities (O/Cotonou) in 2002 and 2005. Results Significant declines in gonorrhoea prevalence among clients of FSWs: Cotonou, from 5.4% in 1998 to 1.6% in 2005; O/Cotonou: from 3.5% in 2002 to 0.59% in 2005. Chlamydia prevalence also declined O/Cotonou, from 4.8% to 1.8%, while HIV prevalence remained stable. Reported condom use by clients with both FSWs and casual non‐FSW partners, but not regular partners, increased significantly. While condom use at last sex with an FSW was similar in Cotonou to O/Cotonou around the time of implementation of the interventions (56% in 1998 vs 49% in 2002, respectively), it had risen to similar levels by 2005 (95% and 96%, respectively). Conclusions These results demonstrate that it is possible to implement preventive and clinical services for clients of FSWs, and suggest that such interventions, integrated with those targeted towards FSWs, can have a significant effect on sexual behaviour and STI prevalence (particularly gonorrhoea) among this population. PMID:17942573

  4. Glutathione prevents preterm parturition and fetal death by targeting macrophage-induced reactive oxygen species production in the myometrium.

    PubMed

    Hadi, Tarik; Bardou, Marc; Mace, Guillaume; Sicard, Pierre; Wendremaire, Maeva; Barrichon, Marina; Richaud, Sarah; Demidov, Oleg; Sagot, Paul; Garrido, Carmen; Lirussi, Frédéric

    2015-06-01

    Preterm birth is an inflammatory process resulting from the massive infiltration of innate immune cells and the production of proinflammatory cytokines in the myometrium. However, proinflammatory cytokines, which induce labor in vivo, fail to induce labor-associated features in human myometrial cells (MCs). We thus aimed to investigate if reactive oxygen species (ROS) production could be the missing step between immune cell activation and MC response. Indeed, we found that ROS production is increased in the human preterm laboring myometrium (27% ROS producing cells, respectively, versus 2% in nonlaboring controls), with 90% ROS production in macrophages. Using LPS-stimulated myometrial samples and cell coculture experiments, we demonstrated that ROS production is required for labor onset. Furthermore, we showed that ROS are required first in the NADPH oxidase (NADPHox)-2/NF-κB-dependent macrophage response to inflammatory stimuli but, more importantly, to trigger macrophage-induced MCs transactivation. Remarkably, in a murine model of LPS-induced preterm labor (inducing delivery within 17 hours, with no pup survival), cotreatment with glutathione delayed labor onset up to 94 hours and prevented in utero fetal distress, allowing 46% pups to survive. These results suggest that targeting ROS production with the macrophage-permeable antioxidant glutathione could constitute a promising strategy to prevent preterm birth. © FASEB.

  5. A systematic analysis of childhood obesity prevention interventions targeting Hispanic children: lessons learned from the previous decade.

    PubMed

    Branscum, P; Sharma, M

    2011-05-01

    Hispanic children suffer from the highest overall rates of prevalence for overweight and obesity in the US. In the last decade some interventions for prevention of childhood obesity have been developed and tailored to target this subgroup. The purpose of this review is to systematically analyze and summarize findings for health education and promotion interventions aimed at the prevention of childhood overweight and obesity among primarily Hispanic children. A systematic review of PubMed, CINAHL, and ERIC was done for the time period 2000 to May 2010. A posteriori effect size for the primary outcome of each intervention was calculated using G*Power. A total of nine interventions were located; five randomized controlled trials and four were either quasi-experimental or pilot studies. Among these studies, only four had significant findings, and calculated effect sizes (Cohen's f) ranged from small to medium with the highest f = 0.26. Interventions were more likely to be successful when participants were at higher risk for obesity, a parental component was included, the intervention contained theoretical underpinnings, the intervention was delivered by a dedicated staff, the intervention served older children and the intervention was longer in duration. More interventions need to be developed for Hispanic children. Future interventions should also develop and utilize culturally appropriate and sensitive materials and approaches. © 2010 The Authors. obesity reviews © 2010 International Association for the Study of Obesity.

  6. Sodium/glucose cotransporter 2 inhibitors and prevention of diabetic nephropathy: targeting the renal tubule in diabetes.

    PubMed

    De Nicola, Luca; Gabbai, Francis B; Liberti, Maria Elena; Sagliocca, Adelia; Conte, Giuseppe; Minutolo, Roberto

    2014-07-01

    Optimal prevention and treatment of chronic kidney disease in diabetes requires implementing therapies that specifically interfere with the pathogenesis of diabetic nephropathy. In this regard, significant attention has been given to alterations of the proximal tubule and resulting changes in glomerular filtration rate. At the onset of diabetes mellitus, hyperglycemia causes increases in proximal tubular reabsorption secondary to induction of tubular growth with associated increases in sodium/glucose cotransport. The increase in proximal reabsorption leads to a decrease in solute load to the macula densa, deactivation of the tubuloglomerular feedback, and increases in glomerular filtration rate. Because glomerular hyperfiltration currently is recognized as a risk factor for progression of kidney disease in diabetic patients, limiting proximal tubular reabsorption constitutes a potential target to reduce hyperfiltration. The recent introduction of sodium/glucose cotransporter 2 (SGLT2) inhibitors opens new therapeutic perspectives for this high-risk patient population. Experimental studies have shown that these new agents attenuate the progressive nature of diabetic nephropathy by blood glucose-dependent and -independent mechanisms. SGLT2 inhibition may prevent glomerular hyperfiltration independent of the effect of lowering blood glucose levels while limiting kidney growth, inflammation, and albuminuria through reductions in blood glucose levels. Clinical data for the potential role of the proximal tubule in the pathophysiology of diabetic nephropathy and the nephroprotective effects of SGLT2 inhibitors currently are limited compared to the more extensive experimental literature. We review the evidence supporting this working hypothesis by integrating the experimental findings with the available clinical data.

  7. Matrix metalloproteinases in cancer metastasis: molecular targets for prostate cancer prevention by green tea polyphenols and grape seed proanthocyanidins.

    PubMed

    Katiyar, Santosh K

    2006-03-01

    Matrix metalloproteinases (MMP) play a crucial role in the development and metastatic spread of cancer. One of the earliest events in the metastatic spread of cancer is the invasion through the basement membrane and proteolytic degradation of the extracellular matrix proteins, such as, collagens, laminin, elastin and fibronectin etc, and non-matrix proteins. MMPs are the important regulators of tumor growth, both at the primary site and in distant metastases. Given the clear implications of MMPs in many human cancers, MMPs remain important targets of cancer therapy. Metastatic spread of cancer continues to be the greatest barrier in prevention or cure of cancer. The recognition that MMPs facilitate tumor cell growth, invasion and metastasis of cancer has led to the development of MMP inhibitors as cancer therapeutic agents. Understanding the molecular mechanism of metastasis is also crucial for the design and effective use of novel therapeutic strategies to combat metastases. In this short review article, we discuss the evidences that MMPs are associated with cancer metastasis and that they make a functional contribution to the process. Further, since considerable interest among human population is increasing with regard to the use of dietary botanical supplements for the prevention of age-associated diseases like some forms of cancer, we also discuss the beneficial effects of dietary botanicals, such as green tea polyphenols and grape seed proanthocyanidins, in chemoprevention of cancer with particular emphasis on the involvement of MMPs in prostate cancer.

  8. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea.

    PubMed

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-18

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2(-/-) mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2(-/-) mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2(-/-) mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention.

  9. NRF2 Is a Key Target for Prevention of Noise-Induced Hearing Loss by Reducing Oxidative Damage of Cochlea

    PubMed Central

    Honkura, Yohei; Matsuo, Hirotaka; Murakami, Shohei; Sakiyama, Masayuki; Mizutari, Kunio; Shiotani, Akihiro; Yamamoto, Masayuki; Morita, Ichiro; Shinomiya, Nariyoshi; Kawase, Tetsuaki; Katori, Yukio; Motohashi, Hozumi

    2016-01-01

    Noise-induced hearing loss (NIHL) is one of the most common sensorineural hearing deficits. Recent studies have demonstrated that the pathogenesis of NIHL is closely related to ischemia-reperfusion injury of cochlea, which is caused by blood flow decrease and free radical production due to excessive noise. This suggests that protecting the cochlea from oxidative stress is an effective therapeutic approach for NIHL. NRF2 is a transcriptional activator playing an essential role in the defense mechanism against oxidative stress. To clarify the contribution of NRF2 to cochlear protection, we examined Nrf2–/– mice for susceptibility to NIHL. Threshold shifts of the auditory brainstem response at 7 days post-exposure were significantly larger in Nrf2–/– mice than wild-type mice. Treatment with CDDO-Im, a potent NRF2-activating drug, before but not after the noise exposure preserved the integrity of hair cells and improved post-exposure hearing levels in wild-type mice, but not in Nrf2–/– mice. Therefore, NRF2 activation is effective for NIHL prevention. Consistently, a human NRF2 SNP was significantly associated with impaired sensorineural hearing levels in a cohort subjected to occupational noise exposure. Thus, high NRF2 activity is advantageous for cochlear protection from noise-induced injury, and NRF2 is a promising target for NIHL prevention. PMID:26776972

  10. Targeting Overconsumption of Sugar-Sweetened Beverages vs. Overall Poor Diet Quality for Cardiometabolic Diseases Risk Prevention: Place Your Bets!

    PubMed Central

    Arsenault, Benoit J.; Lamarche, Benoît; Després, Jean-Pierre

    2017-01-01

    Chronic overconsumption of sugar-sweetened beverages (SSBs) is amongst the dietary factors most consistently found to be associated with obesity, type 2 diabetes (T2D) and cardiovascular disease (CVD) risk in large epidemiological studies. Intervention studies have shown that SSB overconsumption increases intra-abdominal obesity and ectopic lipid deposition in the liver, and also exacerbates cardiometabolic risk. Similar to the prevalence of obesity and T2D, national surveys of food consumption have shown that chronic overconsumption of SSBs is skyrocketing in many parts of the world, yet with marked heterogeneity across countries. SSB overconsumption is also particularly worrisome among children and adolescents. Although the relationships between SSB overconsumption and obesity, T2D, and CVD are rather consistent in epidemiological studies, it has also been shown that SSB overconsumption is part of an overall poor dietary pattern and is particularly prevalent among subgroups of the population with low socioeconomic status, thereby questioning the major focus on SSBs to target/prevent cardiometabolic diseases. Public health initiatives aimed specifically at decreasing SSB overconsumption will most likely be successful in influencing SSB consumption per se. However, comprehensive strategies targeting poor dietary patterns and aiming at improving global dietary quality are likely to have much more impact in addressing the unprecedented public health challenges that we are currently facing. PMID:28608806

  11. Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes.

