Urolithin A suppresses NLRP3 inflammasome activation by inhibiting the generation of reactive oxygen species and prevents monosodium urate crystal-induced peritonitis.

The NOD-like receptor family pyrin domain-containing protein 3 (NLRP3) inflammasome triggers the maturation of interleukin-1ß (IL-1ß) and is implicated in the pathogenesis of various inflammatory diseases. Urolithin A, a gut microbial metabolite of ellagic acid, reportedly exerts antiinflammatory effects in vitro and in vivo. However, whether urolithin A suppresses NLRP3 inflammasome activation is unclear. In this study, urolithin A inhibited the cleavage of NLRP3 inflammasome agonist-induced caspase-1, maturation of IL-1ß, and activation of pyroptosis in lipopolysaccharide-primed mouse bone marrow-derived macrophages. Urolithin A reduced generation of intracellular and mitochondrial reactive oxygen species (ROS) and restricted the interaction between thioredoxin-interacting protein and NLRP3, which attenuated NLRP3 inflammasome activation. Urolithin A administration prevented monosodium urate-induced peritonitis in mice. Collectively, these findings indicate that urolithin A suppresses NLRP3 inflammasome activation, at least partially, by repressing the generation of intracellular and mitochondrial ROS.

Comparison of Three Diagnostic Definitions of Metabolic Syndrome and Estimation of Its Prevalence in Mongolia.

We sought to estimate the prevalence of metabolic syndrome (MS) in the urban population of Mongolia and suggest a preferred definition. This cross-sectional study comprised 2076 representative samples, which were randomly selected to provide blood samples. MS was defined by the National Cholesterol Education Program's Adults Treatment Panel III (NCEP ATP III), the International Diabetes Federation (IDF), and the Joint Interim Statement (JIS). The Cohen's kappa coefficient (κ) was analyzed to determine the agreement between the individual MS components using the three definitions. The prevalence of MS in the 2076 samples was 19.4% by NCEP ATP III, 23.6% by IDF, and 25.4% by JIS criteria. For men, moderate agreement was found between the NCEP ATP III and waist circumference (WC) (κ = 0.42), and between the JIS and fasting blood glucose (FBG) (κ = 0.44) and triglycerides (TG) (κ = 0.46). For women, moderate agreement was found between the NCEP ATP III and high-density lipoprotein cholesterol (HDL-C) (κ = 0.43), and between the JIS and HDL-C (κ = 0.43). MS is highly prevalent in the Mongolian urban population. The JIS definition is recommended as the provisional definition.

Vascular endothelial growth factor isoforms are expressed in the uterus during estrous cycle of golden hamsters (Mesocricetus auratus).

We investigated VEGF expression in the uterus during the estrous cycle in the golden hamster (Mesocricetus auratus). Reverse transcription polymerase chain reaction of genes expressed in the uterus revealed the presence of at least three different VEGF isoforms (hamster VEGF188, VEGF164, and VEGF120). They were highly homologous to the respective mouse and human isoforms. Furthermore, VEGF164 and VEGF120 were predominantly expressed in the hamster uterus during the estrous cycle. In situ hybridization revealed that VEGF is expressed only in the luminal and glandular epithelium of the endometrium but not in the stromal cells or myometrium. The positive reaction of luminal and glandular epithelial cells on day 4 of the estrous cycle (day 1 = day of ovulation) was a little stronger than that of other days of the cycle. These findings suggest that VEGF molecules are secreted by endometrial epithelial cells and play an important role in the maintenance of blood vessels in the endometrial stroma. These results also suggest that uterine changes, such as edema, observed from day 4 to day 1 of the estrous cycle, are expected to occur primarily through the action of VEGF secreted by the uterine endometrial epithelium in preparation for subsequent embryo implantation.

Maternal heated tobacco product use during pregnancy and allergy in offspring.

