Genetic epidemiological analysis of hypouricaemia from 4993 Japanese on non-functional variants of URAT1/SLC22A12 gene.

OBJECTIVES: Up to 0.3% of Japanese have hypouricaemia. Most cases appear to result from a hereditary disease, renal hypouricaemia (RHUC), which causes exercise-induced acute kidney injury and urolithiasis. However, to what extent RHUC accounts for hypouricaemia is not known. We therefore investigated its frequency and evaluated its risks by genotyping a general Japanese population. METHODS: A cohort of 4993 Japanese was examined by genotyping the non-functional variants R90H (rs121907896) and W258X (rs121907892) of URAT1/SLC22A12, the two most common causative variants of RHUC in Japanese. RESULTS: Participants' fractional excretion of uric acid and risk allele frequencies markedly increased at lower serum uric acid (SUA) levels. Ten participants (0.200%) had an SUA level ≤2.0 mg/dl and nine had R90H or W258X and were likely to have RHUC. Logistic regression analysis revealed these URAT1 variants to be significantly and independently associated with the risk of hypouricaemia and mild hypouricaemia (SUA ≤3.0 mg/dl) as well as sex, age and BMI, but these URAT1 variants were the only risks in the hypouricaemia population (SUA ≤2.0 mg/dl). W258X was only a risk in males with SUA ≤3.0 mg/dl. CONCLUSION: Our study accurately reveals the prevalence of RHUC and provides genetic evidence for its definition (SUA ≤2.0 mg/dl). We also show that individuals with SUA ≤3.0 mg/dl, especially males, are prone to RHUC. Our findings will help to promote a better epidemiological understanding of RHUC as well as more accurate diagnosis, especially in males with mild hypouricaemia.

Risk of bladder cancer in male Japanese workers exposed to ortho-toluidine and other aromatic amines.

PURPOSE: Nine bladder cancer (BCa) cases were reported among aromatic amine-exposed male workers at a factory manufacturing organic dye/pigment intermediates in Japan. We aimed to evaluate the characteristics of aromatic amine-exposed workers by cross-sectional observation, and the risk of BCa by assessing the standardized incidence ratio (SIR). METHODS: In the cross-sectional study, our subjects were: 9 BCa patients, 36 aromatic amine-exposed non-patients, and 79 non-exposed workers from 3 factories. We evaluated the subjects' medical history, urinalysis, qualitative determination of nuclear matrix protein 22, and urinary cytology. For SIR assessment, 98 aromatic amine-exposed workers from 1 factory were included, and the Japanese general male population was used as a referent population. Since no direct aromatic amine-exposure data were available, we calculated surrogate exposure levels using information on job sites, exposure potency, and duration. RESULTS: Coexistent aromatic amines were ortho-toluidine (OT), aniline, para-toluidine, ortho-anisidine, 2,4-xylidine, and ortho-chloroaniline. The prevalence rates of cystitis and bladder lesion-related symptoms in both BCa patients and aromatic amine-exposed non-patient workers were significantly higher than those of non-exposed workers. Overall, the SIR for BCa in OT-exposed workers was 56.8 (95% CI 27.7-104.3) and apparent dose-response relationships were revealed between the SIR and the surrogate exposure level in the 0-10-year lagged analyses. Overall, SIRs in other aromatic amine-exposed workers were also significantly high but no or unclear dose-response relationships were observed. CONCLUSIONS: We conclude that OT may be responsible for the increased risk of BCa. Regular monitoring of bladder lesion-related symptoms is essential for the early identification of BCa.

Genome-wide association study revealed novel loci which aggravate asymptomatic hyperuricaemia into gout.

OBJECTIVE: The first ever genome-wide association study (GWAS) of clinically defined gout cases and asymptomatic hyperuricaemia (AHUA) controls was performed to identify novel gout loci that aggravate AHUA into gout. METHODS: We carried out a GWAS of 945 clinically defined gout cases and 1003 AHUA controls followed by 2 replication studies. In total, 2860 gout cases and 3149 AHUA controls (all Japanese men) were analysed. We also compared the ORs for each locus in the present GWAS (gout vs AHUA) with those in the previous GWAS (gout vs normouricaemia). RESULTS: This new approach enabled us to identify two novel gout loci (rs7927466 of CNTN5 and rs9952962 of MIR302F) and one suggestive locus (rs12980365 of ZNF724) at the genome-wide significance level (p<5.0×10-8). The present study also identified the loci of ABCG2, ALDH2 and SLC2A9. One of them, rs671 of ALDH2, was identified as a gout locus by GWAS for the first time. Comparing ORs for each locus in the present versus the previous GWAS revealed three 'gout vs AHUA GWAS'-specific loci (CNTN5, MIR302F and ZNF724) to be clearly associated with mechanisms of gout development which distinctly differ from the known gout risk loci that basically elevate serum uric acid level. CONCLUSIONS: This meta-analysis is the first to reveal the loci associated with crystal-induced inflammation, the last step in gout development that aggravates AHUA into gout. Our findings should help to elucidate the molecular mechanisms of gout development and assist the prevention of gout attacks in high-risk AHUA individuals.