    PubMed

    Canning, Paul; Kenny, Bridget-Ann; Prise, Vivien; Glenn, Josephine; Sarker, Mosharraf H; Hudson, Natalie; Brandt, Martin; Lopez, Francisco J; Gale, David; Luthert, Philip J; Adamson, Peter; Turowski, Patric; Stitt, Alan W

    2016-06-28

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood-retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents.

  12. Lipoprotein-associated phospholipase A2 (Lp-PLA2) as a therapeutic target to prevent retinal vasopermeability during diabetes

    PubMed Central

    Canning, Paul; Kenny, Bridget-Ann; Prise, Vivien; Glenn, Josephine; Sarker, Mosharraf H.; Hudson, Natalie; Brandt, Martin; Lopez, Francisco J.; Gale, David; Luthert, Philip J.; Adamson, Peter; Turowski, Patric; Stitt, Alan W.

    2016-01-01

    Lipoprotein-associated phospholipase A2 (Lp-PLA2) hydrolyses oxidized low-density lipoproteins into proinflammatory products, which can have detrimental effects on vascular function. As a specific inhibitor of Lp-PLA2, darapladib has been shown to be protective against atherogenesis and vascular leakage in diabetic and hypercholesterolemic animal models. This study has investigated whether Lp-PLA2 and its major enzymatic product, lysophosphatidylcholine (LPC), are involved in blood–retinal barrier (BRB) damage during diabetic retinopathy. We assessed BRB protection in diabetic rats through use of species-specific analogs of darapladib. Systemic Lp-PLA2 inhibition using SB-435495 at 10 mg/kg (i.p.) effectively suppressed BRB breakdown in streptozotocin-diabetic Brown Norway rats. This inhibitory effect was comparable to intravitreal VEGF neutralization, and the protection against BRB dysfunction was additive when both targets were inhibited simultaneously. Mechanistic studies in primary brain and retinal microvascular endothelial cells, as well as occluded rat pial microvessels, showed that luminal but not abluminal LPC potently induced permeability, and that this required signaling by the VEGF receptor 2 (VEGFR2). Taken together, this study demonstrates that Lp-PLA2 inhibition can effectively prevent diabetes-mediated BRB dysfunction and that LPC impacts on the retinal vascular endothelium to induce vasopermeability via VEGFR2. Thus, Lp-PLA2 may be a useful therapeutic target for patients with diabetic macular edema (DME), perhaps in combination with currently administered anti-VEGF agents. PMID:27298369

  13. Mitochondria-targeted Ogg1 and aconitase-2 prevent oxidant-induced mitochondrial DNA damage in alveolar epithelial cells.

    PubMed

    Kim, Seok-Jo; Cheresh, Paul; Williams, David; Cheng, Yuan; Ridge, Karen; Schumacker, Paul T; Weitzman, Sigmund; Bohr, Vilhelm A; Kamp, David W

    2014-02-28

    Mitochondria-targeted human 8-oxoguanine DNA glycosylase (mt-hOgg1) and aconitase-2 (Aco-2) each reduce oxidant-induced alveolar epithelial cell (AEC) apoptosis, but it is unclear whether protection occurs by preventing AEC mitochondrial DNA (mtDNA) damage. Using quantitative PCR-based measurements of mitochondrial and nuclear DNA damage, mtDNA damage was preferentially noted in AEC after exposure to oxidative stress (e.g. amosite asbestos (5-25 μg/cm(2)) or H2O2 (100-250 μM)) for 24 h. Overexpression of wild-type mt-hOgg1 or mt-long α/β 317-323 hOgg1 mutant incapable of DNA repair (mt-hOgg1-Mut) each blocked A549 cell oxidant-induced mtDNA damage, mitochondrial p53 translocation, and intrinsic apoptosis as assessed by DNA fragmentation and cleaved caspase-9. In contrast, compared with controls, knockdown of Ogg1 (using Ogg1 shRNA in A549 cells or primary alveolar type 2 cells from ogg1(-/-) mice) augmented mtDNA lesions and intrinsic apoptosis at base line, and these effects were increased further after exposure to oxidative stress. Notably, overexpression of Aco-2 reduced oxidant-induced mtDNA lesions, mitochondrial p53 translocation, and apoptosis, whereas siRNA for Aco-2 (siAco-2) enhanced mtDNA damage, mitochondrial p53 translocation, and apoptosis. Finally, siAco-2 attenuated the protective effects of mt-hOgg1-Mut but not wild-type mt-hOgg1 against oxidant-induced mtDNA damage and apoptosis. Collectively, these data demonstrate a novel role for mt-hOgg1 and Aco-2 in preserving AEC mtDNA integrity, thereby preventing oxidant-induced mitochondrial dysfunction, p53 mitochondrial translocation, and intrinsic apoptosis. Furthermore, mt-hOgg1 chaperoning of Aco-2 in preventing oxidant-mediated mtDNA damage and apoptosis may afford an innovative target for the molecular events underlying oxidant-induced toxicity.

  14. Aiming at a moving target: research ethics in the context of evolving standards of care and prevention.

    PubMed

    Shah, Seema; Lie, Reidar K

    2013-11-01

    In rapidly evolving medical fields where the standard of care or prevention changes frequently, guidelines are increasingly likely to conflict with what participants receive in research. Although guidelines typically set the standard of care, there are some cases in which research can justifiably deviate from guidelines. When guidelines conflict with research, an ethical issue only arises if guidelines are rigorous and should be followed. Next, it is important that the cumulative evidence and the conclusions reached by the guidelines do not eliminate the need for further research. Even when guidelines are rigorous and the study still asks an important question, we argue that there may be good reasons for deviations in three cases: (1) when research poses no greater net risk than the standard of care; (2) when there is a continued need for additional evidence, for example, when subpopulations are not covered by the guidelines; and (3) less frequently, when clinical practice guidelines can be justified by the evidence, but practitioners disagree about the guidelines, and the guidelines are not consistently followed as a result. We suggest that procedural protections may be especially useful in deciding when studies in the third category can proceed.

  15. The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases.

    PubMed

    Redekop, William K; Lenk, Edeltraud J; Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A; Tediosi, Fabrizio; Rijnsburger, Adriana J; Bakker, Roel; Hontelez, Jan A C; Richardus, Jan H; Jacobson, Julie; de Vlas, Sake J; Severens, Johan L

    2017-01-01

    Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)-also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. The economic benefit from productivity gain was estimated to be I$251 billion in 2011-2020 and I$313 billion in 2021-2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large uncertainty, these benefits far exceed the investment

  16. The Socioeconomic Benefit to Individuals of Achieving the 2020 Targets for Five Preventive Chemotherapy Neglected Tropical Diseases

    PubMed Central

    Luyendijk, Marianne; Fitzpatrick, Christopher; Niessen, Louis; Stolk, Wilma A.; Tediosi, Fabrizio; Rijnsburger, Adriana J.; Bakker, Roel; Hontelez, Jan A. C.; Richardus, Jan H.; Jacobson, Julie; de Vlas, Sake J.; Severens, Johan L.

    2017-01-01

    Background Lymphatic filariasis (LF), onchocerciasis, schistosomiasis, soil-transmitted helminths (STH) and trachoma represent the five most prevalent neglected tropical diseases (NTDs). They can be controlled or eliminated by means of safe and cost-effective interventions delivered through programs of Mass Drug Administration (MDA)—also named Preventive Chemotherapy (PCT). The WHO defined targets for NTD control/elimination by 2020, reinforced by the 2012 London Declaration, which, if achieved, would result in dramatic health gains. We estimated the potential economic benefit of achieving these targets, focusing specifically on productivity and out-of-pocket payments. Methods Productivity loss was calculated by combining disease frequency with productivity loss from the disease, from the perspective of affected individuals. Productivity gain was calculated by deducting the total loss expected in the target achievement scenario from the loss in a counterfactual scenario where it was assumed the pre-intervention situation in 1990 regarding NTDs would continue unabated until 2030. Economic benefits from out-of-pocket payments (OPPs) were calculated similarly. Benefits are reported in 2005 US$ (purchasing power parity-adjusted and discounted at 3% per annum from 2010). Sensitivity analyses were used to assess the influence of changes in input parameters. Results The economic benefit from productivity gain was estimated to be I$251 billion in 2011–2020 and I$313 billion in 2021–2030, considerably greater than the total OPPs averted of I$0.72 billion and I$0.96 billion in the same periods. The net benefit is expected to be US$ 27.4 and US$ 42.8 for every dollar invested during the same periods. Impact varies between NTDs and regions, since it is determined by disease prevalence and extent of disease-related productivity loss. Conclusion Achieving the PCT-NTD targets for 2020 will yield significant economic benefits to affected individuals. Despite large

  17. Does Prevention Pay? Costs and Potential Cost-savings of School Interventions Targeting Children with Mental Health Problems.

    PubMed

    Wellander, Lisa; Wells, Michael B; Feldman, Inna

    2016-06-01

    In Sweden, the local government is responsible for funding schools in their district. One funding initiative is for schools to provide students with mental health problems with additional support via extra teachers, personal assistants, and special education classes. There are evidence-based preventive interventions delivered in schools, which have been shown to decrease the levels of students' mental health problems. However, little is known about how much the local government currently spends on students' mental health support and if evidence-based interventions could be financially beneficial. The aim of this study was to estimate the costs of providing additional support for students' mental health problems and the potential cost-offsets, defined as reduced school-based additional support, if two evidence-based school interventions targeting children's mental health problems were implemented in routine practice. This study uses data on the additional support students with mental health problems received in schools. Data was collected from one school district for students aged 6 to 16 years. We modeled two Swedish school interventions, Comet for Teachers and Social and Emotional Training (SET), which both had evidence of reducing mental health problems. We used a cost-offset analysis framework, assuming both interventions were fully implemented throughout the whole school district. Based on the published studies, the expected effects and the costs of the interventions were calculated. We defined the cost-offsets as the amount of predicted averted additional support for students with ongoing mental health problems who might no longer require receiving services such as one-on-one time with an extra teacher, a personal assistant, or to be placed in a special education classroom. A cost-offset analysis, from a payer's perspective (the local government responsible for school financing), was conducted comparing the costs of both interventions with the potential cost

  18. Impact of targeted counseling on reported vaginal hygiene practices and bacterial vaginosis: the HIV Prevention Trials Network 035 study.