BACKGROUND: Little is known about the association between maternal use of heated tobacco products (HTPs) during pregnancy and the onset of allergy among offspring. This study aimed to determine whether maternal HTP smoking is associated with allergy in their offspring and to evaluate the potential dose-response association. METHODS: In this web-based, cross-sectional survey conducted in July and August 2021 in Japan, we investigated 5688 pairs of postpartum women and infants (<3 years). Clinical diagnoses of infant asthma, rhinitis, conjunctivitis, or atopic dermatitis were reported. Using multilevel Poisson regression, we estimated the prevalence ratios (PRs) and 95% confidence intervals (CIs) of allergy in infants with HTP smoking categories cross-classified by pregnancy periods, and adjusted for potential covariates including maternal cigarette smoking and partner's smoking status. Non-smokers served as the reference group. RESULTS: In total, 2.4% women smoked HTPs during pregnancy. Allergy occurred in 7.8% of the infants. The prevalence of allergy increased among the offspring of current HTP smokers during pregnancy at 15.2% (PR = 1.98, 95% CI 1.28-3.05); this association was the most pronounced during the first trimester but attenuated before pregnancy and postpartum. Dose-response associations were observed, for example a one-unit increase in daily maternal HTP use during pregnancy was associated with a 5% increase in allergy onset. Sub-group analyses excluding cigarette smokers during pregnancy and sensitivity analyses using the International Study of Asthma and Allergies in Childhood questionnaire showed a similar pattern. CONCLUSIONS: Maternal HTP smoking during pregnancy is associated with allergy in the offspring.

Occupational disparities in tumor grade and cytosolic HMGB1 expression in renal cell cancer.

OBJECTIVES: We sought to examine occupational disparities in tumor grade and cytosolic expression of high-mobility group box-1 (HMGB1) among renal cell cancer (RCC) patients. METHODS: This retrospective study included 318 RCC patients with complete information on occupation and pathology in Kanagawa Cancer Registry (KCR). Longest-held occupations were grouped into manual workers (e.g., manufacturing, construction) versus "others." Odds ratios (OR) and 95% confidence intervals (CI) for high-grade histology were estimated by logistic regression, adjusted for age and sex. We also examined a sub-sample of 74 low-grade RCC inpatients to estimate the OR for positive cytosolic HMGB1 expression in manual workers, adjusting for age, sex, and other available covariates. RESULTS: High-grade tumors were more prevalent in manual workers compared to other occupations: 23.0% (14/61) versus 10.9% (28/257, p = .01) with an adjusted OR of 2.28 (95% CI, 1.11-4.69). In the sub-sample of low-grade RCCs, positive cytosolic HMGB1 expression was more prevalent in manual workers compared to other occupations: 71.4% (10/14) versus 38.3% (23/60, p = .03) with a sex- and age-adjusted OR of 3.76 (95% CI, 1.03-13.7). CONCLUSIONS: Manual workers are associated with increased risks of high-grade renal cell tumors and cytosolic HMGB1 expression.

Occupational disparities in survival from common cancers in Japan: Analysis of Kanagawa cancer registry.

BACKGROUND: Little is known about occupational disparities in survival for common cancer sites in Japan. METHODS: Using data from a population-based cancer registry, we identified 32,870 cancer patients diagnosed during 1992-2011. We followed the patients for 5 years (median follow-up time 5.0 years). For each individual, we classified their longest-held occupation into 5 classes (upper non-manual, lower non-manual, manual, farmer, and others) following the Erikson-Goldthorpe-Portocarero scheme. Poisson regression models were used to estimate overall and site-specific mortality rate ratios (MRRs) and 95% confidence intervals (CI) for each occupational class, adjusted for sex, age, and diagnosis year. Upper non-manual workers served as the reference group. Additionally, using a binary categorization of occupations (manual workers versus non-manual workers), a causal mediation analysis with 4-way decomposition was performed to investigate the potential mediation of the association between occupation and overall mortality by cancer stage. RESULTS: Overall prognosis was good in this population (5-year overall survival was 81.7%). Compared with upper non-manual workers, both overall and cancer-specific mortality was higher in lower non-manual workers (MRR=1.14, 95% CI 1.05-1.24) and manual workers (MRR=1.40, 95% CI 1.29-1.53). After adjusting for the mediating influence of prognostic factors (stage and treatment), the observed occupational differences were attenuated but remained significant in manual workers: MRR = 1.23 (95% CI 1.08-1.39). Observed occupational disparities tended to be attributable to common cancers, i.e., stomach and lung among men and female breast cancer. Additionally, manual workers had 1.25 times higher odds for advanced stage. In the mediation analysis, the overall proportion explained by mediating effect of cancer stage was 29% (4% due to mediated interaction and 25% due to pure indirect effect). CONCLUSION: We documented occupational disparities in survival from commonly-occurring cancers in Japan. Occupational differences in cancer stage may explain one-third of the survival disparities.