[Study on the Establishment of a Specific Similar Exposure Group (SEG) in Personal Exposure Monitoring: A Case Report of Indium Tin Oxide Target Surface Grinding Process].

Surface grinding workers of Indium Tin Oxide target material are exposed to an indium compound with high toxicity. We divided individual exposure workers into similar exposure groups (SEG) and examined the effectiveness of the classification of SEG. Sampling was carried out twice a day for a total of 10 times, in 9 of which a work environment measurement in unit work area was performed at the same time. The classification examined two methods. One method was to set all the workers in the work place as one group (SEG1), and the other was to classify them depending on whether the workers handled the target material contained indium or not (SEG2). The group handled indium-contained material was SEG2(+) n=9, and the other was SEG2(-) n=9. Only the arithmetic mean value (AM) of four groups 2.8-27.4 µg/m3 in the SEG2(+) was lower than the measurement B value of the work environment measurement, but the AM of all the groups in SEG2(+) 2.8-276.8 µg/m3 was higher than the geometric mean value of measurement A 0.4-12.3 µg/m3. The concentration range of 100 µg/m3 or more of SEG2(+) AM was 20% of the total. This range was not recognized in the other items, and the variation of SEG2(+) was small. Even though the evaluation of SEG1 is control class 2, if revaluated on SEG2(+), 50% of the SEG2(+) were evaluated as control class 3. It is possible to efficiently manage chemical substances by establishing specific SEG properly stratified.

Effects of sulfur dioxide on the respiratory system of Miyakejima child residents 6 years after returning to the island.

OBJECTIVES: This study investigated the health effects of volcanic gas, mainly sulfur dioxide (SO2), exposure on the children of Miyakejima Island. METHODS: Health checkups were conducted in November from 2006 to 2011. Health effects were evaluated through a self-administered questionnaire on respiratory and irritative symptoms, and spirometry. SO2 was measured continuously from February 2005 onward at six fixed monitoring stations in inhabitable areas. Based on mean SO2 concentration during 3 months before each health checkup, inhabitable areas were classified into three categories: (1) lower (area L); (2) higher (area H-1); and (3) highest (area H-2). RESULTS: Average concentrations (ppb) of SO2 decreased year-by-year and ranged from 11.3 to 2.47 in area L, from 32.2 to 12.2 in area H-1, and from 75.1 to 12.1 in area H-2, respectively. In general, prevalence of respiratory and irritative symptoms was higher in area H-2, and the prevalence decreased year-by-year in all three areas by Cochran-Armitage test for trend. We defined a study population in area L in 2008 as a reference population because we had no unexposed population. Applying a logistic regression model, age-, sex-, and hypersusceptibility-adjusted prevalence odds ratios to the reference population showed clear exposure-dependent increases in some irritative symptoms such as "Irritation and/or pain in throat" and "in eyes," and approximately 30 ppb seemed to be the threshold concentration. Spirometry did not show any significant differences. CONCLUSIONS: Though no pulmonary functions were affected, some subjective symptoms were detected dose-dependently by SO2 exposure concentration in child residents during the 6 years after the eruption.

Higher serum dehydroepiandrosterone sulfate levels are protectively associated with depressive symptoms in men, but not in women: a community-based cohort study of older Japanese.