    PubMed

    Kasaro, Margaret P; Husnik, Marla J; Chi, Benjamin H; Reid, Cheri; Magure, Tsitsi; Makanani, Bonus; Tembo, Tchangani; Ramjee, Gita; Maslankowski, Lisa; Rabe, Lorna; Brad Guffey, M

    2017-04-01

    The objective of this study was to describe the impact of intense counseling to reduce vaginal hygiene practices and its effect on bacterial vaginosis. A secondary data analysis of the HIV Prevention Trials Network 035 study was undertaken, focusing on HIV-negative, nonpregnant women who were at least 18 years old, in seven African sites and one US site. At enrollment and during follow-up quarterly visits, vaginal hygiene practices were determined by face-to-face administration of a behavioral assessment questionnaire. Vaginal hygiene practices were categorized as insertion into the vagina of (1) nothing, (2) water only, and (3) other substances with or without water. Each practice was quantified by frequency and type/combination of inserted substances. At quarterly visits, diagnosis of bacterial vaginosis was made using the Nugent score. Trends for vaginal hygiene practices and bacterial vaginosis were evaluated using generalized estimating equation models. A total of 3087 participants from the HIV Prevention Trials Network 035 study were eligible for this analysis. At enrollment, 1859 (60%) reported recent vaginal hygiene practices. By one year, this figure had decreased to 1019 (33%) with counseling. However, bacterial vaginosis prevalence remained consistent across the study observation period, with 36%-38% of women testing positive for the condition ( p for trend = 0.27). Overall, those who reported douching with water only (AOR = 1.03, 95%CI: 0.94-1.13) and those who reported inserting other substances (AOR= 0.98, 95%CI: 0.88-1.09) in the past quarter were not more likely to have bacterial vaginosis compared to those who reported no insertions. However, in South Africa, an increase in bacterial vaginosis was seen among those who reported inserting other substances (AOR: 1.48, 95%CI: 1.17, 1.88). In conclusion, targeted counseling against vaginal hygiene practices resulted in change in self-reported behavior but did not have an impact on bacterial vaginosis

  19. Validation of the Modes of Transmission Model as a Tool to Prioritize HIV Prevention Targets: A Comparative Modelling Analysis

    PubMed Central

    Mishra, Sharmistha; Pickles, Michael; Blanchard, James F.; Moses, Stephen; Shubber, Zara; Boily, Marie-Claude

    2014-01-01

    Background The static Modes of Transmission (MOT) model predicts the annual fraction of new HIV infections acquired across subgroups (MOT metric), and is used to focus HIV prevention. Using synthetic epidemics via a dynamical model, we assessed the validity of the MOT metric for identifying epidemic drivers (behaviours or subgroups that are sufficient and necessary for HIV to establish and persist), and the potential consequence of MOT-guided policies. Methods and Findings To generate benchmark MOT metrics for comparison, we simulated three synthetic epidemics (concentrated, mixed, and generalized) with different epidemic drivers using a dynamical model of heterosexual HIV transmission. MOT metrics from generic and complex MOT models were compared against the benchmark, and to the contribution of epidemic drivers to overall HIV transmission (cumulative population attributable fraction over t years, PAFt). The complex MOT metric was similar to the benchmark, but the generic MOT underestimated the fraction of infections in epidemic drivers. The benchmark MOT metric identified epidemic drivers early in the epidemics. Over time, the MOT metric did not identify epidemic drivers. This was not due to simplified MOT models or biased parameters but occurred because the MOT metric (irrespective of the model used to generate it) underestimates the contribution of epidemic drivers to HIV transmission over time (PAF5–30). MOT-directed policies that fail to reach epidemic drivers could undermine long-term impact on HIV incidence, and achieve a similar impact as random allocation of additional resources. Conclusions Irrespective of how it is obtained, the MOT metric is not a valid stand-alone tool to identify epidemic drivers, and has limited additional value in guiding the prioritization of HIV prevention targets. Policy-makers should use the MOT model judiciously, in combination with other approaches, to identify epidemic drivers. PMID:25014543

  20. Skipping breakfast is detrimental for primary school children: cross-sectional analysis of determinants for targeted prevention.

    PubMed

    Kesztyüs, Dorothea; Traub, Meike; Lauer, Romy; Kesztyüs, Tibor; Steinacker, Jürgen Michael

    2017-03-14

    Skipping breakfast was found to be associated with abdominal obesity in primary school children. The aim of this research was to examine factors associated with skipping breakfast in primary school children in order to develop targeted preventive measures. Baseline data assessment (2010) of a cluster-randomized controlled trial for the evaluation of a school-based health promotion program in primary school children in the state of Baden-Württemberg, Germany. Anthropometric measures of 1,943 primary school children aged 7.1 ± 0.6 years (51.2% boys) were conducted according to ISAK-standards (International Standard for Anthropometric Assessment) by trained staff. Further information on the health and living conditions of the children and their parents were assessed in parental questionnaires. Generalized linear mixed regression analysis was calculated to define correlates for skipping breakfast in terms of odds ratios (OR) and 95% confidence intervals (CI). According to the final regression models, significant correlates of skipping breakfast can be divided into modifiable behavioral components (high consumption of soft drinks (OR 2.49, 95% CI 1.81; 3.43), screen media (OR 2.48, 95% CI 1.77; 3.46) and high levels of physical activity (OR 0.64, 95% CI 0.44; 0.93)) on the one hand, and more or less static socio-economic factors (migration background (OR 2.81, 95% CI 2.02; 3.91), single parenting (OR 2.13, 95% CI 1.34; 3.40), and high family education level (OR 0.42, 95% CI 0.28; 0.64)) on the other hand, and finally individual factors (female gender (OR 1.43, 95% CI 1.03; 1.99) and having a percentage of body fat at or above the 95th percentile (OR 1.47, 95% CI 1.00; 2.17)). Targeted prevention should aim at health-related behaviors accompanying the habit of skipping breakfast. Focusing on vulnerable groups, characterized by not so easily modifiable socio-economic as well as individual factors, may improve results. Interventions should synergistically promote

  1. In Our Own Words: Community Story Traditions To Prevent and Heal Substance Abuse. A Teacher's Guide with Examples from Native American and Rural Contexts.

    ERIC Educational Resources Information Center

    Tierney, Michael

    As the national war on drugs continues, children and youth are told to "just say no" but are seldom given the information and skills to sort out the mixed signals coming from peers, adults, and the mass media. This guidebook presents examples of three approaches to community "storytelling" projects through which children and…

  2. Targeted expression of catalase to mitochondria prevents age-associated reductions in mitochondrial function and insulin resistance.

    PubMed

    Lee, Hui-Young; Choi, Cheol Soo; Birkenfeld, Andreas L; Alves, Tiago C; Jornayvaz, Francois R; Jurczak, Michael J; Zhang, Dongyan; Woo, Dong Kyun; Shadel, Gerald S; Ladiges, Warren; Rabinovitch, Peter S; Santos, Janine H; Petersen, Kitt F; Samuel, Varman T; Shulman, Gerald I

    2010-12-01

    Aging-associated muscle insulin resistance has been hypothesized to be due to decreased mitochondrial function, secondary to cumulative free radical damage, leading to increased intramyocellular lipid content. To directly test this hypothesis, we examined both in vivo and in vitro mitochondrial function, intramyocellular lipid content, and insulin action in lean healthy mice with targeted overexpression of the human catalase gene to mitochondria (MCAT mice). Here, we show that MCAT mice are protected from age-induced decrease in muscle mitochondrial function (∼30%), energy metabolism (∼7%), and lipid-induced muscle insulin resistance. This protection from age-induced reduction in mitochondrial function was associated with reduced mitochondrial oxidative damage, preserved mitochondrial respiration and muscle ATP synthesis, and AMP-activated protein kinase-induced mitochondrial biogenesis. Taken together, these data suggest that the preserved mitochondrial function maintained by reducing mitochondrial oxidative damage may prevent age-associated whole-body energy imbalance and muscle insulin resistance.

  3. Radiotherapy-induced miR-223 prevents relapse of breast cancer by targeting the EGF pathway

    PubMed Central

    Fabris, L; Berton, S; Citron, F; D'Andrea, S; Segatto, I; Nicoloso, M S; Massarut, S; Armenia, J; Zafarana, G; Rossi, S; Ivan, C; Perin, T; Vaidya, J S; Avanzo, M; Roncadin, M; Schiappacassi, M; Bristow, R G; Calin, G; Baldassarre, G; Belletti, B

    2016-01-01

    In breast cancer (BC) patients, local recurrences often arise in proximity of the surgical scar, suggesting that response to surgery may have a causative role. Radiotherapy (RT) after lumpectomy significantly reduces the risk of recurrence. We investigated the direct effects of surgery and of RT delivered intraoperatively (IORT), by collecting irradiated and non-irradiated breast tissues from BC patients, after tumor removal. These breast tissue specimens have been profiled for their microRNA (miR) expression, in search of differentially expressed miR among patients treated or not with IORT. Our results demonstrate that IORT elicits effects that go beyond the direct killing of residual tumor cells. IORT altered the wound response, inducing the expression of miR-223 in the peri-tumoral breast tissue. miR-223 downregulated the local expression of epidermal growth factor (EGF), leading to decreased activation of EGF receptor (EGFR) on target cells and, eventually, dampening a positive EGF–EGFR autocrine/paracrine stimulation loop induced by the post-surgical wound-healing response. Accordingly, both RT-induced miR-223 and peri-operative inhibition of EGFR efficiently prevented BC cell growth and reduced recurrence formation in mouse models of BC. Our study uncovers unknown effects of RT delivered on a wounded tissue and prompts to the use of anti-EGFR treatments, in a peri-operative treatment schedule, aimed to timely treat BC patients and restrain recurrence formation. PMID:26876200

  4. Obesity Prevention from Conception: A Workshop to Guide the Development of a Pan-Canadian Trial Targeting the Gestational Period

    PubMed Central

    Adamo, Kristi B; Shen, Garry X; Mottola, Michelle; Nascimento, Simony; Jean-Philippe, Sonia; Ferraro, Zachary M; Nerenberg, Kara; Smith, Graeme; Chari, Radha; Gaudet, Laura; Piccinini-Vallis, Helena; McDonald, Sarah; Atkinson, Stephanie; Godbout, Ariane; Robitaille, Julie; Davidge, Sandra T; Gruslin, Andrée; Prud’homme, Denis; Stacey, Dawn; Rossiter, Melissa; Goldfield, Gary S; Dodd, Jodie

    2014-01-01

    This report summarizes a meeting, Obesity Prevention from Conception, held in Ottawa in 2012. This planning workshop was funded by the Canadian Institutes of Health Research (CIHR) to bring together researchers with expertise in the area of maternal obesity (OB) and weight gain in pregnancy and pregnancy-related disease to attend a one-day workshop and symposium to discuss the development of a cross-Canada lifestyle intervention trial for targeting pregnant women. This future intervention will aim to reduce downstream OB in children through encouraging appropriate weight gain during the mother’s pregnancy. The workshop served to (i) inform the development of a lifestyle intervention for women with a high pre-pregnancy body mass index (BMI), (ii) identify site investigators across Canada, and (iii) guide the development of a grant proposal focusing on the health of mom and baby. A brief summary of the presentations as well as the focus groups is presented for use in planning future research.

