The Pine River Statement: Human Health Consequences of DDT Use

Objectives: Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction: We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis: Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions: Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT.Dichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure. Data sources and extraction We conducted a PubMed search in October 2008 and retrieved 494 studies. Data synthesis Use restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children. Conclusions Although we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDThttp://dx.doi.org/10.1289/ehp.1174

On the Mechanism and Function of Asymmetric Histone Inheritance

In most tissues, homeostasis is maintained by adult stem cells. These cells have the unique capacity to divide asymmetrically to give rise to both a self-renewing stem cell and a differentiating daughter cell. In the case of the Drosophila germline, Germline Stem Cells (GSCs) divide symmetrically to give rise to both a self-renewing stem cell and a differentiating daughter Gonialblast (GB) cell. The mechanism behind this asymmetric division has long been debated. Previously, in a seminal discovery, the Xin Chen lab found that histones, the primary carriers of the epigenetic information that patterns cell fate, are directly segregated asymmetrically during asymmetric GSC division. In this process, old histones are retained by the GSC while new histones segregate to the GB. This work led to three major questions: to what extent histone inheritance is conserved, what the mechanism is differentially partition histones, and what the exact function of this asymmetric division is. My work has focused on the mechanism and function of this process. Mechanistically, asymmetric histone inheritance is primarily a two-step process in which histones are first differentially incorporated on sister chromatids during DNA replication before these epigenetically distinct sister chromatids are recognized and segregated asymmetrically during mitosis. In our recent work, we have detailed the molecular mechanism by which old and new histones are segregated asymmetrically at the replication fork. We found that low levels of lagging strand polymerases Polα and Polδ, but high levels of RPA drive delayed lagging strand synthesis. This in turn results in old histones recycling preferentially to the leading strand. Functionally, we found that asymmetric histone inheritance is ultimately upstream of cell cycle remodeling. Additionally, related to the function of asymmetric histone inheritance, I tracked histone modifications across the cell cycle and found that a dramatic pattern of chromatin maturation occurs post-replicatively which may control the eventual gene regulatory landscape of the two daughter cells

In vitro assessments of reverse glenoid stability using displacement gages are misleading - recommendations for accurate measurements of interface micromotion

BACKGROUND: Baseplate micromotion of the reverse shoulder glenoid component can lead to implant loosening. We hypothesized that a remotely positioned displacement gage measures elastic deformation of the system rather than actual micromotion at the implant/bone interface. METHODS: Reverse glenoid components were implanted into polyurethane blocks of 3 different densities. A 700 N compressive load was maintained and a vertical 700 N shear load was applied for 1000 cycles. In addition to the typical gage measurement, a digital image analysis of micromotion at the implant/block interface using high resolution cameras was performed. The measurements were validated on human specimens. A finite element model was implemented to study the isolated effect of block deformation on baseplate displacements. FINDINGS: With the gage, typically reported micromotions were measured. Two orders of magnitude lower micromotions were detected using interface image-based analysis. The finite element simulation showed that elastic deformation alone can cause micromotion magnitudes as measured with displacement gages. Polyurethane blocks of 20 and 15 lbs per cubic foot density best reproduced micromotions as measured on human specimens. INTERPRETATION: We found considerably less relative micromotion at the implant/bone interface than previously assumed. Gage measurements quantify elastic deformation and not true interface micromotion. High resolution digital imaging at the implant/bone interface is strongly recommended for an accurate assessment of reverse glenoid component micromotion. Tests should further adopt 20 or 15 pcf bone test surrogates. Further studies are required to identify the failure modes encountered in vivo, and a corresponding in vitro testing methodology can then be developed. Copyright © 2011 Elsevier Ltd. All rights reserved

The Pine River statement: human health consequences of DDT use.

ObjectivesDichlorodiphenyltrichloroethane (DDT) was used worldwide until the 1970s, when concerns about its toxic effects, its environmental persistence, and its concentration in the food supply led to use restrictions and prohibitions. In 2001, more than 100 countries signed the Stockholm Convention on Persistent Organic Pollutants (POPs), committing to eliminate the use of 12 POPs of greatest concern. However, DDT use was allowed for disease vector control. In 2006, the World Health Organization and the U.S. Agency for International Development endorsed indoor DDT spraying to control malaria. To better inform current policy, we reviewed epidemiologic studies published from 2003 to 2008 that investigated the human health consequences of DDT and/or DDE (dichlorodiphenyldichloroethylene) exposure.Data sources and extractionWe conducted a PubMed search in October 2008 and retrieved 494 studies.Data synthesisUse restrictions have been successful in lowering human exposure to DDT, but blood concentrations of DDT and DDE are high in countries where DDT is currently being used or was more recently restricted. The recent literature shows a growing body of evidence that exposure to DDT and its breakdown product DDE may be associated with adverse health outcomes such as breast cancer, diabetes, decreased semen quality, spontaneous abortion, and impaired neurodevelopment in children.ConclusionsAlthough we provide evidence to suggest that DDT and DDE may pose a risk to human health, we also highlight the lack of knowledge about human exposure and health effects in communities where DDT is currently being sprayed for malaria control. We recommend research to address this gap and to develop safe and effective alternatives to DDT