Relationship Between Risk of Hyper-Low-density Lipoprotein Cholesterolemia and Evacuation After the Great East Japan Earthquake.

BACKGROUND: The Great East Japan Earthquake and the Fukushima Daiichi nuclear disaster forced the evacuation of residents and led to many changes in lifestyle for the evacuees. The Comprehensive Health Check was implemented to support the prevention of lifestyle-related disease and we analyzed the effect of prolonged evacuation (average of 3.0 years) on the new onset of hyper-LDL cholesterolemia. METHODS: The study participants were Japanese adults living near the Fukushima Daiichi nuclear power plant in Fukushima Prefecture. Annual health checkups focusing on metabolic syndromes were conducted for persons ≥40 years by the Specific Health Checkup. Based on data from annual checkups from 2011 or 2012, we followed 18,670 participants without hyper-LDL cholesterolemia who underwent at least one other annual checkup during 2013-2015. RESULTS: We found that the new onset of hyper-LDL cholesterolemia was 31% higher in evacuees than in non-evacuees. Evacuees had a significantly higher prevalence of obesity, hypertension, and diabetes, and higher frequency of weight change. Furthermore, logistic regression model analysis showed that the evacuation was significantly associated with the new onset of hyper-LDL cholesterolemia after adjusting age, gender, body mass index, smoking habit, alcohol consumption, diabetes, weight change, sleep deprivation, and exercise. CONCLUSION: The findings of the present study suggest that prolonged evacuation after a disaster is a risk factor for the new onset of hyper-LDL cholesterolemia, and lead to an increase in cardiovascular disease. It is therefore important to follow-up evacuees and recommend lifestyle changes where necessary.

Heated tobacco product use and hypertensive disorders of pregnancy and low birth weight: analysis of a cross-sectional, web-based survey in Japan.

OBJECTIVES: Knowledge on the impact of heated tobacco product (HTP) use in pregnant women with associated maternal and neonatal risks for hypertensive disorders of pregnancy (HDP) and low birth weight (LBW) is limited. We aimed to assess the status of HTP use among pregnant women in Japan and explore the association of HTP use with HDP and LBW. DESIGN: Cross-sectional study. SETTING: Data from the Japan 'COVID-19 and Society' Internet Survey study, a web-based nationwide survey. PARTICIPANTS: We investigated 558 postdelivery and 365 currently pregnant women in October 2020. PRIMARY AND SECONDARY OUTCOME MEASURES: Information on HDP and LBW was collected from the postdelivery women's Maternal and Child Health Handbooks (maternal and newborn records). We estimated the age-adjusted ORs and 95% CIs of ever HTP smokers for HDP and LBW and compared them with those of never HTP smokers in a logistic regression analysis. RESULTS: The prevalence of ever and current HTP use were 11.7% and 2.7% in postdelivery women and 12.6% and 1.1% in currently pregnant women, respectively. Among currently pregnant women who were former combustible cigarette smokers, 4.4% (4/91) were current HTP smokers. Among postdelivery women, ever HTP smokers had a higher HDP incidence (13.8% vs 6.5%, p=0.03; age-adjusted OR=2.48, 95% CI 1.11 to 5.53) and higher LBW incidence (18.5% vs 8.9%, p=0.02; age-adjusted OR=2.36, 95% CI 1.16 to 4.87). CONCLUSIONS: In Japan, the incidence of ever HTP use exceeded 10% among pregnant women, and HTP smoking may be associated with maternal and neonatal risks.

Occupational difference in use of heated tobacco products: a cross-sectional analysis of retail workers in Japan.