  5. NF-kappaB, a mediator for lung carcinogenesis and a target for lung cancer prevention and therapy

    PubMed Central

    Chen, Wenshu; Li, Zi; Bai, Lang; Lin, Yong

    2011-01-01

    Lung cancer ranks as the first malignant tumor killer worldwide. Despite the knowledge that carcinogens from tobacco smoke and the environment constitute the main causes of lung cancer, the mechanisms for lung carcinogenesis are still elusive. Cancer development and progression depend on the balance between cell survival and death signals. Common cell survival signaling pathways are activated by carcinogens as well as by inflammatory cytokines, which contribute substantially to cancer development. As a major cell survival signal, nuclear factor-kappaB (NF-kappaB) is involved in multiple steps in carcinogenesis and in cancer cell’s resistance to chemo- and radiotherapy. Recent studies with animal models and cell culture systems have established the links between NF-kappaB and lung carcinogenesis, highlighting the significance of targeting the NF-kappaB signaling pathway for lung cancer treatment and chemoprevention. In this review, we summarize progresses in understanding the NF-kappaB pathway in lung cancer development as well as in modulating NF-kappaB for lung cancer prevention and therapy. PMID:21196225

  6. Peripheral 5-HT7 receptors as a new target for prevention of lung injury and mortality in septic rats.

    PubMed

    Cadirci, Elif; Halici, Zekai; Bayir, Yasin; Albayrak, Abdulmecit; Karakus, Emre; Polat, Beyzagul; Unal, Deniz; Atamanalp, Sabri S; Aksak, Selina; Gundogdu, Cemal

    2013-10-01

    Sepsis is a complex pathophysiological event involving metabolic acidosis, systemic inflammatory response syndrome, tissue damage and multiple organ dysfunction syndrome. Although many new mechanisms are being investigated to enlighten the pathophysiology of sepsis, there is no effective treatment protocol yet. Presence of 5-HT7 receptors in immune tissues prompted us to hypothesize that these receptors have roles in inflammation and sepsis. We investigated the effects of 5-HT7 receptor agonists and antagonists on serum cytokine levels, lung oxidative stress, lung histopathology, nuclear factor κB (NF-κB) positivity and lung 5-HT7 receptor density in cecal ligation and puncture (CLP) induced sepsis model of rats. Agonist administration to septic rats increased survival time; decreased serum cytokine response against CLP; decreased oxidative stress and increased antioxidant system in lungs; decreased the tissue NF-κB immunopositivity, which is high in septic rats; and decreased the sepsis-induced lung injury. In septic rats, as a result of high inflammatory response, 5-HT7 receptor expression in lungs increased significantly and agonist administration, which decreased inflammatory response and related mortality, decreased the 5-HT7 receptor expression. In conclusion, all these data suggest that stimulation of 5-HT7 receptors may be a new therapeutic target for prevention of impaired inflammatory response related lung injury and mortality.

  7. [Differentiated structures of early prevention measures for families at risk using the example of the project "nobody slips through the net"].

    PubMed

    Eickhorst, Andreas; Borchardt, Silke; Cierpka, Manfred

    2012-01-01

    Against the background of practical experiences from the Early Prevention model project "Nobody slips through the net" (in three counties of Germany) the necessity of differentiated structures of preventive measures for different groups of families will be discussed. Therefore a distribution in three types of families the visiting qualified person could be confronted with during their work in the families' homes is proposed, especially with respect to the degree of risk and available resources. We conclude by illustrating the implications of this approach by means of a case vignette.

  8. "Now That I'm Pregnant, I'm No Longer an Example": Peer Educator Experiences of an HIV Prevention Programme in Cape Town, South Africa

    ERIC Educational Resources Information Center

    Wolf, Kimberly; Africa, Adelene

    2017-01-01

    Despite the popularity of peer education as an HIV prevention strategy across a range of contexts, understanding of the experiences of those intimately placed within these programmes is limited. Instead, the majority of research in this field relies on hegemonic notions of rational human behaviour that operate under the assumption that knowledge…

  9. The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

    2016-01-01

    Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

  10. The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

    ERIC Educational Resources Information Center

    Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

    2016-01-01

    Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

  11. Targeted prevention of excess weight gain and eating disorders in high-risk adolescent girls: a randomized controlled trial.

    PubMed

    Tanofsky-Kraff, Marian; Shomaker, Lauren B; Wilfley, Denise E; Young, Jami F; Sbrocco, Tracy; Stephens, Mark; Ranzenhofer, Lisa M; Elliott, Camden; Brady, Sheila; Radin, Rachel M; Vannucci, Anna; Bryant, Edny J; Osborn, Robyn; Berger, Sarah S; Olsen, Cara; Kozlosky, Merel; Reynolds, James C; Yanovski, Jack A

    2014-10-01

    The high prevalence and incidence of obesity and eating disorders in US adolescent girls are serious health problems. Because of the shared risk factors for obesity and eating disorders, a targeted prevention of both conditions is a priority. We determined whether an adapted interpersonal psychotherapy prevention program is more efficacious for reducing excess weight gain and worsening disordered eating than health education in adolescent girls at high risk of obesity and eating disorders. A parallel-group, randomized controlled trial was conducted between September 2008 and January 2013 in a university-based laboratory and a federal research hospital. The study included 113 adolescent (12-17-y-old) girls deemed at high risk of adult obesity and eating disorders because of a body mass index (BMI) between the 75th and 97th percentiles and reports of episodes of a loss of control over their eating. Girls were randomly assigned to participate in an adapted interpersonal psychotherapy or a health-education group program for 12 weekly 90-min group sessions. Follow-up assessments occurred immediately after group programs and at 6 and 12 mo. Participation in both conditions was associated with decreases in expected BMI gain, age-adjusted BMI metrics, the percentage of fat by using dual-energy X-ray absorptiometry, symptoms of depression and anxiety, and the frequency of loss-of-control eating over 12 mo of follow-up (Ps < 0.001) with no group difference. In follow-up analyses, interpersonal psychotherapy was more efficacious than health education at reducing objective binge eating at the 12-mo follow-up (P < 0.05). The intervention with adolescent girls with loss-of-control eating is associated with lower age-adjusted BMI and percentage of adiposity as well as improved mood symptoms over 1 y. Interpersonal psychotherapy further reduced objective binge eating. Additional research is needed to elucidate the mechanisms by which physical and psychological improvements were

  12. Targeted prevention of excess weight gain and eating disorders in high-risk adolescent girls: a randomized controlled trial12345

    PubMed Central

    Shomaker, Lauren B; Wilfley, Denise E; Young, Jami F; Sbrocco, Tracy; Stephens, Mark; Ranzenhofer, Lisa M; Elliott, Camden; Brady, Sheila; Radin, Rachel M; Vannucci, Anna; Bryant, Edny J; Osborn, Robyn; Berger, Sarah S; Olsen, Cara; Kozlosky, Merel; Reynolds, James C; Yanovski, Jack A

    2014-01-01

    Background: The high prevalence and incidence of obesity and eating disorders in US adolescent girls are serious health problems. Because of the shared risk factors for obesity and eating disorders, a targeted prevention of both conditions is a priority. Objective: We determined whether an adapted interpersonal psychotherapy prevention program is more efficacious for reducing excess weight gain and worsening disordered eating than health education in adolescent girls at high risk of obesity and eating disorders. Design: A parallel-group, randomized controlled trial was conducted between September 2008 and January 2013 in a university-based laboratory and a federal research hospital. The study included 113 adolescent (12–17-y-old) girls deemed at high risk of adult obesity and eating disorders because of a body mass index (BMI) between the 75th and 97th percentiles and reports of episodes of a loss of control over their eating. Girls were randomly assigned to participate in an adapted interpersonal psychotherapy or a health-education group program for 12 weekly 90-min group sessions. Follow-up assessments occurred immediately after group programs and at 6 and 12 mo. Results: Participation in both conditions was associated with decreases in expected BMI gain, age-adjusted BMI metrics, the percentage of fat by using dual-energy X-ray absorptiometry, symptoms of depression and anxiety, and the frequency of loss-of-control eating over 12 mo of follow-up (Ps < 0.001) with no group difference. In follow-up analyses, interpersonal psychotherapy was more efficacious than health education at reducing objective binge eating at the 12-mo follow-up (P < 0.05). Conclusions: The intervention with adolescent girls with loss-of-control eating is associated with lower age-adjusted BMI and percentage of adiposity as well as improved mood symptoms over 1 y. Interpersonal psychotherapy further reduced objective binge eating. Additional research is needed to elucidate the mechanisms

  13. Polymerization of secretory IgM in B lymphocytes is prevented by a prior targeting to a degradation pathway.

    PubMed

    Shachar, I; Amitay, R; Rabinovich, E; Haimovich, J; Bar-Nun, S

    1992-12-05

    incompetence of 38C cells to polymerize. Rather, assembly of sIgM into polymers and their subsequent secretion are prevented in B lymphocytes by preceding targeting of monomeric sIgM to degradation.

