Mostrando recursos 1 - 20 de 2.269

  1. Adherence adjustment in the Coronary Drug Project: A call for better per-protocol effect estimates in randomized trials

    Murray, Eleanor Jane; Hernan, Miguel Angel
    BACKGROUND: In many randomized controlled trials, patients and doctors are more interested in the per-protocol effect than in the intention-to-treat effect. However, valid estimation of the per-protocol effect generally requires adjustment for prognostic factors associated with adherence. These adherence adjustments have been strongly questioned in the clinical trials community, especially after 1980 when the Coronary Drug Project team found that adherers to placebo had lower 5-year mortality than non-adherers to placebo. METHODS: We replicated the original Coronary Drug Project findings from 1980 and re-analyzed the Coronary Drug Project data using technical and conceptual developments that have become established since 1980. Specifically, we used...

  2. “Once the delivery is done, they have finished”: a qualitative study of perspectives on postnatal care referrals by traditional birth attendants in Ebonyi state, Nigeria

    Chukwuma, Adanna Deborah Ugochi; Mbachu, Chinyere; Cohen, Jessica L; Bossert, Thomas John; McConnell, Margaret Anne
    Background While 79% of Nigerian mothers who deliver in facilities receive postnatal care within 48 h of delivery, this is only true for 16% of mothers who deliver outside facilities. Most maternal deaths can be prevented with access to timely and competent health care. Thus, the World Health Organization, International Confederation of Midwives, and International Federation of Gynecology and Obstetrics recommend that unskilled birth attendants be involved in advocacy for skilled care use among mothers. This study explores postnatal care referral behavior by TBAs in Nigeria, including the perceived factors that may deter or promote referrals to skilled health workers. Methods This study...

  3. Health Care Providers’ Experience with a Protocol for the Identification, Treatment, and Referral of Human-Trafficking Victims

    Stoklosa, Hanni; Showalter, Elizabeth; Melnick, Anna; Rothman, Emily Faith
    Abstract The healthcare setting is thought to be one of the most promising places to identify victims of human trafficking. The present study was designed to relay the experiences of a sample of 10 healthcare providers and hospital administrators who developed and have used a protocol to identify victims of human trafficking since February 2014. To our knowledge, the protocol was one of the first to be adopted by any healthcare system in the U.S. Three primary themes emerged from the participant interviews. First, developing the protocol was challenging because at the time there were no predecessor examples. Second, providers reported that...

  4. Human Trafficking Is a Public Health Issue: A Paradigm Expansion in the United States

    Chisolm-Straker, Makini; Stoklosa, Hanni
    This clear-sighted reference examines the public health dimensions of labor and sex trafficking in the United States, the scope of the crisis, and possibilities for solutions. Its ecological lifespan approach globally traces risk and protective factors associated with this exploitation, laying a roadmap towards its prevention. Diverse experts, including survivors, describe support and care interventions across domains and disciplines, from the law enforcement and judicial sectors to community health systems and NGOs, with a robust model for collaboration. By focusing on the humanity of trafficked persons, a public health paradigm broadens our understanding of and ability to address trafficking while...

  5. Human Trafficking, Mental Illness, and Addiction: Avoiding Diagnostic Overshadowing

    Stoklosa, Hanni; Stoklosa, Joseph Brian; MacGibbon, Marti
    This article reviews an emergency department-based clinical vignette of a trafficked patient with co-occurring pregnancy-related, mental health, and substance use disorder issues. The authors, including a survivor of human trafficking, draw on their backgrounds in addiction care, human trafficking, emergency medicine, and psychiatry to review the literature on relevant general health and mental health consequences of trafficking and propose an approach to the clinical complexities this case presents. In their discussion, the authors explicate the deleterious role of implicit bias and diagnostic overshadowing in trafficked patients with co-occurring addiction and mental illness. Finally, the authors propose a trauma-informed, multidisciplinary response...