OBJECTIVE: Although heated tobacco products (HTPs) have become popular worldwide, research on occupational differences in smoking HTPs remains scarce. We aimed to examine the prevalence of smoking HTPs among a working population in Japan. SETTING, DESIGN AND PARTICIPANTS: In 2018, we conducted a cross-sectional study comprised of 7714 retail business workers in the service industry in Japan. PRIMARY AND SECONDARY OUTCOME MEASURES: For the definition of smoking HTPs, we identified current HTP smokers who only smoked HTPs, using five mutual categories of current smoking status (never, former, HTPs only, combustible cigarettes only and dual smokers who smoked both combustible cigarettes and HTPs). Occupational classes were classified into office workers (eg, upper non-manual workers) and other workers. ORs and 95% CIs of office workers were estimated for HTP usage, adjusted for age, sex, employment type and cigarette smoking-related health knowledge. RESULTS: The overall prevalence of smoking HTPs was 3.0% (male 5.0%, female 2.2%). The prevalence of HTP smokers differed across occupational classes (5.6% in office workers vs 2.5% in others; p<0.05). Compared with other workers, the adjusted odds of office workers for smoking HTPs remained elevated (OR: 1.97, 95% CI: 1.40 to 2.77). Sensitivity analyses with workers of all smoking status showed the same pattern. When stratified by sex, the occupational difference only remained significant in male workers. CONCLUSIONS: We found a positive occupational difference in smoking HTPs, particularly among male workers in the retail sector in Japan. National tobacco control should explicitly address this occupational gap and further encourage individuals to quit smoking.

Central sensitization in migraine is related to restless legs syndrome.

OBJECTIVE: We hypothesized that, in migraine patients, central sensitization (CS) could be associated with comorbid restless legs syndrome (RLS). METHODS: We conducted a case-control study including 186 migraine patients and 186 age- and sex-matched healthy controls. Symptoms related to CS syndrome were assessed by the Central Sensitization Inventory (CSI). Individuals with CSI Part A (CSI-A) scores ≥ 40 were defined as having CS. For patients with migraine, the Brief Pain Inventory (BPI) and Patient Health Questionnaire (PHQ)-9 were administered. In the patient group, RLS and migraine were diagnosed through face-to-face interviews. RESULTS: Among migraine patients, 26 (14.0%) suffered from chronic migraine. The mean disease duration was 23.7 ± 11.8 years. Migraine patients showed a higher rate of CS (21.0% vs. 8.6%) than healthy controls, with an adjusted odds ratio (AOR) of 3.039 (95% confidence interval (CI) 1.560-5.992; p = 0.001). Migraine patients in the CS group had higher rates of smoking, chronic migraine and RLS and higher BPI and PHQ-9 scores than migraine patients in the non-CS group. The use of acute and preventive treatment for migraine did not significantly differ between the CS and non-CS groups. Multivariable analysis identified the presence of RLS (AOR, 28.471; 95% CI 6.438-125.918; p < 0.001) and the BPI pain interference score (AOR, 1.398; 95% CI 1.061-1.843; p = 0.017) as the significant determinants of CS among migraine patients. CONCLUSION: Migraine patients were 3 times more likely to have CS than healthy controls. Our study results showed an association between RLS and CS in migraine patients.

Clinical characteristics, treatment methods and prognoses of patients with oral squamous cell carcinoma in Japanese population: a single institution retrospective cohort study.

BACKGROUND: The status of oral cancer therapy in elderly patients in Japan, where ageing is rapidly progressing, may serve as a model for other countries with similar demographics. There is controversy over what kind of treatment should be applied and how aggressively it should be applied to very elderly patients who have exceeded the average life expectancy. Given that 85 years is approximately the overall Japanese life expectancy at birth, we considered a threshold of 85 years and hypothesized that the prognosis of oral squamous cell carcinoma (SCC) patients aged ≥85 years was not inferior to that of those < 85 years. The aim of the present study was to investigate the clinical characteristics, treatment methods, and prognoses of Japanese oral SCC patients aged ≥85 years. METHODS: A retrospective cohort study was performed. The data of patients with primary oral SCC (n = 358) from 2005 to 2018 in our institute were extracted from electronic medical records. A total of 358 patients with oral SCC were divided into two groups (≥85 years group [n = 26] and < 85 years group [n = 332]) based on the age threshold of 85 years at the first visit. Kaplan-Meier survival analyses and Cox proportional hazard models were used to analyse overall survival (OS) and hazard ratios (HRs) according to age group, treatment, and TNM classification. RESULTS: There was no difference in the 5-year OS rate between the ≥85 years and < 85 years groups (80.8% vs. 82.2%, P = 0.359). This finding was the same in the operative (94.7% vs. 85.8%, P = 0.556) and non-operative (42.9% vs. 33.2%, P = 0.762) groups, indicating that age did not affect prognosis. Mortality was lower in the operative group than in the non-operative group (adjusted HR: 0.276, 95% CI: 0.156-0.489, P < 0.001), suggesting that surgery is a superior method. However, non-surgical treatment was selected at a higher rate in the ≥85 years group (26.9% vs. 11.1%, P = 0.028). CONCLUSIONS: This study suggests the prognosis of ≥85-year-old patients was not inferior to that of < 85-year-old patients. We recommend that surgery as the first choice treatment for ≥85-year-old patients with oral SCC who can tolerate surgery should be performed.

