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Genetic alphabet expansion of DNA by introducing unnatural bases (UBs), as a fifth letter, dramatically augments the affinities of DNA aptamers that bind to target proteins. To determine whether UB-containing DNA (UB-DNA) aptamers obtained by affinity selection could spontaneously achieve high specificity, we have generated a series of UB-DNA aptamers (KD: 27−182 pM) targeting each of four dengue non-structural protein 1 (DEN-NS1) serotypes. The specificity of each aptamer is remarkably high, and the aptamers can recognize the subtle variants of DEN-NS1 with at least 96.9% amino acid sequence identity, beyond the capability of serotype identification (69−80% sequence identities). Our UB-DNA aptamers specifically identified two major variants of dengue serotype 1 with 10-amino acid differences in the DEN-NS1 protein (352 aa) in Singaporeans’ clinical samples. These results suggest that the high-affinity UB-DNA aptamers generated by affinity selection also acquire high target specificity. Intriguingly, one of the aptamers contained two different UBs as fifth and sixth letters, which are essential for the tight binding to the target. These two types of unnatural bases with distinct physicochemical properties profoundly expand the potential of DNA aptamers. Detection methods incorporating the UB-DNA aptamers will facilitate precise diagnoses of viral infections and other diseases.

Background:Intermediate Filaments (IFs) are major constituents of the cytoskeletal systems in animal cells.Objective:To gain insights into the structure-function relationship of invertebrate cytoplasmic IF proteins, we characterized an IF protein from the platyhelminth, Dugesia japonica, termed Dif-1.Method:cDNA cloning, in situ hybridization, immunohistochemical analysis, and IF assembly experiments in vitro using recombinant Dif-1, were performed for protein characterization.Results:The structure deduced from the cDNA sequence showed that Djf-1 comprises 568 amino acids and has a tripartite domain structure (N-terminal head, central rod, and C-terminal tail) that is characteristic of IF proteins. Similar to nuclear IF lamins, Djf-1 contains an extra 42 residues in the coil 1b subdomain of the rod domain that is absent from vertebrate cytoplasmic IF proteins and a nuclear lamin-homology segment of approximately 105 residues in the tail domain; however, it contains no nuclear localization signal. In situ hybridization analysis showed that Djf-1 mRNA is specifically expressed in cells located within the marginal region encircling the worm body. Immunohistochemical analysis showed that Djf-1 protein forms cytoplasmic IFs located close to the microvilli of the cells. In vitro IF assembly experiments using recombinant proteins showed that Djf-1 alone polymerizes into IFs. Deletion of the extra 42 residues in the coil 1b subdomain resulted in the failure of IF formation.Conclusions:Together with data from other histological studies, our results suggest that Djf- 1 is expressed specifically in anchor cells within the glandular adhesive organs of the worm and that Djf-1 IFs may play a role in protecting the cells from mechanical stress.

Serologic tests to detect specific IgGs to antigens related to viral infections are urgently needed for diagnostics and therapeutics. We present a diagnostic method for serotype-specific IgG identification of dengue infection by a competitive enzyme-linked immunosorbent assay (ELISA), using high-affinity unnatural-base-containing DNA (UB-DNA) aptamers that recognize the four categorized serotypes. Using UB-DNA aptamers specific to each serotype of dengue NS1 proteins (DEN-NS1), we developed our aptamer-antibody sandwich ELISA for dengue diagnostics. Furthermore, IgGs highly specific to DEN-NS1 inhibited the serotype-specific NS1 detection, inspiring us to develop the competitive ELISA format for dengue serotype-specific IgG detection. Blood samples from Singaporean patients with primary or secondary dengue infections confirmed the highly specific IgG detection of this format, and the IgG production initially reflected the serotype of the past infection, rather than the recent infection. Using this dengue competitive ELISA format, cross-reactivity tests of 21 plasma samples from Singaporean Zika virus-infected patients revealed two distinct patterns: 8 lacked cross-reactivity, and 13 were positive with unique dengue serotype specificities, indicating previous dengue infection. This antigen-detection ELISA and antibody-detection competitive ELISA combination using the UB-DNA aptamers identifies both past and current viral infections and will facilitate specific medical care and vaccine development for infectious diseases. Agency for Science, Technology and Research (A*STAR) National Research Foundation (NRF) Published version This work was supported by the Institute of Bioengineering and Bioengineering (Biomedical Research Council, Agency for Science, Technology and Research, Singapore) and the National Research Foundation of Singapore (NRF-CRP17-2017-07).

A novel technology, genetic alphabet expansion, has rapidly advanced through the successful creation of unnatural base pairs that function as a third base pair in replication. Recently, genetic alphabet expansion has been applied to some practical areas. Among them, the application to DNA aptamer generation is a good example of the broad utility of this technology. A hydrophobic unnatural base pair, Ds-Px, which exhibits high fidelity in replication as a third base pair, has been applied to an evolutionary engineering method called SELEX (Systematic Evolution of Ligands by EXponential enrichment) to generate DNA aptamers that bind to targets. A few Ds bases in DNA aptamers significantly increase the binding affinity to targets, enabling the use of DNA aptamers as an alternative to antibodies. This protocol describes the ExSELEX (genetic alphabet Expansion for SELEX) method to generate Ds-containing DNA aptamers. © 2017 by John Wiley & Sons, Inc.

Intermediate Filaments (IFs) are major constituents of the cytoskeletal systems in animal cells.To gain insights into the structure-function relationship of invertebrate cytoplasmic IF proteins, we characterized an IF protein from the platyhelminth, Dugesia japonica, termed Dif-1.cDNA cloning, in situ hybridization, immunohistochemical analysis, and IF assembly experiments in vitro using recombinant Dif-1, were performed for protein characterization.The structure deduced from the cDNA sequence showed that Djf-1 comprises 568 amino acids and has a tripartite domain structure (N-terminal head, central rod, and C-terminal tail) that is characteristic of IF proteins. Similar to nuclear IF lamins, Djf-1 contains an extra 42 residues in the coil 1b subdomain of the rod domain that is absent from vertebrate cytoplasmic IF proteins and a nuclear lamin-homology segment of approximately 105 residues in the tail domain; however, it contains no nuclear localization signal. In situ hybridization analysis showed that Djf-1 mRNA is specifically expressed in cells located within the marginal region encircling the worm body. Immunohistochemical analysis showed that Djf-1 protein forms cytoplasmic IFs located close to the microvilli of the cells. In vitro IF assembly experiments using recombinant proteins showed that Djf-1 alone polymerizes into IFs. Deletion of the extra 42 residues in the coil 1b subdomain resulted in the failure of IF formation.Together with data from other histological studies, our results suggest that Djf- 1 is expressed specifically in anchor cells within the glandular adhesive organs of the worm and that Djf-1 IFs may play a role in protecting the cells from mechanical stress.