  6. Ribosomal DNA copy number amplification and loss in human cancers is linked to tumor genetic context, nucleolus activity, and proliferation

    Wang, Mengchuan; Silva, Bernardo Lemos
    Ribosomal RNAs (rRNAs) are transcribed from two multicopy DNA arrays: the 5S ribosomal DNA (rDNA) array residing in a single human autosome and the 45S rDNA array residing in five human autosomes. The arrays are among the most variable segments of genomes, exhibit concerted copy number variation (cCNV), encode essential components of the ribosome, and exert global influences on gene expression. Here we combined whole genome data from >700 tumors and paired normal tissues to provide a portrait of rDNA variation in human tissues and cancers of diverse mutational signatures, including stomach and lung adenocarcinomas, ovarian cancers, and others of...

  7. Lactation history, serum concentrations of persistent organic pollutants, and maternal risk of diabetes

    Zong, Geng; Grandjean, Philippe; Wang, Xiaobin; Sun, Qi
    Objective: Lactation may help curb diabetes risk and is also known as an excretion route for some environmental pollutants. We evaluated associations of lifetime lactation history with serum concentrations of persistent organic pollutants (POPs) in the National Health and Nutrition Examination Survey 1999-2006, and examined whether potentially diabetogenic POPs account for associations between lactation and diabetes. Research Design and Methods: Among 4,479 parous women, breastfeeding history was defined as the number of children breastfed ≥1 month. Diabetes was identified by self-report or hemoglobin A1c >6.5%. Twenty-four POPs were measured in serum among subsamples of 668 to 1,073 participants. Results: Compared with women...

  8. Therapeutic Evolution or Revolution? Metaphors and Their Consequences

    Jones, David Shumway
    Evolution and revolution are both models of change over time. It is easy to see the appeal of a claim of revolution for scientists and for their historians: it pronounces a radical break from the past, confident and triumphant. Progress is implied by the decisiveness of the rupture. Such rhetoric is good for marketing, especially when contrasted against the cautious gradualism of evolution. But evolution has its own appeals, especially its reassuring connotations of progressive improvement. It is not enough simply to debate what counts, or not, as revolution or evolution. Instead, much can be gained through serious engagement with...

  9. Serum Concentrations of Polyfluoroalkyl Compounds in Faroese Whale Meat Consumers

    Weihe, Pal; Kato, Kayoko; Calafat, Antonia M.; Nielsen, Flemming; Wanigatunga, Amal A.; Needham, Larry L.; Grandjean, Philippe
    To learn the extent of human exposure to polyfluoroalkyl compounds (PFCs) in a remote fishing population, we measured, in Faroese children and pregnant women, the serum concentrations of nine PFCs, including perfluorooctane sulfonate (PFOS), perfluorooctanoate (PFOA), and perfluorononanoate (PFNA), by using on-line solid-phase extraction coupled to isotope dilution high-performance liquid chromatography-tandem mass spectrometry. The serum samples analyzed had been collected between 1993 and 2005 from 103 children 7 years of age, 79 of these children at 14 years of age, and from 12 pregnant women and their children 5 years later. PFOS was detected in all samples analyzed, and both...

  10. Elimination Half-Lives of Polychlorinated Biphenyl Congeners in Children

    Grandjean, Philippe; Budtz-Jørgensen, Ebsen; Barr, Dana B.; Needham, Larry L.; Weihe, Pal; Heinzow, Birger
    The elimination kinetics of polychlorinated biphenyls (PCBs) in humans is difficult to assess in observational studies, because PCB exposure is never completely abolished. In a community with high dietary PCB exposures from whale blubber, we examined two groups of children with increased body burdens from breast-feeding. Follow-up was from ages 4.5 years to 7.5 years (99 subjects) and 7 to 14 years (101 subjects). The calculations were performed by the use of structural equation models, with adjustment for body weight and dietary blubber intake as the main source of postnatal exposure. As a likely result of background exposures, apparent elimination...