Recent Increasing Incidence of Early-Stage Cervical Cancers of the Squamous Cell Carcinoma Subtype among Young Women.

Few studies have reported on the increase in cervical cancer incidence in Japan. We aimed to determine the relevant trends in the metropolitan regions of Japan and to identify the population with the highest risk, based on histological subtype, cancer stage, and diagnostic processes. Using population-based data (2009-2013), we identified 2110 women, aged ≥20 years, with cervical cancer. We estimated the age-standardized and age-specific incidence rates of cervical cancer for the study period based on the 1985 national model population. The average annual percent change (AAPC) and 95% confidence interval (CI) were calculated using the joinpoint regression analysis. We stratified the analyses based on histological subtypes, stage, and diagnostic process via cancer screening. The increase in the overall age-standardized incidence was not significant. However, the increase was significant for women aged 30-39 years (AAPC 20.0%/year, 95% CI: 9.9-31.1), which was attributable to the increase in the incidence of the squamous cell carcinoma (SCC) subtype (AAPC 23.1%/year, 95% CI: 10.7-36.8). Among younger women, aged <50 years, further stratification showed an increase in the undiagnosed early-stage SCC subtype via cancer screening. In Japan, the incidence of HPV-related cervical cancer has been increasing in undiagnosed younger women.

Association between Passive Smoking from the Mother and Pediatric Crohn's Disease: A Japanese Multicenter Study.

Smoking is a risk factor for adult-onset Crohn's disease (CD). Although passive smoking from family members is a major concern, especially in pediatric CD, the number of existing epidemiological studies is limited. This multicenter case-control study aimed to assess the effects of familial smoking on pediatric CD. We examined 22 pediatric CD cases and 135 controls. The subjects' mothers were given a self-administered questionnaire about family smoking before disease onset in the CD group or the corresponding period in the control group. Univariable logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs), whereas dose-response relationship analyses were performed for more in-depth evaluations. Univariable analyses indicated that passive smoking from the mother (OR, 2.09; 95% CI, 0.61-7.10) was not a significant, but a candidate risk factor for developing pediatric CD. In contrast, the dose-response relationship analyses revealed that passive smoking from the mother (OR, 1.17; 95% CI, 1.04-1.31) was significantly associated with pediatric CD. Therefore, passive smoking from the mother may be predominantly associated with the development of pediatric CD. Further follow-up studies comprising environmental measurements of passive smoking exposure doses and genetic factors interaction analysis are necessary.

Urinary 8-Hydroxy-2'-Deoxyguanosine Levels and Cardiovascular Disease Incidence in Japan.