OBJECTIVE: Dehydroepiandrosterone sulfate (DHEAS) appears to have a protective effect against depression, but evidence from prospective cohort studies is sparse. Therefore, we examined the association between serum DHEAS levels and depressive symptoms in older community-dwelling Japanese. DESIGN: A community-based cohort study. SETTING: Kurabuchi Town, Gunma Prefecture, Japan. PARTICIPANTS: A total of 554 residents (248 men and 306 women) age 65 years or older without depressive symptoms at baseline. MEASUREMENTS: We performed a baseline examination of the subjects between 2005 and 2006 to determine serum DHEAS levels. The subjects were categorized into three groups based on age strata- and sex-specific tertiles of DHEAS. Depressive symptoms were assessed with the Geriatric Depression Scale 15-item version (GDS-15) in face-to-face home visit interviews carried out once in 2007 and once in 2008. The association of DHEAS with depressive symptoms (GDS-15 ≥ 6) was analyzed with the use of logistic regression models. RESULTS: The incidence of depressive symptoms was 12.1% in men and 19.6% in women. In men, the multiadjusted odds ratio of depressive symptoms was 0.24 (95% confidence interval: 0.06-0.94, Wald χ2 = 4.20, degrees of freedom = 1, p = 0.04) for the highest tertile compared with the lowest. The association observed for the highest versus the lowest remained significant even after adjustment for physical performance and cognitive function. In women, DHEAS was not associated with depressive symptoms. CONCLUSIONS: In this study, higher serum DHEAS levels were found to be protectively and independently associated with the risk of developing depressive symptoms in men, but not in women.

Relationship between objective cognitive functioning and work performance among Japanese workers.

OBJECTIVES: We aimed to explore the relationship between objective cognitive functioning and work performance among Japanese workers. METHODS: From February to November 2019, this cross-sectional study enrolled workers aged 18-65 years from 10 companies located in a metropolitan area of Japan. We emailed invitations to participate to employees of companies that had agreed to cooperate with the study. We measured work performance with the question, "How would you rate your performance (compared with your optimum performance) over the past 4 weeks?" Responses were made via a visual analog scale (range: 0-100). Cognitive functioning was assessed using the THINC-integrated tool (THINC-it®). THINC-it® is a brief, objective computerized cognitive assessment battery. Associations between work performance and cognitive functioning tests were examined using logistic regression analysis. RESULTS: In total, 353 individuals provided e-consent to participate, of whom 276 were included in the analysis (after omitting those with missing values). The median work performance was used to divide participants into high- (scoring ≥ 80%) and low- (scoring < 80%) performing groups. The P-values for trends indicated that association between cognitive domains, such as attention, executive functioning and working memory was significant (P < .05). Work performance was significantly associated with cognitive function for the two tests that assess attention, executive functioning, and working memory in general workers. CONCLUSIONS: Our results suggest that objective cognitive functioning may be related to work performance. Longitudinal investigations may allow for the establishment of causality.

Camptocormia in Japanese patients with Parkinson's disease: a multicenter study.

OBJECTIVE: The aim of this work was to investigate the prevalence of camptocormia and the clinical characteristics of patients with camptocormia in a large population of PD patients. BACKGROUND: Although camptocormia has been recognized as a prominent phenomenon in PD, the previous epidemiological reports were limited, especially in terms of sample size. METHODS: We evaluated 531 PD patients (disease duration: 7.0 ± 5.5 years, mean ± standard deviation). We examined their clinical features and the prevalence of camptocormia. RESULTS: Camptocormia was detected in 22 patients (4.1%) and found in patients who were older and had more severe motor symptoms and a higher levodopa (L-dopa) dose (P < 0.05), compared to the patients without camptocormia. Patients with camptocormia showed significantly higher frequencies of autonomic symptoms, such as constipation and urinary incontinence (P < 0.05). CONCLUSIONS: Camptocormia is uncommon in PD and is associated with disease severity, higher L-dopa dose and higher frequencies of autonomic symptoms.

A Proposal for Practical Diagnosis of Renal Hypouricemia: Evidenced from Genetic Studies of Nonfunctional Variants of URAT1/SLC22A12 among 30,685 Japanese Individuals.

