BackgroundClimate models project that heat waves will increase in frequency and severity. Despite many studies of mortality from heat waves, few studies have examined morbidity.ObjectivesIn this study we investigated whether any age or race/ethnicity groups experienced increased hospitalizations and emergency department (ED) visits overall or for selected illnesses during the 2006 California heat wave.MethodsWe aggregated county-level hospitalizations and ED visits for all causes and for 10 cause groups into six geographic regions of California. We calculated excess morbidity and rate ratios (RRs) during the heat wave (15 July to 1 August 2006) and compared these data with those of a reference period (8–14 July and 12–22 August 2006).ResultsDuring the heat wave, 16,166 excess ED visits and 1,182 excess hospitalizations occurred statewide. ED visits for heat-related causes increased across the state [RR = 6.30; 95% confidence interval (CI), 5.67–7.01], especially in the Central Coast region, which includes San Francisco. Children (0–4 years of age) and the elderly (≥ 65 years of age) were at greatest risk. ED visits also showed significant increases for acute renal failure, cardiovascular diseases, diabetes, electrolyte imbalance, and nephritis. We observed significantly elevated RRs for hospitalizations for heat-related illnesses (RR = 10.15; 95% CI, 7.79–13.43), acute renal failure, electrolyte imbalance, and nephritis.ConclusionsThe 2006 California heat wave had a substantial effect on morbidity, including regions with relatively modest temperatures. This suggests that population acclimatization and adaptive capacity influenced risk. By better understanding these impacts and population vulnerabilities, local communities can improve heat wave preparedness to cope with a globally warming future.

With the release of the landmark report Toxicity Testing in the 21st Century: A Vision and a Strategy, the U.S. National Academy of Sciences, in 2007, precipitated a major change in the way toxicity testing is conducted. It envisions increased efficiency in toxicity testing and decreased animal usage by transitioning from current expensive and lengthy in vivo testing with qualitative endpoints to in vitro toxicity pathway assays on human cells or cell lines using robotic high-throughput screening with mechanistic quantitative parameters. Risk assessment in the exposed human population would focus on avoiding significant perturbations in these toxicity pathways. Computational systems biology models would be implemented to determine the dose-response models of perturbations of pathway function. Extrapolation of in vitro results to in vivo human blood and tissue concentrations would be based on pharmacokinetic models for the given exposure condition. This practice would enhance human relevance of test results, and would cover several test agents, compared to traditional toxicological testing strategies. As all the tools that are necessary to implement the vision are currently available or in an advanced stage of development, the key prerequisites to achieving this paradigm shift are a commitment to change in the scientific community, which could be facilitated by a broad discussion of the vision, and obtaining necessary resources to enhance current knowledge of pathway perturbations and pathway assays in humans and to implement computational systems biology models. Implementation of these strategies would result in a new toxicity testing paradigm firmly based on human biology.

We examined the hypothesis that insulin resistance in skeletal muscle promotes the development of atherogenic dyslipidemia, associated with the metabolic syndrome, by altering the distribution pattern of postprandial energy storage. Following ingestion of two high carbohydrate mixed meals, net muscle glycogen synthesis was reduced by Ϸ60% in young, lean, insulin-resistant subjects compared with a similar cohort of age-weight-body mass indexactivity-matched, insulin-sensitive, control subjects. In contrast, hepatic de novo lipogenesis and hepatic triglyceride synthesis were both increased by >2-fold in the insulin-resistant subjects. These changes were associated with a 60% increase in plasma triglyceride concentrations and an Ϸ20% reduction in plasma high-density lipoprotein concentrations but no differences in plasma concentrations of TNF-␣, IL-6, adiponectin, resistin, retinol binding protein-4, or intraabdominal fat volume. These data demonstrate that insulin resistance in skeletal muscle, due to decreased muscle glycogen synthesis, can promote atherogenic dyslipidemia by changing the pattern of ingested carbohydrate away from skeletal muscle glycogen synthesis into hepatic de novo lipogenesis, resulting in an increase in plasma triglyceride concentrations and a reduction in plasma high-density lipoprotein concentrations. Furthermore, insulin resistance in these subjects was independent of changes in the plasma concentrations of TNF-␣, IL-6, highmolecular-weight adiponectin, resistin, retinol binding protein-4, or intraabdominal obesity, suggesting that these factors do not play a primary role in causing insulin resistance in the early stages of the metabolic syndrome.type 2 diabetes ͉ nonalcoholic fatty liver disease ͉ adipocytokines ͉ abdominal obesity ͉ atherogenic dyslipidemia T he metabolic syndrome is characterized by a clustering of risk factors for cardiovascular disease that include insulin resistance, abdominal obesity, atherogenic dyslipidemia, hypertension, hyperuricemia, a prothrombotic state, and a proinflammatory state (1, 2). The metabolic syndrome is estimated to afflict Ͼ50 million Americans, and approximately half of all Americans are predisposed to it (2). Individuals with the metabolic syndrome are at increased risk for the development of coronary heart disease and other diseases related to plaque buildup in artery walls, such as stroke and peripheral vascular disease, as well as type 2 diabetes mellitus (T2DM).Abdominal obesity and insulin resistance have each been hypothesized to be the primary factors underlying the metabolic syndrome; however, the biologic mechanisms linking these and other metabolic risk factors associated with the metabolic syndrome are not fully understood and appear to be complex.In this study we examined the hypothesis that insulin resistance in skeletal muscle may promote the development of atherogenic dyslipidemia by diverting ingested carbohydrate away from muscle glycogen storage and into hepatic de novo lipogenesis, resulting in hypertriglyceridemia. To exam...

Research on environmentally related chemical contaminants in breast milk spans several decades and dozens of countries. The ability to use this research as an environmental indicator is limited because of a lack of consistent protocols. Data on xenobiotics in breast milk are influenced by choices in sample selection, sample pooling, analysis, and reporting. In addition, most studies have focused only on a small panel of persistent organic pollutants, despite indications that a wide range of additional chemical contaminants may also enter breast milk. Despite these limitations, however, it is possible to draw some generalizations. In this paper we review available data on levels of organochlorine pesticides, polychlorinated biphenyls (PCBs), polychlorinated dibenzodioxins (PCDDs), polybrominated diphenyl ethers (PBDEs), metals, and solvents in breast milk. Examples drawn from around the world illustrate the available data and the patterns that have appeared in various areas over time. Over the past few decades, levels of the organochlorine pesticides, PCBs, and dioxins have declined in breast milk in countries where these chemicals have been banned or otherwise regulated. In contrast, the levels of PBDEs are rising. Regional differences in levels of xenobiotics in breast milk are related to historical and current local use patterns. Diet is a major factor that influences breast milk levels of persistent organic pollutants, with patterns in fish consumption playing a particularly significant role. Improved global breast milk monitoring programs would allow for more consistent data on trends over time, detection of new xenobiotics in breast milk, and identification of disproportionately exposed populations.