  14. HIV among immigrants living in high-income countries: a realist review of evidence to guide targeted approaches to behavioural HIV prevention

    PubMed Central

    2012-01-01

    Background Immigrants from developing and middle-income countries are an emerging priority in HIV prevention in high-income countries. This may be explained in part by accelerating international migration and population mobility. However, it may also be due to the vulnerabilities of immigrants including social exclusion along with socioeconomic, cultural and language barriers to HIV prevention. Contemporary thinking on effective HIV prevention stresses the need for targeted approaches that adapt HIV prevention interventions according to the cultural context and population being addressed. This review of evidence sought to generate insights into targeted approaches in this emerging area of HIV prevention. Methods We undertook a realist review to answer the research question: ‘How are HIV prevention interventions in high-income countries adapted to suit immigrants’ needs?’ A key goal was to uncover underlying theories or mechanisms operating in behavioural HIV prevention interventions with immigrants, to uncover explanations as how and why they work (or not) for particular groups in particular contexts, and thus to refine the underlying theories. The realist review mapped seven initial mechanisms underlying culturally appropriate HIV prevention with immigrants. Evidence from intervention studies and qualitative studies found in systematic searches was then used to test and refine these seven mechanisms. Results Thirty-four intervention studies and 40 qualitative studies contributed to the analysis and synthesis of evidence. The strongest evidence supported the role of ‘consonance’ mechanisms, indicating the pivotal need to incorporate cultural values into the intervention content. Moderate evidence was found to support the role of three other mechanisms – ‘understanding’, ‘specificity’ and ‘embeddedness’ – which indicated that using the language of immigrants, usually the ‘mother tongue’, targeting (in terms of ethnicity) and the use of

  15. Targeting Th17-IL-17 Pathway in Prevention of Micro-Invasive Prostate Cancer in a Mouse Model.

    PubMed

    Zhang, Qiuyang; Liu, Sen; Ge, Dongxia; Cunningham, David M; Huang, Feng; Ma, Lin; Burris, Thomas P; You, Zongbing

    2017-06-01

    Chronic inflammation has been associated with the development and progression of human cancers including prostate cancer. The exact role of the inflammatory Th17-IL-17 pathway in prostate cancer remains unknown. In this study, we aimed to determine the importance of Th17 cells and IL-17 in a Pten-null prostate cancer mouse model. The Pten-null mice were treated by Th17 inhibitor SR1001 or anti-mouse IL-17 monoclonal antibody from 6 weeks of age up to 12 weeks of age. For SR1001 treatment, the mice were injected intraperitoneally (i.p.) twice a day with vehicle or SR1001, which was dissolved in a dimethylsulfoxide (DMSO) solution. All mice were euthanized for necropsy at 12 weeks of age. For IL-17 antibody treatment, the mice were injected intravenously (i.v.) once every two weeks with control IgG or rat anti-mouse IL-17 monoclonal antibody, which was dissolved in PBS. The injection time points were at 6, 8, and 10 weeks old. All mice were analyzed for the prostate phenotypes at 12 weeks of age. We found that either SR1001 or anti-IL-17 antibody treatment decreased the formation of micro-invasive prostate cancer in Pten-null mice. The SR1001 or anti-IL-17 antibody treated mouse prostates had reduced proliferation, increased apoptosis, and reduced angiogenesis, as well as reduced inflammatory cell infiltration. By assessing the epithelial-to-mesenchymal transition (EMT) markers, we found that SR1001 or anti-IL-17 antibody treated prostate tissues had weaker EMT phenotype compared to the control treated prostates. These results demonstrated that Th17-IL-17 pathway plays a key role in prostate cancer progression in Pten-null mice. Targeting Th17-IL-17 pathway could prevent micro-invasive prostate cancer formation in mice. Prostate 77:888-899, 2017. © 2017 Wiley Periodicals, Inc. © 2017 Wiley Periodicals, Inc.

  16. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic acid: a Potential Role in Cancer Prevention

    PubMed Central

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D. Ramesh; Sadhu, Satya S.; Tummala, Hemachand; Bhat, G. Jayarama

    2015-01-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anti-cancer effects are still being elucidated. We hypothesized that aspirin’s chemopreventive actions may involve cell cycle regulation through modulation of the levels or activity of cyclin A2/cyclin dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The down regulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. Firstly, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Secondly, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, pre-incubation of CDK2 with salicylic acid, dose-dependently quenched the fluorescence due to ANS. Thirdly, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid down-regulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Implications Biochemical and structural studies indicate that the anti-proliferative actions of aspirin are mediated through cyclin A2/CDK2. PMID:26685215

  17. Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii.

    PubMed

    Mancini, Stefano; Menzi, Carmen; Oechslin, Frank; Moreillon, Philippe; Entenza, José Manuel

    2016-12-01

    Streptococcus gordonii and related species of oral viridans group streptococci (VGS) are common etiological agents of infective endocarditis (IE). We explored vaccination as a strategy to prevent VGS-IE, using a novel antigen-presenting system based on non-genetically modified Lactococcus lactis displaying vaccinogens on its surface. Hsa and PadA are surface-located S. gordonii proteins implicated in platelet adhesion and aggregation, which are key steps in the pathogenesis of IE. This function makes them ideal targets for vaccination against VGS-IE. In the present study, we report the use of nonliving L. lactis displaying at its surface the N-terminal region of Hsa or PadA by means of the cell wall binding domain of Lactobacillus casei A2 phage lysine LysA2 (Hsa-LysA2 and PadA-LysA2, respectively) and investigation of their ability to elicit antibodies in rats and to protect them from S. gordonii experimental IE. Immunized and control animals with catheter-induced sterile aortic valve vegetations were inoculated with 10(6) CFU of S. gordonii The presence of IE was evaluated 24 h later. Immunization of rats with L. lactis Hsa-LysA2, L. lactis PadA-LysA2, or both protected 6/11 (55%), 6/11 (55%), and 11/12 (91%) animals, respectively, from S. gordonii IE (P < 0.05 versus controls). Protection correlated with the induction of high levels of functional antibodies against both Hsa and PadA that delayed or totally inhibited platelet aggregation by S. gordonii These results support the value of L. lactis as a system for antigen delivery and of Hsa and PadA as promising candidates for a vaccine against VGS-IE. Copyright © 2016, American Society for Microbiology. All Rights Reserved.

  18. Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii

    PubMed Central

    Mancini, Stefano; Menzi, Carmen; Oechslin, Frank; Moreillon, Philippe

    2016-01-01

    Streptococcus gordonii and related species of oral viridans group streptococci (VGS) are common etiological agents of infective endocarditis (IE). We explored vaccination as a strategy to prevent VGS-IE, using a novel antigen-presenting system based on non-genetically modified Lactococcus lactis displaying vaccinogens on its surface. Hsa and PadA are surface-located S. gordonii proteins implicated in platelet adhesion and aggregation, which are key steps in the pathogenesis of IE. This function makes them ideal targets for vaccination against VGS-IE. In the present study, we report the use of nonliving L. lactis displaying at its surface the N-terminal region of Hsa or PadA by means of the cell wall binding domain of Lactobacillus casei A2 phage lysine LysA2 (Hsa-LysA2 and PadA-LysA2, respectively) and investigation of their ability to elicit antibodies in rats and to protect them from S. gordonii experimental IE. Immunized and control animals with catheter-induced sterile aortic valve vegetations were inoculated with 106 CFU of S. gordonii. The presence of IE was evaluated 24 h later. Immunization of rats with L. lactis Hsa-LysA2, L. lactis PadA-LysA2, or both protected 6/11 (55%), 6/11 (55%), and 11/12 (91%) animals, respectively, from S. gordonii IE (P < 0.05 versus controls). Protection correlated with the induction of high levels of functional antibodies against both Hsa and PadA that delayed or totally inhibited platelet aggregation by S. gordonii. These results support the value of L. lactis as a system for antigen delivery and of Hsa and PadA as promising candidates for a vaccine against VGS-IE. PMID:27736784

  19. Cyclin A2 and CDK2 as Novel Targets of Aspirin and Salicylic Acid: A Potential Role in Cancer Prevention.

    PubMed

    Dachineni, Rakesh; Ai, Guoqiang; Kumar, D Ramesh; Sadhu, Satya S; Tummala, Hemachand; Bhat, G Jayarama

    2016-03-01

    Data emerging from the past 10 years have consolidated the rationale for investigating the use of aspirin as a chemopreventive agent; however, the mechanisms leading to its anticancer effects are still being elucidated. We hypothesized that aspirin's chemopreventive actions may involve cell-cycle regulation through modulation of the levels or activity of cyclin A2/cyclin-dependent kinase-2 (CDK2). In this study, HT-29 and other diverse panel of cancer cells were used to demonstrate that both aspirin and its primary metabolite, salicylic acid, decreased cyclin A2 (CCNA2) and CDK2 protein and mRNA levels. The downregulatory effect of either drugs on cyclin A2 levels was prevented by pretreatment with lactacystin, an inhibitor of proteasomes, suggesting the involvement of 26S proteasomes. In-vitro kinase assays showed that lysates from cells treated with salicylic acid had lower levels of CDK2 activity. Importantly, three independent experiments revealed that salicylic acid directly binds to CDK2. First, inclusion of salicylic acid in naïve cell lysates, or in recombinant CDK2 preparations, increased the ability of the anti-CDK2 antibody to immunoprecipitate CDK2, suggesting that salicylic acid may directly bind and alter its conformation. Second, in 8-anilino-1-naphthalene-sulfonate (ANS)-CDK2 fluorescence assays, preincubation of CDK2 with salicylic acid dose-dependently quenched the fluorescence due to ANS. Third, computational analysis using molecular docking studies identified Asp145 and Lys33 as the potential sites of salicylic acid interactions with CDK2. These results demonstrate that aspirin and salicylic acid downregulate cyclin A2/CDK2 proteins in multiple cancer cell lines, suggesting a novel target and mechanism of action in chemoprevention. Biochemical and structural studies indicate that the antiproliferative actions of aspirin are mediated through cyclin A2/CDK2. ©2015 American Association for Cancer Research.

  20. Testing the effect of a targeted intervention on nurses' compliance with "best practice" mechanical venous thromboembolism prevention.

