17 research outputs found

    Body Burdens of Polybrominated Diphenyl Ethers among Urban Anglers

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    Polybrominated diphenyl ethers (PBDEs) have been widely used in the United States and worldwide as flame retardants. Recent PBDE production figures show that worldwide use has increased. To determine whether fish consumption is a source of PBDE exposure for humans, a cross-sectional epidemiologic study of New York and New Jersey urban anglers was conducted during the summers of 2001–2003. Frequency of local fish consumption was assessed by questionnaire, and blood samples for PBDE analysis were collected from 94 anglers fishing from piers on the lower Hudson River and Newark Bay. We analyzed PBDEs by gas chromatography–isotope dilution–high-resolution mass spectrometry. The congeners found in anglers’ serum at the highest concentrations were, by International Union of Pure and Applied Chemistry numbers, BDE-47, BDE-153, and BDE-99. Anglers reporting consumption of local fish had higher, but nonstatistically significantly different, concentrations of PBDEs than did anglers who did not eat local fish. For some congeners (BDE-100 and BDE-153), we observed moderate dose–response relationships between serum PBDE levels and frequency of reported fish intake. These findings suggest that consumption of locally caught fish is not a major route of human exposure for this study population

    Children\u27s Health in Latin America: The Influence of Environmental Exposures

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    Background:Chronic diseases are increasing among children in Latin America. Objective and Methods:To examine environmental risk factors for chronic disease in LatinAmerican children and to develop a strategic initiative for control of these exposures, the WorldHealth Organization (WHO) including the Pan American Health Organization (PAHO), the Collegium Ramazzini, and Latin American scientists reviewed regional and relevant global data. Findings: Industrial development and urbanization are proceeding rapidly in Latin America and environmental pollution has become widespread. Environmental threats to children\u27s health include traditional hazards such as indoor air pollution and drinking water contamination; as well as the newer hazards of urban air pollution; toxic chemicals such as lead, asbestos, mercury,arsenic, and pesticides;hazardous and electronic waste;and climate change. The mix of traditional and modern hazards varies greatly across and within countries reflecting industrialization, urbanization and socioeconomic forces. Conclusions: To control environmental threats to children\u27s health in Latin America, WHO, including PAHO will focus on the most highly prevalent and serious hazards - indoor and outdoor air pollution, water pollution, and toxic chemicals. Strategies for controlling these hazards include developing tracking data on regional trends in children\u27s environmental health(CEH); building a network of Collaborating Centres; promoting biomedical research in CEH;building regional capacity; supporting development of evidence-based prevention policies; studying the economic costs of chronic diseases in children; and developing platforms for dialogue with relevant stakeholders.

    PRC2 loss induces chemoresistance by repressing apoptosis in T cell acute lymphoblastic leukemia

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    The tendency of mitochondria to undergo or resist BCL2-controlled apoptosis (so-called mitochondrial priming) is a powerful predictor of response to cytotoxic chemotherapy. Fully exploiting this finding will require unraveling the molecular genetics underlying phenotypic variability in mitochondrial priming. Here, we report that mitochondria) apoptosis resistance in T cell acute lymphoblastic leukemia (T-ALL) is mediated by inactivation of polycomb repressive complex 2 (PRC2). In T-ALL clinical specimens, loss-of-function mutations of PRC2 core components (EZH2, FED, or SUZ12) were associated with mitochondrial apoptosis resistance. In T-ALL cells, PRC2 depletion induced resistance to apoptosis induction by multiple chemotherapeutics with distinct mechanisms of action. PRC2 loss induced apoptosis resistance via transcriptional up-regulation of the LIM domain transcription factor CRIP2 and downstream up-regulation of the mitochondrial chaperone TRAP1. These findings demonstrate the importance of mitochondrial apoptotic priming as a prognostic factor in T-ALL and implicate mitochondrial chaperone function as a molecular determinant of chemotherapy response

    Sustainable deimplementation of continuous pulse oximetry monitoring in children hospitalized with bronchiolitis: study protocol for the Eliminating Monitor Overuse (EMO) type III effectiveness-deimplementation cluster-randomized trial.