The creation of unnatural base pairs (UBPs) has rapidly advanced the genetic alphabet expansion technology of DNA, requiring a new sequencing method for UB-containing DNAs with five or more letters. The hydrophobic UBP, Ds-Px, exhibits high fidelity in PCR and has been applied to DNA aptamer generation involving Ds as a fifth base. Here, we present a sequencing method for Ds-containing DNAs, in which Ds bases are replaced with natural bases by PCR using intermediate UB substrates (replacement PCR) for conventional deep sequencing. The composition rates of the natural bases converted from Ds significantly varied, depending on the sequence contexts around Ds and two different intermediate substrates. Therefore, we made an encyclopedia of the natural-base composition rates for all sequence contexts in each replacement PCR using different intermediate substrates. The Ds positions in DNAs can be determined by comparing the natural-base composition rates in both the actual and encyclopedia data, at each position of the DNAs obtained by deep sequencing after replacement PCR. We demonstrated the sequence determination of DNA aptamers in the enriched Ds-containing DNA libraries isolated by aptamer generation procedures targeting proteins. This study also provides valuable information about the fidelity of the Ds-Px pair in replication.

Background and Aim No previous study has performed multivariate analysis of the risk factors of fatty liver disease (FL), focusing on the effect of weight gain of ≥ 10 kg since the age of 20, and no analysis model exists that simultaneously evaluates body mass index (BMI) and body fat percentage (BFP) as adjustment variables. Methods To investigate these, we collected anthropometric data from health checkups, and conducted a cross-sectional study (targeting 1851 males and 1259 females aged 30 years or over). Results Regardless of sex, weight gain of ≥10 kg since the age of 20 was positively associated with FL. Our stratified analysis of BFP into two categories, to evaluate the interaction between BMI and BFP in FL, indicated an approximately fivefold increase in the odds ratio in the male group with high BMI and BFP values compared to those with low BMI and BFP values, with a synergy index of 1.77 > 1. On the other hand, females demonstrated no significant additive interaction, with a synergy index of 0.49

DNA aptamers produced with natural or modified natural nucleotides often lack the desired binding affinity and specificity to target proteins. Here we describe a method for selecting DNA aptamers containing the four natural nucleotides and an unnatural nucleotide with the hydrophobic base 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). We incorporated up to three Ds nucleotides in a random sequence library, which is expected to increase the chemical and structural diversity of the DNA molecules. Selection experiments against two human target proteins, vascular endothelial cell growth factor-165 (VEGF-165) and interferon-γ (IFN-γ), yielded DNA aptamers that bind with KD values of 0.65 pM and 0.038 nM, respectively, affinities that are >100-fold improved over those of aptamers containing only natural bases. These results show that incorporation of unnatural bases can yield aptamers with greatly augmented affinities, suggesting the potential of genetic alphabet expansion as a powerful tool for creating highly functional nucleic acids.

The novel evolutionary engineering method ExSELEX (genetic alphabet expansion for systematic evolution of ligands by exponential enrichment) provides high-affinity DNA aptamers that specifically bind to target molecules, by introducing an artificial hydrophobic base analogue as a fifth component into DNA aptamers. Here, we present a newer version of ExSELEX, using a library with completely randomized sequences consisting of five components: four natural bases and one unnatural hydrophobic base, 7-(2-thienyl)imidazo[4,5-b]pyridine (Ds). In contrast to the limited number of Ds-containing sequence combinations in our previous library, the increased complexity of the new randomized library could improve the success rates of high-affinity aptamer generation. To this end, we developed a sequencing method for each clone in the enriched library after several rounds of selection. Using the improved library, we generated a Ds-containing DNA aptamer targeting von Willebrand factor A1-domain (vWF) with significantly higher affinity (K

Early detection of cancer incidence and tobacco control are prioritized in the second-term of the Basic Plan for Promotion of Cancer Measures. However, the cancer screening rate is low and smoking prevalence high in Japan. Smokers may not participate in cancer screening, although they are a high-risk population for cancer mortality. This study examined whether smoking status, including number of cigarettes smoked per day and the Brinkman index (BI), was associated with participation in screening for lung, gastric, and colorectal cancers.In 2011, we conducted a cross-sectional study in Osaka city: 2,016 subjects aged 40 to 64 (men, N=966; women, N=1,050) were analyzed (response rate=52.4%). We used multivariable logistic regression with stratification by sex to calculate odds ratios (ORs) for participation in screening for lung, gastric, and colorectal cancers according to smoking status, such as number of cigarettes smoked per day and the BI.Compared with non-current smokers, current smokers were less likely to participate in all cancer screenings. Men who currently smoke had significantly lower odds for gastric and colorectal cancer screening participation than non-current smokers (gastric : OR=0.71, P=0.036 ; colorectal : OR=0.67, P=0.012). Furthermore, compared with non-current smokers, men who smoked more than 20 cigarettes per day had significantly lower odds for all cancer screenings (lung: OR=0.61, P=0.009; gastric: OR=0.61, P=0.009; colorectal: OR=0.59, P=0.004). Similar results were observed in smokers with a BI≧600 (lung: OR=0.55, P=0.006; gastric: OR=0.62, P=0.028; colorectal: OR=0.56, P=0.006). Among the women, significant associations between number of cigarettes smoked per day, BI, and colorectal cancer screening participation were observed (more than 20 cigarettes per day: OR=0.39, P=0.004; BI≧400: OR=0.51, P=0.020).Current smokers were less likely to undergo cancer screening compared with non-current smokers. These associations were stronger in men with greater numbers of cigarettes smoked per day and a higher BI score. Because smokers do not receive cancer screening, they may be at higher risk for cancer mortality. Counseling at the chance of cancer screening should be considered as a good opportunity to provide useful information on smoking cessation, as well as to promote cancer screening participation.

Maternal nutritional status during pregnancy is an important determinant of fetal growth. Although the effects of several nutrients and foods have been well examined, little is known about the relationship of overall maternal diet in pregnancy to fetal growth, particularly in non-Western populations. We prospectively examined the relationship of maternal dietary patterns in pregnancy to neonatal anthropometric measurements at birth and risk of small-for-gestational-age (SGA) birth among 803 Japanese women with live-born, singleton, term deliveries. Maternal diet in pregnancy was assessed using a validated, self-administered diet history questionnaire. Dietary patterns from thirty-three predefined food groups (g/4184 kJ) were extracted by cluster analysis. The following three dietary patterns were identified: the ‘meat and eggs’ (n 326), ‘wheat products’, with a relatively high intake of bread, confectioneries and soft drinks (n 303), and ‘rice, fish and vegetables’ (n 174) patterns. After adjustment for potential confounders, women in the ‘wheat products’ pattern had infants with the significantly lowest birth weight (P = 0·045) and head circumference (P = 0·036) among those in the three dietary patterns. Compared with women in the ‘rice, fish and vegetables’ pattern, women in the ‘wheat products’ pattern had higher odds of having a SGA infant for weight (multivariate OR 5·2, 95 % CI 1·1, 24·4), but this was not the case for birth length or head circumference. These results suggest that a diet high in bread, confectioneries, and soft drinks and low in fish and vegetables during pregnancy might be associated with a small birth weight and an increased risk of having a SGA infant.