AIM: The association between urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), an oxidative stress marker, and the incidence of cardiovascular disease (CVD) has not been confirmed because no previous studies evaluated 24-hour 8-OHdG excretion levels in the general population. We aimed to confirm the association between 24-hour urinary 8-OHdG levels and CVD risk among Japanese men and women. METHODS: A nested case-control study was performed based on a 24-hour urine collection in a community-based cohort study performed from 1996 to 2005. Seventy-six cases (55 men and 21 women) who experienced their first CVD incidence during the follow-up period (median: 5.9 years) were recruited. The controls were frequency-matched 1:2, with each case for sex, age, area of residence, and baseline year. The 8-OHdG level was measured by enzyme-linked immunosorbent assay. Odds ratios (ORs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression models adjusted for body mass index, ethanol intake, smoking status, and estimated glomerular filtration rate. RESULTS: The geometric mean and geometric standard deviation (SD) of 8-OHdG levels (nmol/day) for cases and controls were 35.5 (1.55) and 35.5 (1.54) for men and 32.1 (1.35) and 25.0 (1.39) for women, respectively. The multivariable OR (95% CI) of CVD incidence according to the 1-SD increment of the log-transformed 8-OHdG level was 2.08 (0.99-4.37) for women. The multivariable ORs (95% CIs) for the 1st (lowest) and 4th versus 2nd quartile according to 8-OHdG for men were 3.29 (1.02-10.61) and 2.77 (0.96-7.96), respectively. CONCLUSION: A high 8-OHdG level tended to be associated with CVD incidence among women.

Incidence of Metabolic Syndrome in Young Japanese Adults in a 6-Year Cohort Study: The Uguisudani Preventive Health Large-Scale Cohort Study (UPHLS).

INTRODUCTION: To clarify the incidences of metabolic syndrome (MS) and risks in young Japanese adults by gender. METHODS: A total of 58,901 adults who had undergone annual health check-ups in 2010 without a diagnosis of MS or missing data were divided into three age groups (20s through 40s) by gender. Participants were followed up for 6 years for new-onset MS according to Japanese criteria. The incidences of MS and risks were analyzed using the Cox proportional hazards model to adjust for confounding factors. RESULTS: The incidences of MS per 1,000 person-years were 2.2, 5.5, and 10.2 for women aged in their 20s, 30s, and 40s, respectively, and 26.3, 40.5, and 57.4 in the respective men groups. Compared with the group aged in their 40s, the hazard ratios of new MS were 0.19 (95% confidence interval [CI], 0.13-0.29) for women in their 20s and 0.50 (95% CI, 0.41-0.61) for women in their 30s, and 0.46 (95% CI, 0.42-0.50) and 0.70 (95% CI, 0.66-0.73) for men in their 20s and 30s, respectively, after adjustment for lifestyle factors. For women, MS was associated with smoking in their 20s and 30s, and eating speed in their 30s, and for men, was associated with physical activity, eating speed, alcohol intake in their 20s and 30s, and smoking in their 30s. CONCLUSION: Our findings suggest that the incidences of MS in the 20s and 30s are lower, but account for about 20-50% of women with MS and 50-70% of men with MS in their 40s. However, the data are not negligible and early lifestyle intervention for MS is necessary in young adults.

Recurrent sick leave and resignation rates among female cancer survivors after return to work: the Japan sickness absence and return to work (J-SAR) study.

BACKGROUND: To date, there have not been any workforce-based Japanese cohort studies investigating work sustainability after return to work (RTW). The objective of this study was to investigate the post-RTW cumulative recurrent sick leave rate and cumulative resignation rate among female cancer survivors. METHODS: Among Japanese employees who were registered in the Japan sickness absence and return to work (J-SAR) study, the subjects were those female employees who returned to work after sick leave due to newly clinically diagnosed cancer (C01-C99; ICD-10), based on a physician's certificate, between 2000 and 2011. The last day of the follow-up period was December 31, 2012. The recurrent sickness leave rate and resignation rate were calculated using competing risk survival analysis. RESULTS: Of 223 cancer survivors, 61 took further physician-certified sick leave after their RTW. The median duration of the post-RTW work period among all cancer survivors was 10.6 years. The work continuance rates of the female cancer survivors were 83.2 and 60.4% at 1 and 5 years after they returned to work, respectively. There was a steep reduction in the work continuance rate during the first post-RTW year. There were considerable differences in the work continuance rate according to the primary cancer site. Cumulative recurrent sick leave rates of 11.8 and 28.9% were seen at 1 and 5 years after the subjects returned to work. The cumulative resignation rate was 5.0 and 10.7% at 1 and 5 years after the subjects returned to work. Most recurrent sick leave occurred in the first year after the subjects returned to work, followed by the second year. CONCLUSIONS: Sixty percent of female cancer survivors were still working at 5 years after returning to work, although the work continuance rates for different types of cancer varied significantly.