BACKGROUND: Renal hypouricemia (RHUC) is characterized by a low serum uric acid (SUA) level and high fractional excretion of uric acid (FEUA). Further studies on FEUA in hypouricemic individuals are needed for a more accurate diagnosis of RHUC. METHODS: In 30,685 Japanese health-examination participants, we genotyped the two most common nonfunctional variants of URAT1 (NFV-URAT1), W258X (rs121907892) and R90H (rs121907896), in 1040 hypouricemic individuals (SUA ≤ 3.0 mg/dL) and 2240 individuals with FEUA data. The effects of NFV-URAT1 on FEUA and SUA were also investigated using linear and multiple regression analyses. RESULTS: Frequency of hypouricemic individuals (SUA ≤ 3.0 mg/dL) was 0.97% (male) and 6.94% (female) among 30,685 participants. High frequencies of those having at least one allele of NFV-URAT1 were observed in 1040 hypouricemic individuals. Furthermore, NFV-URAT1 significantly increased FEUA and decreased SUA, enabling FEUA and SUA levels to be estimated. Conversely, FEUA and SUA data of hypouricemic individuals are revealed to be useful to predict the number of NFV-URAT1. CONCLUSIONS: Our findings reveal that specific patterns of FEUA and SUA data assist with predicting the number of nonfunctional variants of causative genes for RHUC, and can also be useful for practical diagnosis of RHUC even before genetic tests.

[Nine-month observation of effects of SO2 on the respiratory system in child Miyakejima citizens].

BACKGROUND: Mt. Oyama on Miyakejima Island erupted in June 2000 and all Miyake village citizens were forced to evacuate the island in the September, due to continuous eruptions and emission of unsafe amounts of volcanic gas, mainly sulfur dioxide (SO2). Beginning in February 2005, residents returned to live on the island despite the fact that volcanic gas was still being emitted. OBJECTIVE: To examine changes in the respiratory systems of included children from February 2006 to November 2006. METHODS: The study population was 141 children who participated in health checkups in November 2006, including 33 SO2 hypersusceptible children who had a current or past history of asthma, obstructive lung function, current symptoms of whistling and wheezing, and/or deterioration of respiratory symptoms. Respiratory effects were evaluated by a questionnaire for respiratory symptoms and by spirometry. SO2 was monitored at 7 sampling points within inhabited areas, and the mean SO2 concentration from February 2005 to November 2006 was 0.031 ppm. The area was categorized into four areas by average SO2 concentration, namely, areas L, H-1, H-2, and H-3, where the average SO2 levels were 0.019, 0.026, 0.032, and 0.045 ppm, respectively. RESULTS: Compared to children in area L, the frequencies of "phlegm" and "irritation of the nose" were significantly greater in the children in areas H-2 and H-3. %FVC and %FEV1 in hypersusceptible children were significantly reduced in November 2006 as compared to February 2006 (P = 0.047, 0.027), though no reduction observed in normosusceptible children. CONCLUSION: Respiratory functions in hypersusceptible Miyakejima children may be affected by SO2 exposure, and further follow-up observation is necessary.

Lifestyle factors and visible skin aging in a population of Japanese elders.

BACKGROUND: The number of studies that use objective and quantitative methods to evaluate facial skin aging in elderly people is extremely limited, especially in Japan. Therefore, in this cross-sectional study we attempted to characterize the condition of facial skin (hyperpigmentation, pores, texture, and wrinkling) in Japanese adults aged 65 years or older by using objective and quantitative imaging methods. In addition, we aimed to identify lifestyle factors significantly associated with these visible signs of aging. METHODS: The study subjects were 802 community-dwelling Japanese men and women aged at least 65 years and living in the town of Kurabuchi (Takasaki City, Gunma Prefecture, Japan), a mountain community with a population of approximately 4800. The facial skin condition of subjects was assessed quantitatively using a standardized facial imaging system and subsequent computer image analysis. Lifestyle information was collected using a structured questionnaire. The association between skin condition and lifestyle factors was examined using multivariable regression analysis. RESULTS: Among women, the mean values for facial texture, hyperpigmentation, and pores were generally lower than those among age-matched men. There was no significant difference between sexes in the severity of facial wrinkling. Older age was associated with worse skin condition among women only. After adjusting for age, smoking status and topical sun protection were significantly associated with skin condition among both men and women. CONCLUSIONS: Our study revealed significant differences between sexes in the severity of hyperpigmentation, texture, and pores, but not wrinkling. Smoking status and topical sun protection were significantly associated with signs of visible skin aging in this study population.

Gender-specific associations of vision and hearing impairments with adverse health outcomes in older Japanese: a population-based cohort study.

