Background: The environmental health community needs transparent, methodologically rigorous, and rapid approaches for updating human health risk assessments. These assessments often contain reference values for cancer and/or noncancer effects. Increasingly, the use of systematic review methods are preferred when developing these assessments. Systematic evidence maps are a type of analysis that has the potential to be very helpful in the update process, especially when combined with machine-learning software advances designed to expedite the process of conducting a review. Objectives: To evaluate the applicability of evidence mapping to determine whether new evidence is likely to result in a change to an existing health reference value, using inhalation exposure to the air pollutant acrolein as a case example. Methods: New literature published since the 2008 California Environmental Protection Agency’s Office of Environmental Health Hazard Assessment (OEHHA) Reference Exposure Level (REL) for acrolein was assessed. Systematic review methods were used to search the literature and screening included the use of machine-learning software. The Populations, Exposures, Comparators and Outcomes (PECO) criteria were kept broad to identify studies that characterized acute and chronic exposure and could be informative for hazard characterization. Studies that met the PECO criteria after full-text review were briefly summarized before their suitability for chronic point of departure (POD) derivation and calculation of a reference value was considered. Studies considered potentially suitable underwent a targeted evaluation to determine their suitability for use in dose–response analysis. Results: Over 15,000 studies were identified from scientific databases. Both machine-learning and manual screening processes were used to identify 60 studies considered PECO-relevant after full-text review. Most of these PECO-relevant studies were short-term exposure animal studies (acute or less than 1 month of exposure) and considered less suitable for deriving a chronic reference value when compared to the subchronic study in rats used in the 2008 OEHHA assessment. Thirteen epidemiological studies were identified but had limitations in the exposure assessment that made them less suitable for dose–response compared to the subchronic rat study. Among the 13 studies, there were four controlled trial studies that have the potential to be informative for future acute reference value derivation. Thus, the 2008 subchronic rat study used by OEHHA appears to still be the most appropriate study for chronic reference value derivation. In addition, advances in dosimetric modeling for gases, including new evidence pertinent to acrolein, could be considered when updating existing acrolein toxicity values. Conclusions: Evidence mapping is a very useful tool to assess the need for updating an assessment based on understanding...

Septin 3 is a novel member of the septin subfamily of GTPase domain proteins that was recently identified in human neuronal cells. These proteins are involved in vesicle trafficking, neurite outgrowth, and neurofibrillary tangle formation; however, the expression and functional role of septin 3 in normal neuronal tissues and as an etiological agent in neurological disorders is currently unclear. To further characterize these parameters, the present study analyzed the expression of three isoforms of septin 3 (A, B, and C) in fetal and adult human brains and polymorphism of the septin 3 exon 11 microsatellite in control, pure Alzheimer's disease (AD), Lewy body variant (LBV) of AD, and Parkinson's disease. Septin 3 mRNAs for isoforms A and B, but not C, were detected in the frontal cortex of fetus and adult human samples, as measured by reverse transcription-coupled polymerase chain reaction. Genotype analyses indicated that polymorphic septin 3 alleles were distributed in two peaks of frequency in both control and disease groups. Categorization of the alleles into short (S) and long (L) types revealed a significant difference between AD patients and controls ( p = 0.034 by chi-square test). Furthermore, the S-allele homozygosity was significantly underrepresented in AD compared with control (p = 0.015 by chisquare test). These results suggest that polymorphism in exon 11 of septin 3 may have a determinative role in the pathogenesis of AD.

We have established an animal model of coronary arteritis which is histopathologically similar to that observed in cases of Kawasaki disease (KD), is a well‐known childhood vasculitis syndrome. Coronary arteritis in this mouse model has been induced by intraperitoneal injection of Candida albicans‐derived substances (CADS). Arteritis varied by mouse strain with the highest incidence by 71.1% (27/38) found in C3H/HeN mice, but absent in CBA/JN mice (0%, 0/27), suggesting association of genomic background to develop the disease. The present study aims to elucidate the susceptibility loci associated with coronary arteritis by using this animal model. The association of the onset of arteritis with polymorphic microsatellite markers between the two strains was examined using one hundred and fifteen of N1 backcross progeny [(CBA×C3H)F1×C3H]. Based on our analysis, arteritis‐susceptibility loci with suggestive linkage were mapped on D1Mit171 and D1Mit245 (map position 20.2 cM) on chromosome 1 (P=0.0019). These loci include several kinds of inflammatory cytokine receptors, such as interleukin 1 receptor and tumor necrosis factor receptor. We also found the cytokine response against CADS, levels of inflammatory cytokines interleukin‐1β, tumor necrosis factor‐α, and interleukin‐6 in sera increased within 24 hr after CADS injection. Our results may indicate based on genomics that ligand‐receptor interaction between these inflammatory cytokines and the receptors of these cytokines may affect the onset of arteritis.

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