Purpose The effects of formaldehyde (FA) exposure on allergic disorders are not clearly understood. This cross-sectional study examined the relationship between FA exposure and the prevalence of allergic disorders in Japan. Metohds Subjects were 998 pregnant women. Participants were considered to have asthma, atopic eczema, or allergic rhinitis (including cedar pollinosis) if they had received any medical treatment for any of these allergic disorders during the previous 12 months. Passive air sampling tubes were worn for 24 hours and analyzed for FA. Results When FA levels were categorized into four groups, there was a tendency for a positive exposure-response relationship between FA levels and the prevalence of atopic eczema, although the adjusted odds ratio for highest vs. lowest FA categories did not reach statistical significance. When FA levels were categorized into two groups to assess the effects of exposure to high levels of FA on allergic disorders, FA levels of 47 ppb or more were independently associated with an increased prevalence of atopic eczema (adjusted odds ratio = 2.25; 95% confidence interval, 1.01–5.01). The positive association was more pronounced in women with a negative familial allergic history than in those with a positive familial allergic history. No clear association was found between FA levels and the prevalence of asthma or allergic rhinitis. Conclusions FA exposure may be associated with an increased prevalence of atopic eczema in Japanese pregnant women.

Half a century ago, Alexander Rich proposed a genetic alphabet expansion system by the creation of an artificial extra base pair, known as an unnatural base pair. Now, as an ultimate modification technology, the development of unnatural base pairs and their applications has rapidly advanced. Introducing new components into nucleic acids could increase their functionality and moreover create new types of functional molecules. Three types of unnatural base pairs have been shown to function as a third base pair in replication and transcription. By using the unnatural base pairs, high-affinity DNA aptamers that specifically bind to target proteins and cells have been generated. Furthermore, bacteria bearing an unnatural base pair in their plasmids have been created. Here, we introduce a series of unnatural base pairs that function in replication and transcription, as well as their application to DNA aptamer generation targeting specific proteins.

Genetic alphabet expansion of DNA using unnatural base pair systems is expected to provide a wide variety of novel tools and methods. Recent rapid progress in this area has enabled the creation of several types of unnatural base pairs that function as a third base pair in polymerase reactions. Presently, a major topic is whether the genetic alphabet expansion system actually increases nucleic acid functionalities. We recently applied our unnatural base pair system to in vitro selection (SELEX), using a DNA library containing four natural bases and an unnatural base, and succeeded in the generation of high-affinity DNA aptamers that specifically bind to target proteins. Only a few hydrophobic unnatural bases greatly augmented the affinity of the aptamers. Here, we describe a new approach (genetic alphabet Expansion SELEX, ExSELEX), using our hydrophobic unnatural base pair system for high affinity DNA aptamer generation.

It remains uncertain whether intake of fish or n-3 polyunsaturated fatty acids is preventive against allergic disorders. This cross-sectional study investigated the association of intake of selected high-fat foods and specific types of fatty acids with the prevalence of allergic rhinitis in Japan where intake of fish is high.Study subjects were 1002 Japanese pregnant females. Allergic rhinitis (including cedar pollinosis) was defined as present if subjects had received drug treatment at some point during the previous 12 months. Information on dietary factors was collected using a validated self-administered diet history questionnaire. Adjustment was made for age, gestation, parity, cigarette smoking, passive smoking at home and at work, indoor domestic pets, family history of asthma, atopic eczema, and allergic rhinitis, family income, education, mite antigen level in house dust, changes in diet in the previous month, season when data were collected, and body mass index.There was a tendency for an inverse dose-response association between fish intake and allergic rhinitis although the adjusted odds ratio for comparison of the highest with the lowest quartile was not statistically significant (p for trend = 0.09). Intake of eicosapentaenoic and docosahexaenoic acids was independently associated with a decreased prevalence of allergic rhinitis: the multivariate odds ratio for the highest quartile was 0.56 (95% confidence interval: 0.32-0.96, p for trend = 0.03). Intake of n-6 polyunsaturated fatty acids in the third quartile but not the second and fourth quartiles showed a tendency for an inverse association with the prevalence of allergic rhinitis. No measurable relationship was found between consumption of meat, eggs, dairy products, total fat, saturated, monounsaturated, and n-3 polyunsaturated fatty acids, and cholesterol or the ratio of n-3 to n-6 polyunsaturated fatty acids and allergic rhinitis.Our findings suggest that the intake of eicosapentaenoic and docosahexaenoic acids may be associated with a reduced prevalence of allergic rhinitis.

In order to examine the actual condition of health problems of workers working at new special nursing homes for the aged, we conducted an interview survey with the managers and a questionnaire survey among the workers. Subjects of the interview survey were managers at the 7 nursing homes. Subjects of the questionnaire survey were 362 workers employed at the 7 nursing homes, 214 care workers (CWs) and 104 workers other than care workers (non-CWs); 299 questionnaires were returned. The response rate was 82.6%. We asked the managers "How many CWs are complaining of low back pain (LBP) and upper extremity pain at your nursing home?" One manager answered that 80% of CWs were complaining of LBP, but other managers answered that a few but no more than 5 CWs were complaining of LBP. On the other hand, the prevalence of LBP among CWs by the questionnaire survey was high. The point prevalence of LBP was 70.0%, the one month prevalence of LBP was 81.6%, and the period prevalence of LBP in present job was 88.6%. The managers had less interest in upper extremity pain than in LBP. But more than 60% of CWs had complained of upper extremity pain in the previous 1 month. Seventy-three percent of CWs had not received any education about work-related musculoskeletal disorders although about half of them had got some education or training to minimize the risk of injury in training school. Regarding female workers (77% of all CWs, 73% of all non-CWs), the percentages of current smokers and night shift workers were higher in CWs than in non-CWs with statistically significant differences. The percentages of workers working without work breaks and working overtime were higher in non-CWs than in CWs with statistically significant differences. For prevalence of LBP among female CWs and female non-CWs, the workers having LBP now, having had LBP in present job, and having first experienced LBP in present job were higher in CWs than in non-CWs with statistically significant differences. All nursing homes surveyed had provided no special health examination for LBP. For managers to grasp the actual condition of musculoskeletal disorders of workers working at the nursing homes for the aged, we recommend that care workers should have a special health examination for LBP.