  11. Within-person reproducibility of red blood cell mercury over a 10- to 15-year period among women in the Nurses’ Health Study II

    Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L; Nielsen, Flemming; Tworoger, Shelley Slate; Grandjean, Philippe; Weisskopf, Marc G.
    Background Most epidemiologic studies of methylmercury (MeHg) health effects rely on a single measurement of a MeHg biomarker to assess long-term exposures. Long-term reproducibility data are, therefore, needed to assess the reliability of a single measure to reflect long-term exposures. In this study we assessed within-person reproducibility of red blood cell (RBC) mercury (Hg), a marker of methyl-mercury, over 10–15-years in a sample of 57 women. Methods Fifty-seven women from the Nurses’ Health Study II provided two blood samples 10–15-years apart (median:12 years), which were analyzed for mercury levels in the red blood cells (B-Hg*). To characterize within-person reproducibility we estimated correlation and...

  12. Within-person reproducibility of red blood cell mercury over a 10- to 15-year period among women in the Nurses’ Health Study II

    Kioumourtzoglou, Marianthi-Anna; Roberts, Andrea L; Nielsen, Flemming; Tworoger, Shelley Slate; Grandjean, Philippe; Weisskopf, Marc G.
    Background Most epidemiologic studies of methylmercury (MeHg) health effects rely on a single measurement of a MeHg biomarker to assess long-term exposures. Long-term reproducibility data are, therefore, needed to assess the reliability of a single measure to reflect long-term exposures. In this study we assessed within-person reproducibility of red blood cell (RBC) mercury (Hg), a marker of methyl-mercury, over 10–15-years in a sample of 57 women. Methods Fifty-seven women from the Nurses’ Health Study II provided two blood samples 10–15-years apart (median:12 years), which were analyzed for mercury levels in the red blood cells (B-Hg*). To characterize within-person reproducibility we estimated correlation and...

  13. Paracelsus Revisited: The Dose Concept in a Complex World

    Grandjean, Philippe
    At the time that Paracelsus coined his famous dictum, “What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison,” embryonic toxicology was a fairly focused discipline that mainly dealt with occupational poisonings and side effects of pharmaceuticals, such as mercury. While Paracelsus paved the way for the modern threshold concept and the no-adverse effect level, modern-day toxicology is now tussling with highly complex issues, such as developmental exposures, genetic predisposition and other sources of hypersusceptibility, multiple causes of underestimated toxicity, and the continuous...

  14. Paracelsus Revisited: The Dose Concept in a Complex World

    Grandjean, Philippe
    At the time that Paracelsus coined his famous dictum, “What is there that is not poison? All things are poison and nothing is without poison. Solely the dose determines that a thing is not a poison,” embryonic toxicology was a fairly focused discipline that mainly dealt with occupational poisonings and side effects of pharmaceuticals, such as mercury. While Paracelsus paved the way for the modern threshold concept and the no-adverse effect level, modern-day toxicology is now tussling with highly complex issues, such as developmental exposures, genetic predisposition and other sources of hypersusceptibility, multiple causes of underestimated toxicity, and the continuous...

  15. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

    Hsieh, Chen-Lin; Fei, Teng; Chen, Yiwen; Li, Tiantian; Gao, Yanfei; Wang, Xiaodong; Sun, Tong; Sweeney, Christopher J; Lee, Gwo-Shu Mary; Chen, Shaoyong; Balk, Steven Paul; Liu, Xiaole (Shirley) Shirley; Brown, Myles Avery; Kantoff, Philip Wayne
    The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer–promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required...