BACKGROUND: Several epidemiological studies have shown that self-reported vision and hearing impairments are associated with adverse health outcomes (AHOs) in older populations; however, few studies have used objective sensory measurements or investigated the role of gender in this association. Therefore, we examined the association of vision and hearing impairments (as measured by objective methods) with AHOs (dependence in activities of daily living or death), and whether this association differed by gender. METHODS: From 2005 to 2006, a total of 801 residents (337 men and 464 women) aged 65 years or older of Kurabuchi Town, Gunma, Japan, participated in a baseline examination that included vision and hearing assessments; they were followed up through September 2008. Vision impairment was defined as a corrected visual acuity of worse than 0.5 (logMAR = 0.3) in the better eye, and hearing impairment was defined as a failure to hear a 30 dB hearing level signal at 1 kHz in the better ear. Information on outcomes was obtained from the town hall and through face-to-face home visit interviews. We calculated the risk ratios (RRs) of AHOs for vision and hearing impairments according to gender. RESULTS: During a mean follow-up period of 3 years, 34 men (10.1%) and 52 women (11.3%) had AHOs. In both genders, vision impairment was related to an elevated risk of AHOs (multi-adjusted RR for men and women together = 1.60, 95% CI = 1.05-2.44), with no statistically significant interaction between the genders. In contrast, a significant association between hearing impairment and AHOs (multi-adjusted RR = 3.10, 95% CI = 1.43-6.72) was found only in the men. CONCLUSION: In this older Japanese population, sensory impairments were clearly associated with AHOs, and the association appeared to vary according to gender. Gender-specific associations between sensory impairments and AHOs warrant further investigation.

Gender difference in the relationships between vision and hearing impairments and negative well-being.

OBJECTIVES: To evaluate the association of hearing impairment, vision impairment and their combination (dual sensory impairment) with negative well-being such as depression, subjective poor health and the reduced functional ability in community-dwelling older adults, and to determine whether any association varies by gender. METHODS: Between 2005 and 2006, we objectively examined vision and hearing impairment (using best-corrected visual acuity and pure-tone audiometric test) in 843 people aged 65 years and older (351 males, 492 females) in a rural Japanese town. Through a home visit interview survey using a structured questionnaire, we also collected information on depression (the five-item Geriatric Depression Scale), subjective poor health, and reduced functional activity (the Tokyo Metropolitan Institute of Gerontology's Index of Competence). RESULTS: We observed gender differences in the association between sensory impairment and depression. Multiple logistic regression analysis revealed that hearing impairment in males (adjusted odds ratio: 2.22, 95% confidence interval; 1.07-4.61) and vision impairment in females (1.91, 1.14-3.21) were related to depression. Vision impairment and dual sensory impairment were also associated with subjective poor health and reduced functional activity in both sexes. CONCLUSIONS: Sensory impairment is significantly associated with negative well-being in older persons, and its association with depression may differ between males and females.

Personal indium exposure concentration in respirable dusts and serum indium level.

The aim of this study was to assess the relationship between indium exposure concentration in the respirable dust fraction (In-E) and indium in serum (In-S) in workers. METHODS: A total of 39 workers were studied. The study subjects were categorized into 3 groups, namely, smelting workers (n=7), ITO workers (n=6) in an ITO grinding plant, and other workers (n=26). In-E and In-S ranged from 0.004-24.0 µg/m3 and 0.1-8.50 µg/L, respectively. The simple regression equation was log(In-S)=0.322×log(In-E)-0.443. The simple correlation coefficients for the smelting workers, ITO workers and other workers were 0.489, 0.812 and 0.163, respectively. The differences in the relationships among the three groups suggest that In-S may vary with the chemical form to which the workers were exposed. In-E and In-S seem to be positively correlated. The correlation coefficient was higher for both smelting and ITO workers than for other workers.

Changes of median nerve conduction velocity in rayon manufacturing workers: A 6-year cohort study.

OBJECTIVES: We conducted a 6-year cohort study to evaluate the relationship between carbon disulfide (CS2) exposure and reductions in the motor and sensory nerve conduction velocity (MCV and SCV) of the median nerve. METHODS: Study subjects at baseline included 432 exposed workers and 402 unexposed workers. Among the exposed workers, 145 workers terminated CS2 exposure during the follow-up period (ex-exposed workers). MCV and SCV were measured at baseline and followed up. CS2 personal exposure concentration was measured two times a year during a 6-year follow-up period and mean (range) CS2 exposure concentrations (ppm) were 5.96 (0.8-16.0) and 3.93 (0.6-9.9) in the exposed and ex-exposed workers, respectively. RESULTS: Reductions in MCV during the follow-up period did not differ among the exposed, ex-exposed, and unexposed workers. Reduction in SCV (m/s) of the exposed workers (-4.47±3.94) was significantly larger than that of the unexposed (-3.38±3.97) and ex-exposed workers (-3.26±3.79). For SCV reduction, a partial multiple regression coefficient of (ex-exposed workers) / (unexposed workers) was significantly positive (+0.915, p < 0.01) after adjustment for confounding variables. CONCLUSIONS: This cohort study showed that 6-year CS2 exposure around a mean level of 6 ppm did not affect MCV reduction but induced significant SCV reduction beyond the influence of aging. The effect of CS2 on SCV around a mean exposure level of 4 ppm may be reversible, since it disappeared in the ex-exposed workers after CS2 exposure cessation for a mean period of 4.1 years.