We present a remodeling method for high-affinity unnatural-base DNA aptamers to augment their thermal stability and nuclease resistance, for use as drug candidates targeting specific proteins. Introducing a unique mini-hairpin DNA provides robust stability to unnatural-base DNA aptamers generated by SELEX using genetic alphabet expansion, without reducing their high affinity. By this method, >80% of the remodeled DNA aptamer targeting interferon-γ (KD of 33 pM) survived in human serum at 37 °C after 3 days under our experimental conditions and sustainably inhibited the biological activity of interferon-γ.

Genetic alphabet expansion of DNA using unnatural base pair systems is expected to provide a wide variety of novel tools and methods. Recent rapid progress in this area has enabled the creation of several types of unnatural base pairs that function as a third base pair in polymerase reactions. Presently, a major topic is whether the genetic alphabet expansion system actually increases nucleic acid functionalities. We recently applied our unnatural base pair system to in vitro selection (SELEX), using a DNA library containing four natural bases and an unnatural base, and succeeded in the generation of high-affinity DNA aptamers that specifically bind to target proteins. Only a few hydrophobic unnatural bases greatly augmented the affinity of the aptamers. Here, we describe a new approach (genetic alphabet Expansion SELEX, ExSELEX), using our hydrophobic unnatural base pair system for high affinity DNA aptamer generation.

Air pollution in the cabins of 101 Japanese cars due to organic compounds diffusing from the interior materials has been described in our previous report. In the present study, the influence of the manufacturer, specifications and usage status of these cars on the interior air pollution was evaluated by covariance analysis. Also, the levels of air pollution in the initial phases of delivery as a new car were estimated using previous data for the time-courses of interior concentrations of organic compounds measured in another new car. The findings showed greater air pollution in the cabins of luxury cars, with leather seats or leather steering wheels, or high-end catalogue prices. Differences in the specifications contributed more markedly to interior air pollution than differences in manufacturers. Also, usage status, such as everyday ventilation affected the long-term interior air quality. The sum values of interior concentrations of 154 compounds, for which there were time-course data, were estimated to be approximately 1700 μg·m-3 as a median (max. 11,000 μg·m-3) at 1 month from delivery (interior temperature, 32°C; interior humidity, 45%).

The types and concentrations of organic compounds in the interior air of 101 different types of Japanese domestically produced private-use cars were examined. All the vehicles had been registered in the summer season as new cars and were less than 3 years old. The airborne compounds in the cabins were collected for 24h under static condition with the engine stopped and the windows, doors and vents closed. A total of 275 organic compounds, including many aliphatic hydrocarbons and aromatic hydrocarbons, were identified, and 242 of them could be quantitated for each cabin. The sum of the concentrations of 241 compounds excluding formaldehyde was approximately 600 g·m-3 as a median, ranging from 136 to 3968 g·m-3 for the tested cars. The findings demonstrated that the air in the cabin of these cars was contaminated by high concentrations of a large variety of organic compound diffusing from the interior materials.

Purpose It may be worthwhile to assess the possible protective effect of the traditional Japanese diet on allergic disorders. This cross-sectional study investigated the relationship between dietary intake of seaweed, vegetables, fruit, antioxidants, fiber, and minerals and the prevalence of allergic rhinitis. Methods Study subjects were 1002 Japanese pregnant women. Allergic rhinitis (including cedar pollinosis) was defined as present if subjects had received drug treatment at some point during the previous 12 months. Information on dietary factors was collected by using a self-administered diet history questionnaire. Results Seaweed intake was associated independently with a decreased prevalence of allergic rhinitis. Significant inverse dose-response relationships were found between calcium and phosphorus intake and allergic rhinitis prevalence. There also was a tendency for an inverse association between magnesium consumption and allergic rhinitis. Additional adjustment for calcium or magnesium intake apparently did not influence the inverse association with seaweed consumption. Consumption of vegetables, fruit, vitamins C and E, fiber, and zinc showed no association with allergic rhinitis, whereas a significant positive relationship was observed between beta-carotene intake and allergic rhinitis. Conclusions High dietary intake of seaweed, calcium, magnesium, and phosphorus may be associated with a decreased prevalence of allergic rhinitis.

The cabin of an automobile can be considered to be a part of the living environment because many people spend long periods of time during business, shopping, recreation or travel activities. However, little is known about the interior air contamination due to organic compounds diffusing from the interior materials used in the interior of automobiles. In the present study, the compounds in the interior air of a new car were identified, and the time courses of their concentrations were examined for over 3 years after the delivery (July, 1999). A total of 162 organic compounds, involving many aliphatic hydrocarbons and aromatic hydrocarbons, were identified. High concentrations of n-nonane (458 μg/m3 on the day following delivery), n-decane (1301 μg/m3), n-undecane (1616 μg/m3), n-dodecane (716 μg/m3), n-tridecane (320 μg/m3), 1-hexadecene (768 μg/m3), ethylbenzene (361 μg/m3), xylene (4003 μg/m3) and 2,2′-azobis(isobutyronitrile) (429 μg/m3) were detected, and the sum of the concentrations determined for all compounds excluding formaldehyde (TVOC) was approximately 14 mg/m3 on the day after the delivery. The concentrations of most compounds decreased with time, but increased with a rise of the interior temperature. The TVOC concentration in the next summer (July, 2000) was approximately one-tenth of the initial concentration. During the 3-year study period, the TVOC concentrations in summer exceeded the indoor guideline value (300 μg/m3) proposed by Seifert (1995) [Seifert B. Volatile organic compounds. In: Maroni M, Seifert B, Lindvall T, editors. Indoor air quality. A comprehensive reference book. Air quality monographs, vol. 3. Netherlands: Elsevier Science; 1995. p. 819–21]. The interior temperature and days lapsed after delivery were the main factors affecting the interior concentrations of most compounds according to multiple linear regression analysis. The results of this study offer useful fundamental data for investigations on air pollution in automotive cabins due to the organic compounds diffusing from the interior materials. Keywords: Interior temperature, Interior humidity, Number of lapsed days, Multiple linear regression analysis, Indoor air pollution

Background It has been hypothesized that isoflavones reduce the risk of many chronic diseases, but there are no data on the effects of dietary soy and isoflavone consumption on allergic disorders. Objective This cross-sectional study examined the relationship between dietary soy products and isoflavone intake and the prevalence of allergic rhinitis. Methods Study subjects were 1002 Japanese pregnant women. Allergic rhinitis (including cedar pollinosis) was defined as present if subjects had received drug treatment at some point during the previous 12 months. Adjustment was made for age; gestation; parity; cigarette smoking; passive smoking at home and at work; indoor domestic pets; family history of asthma, atopic eczema, and allergic rhinitis; family income; education; mite allergen level in house dust; changes in diet in the previous month; season when data were collected; and body mass index. Results Compared with dietary intake of total soy product, soy protein, daidzein, and genistein in the first quartile, consumption of these substances in the fourth quartile was independently associated with a reduced prevalence of allergic rhinitis, although no significant dose-response relationships were observed. A clear inverse linear trend for miso intake across quartiles was found, whereas the adjusted odds ratio for comparison of the highest with the lowest quartile was not statistically significant. Consumption of tofu, tofu products, fermented soybeans, boiled soybeans, and miso soup was not related to the prevalence of allergic rhinitis. Conclusion A high intake of soy and isoflavones may be associated with a reduced prevalence of allergic rhinitis.