    PubMed

    Li, Francesca; Walker, Kim; McInnes, Elizabeth; Duff, Jed

    2010-09-01

    The aim of this study was to examine whether educational outreach visits improve nurses' compliance with applying best practice mechanical venous thromboembolism prophylaxis. The design was as a pretest/posttest study with a 7-week follow-up. It was conducted in a mixed medical/surgical unit in a 250-bed private hospital in Sydney, Australia. The target population was 25 medical/surgical nurses in educational outreach visits (EOVs). The main outcome measures included change in percentage between baseline and endpoint of eligible patients receiving mechanical VTE prophylaxis and all patients having VTE risk documented in their medication charts, as well as nurses' feedback on how supportive and useful they found EOVs. The results showed an overall, but not significant increase (p = 0.201) in the percentage of patients who received mechanical VTE prophylaxis (59.4% baseline to 75% endpoint). There was a significant increase in the percentage of patients having VTE risk status documented in the medication chart (0%-28%) (p = 0.002). Improvements in compliance were more likely for surgical than medical patients (95% and 35%, respectively) and risk documentation (47% and 6%, respectively). Most nurses reported that the EOVs supported them in implementing best practice VTE mechanical prophylaxis. Researchers conclude that improvements in compliance with best practice VTE prevention can be achieved using EOVs which were easily conducted and well-received in a busy unit setting. More work is needed to increase the compliance rate with medical patients. Copyright 2010 Society for Vascular Nursing, Inc. Published by Mosby, Inc. All rights reserved.

  1. A Mitochondrial-Targeted Coenzyme Q Analog Prevents Weight Gain and Ameliorates Hepatic Dysfunction in High-Fat–Fed Mice

    PubMed Central

    Fink, Brian D.; Herlein, Judith A.; Guo, Deng Fu; Kulkarni, Chaitanya; Weidemann, Benjamin J.; Yu, Liping; Grobe, Justin L.; Rahmouni, Kamal; Kerns, Robert J.

    2014-01-01

    We hypothesized that the mitochondrial-targeted antioxidant, mitoquinone (mitoQ), known to have mitochondrial uncoupling properties, might prevent the development of obesity and mitigate liver dysfunction by increasing energy expenditure, as opposed to reducing energy intake. We administered mitoQ or vehicle (ethanol) to obesity-prone C57BL/6 mice fed high-fat (HF) or normal-fat (NF) diets. MitoQ (500 µM) or vehicle (ethanol) was added to the drinking water for 28 weeks. MitoQ significantly reduced total body mass and fat mass in the HF-fed mice but had no effect on these parameters in NF mice. Food intake was reduced by mitoQ in the HF-fed but not in the NF-fed mice. Average daily water intake was reduced by mitoQ in both the NF- and HF-fed mice. Hypothalamic expression of neuropeptide Y, agouti-related peptide, and the long form of the leptin receptor were reduced in the HF but not in the NF mice. Hepatic total fat and triglyceride content did not differ between the mitoQ-treated and control HF-fed mice. However, mitoQ markedly reduced hepatic lipid hydroperoxides and reduced circulating alanine aminotransferase, a marker of liver function. MitoQ did not alter whole-body oxygen consumption or liver mitochondrial oxygen utilization, membrane potential, ATP production, or production of reactive oxygen species. In summary, mitoQ added to drinking water mitigated the development of obesity. Contrary to our hypothesis, the mechanism involved decreased energy intake likely mediated at the hypothalamic level. MitoQ also ameliorated HF-induced liver dysfunction by virtue of its antioxidant properties without altering liver fat or mitochondrial bioenergetics. PMID:25301169

  2. Preventive healthcare and health promotion in local governments based on the example of health policy programmes concerned with cardiovascular diseases implemented in Poland in 2009-2014.

    PubMed

    Augustynowicz, Anna; Czerw, Aleksandra; Kowalska, Mariola; Bobiński, Krzysztof; Fronczak, Adam

    2017-01-01

    Cardiovascular diseases (CVD) are the cause of over 4.3 million deaths in the World Health Organisation European Region and around 1.9 million deaths in the European Union member states alone. They are also the number-one cause of death in Poland. In 2010 CVDs accounted for 46% of all deaths, and in 2013 - 45.8%. The aim of the study was to evaluate the performance of the tasks of local government units in the area of preventive healthcare and health promotion on the basis of health policy programmes concerning CVD. The study was based on a desk research. The data included in the annual reports submitted to the Minister of Health concerning completed health policy programmes concerned with CVD, was used. A total of 795 programmes were completed in 2009-2014. The greatest number of programmes were completed by municipalities followed by counties. The costs incurred by voivodeships in connection with the programmes were significantly higher compared to the costs paid by municipalities and counties. Diagnostic programmes accounted for 74% of the overall number of programmes, and preventive programmes made up only 24%. The greatest number of programmes were completed in Mazowieckie and Swietokrzyskie voivodeships. The smallest number of programmes were completed in Lubelskie, Lubuskie, and Podlaskie voivodeships. Insignificant involvement of local government units can be seen in the fight against CVD. Particular types of local government units demonstrate a varied degree of involvement in the performance of health policy programmes. The small number of preventive programmes points to the fragmentary completion of tasks concerned with preventive healthcare and health promotion. Some of the voivodeships failed to properly address the health needs of local communities in respect of CVD. More programmes need to be completed, and they need to cover more people. Some guidelines should be developed for local government units concerning their involvement in the fight against

  3. Shining examples

    SciTech Connect

    Flavin, C.; O`Meara, M.

    1997-05-01

    Creative financing for setting up individual solar power systems and energy efficient appliances is beginning to come of age in developing countries. This article describes the practical implementation of such solar energy financing as well as the broader implications, using India, Indonesia and the Dominican Republic as examples. Also included is a discussion of the government and publically supported organizations which are encouraging solar energy use and realistic financing.

  4. Promises and limitations of nanoparticles in the era of cell therapy: Example with CD19-targeting chimeric antigen receptor (CAR)-modified T cells.

    PubMed

    Jakobczyk, Hélène; Sciortino, Flavien; Chevance, Soizic; Gauffre, Fabienne; Troadec, Marie-Bérengère

    2017-07-29

    A number of nanoparticles has been developed by chemists for biomedical applications to meet imaging and targeting needs. In parallel, adoptive T therapy with chimeric antigen receptor engineered T cells (CART cells) has recently held great promise in B-cell malignancy treatments thanks to the development of anti-CD19 CAR T cells. Indeed, CD19 is a reliable B cell marker and a validated target protein for therapy. In this perspective article, we propose to discuss the advantages, limits and challenges of nanoparticles and CAR T cells, focusing on CD19 targeting objects: anti-CD19 nanoparticles and anti-CD19 CAR T cells, because those genetically-modified cells are the most widely developed in clinical setting. In the first part, we will introduce B cell malignancies and the CD19 surface marker. Then we will present the positioning of nanomedicine in the topic of B cell malignancy, before exposing CAR T technology. Finally, we will discuss the complementary approaches between nanoparticles and CAR T cells. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Review: biosafety assessment of Bt rice and other Bt crops using spiders as example for non-target arthropods in China.

    PubMed

    Yang, Huilin; Peng, Yuande; Tian, Jianxiang; Wang, Juan; Hu, Jilin; Song, Qisheng; Wang, Zhi

    2017-04-01

    Since the birth of transgenic crops expressing Bacillus thuringiensis (Bt) toxin for pest control, the public debate regarding ecological and environmental risks as well as benefits of Bt crops has continued unabated. The impact of Bt crops, especially on non-target invertebrates, has received particular attention. In this review, we summarize and analyze evidences for non-target effects of Bt rice on spiders, major predators in rice fields. Bt rice has been genetically modified to express the Bt protein, which has been shown to be transferred and accumulate in spiders as part of their food chain. Moreover, the Bt protein exhibits unintended effects on the physiology of spiders and spreads to higher trophic levels. Spiders possess unique physiological and ecological characteristics, revealing traits of surrogate species, and are thus considered to be excellent non-target arthropod model systems for study of Bt protein impacts. Due to the complexities of Bt protein transfer and accumulation mechanisms, as well as the apparent lack of information about resulting physiological, biochemical, and ecological effects on spiders, we raise questions and provide recommendations for promising further research.

  6. Qualitative Sybr Green real-time detection of single nucleotide polymorphisms responsible for target-site resistance in insect pests: the example of Myzus persicae and Musca domestica.

    PubMed

    Puggioni, V; Chiesa, O; Panini, M; Mazzoni, E

    2017-02-01

    Chemical insecticides have been widely used to control insect pests, leading to the selection of resistant populations. To date, several single nucleotide polymorphisms (SNPs) have already been associated with insecticide resistance, causing reduced sensitivity to many classes of products. Monitoring and detection of target-site resistance is currently one of the most important factors for insect pest management strategies. Several methods are available for this purpose: automated and high-throughput techniques (i.e. TaqMan or pyrosequencing) are very costly; cheaper alternatives (i.e. RFLP or PASA-PCRs) are time-consuming and limited by the necessity of a final visualization step. This work presents a new approach (QSGG, Qualitative Sybr Green Genotyping) which combines the specificity of PASA-PCR with the rapidity of real-time PCR analysis. The specific real-time detection of Cq values of wild-type or mutant alleles (amplified used allele-specific primers) allows the calculation of ΔCqW-M values and the consequent identification of the genotypes of unknown samples, on the basis of ranges previously defined with reference clones. The methodology is applied here to characterize mutations described in Myzus persicae and Musca domestica and we demonstrate it represents a valid, rapid and cost-effective technique that can be adopted for monitoring target-site resistance in field populations of these and other insect species.