Influence of sulfur dioxide on the respiratory system of Miyakejima adult residents 6 years after returning to the island.

BACKGROUND: Mount Oyama, on the Japanese island of Miyakejima, began erupting in June 2000, necessitating the evacuation of 3,000 island residents. Volcanic gas emissions, primarily consisting of sulfur dioxide (SO2), gradually decreased and residents returned to the island after the evacuation order was lifted in February 2005. OBJECTIVES: To assess the exposure-effect and exposure-response relationships between SO2 exposure and effects on respiratory system in adult Miyakejima residents. METHOD: Health checkups focusing on pulmonary function and respiratory/irritative symptoms were conducted six times every November from 2006 to 2011. The study population comprised 168 subjects who underwent all health checkups. SO2 concentrations were measured at six fixed monitoring stations in inhabitable areas. RESULT: Based on the annual mean SO2 concentration, inhabitable areas were classified into three categories; namely, lower (L), higher (H-1), and highest (H-2) areas. Average SO2 concentrations (ppb) during 3 months prior to each health checkup dropped from 11.3 to 3.29, 32.2 to 13.4 and 75.1 to 12.6 from 2006 to 2010/2011 in L, H-1, and H-2. No significant declines in pulmonary function were observed in all areas. However, prevalence of subjective symptoms such as "Cough," "Irritation and/or pain in throat," "Irritation, runny nose, and/or nasal sniffles," and "Irritation and/or pain in the eyes," dependently increased on SO2 concentration. Odds ratios were statistically significant at approximately 70 ppb of SO2 or above. CONCLUSION: Adult residents of Miyakejima island showed no deterioration in pulmonary function at SO2 levels, but complained of respiratory/irritative symptoms in an SO2 concentration-dependent manner.

Pulmonary effects in workers exposed to indium metal: A cross-sectional study.

OBJECTIVES: Indium was added to the list of substances regulated by the Ordinance on Prevention of Hazards due to Specified Chemical Substances (OPHSCS) in 2013. Indium metal (IM), however, is not regulated by the OPHSCS due to insufficient information on pulmonary effects following exposure. METHODS: From 2011 to 2013, a cross-sectional study was conducted on 141 IM-exposed workers at 11 factories. Subjective symptoms were assessed, including levels of serum biomarkers, spirometry readings and total and diffuse lung capacity. Krebs von den Lungen-6 (KL-6) and surfactant protein D (SP-D) were selected as biomarkers of interstitial pneumonia. Indium serum concentration (In-S) and personal air sampling data were used to estimate exposure. Subjects were categorized into 5 groups based on occupation and type of exposure: smelting, soldering, dental technician, bonding and other. RESULTS: The highest level of In-S was 25.4 µg/l, and the mean In-S level was significantly higher in the smelting group than in other groups. In the smelting group, the prevalence of increased In-S levels was 9.1%, while that of abnormal KL-6 was 15.2%. A significant dose-effect relationship was observed between the In-S and KL-6 levels. No marked differences were observed between any of the groups in SP-D values, pulmonary symptoms, or pulmonary function test results. A total of 31% of the subjects worked in an environment with IM levels exceeding 0.3 µg/m(3), which requires a protective mask to be worn. CONCLUSIONS: For workers exposed to IM, work environments should be monitored, appropriate protective masks should be worn, and medical monitoring should be conducted according to the OPHSCS.

Screening for impaired cognitive domains in a large Parkinson's disease population and its application to the diagnostic procedure for Parkinson's disease dementia.