Inhalation toxicokinetics of p-dichlorobenzene ( p-DCB) in humans was evaluated, and the amounts of daily absorption and internal accumulation were estimated in order to obtain fundamental data for the risk assessment of chronic low-level exposure in the general population. Seven male subjects continuously inhaled about 2.5 ppm of p-DCB vapor for 1 h, and the concentration-time courses of p-DCB in their exhaled air and serum and of urinary 2,5-dichlorophenol (2,5-DCP), a major metabolite of p-DCB, were examined. The toxicokinetics of p-DCB was evaluated on the basis of the time courses using a linear two-compartment model. The amounts of p-DCB absorbed daily and the internal accumulation in chronic low-level exposure were extrapolated using the estimated toxicokinetic parameters. p-DCB was transferred from inhaled air to the body with a constant high absorption rate during exposure. The major route for elimination from the body was urinary excretion followed by metabolism, not exhalation. However, during 9-11 h after the start of exposure, the fraction of p-DCB excreted in urine was only 5-16% of the amount absorbed. Furthermore, most of the absorbed p-DCB seemed to be distributed rapidly to the tissues, such as fat, according to toxicokinetic analysis. Consequently, p-DCB seems to require a long time to be completely eliminated from the body. The amounts of daily absorption and internal accumulation were extrapolated to average 0.27 mg/day and 2.9 mg, respectively, in the subjects exposed chronically to 1 ppb of p-DCB. The amount absorbed daily agreed approximately with that extrapolated from rats which inhaled p-DCB in our previous study.

In order to evaluate occupational exposure conditions, it is necessary to determine the 8-hr time-weighted average (8-hr TWA) of exposure concentrations and compare the 8-hr TWA value with the permissible exposure limit, but 8-hr sampling is difficult for the outside laboratories because of trip time. For working environment measurement, because sampling duration in a unit work area may be one hour, the measurement can be conducted in several work areas in a day. If exposure conditions can be evaluated with the 1-hr TWA values, sampling to determine the exposure concentration would be efficient and able to be completed during the work area sampling. From this point of view, methods for evaluating exposure conditions with 1-hr or more TWA values are proposed in this paper.

The analytical method for identifying hinokitiol (HN) in antimicrobial/deodorant processed textiles was examined by high performance liquid chromatography (HPLC) with a photo diode array detector. The detection limit at 240nm wavelength was 3ng as S/N=5. First, the presence of HN in hiba oil was determined, and then the extraction method from hiba oil filled microcapusules was examined. Second, HN in the hiba oil filled microcapusules which adhered to the cloth was analyzed. As a result, HN was surely found in the cloth immediately after processing. To analyze the level of HN in antimicrobial/deodorant processed textiles, HN was extracted from samples with methanol under reflux at 70°C. To remove the polar materials, 20mM phosphate buffer (pH=2.4) was added to the extract, and HN was then reextracted into cyclohexane from the methanolic phase. After the extract was concentrated, it was applied to a C18 cartridge column, HN was then eluted with methanol. After concentration, the elute was applied to the HPLC. Although good recoveries of HN were developed in each operating step, the overall recoveries from textiles fortified at 10μg and 100μg were only 10∼14% and 40∼55%, respectively. Probably, the cause of such low recoveries was due to the photolysis and sublimation ability of HN. Therefore, quantitative analysis of HN was difficult using this method, but qualitative analysis was possible above the range of 10μg. Five brands of antimicrobial/deodorant processed textiles using HN were analyzed by this method, however HN was not detected in any of the samples. Consequently, it is doubtful that the antimicrobial effect of those products was dependent on the activity of HN.

In order to grasp the actual conditions of use of three kinds of organoiodine compounds, 3-iodo-2propynylbutylcarbamate (IPBC), 1-bromo-3-ethoxycarbonyloxy-1,2-diiodo-1-propene (BECDIP), and 4-chlorophenyl3-iodopropargylformal (CPIP), which are used as household antimicrobial/antifungal agents and wood preservatives, an analytical method using a gas chromatograph equipped with a flame ionization detector (FID-GC) and gas chromatography mass spectrometry (GC/MS) was employed. The calibration curve (peak area) by FID-GC showed good linearity in the range from 20 µg/ml to 100 µg/ml (correlation coefficient R = 0.99 or more). A purification method using a liquid‐liquid partition by n-hexane/water and the cartridge column (florisil or alumina) was established, and the addition recovery exceeded 90% by this method. By employing this method, the analysis was carried out for 18 commercially available samples. As a result, IPBC was detected from 2 samples of aerosol type fungicides, BECDIP from 4 samples of wood preservatives, and CPIP from one sample of an aerosol type antifungal/ insecticidal paint.

To reduce formaldehyde in indoor environments, non-formalin products for wallpaper adhesives have been increased in number. In this study, an analysis method using gas chromatography (GC) and gas chromatography mass spectrometry (GC/MS) specific to each of several antimicrobial agents (2-methyl-4-isothiazolin-3-one (MIT), 5-chloro-2-methyl-4-isothiazolin-3-one (Cl-MIT), 1,2-benzisothiazolin-3-one (BIT), 2-n-octyl-4-isothiazolin-3-one (OIT) and 2,4,5,6-tetrachloro-isophthalonitrile (TPN)) was developed aiming to clarify the actual states of utilization of these agents. These antimicrobials have been reported to induce health impairments such as contact dermatitis. Furthermore, seven non-formalin adhesives for wallpaper sold as building materials were analyzed according to the established method. The present results demonstrated that these adhesives contained a combination of antimicrobials (MIT, Cl-MIT, OIT and TPN), and one of them contained TPN at a high concentration (2,480 µg/g), which is highly contact-allergenic.