  16. Enhancer RNAs participate in androgen receptor-driven looping that selectively enhances gene activation

    Hsieh, Chen-Lin; Fei, Teng; Chen, Yiwen; Li, Tiantian; Gao, Yanfei; Wang, Xiaodong; Sun, Tong; Sweeney, Christopher J; Lee, Gwo-Shu Mary; Chen, Shaoyong; Balk, Steven Paul; Liu, Xiaole (Shirley) Shirley; Brown, Myles Avery; Kantoff, Philip Wayne
    The androgen receptor (AR) is a key factor that regulates the behavior and fate of prostate cancer cells. The AR-regulated network is activated when AR binds enhancer elements and modulates specific enhancer–promoter looping. Kallikrein-related peptidase 3 (KLK3), which codes for prostate-specific antigen (PSA), is a well-known AR-regulated gene and its upstream enhancers produce bidirectional enhancer RNAs (eRNAs), termed KLK3e. Here, we demonstrate that KLK3e facilitates the spatial interaction of the KLK3 enhancer and the KLK2 promoter and enhances long-distance KLK2 transcriptional activation. KLK3e carries the core enhancer element derived from the androgen response element III (ARE III), which is required...

  17. REST and Stress Resistance in Ageing and Alzheimer’s Disease

    Lu, Tao; Aron, Liviu; Zullo, Joseph M.; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek Mark; Liu, Xiaole (Shirley) Shirley; Bennett, David A.; Colaiacovo, Monica P.; Yankner, Bruce Albert
    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons...

  18. REST and Stress Resistance in Ageing and Alzheimer’s Disease

    Lu, Tao; Aron, Liviu; Zullo, Joseph M.; Pan, Ying; Kim, Haeyoung; Chen, Yiwen; Yang, Tun-Hsiang; Kim, Hyun-Min; Drake, Derek Mark; Liu, Xiaole (Shirley) Shirley; Bennett, David A.; Colaiacovo, Monica P.; Yankner, Bruce Albert
    Human neurons are functional over an entire lifetime, yet the mechanisms that preserve function and protect against neurodegeneration during ageing are unknown. Here we show that induction of the repressor element 1-silencing transcription factor (REST; also known as neuron-restrictive silencer factor, NRSF) is a universal feature of normal ageing in human cortical and hippocampal neurons. REST is lost, however, in mild cognitive impairment and Alzheimer’s disease. Chromatin immunoprecipitation with deep sequencing and expression analysis show that REST represses genes that promote cell death and Alzheimer’s disease pathology, and induces the expression of stress response genes. Moreover, REST potently protects neurons...

  19. Perioperative Inflammation as Triggering Origin of Metastasis Development

    Retsky, Michael W.; Demicheli, Romano
    A multimodal pattern of hazard of relapse among early stage breast cancer patients has been identified in multiple databases from US, Europe and Asia. What began as a simple investigation of these anomalous data has taken the authors on a path through a diverse variety of clinical topics involving a number of medical specialties and now proposing a clinical trial in Nigeria. We have been studying these data to determine if this can lead to new ideas on how to prevent relapse in breast cancer. Using computer simulation and access to a very high quality database from Milan for patients...

  20. Treadmill Slope Modulates Inflammation, Fiber Type Composition, Androgen, and Glucocorticoid Receptors in the Skeletal Muscle of Overtrained Mice

    da Rocha, Alisson L.; Pereira, Bruno C.; Teixeira, Giovana R.; Pinto, Ana P.; Frantz, Fabiani G.; Elias, Lucila L. K.; Lira, Fábio S.; Pauli, José R.; Cintra, Dennys E.; Ropelle, Eduardo R.; de Moura, Leandro P.; Mekary, Rania A.; de Freitas, Ellen C.; da Silva, Adelino S. R.
    Overtraining (OT) may be defined as an imbalance between excessive training and adequate recovery period. Recently, a downhill running-based overtraining (OTR/down) protocol induced the nonfunctional overreaching state, which is defined as a performance decrement that may be associated with psychological and hormonal disruptions and promoted intramuscular and systemic inflammation. To discriminate the eccentric contraction effects on interleukin 1beta (IL-1β), IL-6, IL-10, IL-15, and SOCS-3, we compared the release of these cytokines in OTR/down with other two OT protocols with the same external load (i.e., the product between training intensity and volume), but performed in uphill (OTR/up) and without inclination (OTR)....

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