  7. High Molecular Weight Fibroblast Growth Factor-2 in the Human Heart Is a Potential Target for Prevention of Cardiac Remodeling

    PubMed Central

    Santiago, Jon-Jon; McNaughton, Leslie J.; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E.; Fandrich, Robert R.; Wigle, Jeffrey T.; Freed, Darren H.; Arora, Rakesh C.; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  8. Genetic Targeting of Arginase-II in Mouse Prevents Renal Oxidative Stress and Inflammation in Diet-Induced Obesity

    PubMed Central

    Huang, Ji; Rajapakse, Angana; Xiong, Yuyan; Montani, Jean-Pierre; Verrey, François; Ming, Xiu-Fen; Yang, Zhihong

    2016-01-01

    Obesity is associated with development and progression of chronic kidney disease (CKD). Recent evidence demonstrates that enhanced levels of the L-arginine:ureahydrolase, including the two isoenzymes arginase-I (Arg-I) and arginase-II (Arg-II) in vascular endothelial cells promote uncoupling of endothelial nitric oxide synthase (eNOS), leading to increased superoxide radical anion and decreased NO production thereby endothelial dysfunction. Arg-II but not Arg-I is abundantly expressed in kidney and the role of Arg-II in CKD is uncertain and controversial. We aimed to investigate the role of Arg-II in renal damage associated with diet-induced obesity mouse model. Wild type (WT) C57BL/6 mice and mice deficient in Arg-II gene (Arg-II−/−) were fed with either a normal chow (NC) or a high-fat-diet (HFD) for 14 weeks (starting at the age of 7 weeks) to induce obesity. In WT mice, HFD feeding caused frequent renal lipid accumulation, enhancement of renal reactive oxygen species (ROS) levels which could be attenuated by a NOS inhibitor, suggesting uncoupling of NOS in kidney. HFD feeding also significantly augmented renal Arg-II expression and activity. All the alterations in the kidney under HFD feeding were reduced in Arg-II−/− mice. Moreover, mesangial expansion as analyzed by Periodic Acid Schiff (PAS) staining and renal expression of vascular adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) in HFD-fed WT mouse assessed by immunoblotting were reduced in the HFD-fed Arg-II−/− mice, although there was no significant difference in body weight and renal weight/body weight ratio between the WT and Arg-II−/− mice. Thus, Arg-II expression/activity is enhanced in kidney of diet-induced obesity mice. Genetic targeting of Arg-II prevents renal damage associated with obesity, suggesting an important role of Arg-II in obesity-associated renal disease development. PMID:27920727

  9. Population-based analysis of health care contacts among suicide decedents: identifying opportunities for more targeted suicide prevention strategies.

    PubMed

    Schaffer, Ayal; Sinyor, Mark; Kurdyak, Paul; Vigod, Simone; Sareen, Jitender; Reis, Catherine; Green, Diane; Bolton, James; Rhodes, Anne; Grigoriadis, Sophie; Cairney, John; Cheung, Amy

    2016-06-01

    The objective of this study was to detail the nature and correlates of mental health and non-mental health care contacts prior to suicide death. We conducted a systematic extraction of data from records at the Office of the Chief Coroner of Ontario of each person who died by suicide in the city of Toronto from 1998 to 2011. Data on 2,835 suicide deaths were linked with provincial health administrative data to identify health care contacts during the 12 months prior to suicide. Sub-populations of suicide decedents based on the presence and type of mental health care contact were described and compared across socio-demographic, clinical and suicide-specific variables. Time periods from last mental health contact to date of death were calculated and a Cox proportional hazards model examined covariates. Among suicide decedents, 91.7% had some type of past-year health care contact prior to death, 66.4% had a mental health care contact, and 25.3% had only non-mental health contacts. The most common type of mental health contact was an outpatient primary care visit (54.0%), followed by an outpatient psychiatric visit (39.8%), an emergency department visit (31.1%), and a psychiatric hospitalization (21.0%). The median time from last mental health contact to death was 18 days (interquartile range 5-63). Mental health contact was significantly associated with female gender, age 25-64, absence of a psychosocial stressor, diagnosis of schizophrenia or bipolar disorder, past suicide attempt, self-poisoning method and absence of a suicide note. Significant differences between sub-populations of suicide decedents based on the presence and nature of their health care contacts suggest the need for targeting of community and clinical-based suicide prevention strategies. The predominance of ambulatory mental health care contacts, often close to the time of death, reinforce the importance of concentrating efforts on embedding risk assessment and care pathways into all routine primary

  10. SiRNA Targeting mTOR Effectively Prevents the Proliferation and Migration of Human Lens Epithelial Cells

    PubMed Central

    Zhang, Chunmei; Liu, Jingjing; Jin, Na; Zhang, Guiming; Xi, Yahui; Liu, Hongling

    2016-01-01

    Posterior capsule opacification (PCO) is the most common complication that causes visual decrease after extracapsular cataract surgery. The primary cause of PCO formation is the proliferation of the residual lens epithelial cells (LECs). The mammalian target of rapamycin (mTOR) plays an important role in the growth and migration of LECs. In the current study, we used small interfering RNA (siRNA) to specifically attenuate mTOR in human lens epithelial B3 cells (HLE B3). We aimed to examine the effect of mTOR-siRNA on the proliferation, migration and epithelial-to-mesenchymal transition (EMT) of HLE B3 cells and explore the underlying mechanisms. The mTOR-siRNA was transfected into HLE B3 cells using lipofectamine 2000. The mRNA and protein levels of mTOR were examined to confirm the efficiency of mTOR-siRNA. The levels of mRNA and protein as well as the activity of mTOR down-stream effectors p70 ribosomal protein S6 kinase (p70S6K) and protein kinase B (PKB, AKT) were examined using real-time PCR or Western blot, respectively. The cell proliferation was determined using cell counting kit (CCK) 8 and cell growth curve assay. The cell migration was examined using Transwell system and Scratch assay. MTOR-siRNA effectively eliminated mTOR mRNA and protein. The proliferation and migration were significantly suppressed by mTOR-siRNA transfection. mTOR-siRNA reduced the mRNA of p70S6K and AKT in a time-dependent manner. Furthermore, the phosphorylation of p70S6K and AKT was decreased by mTOR-siRNA. MTOR-siRNA also eliminated the formation of mTORC1 and mTORC2 protein complex and blocked the transforming growth factor (TGF)-β-induced EMT. Our results suggested that mTOR-siRNA could effectively inhibit the proliferation, migration and EMT of HLE B3 cells through the inhibition of p70S6K and AKT. These results indicated that mTOR-siRNA might be an effective agent inhibiting HLE cells growth and EMT following cataract surgery and provide an alternative therapy for preventing

  11. High molecular weight fibroblast growth factor-2 in the human heart is a potential target for prevention of cardiac remodeling.

    PubMed

    Santiago, Jon-Jon; McNaughton, Leslie J; Koleini, Navid; Ma, Xin; Bestvater, Brian; Nickel, Barbara E; Fandrich, Robert R; Wigle, Jeffrey T; Freed, Darren H; Arora, Rakesh C; Kardami, Elissavet

    2014-01-01

    Fibroblast growth factor 2 (FGF-2) is a multifunctional protein synthesized as high (Hi-) and low (Lo-) molecular weight isoforms. Studies using rodent models showed that Hi- and Lo-FGF-2 exert distinct biological activities: after myocardial infarction, rat Lo-FGF-2, but not Hi-FGF-2, promoted sustained cardioprotection and angiogenesis, while Hi-FGF-2, but not Lo-FGF-2, promoted myocardial hypertrophy and reduced contractile function. Because there is no information regarding Hi-FGF-2 in human myocardium, we undertook to investigate expression, regulation, secretion and potential tissue remodeling-associated activities of human cardiac (atrial) Hi-FGF-2. Human patient-derived atrial tissue extracts, as well as pericardial fluid, contained Hi-FGF-2 isoforms, comprising, respectively, 53%(±20 SD) and 68% (±25 SD) of total FGF-2, assessed by western blotting. Human atrial tissue-derived primary myofibroblasts (hMFs) expressed and secreted predominantly Hi-FGF-2, at about 80% of total. Angiotensin II (Ang II) up-regulated Hi-FGF-2 in hMFs, via activation of both type 1 and type 2 Ang II receptors; the ERK pathway; and matrix metalloprotease-2. Treatment of hMFs with neutralizing antibodies selective for human Hi-FGF-2 (neu-AbHi-FGF-2) reduced accumulation of proteins associated with fibroblast-to-myofibroblast conversion and fibrosis, including α-smooth muscle actin, extra-domain A fibronectin, and procollagen. Stimulation of hMFs with recombinant human Hi-FGF-2 was significantly more potent than Lo-FGF-2 in upregulating inflammation-associated proteins such as pro-interleukin-1β and plasminogen-activator-inhibitor-1. Culture media conditioned by hMFs promoted cardiomyocyte hypertrophy, an effect that was prevented by neu-AbHi-FGF-2 in vitro. In conclusion, we have documented that Hi-FGF-2 represents a substantial fraction of FGF-2 in human cardiac (atrial) tissue and in pericardial fluid, and have shown that human Hi-FGF-2, unlike Lo-FGF-2, promotes deleterious

  12. Population‐based analysis of health care contacts among suicide decedents: identifying opportunities for more targeted suicide prevention strategies

    PubMed Central

    Schaffer, Ayal; Sinyor, Mark; Kurdyak, Paul; Vigod, Simone; Sareen, Jitender; Reis, Catherine; Green, Diane; Bolton, James; Rhodes, Anne; Grigoriadis, Sophie; Cairney, John; Cheung, Amy

    2016-01-01

    The objective of this study was to detail the nature and correlates of mental health and non‐mental health care contacts prior to suicide death. We conducted a systematic extraction of data from records at the Office of the Chief Coroner of Ontario of each person who died by suicide in the city of Toronto from 1998 to 2011. Data on 2,835 suicide deaths were linked with provincial health administrative data to identify health care contacts during the 12 months prior to suicide. Sub‐populations of suicide decedents based on the presence and type of mental health care contact were described and compared across socio‐demographic, clinical and suicide‐specific variables. Time periods from last mental health contact to date of death were calculated and a Cox proportional hazards model examined covariates. Among suicide decedents, 91.7% had some type of past‐year health care contact prior to death, 66.4% had a mental health care contact, and 25.3% had only non‐mental health contacts. The most common type of mental health contact was an outpatient primary care visit (54.0%), followed by an outpatient psychiatric visit (39.8%), an emergency department visit (31.1%), and a psychiatric hospitalization (21.0%). The median time from last mental health contact to death was 18 days (interquartile range 5‐63). Mental health contact was significantly associated with female gender, age 25‐64, absence of a psychosocial stressor, diagnosis of schizophrenia or bipolar disorder, past suicide attempt, self‐poisoning method and absence of a suicide note. Significant differences between sub‐populations of suicide decedents based on the presence and nature of their health care contacts suggest the need for targeting of community and clinical‐based suicide prevention strategies. The predominance of ambulatory mental health care contacts, often close to the time of death, reinforce the importance of concentrating efforts on embedding risk assessment and care pathways

  13. First example of peptides targeting the dimer interface of Leishmania infantum trypanothione reductase with potent in vitro antileishmanial activity().