Respiratory uptake was investigated for 10 polar organic solvents with high blood/air partition coefficients (lambda(blood/air)): ethyl acetate (lambda(blood/air), 77), methyl iso-butyl ketone (90), methyl acetate (90), methyl propyl ketone (150), acetone (245), iso-pentyl alcohol (381), iso-propyl alcohol (848), methyl alcohol (2590), ethylene glycol monobutyl ether (EGBE, 7970), and propylene glycol monomethyl ether (PGME, 12380). Test-air concentrations (Cinh) were 25 to 200 ppm. Four healthy male volunteers inhaled the test air for 10 min at rest and then room air for 5 min. The percentage of solvent in the end-exhaled air and in the mixed-exhaled air increased after the start of the test-air respiration, and reached a quasi-steady-state level within a few min. The speeds of these increases at the start of the test-air respiration became lower as lambda(blood/air) increased. The mean uptakes (U) for the last five min of the test air respiration were 67.3, 52.9, 60.4, 53.0, 52.6, 63.0, 60.3, 60.8, 79.7, and 81.3%, respectively, for ethyl acetate, methyl iso-butyl ketone, methyl acetate, methyl propyl ketone, acetone, iso-pentyl alcohol, iso-propyl alcohol, methyl alcohol, EGBE and PGME. Thus, U values of the alcohols were higher than those of the ketones and lower than the glycol ethers. The overall view, except for esters, showed that U increased with lambda(water/air) increases. This tendency can be explained by a hypothesis that solvent absorbed in the mucus layer of the respiratory tract is removed by the bronchial blood circulation. U values of ethyl acetate and methyl acetate were higher than those of methyl iso-butyl ketone and methyl propyl ketone, though the lambda(blood/air) values of these esters were nearly equal to those of the ketones. For the respiration of the esters, their metabolites, ethyl alcohol and methyl alcohol, were detected in the exhaled air. The exhalation percentage of the metabolites increased after the start of test-air respiration and reached a quasi-steady-state level of 2 and 3%, respectively, by the 5th min. These data suggest that removal of the solvent via metabolism in the wall tissue of the respiratory tract plays an important role for the esters.

This study examined the degree of within-shift variability of short-term exposure concentrations for workers exposed to organic solvents in indoor workplaces. For this purpose, 117 exposure data sets of 15-minute time-weighted average (15-min TWA) and those of 60-min TWA were collected from 53 workers employed in the offset printing, gravure printing, screen printing, machine control board production, fiber-reinforced plastic production, hard metal production, electrical parts production, and chemical synthesizing industries. Data analysis showed that the tenth, fiftieth, and ninetieth percentiles of the geometric standard deviations of 15-min TWA values [GSD(15m)] were 1.4, 2.3, and 4.5, respectively; and those of GSD(60m) were 1.2, 1.7, and 3.4, respectively. Based on an assumption of lognormal exposure distribution, the maximum values of 15-min TWA (the 98.4th percentile) were estimated to be 4.3, 36, and 650 times as high as the minimum one (the 1.6th percentile) for the low, middle, and high exposure variabilities, respectively; and to be 2.0, 4.3, and 8.2 times the 8-hour TWA value, respectively. Consequently, when the 8-hour TWA exceeds 0.23 times (1/4.3) the short-term exposure limit value, the high short-term exposure condition should be evaluated. The maximum values of 60-min TWA (the 93.8th percentile) were estimated to be 1.8, 5.1 and 43 times as high as the minimum one, respectively; and to be 1.3, 2.0, and 3.1 times the 8-hour TWA value, respectively. The relationship between production factors and within-shift exposure variability was also examined. The intermittent solvent use group had significantly higher median values of GSD(15m) and GSD(60m) than the continuous group. The mobile pollutant source group had a significantly higher median value of GSD(60m) than the stationary group.

Dear Editor, Recently, Tabuchi et al. (Cancer Sci 2015; 106: 108–14)1 investigated “determinants of prostate-specific antigen (PSA)-based screening participation while simultaneously taking into account factors associated with fecal occult blood test (FOBT).” They found “three factors related to healthy-user bias: i.e., older age, a technical or junior college education, and adherence to doctors’ suggestions,” and concluded that “it may be necessary to increase participation in the former (FOBT) and decrease it in the latter (PSA testing).” However, their observations appeared to be associated with the characteristics of screenees, but do not seem to be a solid reason for reducing participation in PSA-based screening. It appears that no problem exists in the statement for FOBT, but seems at least premature for PSA testing. Prostate cancer (PCa) was very rare 30–40 years ago in Japan. The incidence has been rapidly growing,2 and PCa is now one of the major cancers. It is predicted to become the second most common cancer by 2020, following lung cancer, according to Globocan 2012.3 Not only primary prevention but also secondary prevention is crucial. However, because no definite preventive or risk factors for PCa are known,4 convincing primary prevention is unavailable at present. Thus, there is nothing else to adopt for early detection and treatments, including digital rectal examination, transrectal ultrasound examination, and PSA testing. Of these, PSA-based screening seems the most useful. Randomized controlled trials (RCTs) were conducted to evaluate a PCa mortality-lowering effect of PSA testing; the findings were controversial in two major RCTs carried out in European countries (European Randomized Study of Screening for Prostate Cancer [ERSPC]),5 and the USA (US Prostate, Lung, Colorectal, and Ovarian [PLCO] Cancer Screening Trial).6 Both RCTs should be criticized in view of their limitations, statistical power, observation period, or biases. The higher contamination (or self-selection) of participation in PSA testing in the control arm in the US PLCO Cancer Screening Trial, in particular, poses a serious problem.7 Formerly, the Japanese Urological Association recommended PSA testing8 in line with the results of the ERSPC study, which were confirmed by the inclusion of follow-up data up to 13 years.9 On the other hand, as also discussed by the authors, the US Preventive Services Task Force (USPSTF) declared an opposite statement,10 mostly based on the findings of the US PLCO Cancer Screening Trial. According to the guideline, which depended on a systematic literature review by a research group11 under the auspices of the Ministry of Health, Labour and Welfare, Japan, the Ministry decided not to include PSA testing as a population-based screening program for PCa.12 For the PSA test performance with a cut-off figure of 4.0 ng/mL, the sensitivity was reported to be approximately 20%, specificity ∼90%, and a positive predictive value of ∼30%.13 The values appear rather low, but are acceptably robust. Problems include the fact that it detects certain latent/low-risk PCa along with prostate hypertrophy and inflammation as well as PCa to be treated; that is, there are some over-diagnoses and over-treatments. However, the USPSTF acknowledged: “This recommendation does not include the use of the PSA test for surveillance after diagnosis or treatment of PCa,”10 suggesting that the test is useful. Accordingly, PSA testing appears to be a double-edged sword, so we must handle it properly. At least two proposals could be made regarding PSA-based screening. Provided that RCT is actually impractical, a case–control study should be conducted to assess the effectiveness of PSA screening in Japanese men having specific genetic backgrounds and lifestyle factors, while the prevalence of PCa and PSA testing remain low/lower. In order to reduce PCa mortality, prolong patients’ healthy life, and improve quality of life, while lessening undue medical expenditure, risk communication (informed decision-making) on the screening should be undertaken among physicians, patients, and responsible parties, including work-site, municipal, and governmental health sectors.