BACKGROUND: Dementia is a new focus of research on improved treatment for Parkinson's disease (PD). In 2007, a screening tool for PD dementia (PD-D) was developed by the Movement Disorder Society (Level I testing), which still requires verification by a large population study. METHODS: We conducted a cross-sectional and multicenter study including 13 institutions administering the Mini-Mental State Examination (MMSE) and Montreal Cognitive Assessment (MoCA) to 304 PD patients (mean age: 70.6 ± 8.3 years; mean Hoehn and Yahr stage: 2.7 ± 0.7). RESULTS: In all, 34.5% of the patients had MMSE scores <26; 94.3% of these patients had impairments in ≥2 cognitive domains and met the criteria for probable PD-D by Level I testing. Executive dysfunction combined with attention and memory impairment was most common (51.4%). In the Level I subtests of executive function, the score for phonemic fluency declined by <50% in patients with high MoCA scores (24-30 points) and lacked specificity for PD-D. No patient had visuospatial impairment (measured by the pentagon copying subtest) alone, and the score for pentagon copying stayed at ≥70% even in patients with low MMSE scores (12-25 points), therefore lacking sensitivity for PD-D. CONCLUSIONS: Level I testing with administration of the MMSE and MoCA is a practical and efficient screening tool for PD-D. However, the phonemic fluency and pentagon copying tests should be replaced by more specific/sensitive ones when screening for PD-D.

Spinal posture in the sagittal plane is associated with future dependence in activities of daily living: a community-based cohort study of older adults in Japan.

BACKGROUND: Accumulated evidence shows how important spinal posture is for aged populations in maintaining independence in everyday life. However, the cross-sectional designs of most previous studies prevent elucidation of the relationship between spinal posture and future dependence in activities of daily living (ADL). We tried to clarify the association by measuring spinal posture noninvasively in a community-based prospective cohort study of older adults, paying particular attention to thoracic curvature, lumbar curvature, sacral hip angle, and inclination to determine which parameter is most strongly associated with dependence in ADL. METHODS: Spinal posture was evaluated in 804 participants (338 men, 466 women, age range: 65-94 years) who were independent in ADL at baseline. We defined dependence in ADL as admission to a nursing home or need of home assistance. During the 4.5-year follow-up period, 126 (15.7%) participants became dependent in ADL. The relationship between the spinal posture parameters and outcome was assessed by dividing the participants into sex-specific quartiles of the parameters. RESULTS: Only inclination (angle subtended between the vertical and a line joining C7 to the sacrum) was associated with outcome, although lumbar curvature also showed a marginal association. The age- and sex-adjusted odds ratio for a 1 unit increase in the quartiles of inclination was 1.79 (confidence interval: 1.44, 2.23). After mutual adjustment for the 4 parameters, statistical significance for inclination still remained, with no substantial changes in the association estimates. CONCLUSIONS: This study indicates that spinal inclination is associated with future dependence in ADL among older adults.

Clinical features and varieties of non-motor fluctuations in Parkinson's disease: a Japanese multicenter study.

OBJECTIVE: This multicenter cross-sectional study aimed to investigate the clinical features and varieties of non-motor fluctuation in Parkinson's disease (PD). METHODS: To identify motor and non-motor fluctuation, we employed the wearing-off questionnaire of 19 symptoms (WOQ-19) in 464 PD patients. We compared the frequency of levodopa-related fluctuation as identified by the WOQ-19 with recognition by neurologists. We compared patients with both motor and non-motor fluctuations with those who only had motor fluctuations. Non-motor fluctuations were separated into psychiatric, autonomic, and sensory categories for further analysis. RESULTS: The patients' average age was 70.8 ± 8.4 years (mean ± SD) and disease duration was 6.6 ± 5.0 years. The frequency of motor fluctuations was 69% and for non-motor fluctuation 40%. Fifty-three percent of patients with motor fluctuations also had non-motor fluctuations, whereas 93% of patients with non-motor fluctuations also had motor fluctuations. The WOQ-19 showed a sensitivity of 82% but a specificity of only 40%. The patients with both non-motor and motor fluctuations exhibited more severe motor symptoms, more non-motor symptoms and higher levodopa daily doses (p < 0.05). Patients had significantly higher fluctuation rates if they had psychiatric (49%) and sensory (45%) symptoms than patients with autonomic symptoms (32%, p < 0.01). Forty-eight percent of patients with non-motor fluctuations exhibited more than one type of non-motor fluctuation. CONCLUSION: Forty percent of PD patients presented with non-motor fluctuations, and almost half of these exhibited more than one type. Appropriate recognition of levodopa-related fluctuations, both motor and non-motor, can lead to treatment modifications in PD patients.