    PubMed

    Ruiz-Santaquiteria, Marta; Sánchez-Murcia, Pedro A; Toro, Miguel A; de Lucio, Héctor; Gutiérrez, Kilian Jesús; de Castro, Sonia; Carneiro, Filipa A C; Gago, Federico; Jiménez-Ruiz, Antonio; Camarasa, María-José; Velázquez, Sonsoles

    2017-07-28

    A series of 9-mer and 13-mer amide-bridged cyclic peptides derived from the linear prototype Ac-PKIIQSVGIS-Nle-K-Nle-NH2 (Toro et al. ChemBioChem2013) has been designed and synthesized by introduction of the lactam between amino acid side chains that are separated by one helical turn (i, i+4). All of these compounds were tested in vitro as both dimerization and enzyme inhibitors of Leishmania infantum trypanothione reductase (Li-TryR). Three of the 13-mer cyclic peptide derivatives (3, 4 and 6) inhibited the oxidoreductase activity of Li-TryR in the low micromolar range and they also disrupted enzyme dimerization. Cyclic analogues 3 and 4 were more resistant to proteases than was the linear prototype. Furthermore, the most potent TryR inhibitors in the linear and cyclic series displayed potent in vitro activity against Leishmania infantum upon conjugation with cationic cell-penetrating peptides. To date, these conjugated peptides can be considered the first example of TryR dimerization inhibitors that are active in cell culture. Copyright © 2017 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  14. Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

    DTIC Science & Technology

    2015-11-01

    a range of Ac-PhScN-NH2 concentrations. Figure 4D presents a typical Western blot indicating that PhScN does rapidly induce a dose– dependent ...receptor tyrosine–protein kinase erbB- 2 or HER2, a member of the EGF receptor family, causes constitutive, serum–induced, pFn– dependent – mediated...Example of a Western blot showing dose– dependent upregulation of activated Caspase–3 in adherent SUM149PT cells by a one–hour treatment with a range of Ac

  15. Targeting Alpha5 Beta1 Integrin to Prevent Metastatic Breast Cancer Cell Invasion: PhScN Target Site Definition and Plasma Stability

    DTIC Science & Technology

    2015-11-01

    a typical Western blot indicating that PhScN does rapidly induce a dose– dependent upregulation of activated Caspase–3 in adherent SUM149PT cells...receptor tyrosine–protein kinase erbB- 2 or HER2, a member of the EGF receptor family, causes constitutive, serum–induced, pFn– dependent α5β1– mediated...Medium; green tissue from actin staining. Panel D. Example of a Western blot showing dose– dependent upregulation of activated Caspase–3 in adherent

  16. [Parents as partners in school-based health promotion and addiction prevention: an empirical study for the example of Class2000].

    PubMed

    Kraus, D; Duprée, T; Bölcskei, P L

    2003-06-01

    Starting from the premise of the incomparable importance of the parent-child relationship for development, Class2000, a wide-reaching programme for the promotion of health and prevention of addiction in primary schools, focuses especially on the integration of parents. A questionnaire survey among 1430 parents in Hesse with children in the second primary class shows that the overriding majority of pupils (90 %) speak about Class2000 at home and initiate discussions with their parents on health-related topics. The various Class2000 information materials are acknowledged by up to 77 % of parents (comparatively more rarely in the case of the fathers) and are read, as a rule, with interest. Specific information on the contents of the programme is for the parents rather more important than general stimuli. Invitations to special informative events are accepted by well 80 % of the parents. Class2000 convinces more than 82 % of the participants. 71 % of the parents are prepared to contribute to the costs of Class2000. 12 % are undecided in this regard. Participation in parent evenings increases the readiness for financial involvement.

  17. Applying Spatial Analysis Tools in Public Health: An Example Using SaTScan to Detect Geographic Targets for Colorectal Cancer Screening Interventions

    PubMed Central

    Henry, Kevin A.; Tannenbaum, Stacey L.; Feaster, Daniel J.; Kobetz, Erin; Lee, David J.

    2014-01-01

    Epidemiologists are gradually incorporating spatial analysis into health-related research as geocoded cases of disease become widely available and health-focused geospatial computer applications are developed. One health-focused application of spatial analysis is cluster detection. Using cluster detection to identify geographic areas with high-risk populations and then screening those populations for disease can improve cancer control. SaTScan is a free cluster-detection software application used by epidemiologists around the world to describe spatial clusters of infectious and chronic disease, as well as disease vectors and risk factors. The objectives of this article are to describe how spatial analysis can be used in cancer control to detect geographic areas in need of colorectal cancer screening intervention, identify issues commonly encountered by SaTScan users, detail how to select the appropriate methods for using SaTScan, and explain how method selection can affect results. As an example, we used various methods to detect areas in Florida where the population is at high risk for late-stage diagnosis of colorectal cancer. We found that much of our analysis was underpowered and that no single method detected all clusters of statistical or public health significance. However, all methods detected 1 area as high risk; this area is potentially a priority area for a screening intervention. Cluster detection can be incorporated into routine public health operations, but the challenge is to identify areas in which the burden of disease can be alleviated through public health intervention. Reliance on SaTScan’s default settings does not always produce pertinent results. PMID:24650619

  18. The Mitochondria-Targeted Antioxidant MitoQ Prevents Loss of Spatial Memory Retention and Early Neuropathology in a Transgenic Mouse Model of Alzheimer’s Disease

    PubMed Central

    McManus, Meagan J.; Murphy, Michael P.; Franklin, James L.

    2012-01-01

    Considerable evidence suggests that mitochondrial dysfunction and oxidative stress contribute to the progression of Alzheimer’s disease (AD). We examined the ability of the novel mitochondria-targeted antioxidant MitoQ (mitoquinone mesylate: [10-(4,5-dimethoxy-2-methyl-3,6-dioxo-1,4-cycloheexadienlyl) decyl triphenylphosphonium methanesulfonate]) to prevent AD-like pathology in mouse cortical neurons in cell culture and in a triple transgenic mouse model of AD (3xTg-AD). MitoQ attenuated β-amyloid (Aβ)-induced neurotoxicity in cortical neurons and also prevented increased production of reactive species and loss of mitochondrial membrane potential (Δψm) in them. To determine whether the mitochondrial protection conferred by MitoQ was sufficient to prevent the emergence of AD-like neuropathology in vivo, we treated young female 3xTg-AD mice with MitoQ for 5 months and analyzed the effect on the progression of AD-like pathologies. Our results show that MitoQ prevented cognitive decline in these mice as well as oxidative stress, Aβ accumulation, astrogliosis, synaptic loss, and caspase activation in their brains. The work presented herein suggests a central role for mitochondria in neurodegeneration and provides evidence supporting the use of mitochondria-targeted therapeutics in diseases involving oxidative stress and metabolic failure, namely AD. PMID:22049413

  19. Targeting antigens to Dec-205 on dendritic cells induces a higher immune response in chickens: Hemagglutinin of avian influenza virus example.

    PubMed

    Jáuregui-Zúñiga, David; Pedraza-Escalona, Martha; Espino-Solís, Gerardo Pavel; Quintero-Hernández, Verónica; Olvera-Rodríguez, Alejandro; Díaz-Salinas, Marco Aurelio; López, Susana; Possani, Lourival Domingos

    2017-04-01

    It is widely known that targeting a variety of antigens to the DEC-205 receptor on dendritic cells (DCs) significantly potentiate immunity. This communication reports the development of a new murine monoclonal antibody (mAb) against the chicken DEC-205, using as immunogen the carbohydrate recognition domain-2 (CRD-2) heterologously expressed. This mAb recognizes a protein band of 250kDa by immunoprecipitation analysis and shows strong cross-reactivity with human and pig DEC-205. Furthermore, the hemagglutinin (HA) of avian influenza H5N2 virus was cloned and expressed using insect cell-baculovirus expression system. We chemically conjugated the anti-chicken DEC-205 antibody with the highly purified HA to direct the antigen to the dendritic cells and evaluate the immune response elicited in vivo by this conjugate. A single dose of chemical conjugate was sufficient to elicit a strong immune response in chickens as early as fourteen days after priming. In addition, the conjugate induced an earlier and higher response compared to unconjugated HA. These results suggest that the strategy described here has potential to be used in the future design and development of successful vaccines against different chicken infectious diseases with direct impact in biotechnology and veterinary fields.

  20. A protocol for targeted enrichment of intron-containing sequence markers for recent radiations: A phylogenomic example from Heuchera (Saxifragaceae)1

    PubMed Central

    Folk, Ryan A.; Mandel, Jennifer R.; Freudenstein, John V.

    2015-01-01

    Premise of the study: Phylogenetic inference is moving to large multilocus data sets, yet there remains uncertainty in the choice of marker and sequencing method at low taxonomic levels. To address this gap, we present a method for enriching long loci spanning intron-exon boundaries in the genus Heuchera. Methods: Two hundred seventy-eight loci were designed using a splice-site prediction method combining transcriptomic and genomic data. Biotinylated probes were designed for enrichment of these loci. Reference-based assembly was performed using genomic references; additionally, chloroplast and mitochondrial genomes were used as references for off-target reads. The data were aligned and subjected to coalescent and concatenated phylogenetic analyses to demonstrate support for major relationships. Results: Complete or nearly complete (>99%) sequences were assembled from essentially all loci from all taxa. Aligned introns showed a fourfold increase in divergence as opposed to exons. Concatenated analysis gave decisive support to all nodes, and support was also high and relationships mostly similar in the coalescent analysis. Organellar phylogenies were also well-supported and conflicted with the nuclear signal. Discussion: Our approach shows promise for resolving a recent radiation. Enrichment for introns is highly successful with little or no sequencing dropout at low taxonomic levels despite higher substitution and indel frequencies, and should be exploited in studies of species complexes. PMID:26312196

  1. Communication Skills for Patient Engagement: Argumentation Competencies As Means to Prevent or Limit Reactance Arousal, with an Example from the Italian Healthcare System.

    PubMed

    Bigi, Sarah

    2016-01-01

    The paper discusses the role of argumentative competencies for the achievement of patient engagement through communication in doctor-patient consultations. The achievement of patient engagement is being proposed by recent studies as a condition that can facilitate in particular patient adherence, which involves behavior change. One obstacle to behavior change that has been observed is reactance, i.e., resistance to persuasive messages when a threat to freedom is perceived. In the medical field, reactance theory has been mostly applied in the field of mental health, less frequently to understand non-adherence in general. However, a few studies have revealed that reactance can actually explain in part the motives behind non-adherence. These studies propose that the arousal of reactance could be limited or prevented by adopting relational measures aimed at giving patients the feeling that they still hold some control over the process of care and that t