Using a physiologically based pharmacokinetic (PBPK) model, the effects of variation of exposure concentration of acetone on three biological indicators--acetone concentrations in blood, urine, and exhaled air--were investigated. The effect of the difference in work load was also examined. It was confirmed that the model could be used to estimate acetone concentrations during fluctuating exposure by comparing simulated acetone concentrations with the corresponding values observed in field surveys. By inputting the exposure situations into the PBPK model, the variabilities of the biological indicators were simulated. The variation of acetone exposure was expressed by seven 1-hour time-weighted averages (CEXPs). The arithmetic means of the CEXPS were 200 and 750 ppm. The geometric standard deviations (GSDs) were 1.5, 2.0, and 3.0, representing low, moderate, and high variations, respectively. Work loads were set at 15 and 50 W. Consequently, there were 12 exposure situations. The acetone concentrations in venous blood (CB) and exhaled alveolar air (CA) at 1 minute after the end of the work shift were selected as biological indicators of exposure because they were predicted to decrease rapidly at the end of exposure and become relatively stable after 1 minute. The acetone concentration in urine excreted during the last 2 hours of the work shift (CU) was also used as a biological indicator. Simulation was repeated 100 times with randomly permuting CEXPs for each situation. The mean values of CB, CU, and CA showed almost no variation regardless of the difference in the GSD of CEXPs. The coefficients of variation increased with the GSD of CEXPs but were less than 0.2. Consequently, these variables were acceptable as biological indicators of daily average exposure for the same work load. However, the difference in work load greatly changed the mean values of CB, CU, and CA, thus making it difficult to use these variables as indicators of daily average exposure for different work loads.

In order to evaluate the load on the low back of teachers in kindergartens, basic activity and working posture were analyzed for four teachers by means of video recording. The trunk inclination angle (TIA) was also measured continuously during full workshifts for 12 kindergarten teachers by means of an inclination monitor. The kindergarten teachers spent 67% of the workshift on activities in contact with children, "indoor group childcare", "indoor free playing", "outdoor childcare", "preparation and clearing away" and "help and care", and did not take a recess during the workshift. They spent 36% of the workshift in three working postures with the load on the low back, "standing bent forward", "squatting" and "kneeling". Cumulative time at a TIA of 20 degrees or more represented 43% of the workshift. The frequency of trunk-lifting from severe bending forward (TIA > 45 degrees) was 95 times/hr on average. A comparison of the kindergarten teachers and nursery teachers in 4-5 year age classes showed that the time distributions of basic activities were generally similar to each other. Although the time distributions of working postures were also similar, time spent "standing bent forward", "squatting" and "kneeling" was longer in the kindergarten teachers than in the nursery teachers. Cumulative time at a TIA of 45 degrees or more was significantly longer in the kindergarten teachers. Although the frequency of trunklifting was not significantly different, the kindergarten teachers tended to lift their trunk more frequently. The present study found that the load on the low back was considerably great in the kindergarten teachers.

In order to evaluate the safety of antimicrobial/deodorant agents, a research on totally 1113 kinds of commercially available products in 47 stores has been performed in cooperation with the public health institutes and the administrative departments of Osaka prefecture for 6 years since 1991. For the classification of these research products, a new classification on household products was made. Furthermore, the results of this research were gathered in"the data base (DB) on commercially available products research, "which is a component of"the DB system on antimicrobial/deodorant agents."The DB system includes the DB on active ingredients (AIs) and so on. As a result of this research, AIs were directly shown in the labellings of 226 out of 1113 products investigated (20.3%). And then, AIs could be estimated from the names of processing in the labellings of 210 out of 1113 products (18.9%). Namely, consumers may be informed of AIs in only 39.2% of processed products. In other words, the results of our research revealed that AIs of antimicrobial/deodorant agents in commercially available products were inadequately informed of package labellings. Therefore, consumers cannot obtain enough information on antimicrobial/deodorant agents in commercially available products. Moreover, the results of this research have been utilized in the beginning of other investigations such as analytical investigation and so on, and have been used for the maintenance of the safety management of household products.

High short-term exposure to toxic chemicals can occur during a workday, even if the daily average exposure is lower than the permissible exposure limit, because the exposure concentration varies from minute to minute. To protect workers from acute health effects due to high short-term exposure, the Japan Society for Occupational Health recommends that the maximum value for 15-min time-weighted average (15-min TWA) exposure during a workday should not exceed 1.5 times the occupational exposure limit for 8-hr TWA, and the American Conference of Governmental Industrial Hygienists issues the threshold limit value-short-term exposure limit (TLV-STEL), that is a 15-min TWA exposure which should not be exceeded at any time during a workday. A workday (8 hr) consists of thirty two 15-min periods. If the thirty-two 15-min TWAs are measured, the short-term exposure situation can be appropriately evaluated by comparing the highest measured value with the standard value (e.g. TLV-STEL), but such continuous monitoring consumes a lot of cost and time. In this paper, we propose a method for evaluating short-term exposure by using three or more measured values. This evaluation method corresponds to two different types of selection of sampling periods. One is a random selection of three or more 15-min periods among the 32 periods. If this selection is adopted, a comparison between the 98.44 percentile of the within-day distribution of 15-min TWAs and the standard value can be made by using one-sided tolerance factors, KI, KII and KIII, and the exposure situation is classified into four exposure classes at 95% and 50% confidence levels. Another is a random selection among high exposure periods. If this selection is adopted, a comparison between the specific percentile of the distribution and the standard value can be made with modified one-sided tolerance factors, and the exposure class is determined similarly. This method can provide a precise evaluation of exposure, so that it is useful in the industrial hygiene field.

Occupational exposure concentrations are generally assumed to vary in a log-normal manner. However, because the mean of random samples from a log-normal distribution is not lognormally distributed, it cannot, in theory, deal with the changes in the distribution of timeweighted average (TWA) values when the averaging time varies. On the other hand, inverse Gaussian distribution, which is similar to a log-normal one, offers the advantage of reproducibility. This paper proposes the application of inverse Gaussian distribution to occupational exposure data. First, inverse Gaussian distribution was compared with the log-normal one. Second, in order to simplify the application, the percentiles of inverse Gaussian distribution with CV = 0.25 to 4 were calculated. Finally, this distribution was applied to occupational exposure data.