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    BACKGROUND: Methods of sustaining the deimplementation of overused medical practices (i.e., practices not supported by evidence) are understudied. In pediatric hospital medicine, continuous pulse oximetry monitoring of children with the common viral respiratory illness bronchiolitis is recommended only under specific circumstances. Three national guidelines discourage its use for children who are not receiving supplemental oxygen, but guideline-discordant practice (i.e., overuse) remains prevalent. A 6-hospital pilot of educational outreach with audit and feedback resulted in immediate reductions in overuse; however, the best strategies to optimize sustainment of deimplementation success are unknown. METHODS: The Eliminating Monitor Overuse (EMO) trial will compare two deimplementation strategies in a hybrid type III effectiveness-deimplementation trial. This longitudinal cluster-randomized design will be conducted in Pediatric Research in Inpatient Settings (PRIS) Network hospitals and will include baseline measurement, active deimplementation, and sustainment phases. After a baseline measurement period, 16-19 hospitals will be randomized to a deimplementation strategy that targets unlearning (educational outreach with audit and feedback), and the other 16-19 will be randomized to a strategy that targets unlearning and substitution (adding an EHR-integrated clinical pathway decision support tool). The primary outcome is the sustainment of deimplementation in bronchiolitis patients who are not receiving any supplemental oxygen, analyzed as a longitudinal difference-in-differences comparison of overuse rates across study arms. Secondary outcomes include equity of deimplementation and the fidelity to, and cost of, each deimplementation strategy. To understand how the deimplementation strategies work, we will test hypothesized mechanisms of routinization (clinicians developing new routines supporting practice change) and institutionalization (embedding of practice change into existing organizational systems). DISCUSSION: The EMO trial will advance the science of deimplementation by providing new insights into the processes, mechanisms, costs, and likelihood of sustained practice change using rigorously designed deimplementation strategies. The trial will also advance care for a high-incidence, costly pediatric lung disease. TRIAL REGISTRATION: ClinicalTrials.gov, NCT05132322 . Registered on November 10, 2021

    Developmental origins of health and disease: Integrating environmental influences

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    There are now robust data supporting the Developmental Origins of Health and Disease (DOHaD) paradigm. This includes human and animal data focusing on nutrition or environmental chemicals during development. However, the term DOHaD has not been generally accepted as the official term to be used when one is concerned with understanding the pathophysiological basis for how environmental influences acting during early development influence the risk of later noncommunicable diseases. Similarly, there is no global research or public health program built around the DOHaD paradigm that encompasses all aspects of environment. To better inform the global health efforts aimed at addressing the growing epidemic of chronic noncommunicable diseases of environmental origin, we propose a two-pronged approach: first, to make it clear that the current concept of DOHaD comprehensively includes a range of environmental factors and their relevance to disease occurrence not just throughout the life span but potentially across several generations; and second, to initiate the discussion of how adoption of DOHaD can promote a more realistic, accurate, and integrative approach to understanding environmental disruption of developmental programming and better inform clinical and policy interventions

    Cultivating Skills for 21st Century Professionals: Development and Assessment of Process Skills in Ecology and Conservation Biology Students

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    Background/Question/Methods: Understanding and conserving the biosphere increasingly requires proficiency in skills including critical thinking, data analysis, oral communication, broad synthesis of information and teamwork across diverse groups. However, a real concern exists that US undergraduate science students do not currently develop these important process skills needed as professionals. First, our work asks “how can we best ‘operationalize’ teaching of process skills?” Second, we must also discover how to evaluate development of specific process skills in our students. Such assessment allows us to determine if we have succeeded in teaching these skills with a gain or loss in content understanding. Here, we present the design and preliminary results of a recently launched experimental study aimed at these two tasks. The study brings together faculty from diverse institutions and professional conservation biologists to create and validate a set of instructional materials for process skills development. Following development, selected faculty will pilot teaching and assessment materials in diverse classroom settings. Project participants, led by investigators from the American Museum of Natural History’s Center for Biodiversity and Conservation, designed a multi-year research experiment in two stages: (1) development of instructional materials and associated assessment tools for three skills (i.e., critical thinking, oral communication, and data analysis), and (2) application of these materials in the classroom under two different instruction modalities, individual reflection versus intensive classroom discussion of the skill. These two modalities investigate student development of the targeted process skill and how intensity of a teaching intervention influences student success. Results/Conclusions: For each selected skill, faculty participants and consultants developed two exercises that focused on ecology and conservation biology topics, either new or based on the modules produced by the Network of Conservation Educators and Practitioners (NCEP; http://ncep.amnh.org). Participants also created the following assessment tools: student self-assessment questionnaires focusing on their confidence for each skill, content gains assessments, and rubrics for assessing skill performance. These will be applied pre and post application of the instructional materials. Our plans include validation and finalization of materials over summer 2011 and pilots in the classrooms occurring in at least 14 US institutions (including Puerto Rico) beginning in fall 2011. While the study focuses on these skills in the context of ecology and conservation biology, our approach and results should be of direct use for other related, integrative fields such as natural resource management, sustainable development studies, and public health. We welcome faculty input and interest in the project
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