Review of Pesticide Urinary Biomarker Measurements from Selected US EPA Children’s Observational Exposure Studies

Children are exposed to a wide variety of pesticides originating from both outdoor and indoor sources. Several studies were conducted or funded by the EPA over the past decade to investigate children’s exposure to organophosphate and pyrethroid pesticides and the factors that impact their exposures. Urinary metabolite concentration measurements from these studies are consolidated here to identify trends, spatial and temporal patterns, and areas where further research is required. Namely, concentrations of the metabolites of chlorpyrifos (3,5,6-trichloro-2-pyridinol or TCPy), diazinon (2-isopropyl-6-methyl-4-pyrimidinol or IMP), and permethrin (3-phenoxybenzoic acid or 3-PBA) are presented. Information on the kinetic parameters describing absorption and elimination in humans is also presented to aid in interpretation. Metabolite concentrations varied more dramatically across studies for 3-PBA and IMP than for TCPy, with TCPy concentrations about an order of magnitude higher than the 3-PBA concentrations. Temporal variability was high for all metabolites with urinary 3-PBA concentrations slightly more consistent over time than the TCPy concentrations. Urinary biomarker levels provided only limited evidence of applications. The observed relationships between urinary metabolite levels and estimates of pesticide intake may be affected by differences in the contribution of each exposure route to total intake, which may vary with exposure intensity and across individuals

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 receptors. Further studies of these host factor targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19

Randomized Phase III Study of Canfosfamide in Combination With Pegylated Liposomal Doxorubicin Compared With Pegylated Liposomal Doxorubicin Alone in Platinum-Resistant Ovarian Cancer

status: publishe

EIA and EMS integration : Not wasting the opportunity

Environmental tools such as environmental impact assessment (EIA) and environmental management systems (EMS) can be applied to ensure that major projects are constructed and operated using an approach that enables effective environmental protection. Previous research has shown that these tools are frequently applied in isolation at different stages of the project life cycle. The extent of EIA/EMS integration amongst nine of the biggest UK waste management companies was investigated through semi-structured interviews with environmental staff and thematic analysis of their responses. The research found that partial integration of EIA and EMS is widespread. Companies recognised a range of potential benefits to more closely integrating their processes such as system efficiencies, data availability and recognition from the regulator. However, significant barriers to further integration were identified in the form of cost, company structure and the size of the organisation. In a context where the regulation of the waste industry is increasingly aligned towards a risk-based approach, there is a new opportunity to use EIA outputs in an enhanced EMS. More generally, companies should seek to maintain continuity of personnel across the project life cycle and structure their environmental functions so that EIA and EMS staff can work more closely. This would help ensure that the greatest benefit is derived from both tools.Peer reviewe