Relations between Exposure to o- Dichlorobenzene and Concentrations of Urinary Metabolites: Shinji KUMAGAI, et al. Department of Occupational Health, Osaka Prefectural Institute of Public Health—The present study aimed to examine the relation between exposure to airborne o-dichlorobenzene (o-DCB) and concentrations of four urinary metabolites, i.e., 3,4-dichlorocatechol (3,4-DCC), 4,5-dichlorocatechol (4,5-DCC), 2,3-dichlorophenol (2,3-DCP) and 3,4- dichlorophenol (3,4-DCP). Subjects were ten male workers exposed to o-DCB in synthesizing intermediate products for dyes. Individual exposure to o-DCB was monitored with a passive dosimeter. Urine samples were collected during the workshift and at the end of the workshift. The concentrations of urinary 3,4-DCC, 4,5- DCC, 2,3-DCP and 3,4-DCP were determined with a high performance liquid chromatograph. The mean recovery rates for urinary metabolites obtained by our analytical method were 93.2 to 102% with coefficients of variance of 2.7 to 7.5%. The concentrations of 3,4-DCC, 4,5-DCC, 2,3-DCP and 3,4-DCP in urine collected at the end of the workshift and those during the last four hours of the workshift were shown to be well correlated to the 8-hr time weighted average (8-hr TWA) value for the exposure concentration of o-DCB. The mean ratios (as moles) of 3,4-DCC to 4,5-DCC, that of 2,3-DCP and that of 3,4- DCP at the end of the workshift were 0.78, 0.42 and 0.37, respectively. The time series of the concentrations of the four metabolites showed that these concentrations varied with time in a similar pattern. (J Occup Health 1997; 39: 124-129)

o-Dichlorobenzene (o-DCB) is used as an organic solvent, as a chemical intermediate, and as a heat transfer medium. In humans, o-DCB is metabolized to 2, 3- and 3, 4-dichlorophenols, and 3, 4- and 4, 5-dichlorocatechols, and these metabolites are eliminated via the kidneys. In this study, we tried to determine the concentrations of urinary 2, 3- and 3, 4-dichlorophenols using a gas chromatograph (GC). When control urine specimens were spiked at concentrations of 10, 20 and 40mg/l, the mean recovery rates of 2, 3- and 3, 4-dichlorophenols were 98.3 to 101.9% (CV=4.0 to 4.8%) and 100.6 to 105.4% (CV=2.5 to 7.0%), respectively. Next, urine samples collected from ten male workers exposed to o-DCB were analyzed. The concentrations of urinary 2, 3- and 3, 4-dichlorophenols determined by the GC method closely agreed with those by the HPLC method, which we had developed in a previous study, and these metabolite concentrations were linearly correlated to the 8-h TWA values of o-DCB in the range of 0.1 to 2.3ppm. Consequently, the GC method can be used for biological monitoring of o-DCB, though it is necessary that the linear relation is confirmed in a higher range of exposure.

Background Several studies have reported that individualized residential place-based discrimination (PBD) affects residents’ health. However, studies exploring the association between institutionalized PBD and health are scarce, especially in Asian countries including Japan. Methods A cross-sectional study was conducted with random two-stage sampling of 6191 adults aged 25–64 years in 100 census tracts across Osaka city in 2011. Of 3244 respondents (response rate 52.4%), 2963 were analyzed using multilevel logistic regression to examine the association of both individualized and institutionalized PBD with self-rated health (SRH) after adjustment for individual-level factors such as socioeconomic status (SES). An area-level PBD indicator was created by aggregating individual-level PBD responses in each tract, representing a proxy for institutionalized PBD, i.e., the concept that living in a stigmatized neighborhood affects neighborhood health. 100 tracts were divided into quartiles in order. The health impact of area-level PBD was compared with that of area-level SES indicators (quartile) such as deprivation. Results After adjustment for individual-level PBD, the highest and third area-level PBD quartiles showed odds ratio (OR) 1.57 (95% credible interval: 1.13-2.18) and 1.38 (0.99-1.92), respectively, for poor SRH compared with the lowest area-level PBD quartile. In a further SES-adjusted model, ORs of area-level PBD (highest and third quartile) were attenuated to 1.32 and 1.31, respectively, but remained marginally significant, although those of the highest area-level not-home-owner (census-based indicator) and deprivation index quartiles were attenuated to 1.26 and 1.21, respectively, and not significant. Individual-level PBD showed significant OR 1.89 (1.33-2.81) for poor SRH in an age, sex, PBD and SES-adjusted model. Conclusion Institutionalized PBD may be a more important environmental determinant of SRH than other area-level SES indicators such as deprivation. Although it may have a smaller health impact than individualized PBD, attention should be paid to invisible and unconscious aspects of institutionalized PBD to improve residents’ health.

No previous study has performed multivariate analysis of the risk factors of fatty liver disease (FL), focusing on the effect of weight gain of ≥ 10 kg since the age of 20, and no analysis model exists that simultaneously evaluates body mass index (BMI) and body fat percentage (BFP) as adjustment variables.To investigate these, we collected anthropometric data from health checkups, and conducted a cross-sectional study (targeting 1851 males and 1259 females aged 30 years or over).Regardless of sex, weight gain of ≥10 kg since the age of 20 was positively associated with FL. Our stratified analysis of BFP into two categories, to evaluate the interaction between BMI and BFP in FL, indicated an approximately fivefold increase in the odds ratio in the male group with high BMI and BFP values compared to those with low BMI and BFP values, with a synergy index of 1.77 1. On the other hand, females demonstrated no significant additive interaction, with a synergy index of 0.49 1.We revealed that weight gain ≥ 10 kg since the age of 20 is significantly associated with FL regardless of sex. In addition, by performing a synergy index (S), we showed that the additive interaction between BMI and BFP in FL differs according to gender.

Short-term exposure datasets of 10 workers exposed to organic solvents and daily average exposure datasets of seven workers exposed to cobalt and organic solvents were analyzed in order to clarify whether these exposure data fit an inverse Gaussian distribution. The goodness-of-fit test showed that time-weighted average (TWA) values with averaging times of 30 min, 60 min and 8 hours can be described by an inverse Gaussian distribution, but not those with averaging times of 7.5 min and 15 min.

To examine inter-relationships between short-term exposure levels of two chemicals A and B, consecutive 7.5-min time-weighted average values collected over full shifts were analysed for six workers. In the cases of two chemicals mixed in a fixed ratio the correlation coefficients (rABs) between the two exposure concentrations were more than 0.95. In the case of two chemicals mixed in various ratios, rABs was 0.59. In the cases of two chemicals used in separate processes, rABs ranged from −0.32 to 0.27. The data were analysed using a previously proposed model describing the inter-relationships by classifying the causes of exposure level variation into a common factor for the two chemicals and a specific factor for each chemical. The model fitted four cases with positive rABs, but not three cases with negative rABs. Thus, the model was modified by introducing a timing factor for the two chemicals for application to the negative correlation cases. The original model was also developed further to make it possible to describe the autocorrelation in an exposure-time series. In some cases, this developed model could divide total autocorrelation between that related to the common factor and that related to the specific factor, although it could not explain a cyclical autocorrelation function which was observed in workplaces.