Diagnostic value of a nested polymerase chain reaction for diagnosing cutaneous sporotrichosis from paraffin-embedded skin tissue.

BACKGROUND: The gold standard for diagnosis of cutaneous sporotrichosis involves the isolation of the fungus, Sporothrix, by a culture test. Generally, the sampling for the culture test is performed at the same time as skin biopsy under local anaesthesia. However, the culture test may occasionally return a false negative result. OBJECTIVE: The aim of our study was to investigate the diagnostic value of a molecular method for diagnosing cutaneous sporotrichosis from formalin-fixed and paraffin-embedded (FFPE) tissues. METHODS: Over a 30-year period, we collected 52 cases of cutaneous sporotrichosis from biopsied specimens that had been positively diagnosed by a culture test. A nested PCR specific for Sporothrix detection was applied using FFPE tissue as template. The results were compared with control samples from 79 patients diagnosed with other cutaneous diseases according to histopathological, clinical findings and a cutler test. RESULTS: Of the 52 patients who were tested positive on the culture test, all cutaneous diseases were detected by PCR. Of the 59 patients in the control group, 58 tested negative by PCR. Under our conditions, the calculated sensitivity of this method was 100%, the specificity was 98.7% and the kappa coefficient was 0.984 (95% CI: 0.953-1.000). CONCLUSIONS: The specific PCR assay used appears to be a useful tool for the prompt and accurate diagnosis of sporotrichosis. Using this method, it would be possible to diagnose cutaneous sporotrichosis for patients who were suspected of cutaneous sporotrichosis but tested negative on culturing, and for pathologically suspected cutaneous sporotrichosis patients for whom the culture test was not undertaken.

Association between hypertension and hearing impairment in health check-ups among Japanese workers: a cross-sectional study.

OBJECTIVES: Prevention of hearing impairment (HI) is important because recovery of hearing is typically difficult. Epidemiological studies have examined the risk factors for HI. However, the association between hypertension and HI remains unclear. We aimed to clarify the association between hypertension and HI. DESIGN: Cross-sectional study. SETTING: Japanese workers in an information and communication technologies company. PARTICIPANTS: Of 24 823 employees of the same company, we recruited 13 475 participants who underwent hearing testing by audiometry in annual health check-ups and did not have missing data regarding body measurement, blood test results and drinking/smoking status (mean age: 49.4 years; males: 86.4%). PRIMARY OUTCOMES: Hearing tests were performed at two frequencies (1 kHz, 4 kHz). We defined the inability of participants to respond to 30 dB at 1 kHz and/or 40 dB at 4 kHz as overall moderate HI. We also defined moderate HI at 1 or 4 kHz as an abnormal finding at 1 or 4 kHz. We defined hypertension as ≥140 mm Hg systolic blood pressure and/or ≥90 mm Hg diastolic blood pressure and/or taking medication for hypertension. We examined the association between hypertension and HI after adjusting for age, sex, body mass index, smoking/drinking status, diabetes mellitus, hyperlipidaemia and proteinuria. RESULTS: Moderate HI was identified in 980 participants (7.3%). Of these, 441 participants (3.3%) exhibited moderate HI at 1 kHz, and 787 participants (5.8%) exhibited moderate HI at 4 kHz. Subjects with hypertension showed a higher prevalence of any HI. The prevalence of overall moderate HI, moderate HI at 1 kHz and moderate HI at 4 kHz among subjects with hypertension was 8.7%, 4.3% and 6.8%, while those among subjects without hypertension was 6.9%, 3.0% and 5.6% (p<0.01, p<0.01 and p=0.01, respectively). CONCLUSIONS: Hypertension was associated with moderate HI in Japanese workers.

Prospective clinical trial of 12-fraction carbon-ion radiotherapy for primary renal cell carcinoma.

The aims of this study were to clarify the safety and efficacy of 12-fraction carbon-ion radiotherapy (CIRT) for primary renal cell carcinoma (RCC) and to confirm the recommended dose in a prospective clinical trial. This clinical trial was planned as a non-randomized, open-label, single-center phase I/II study of CIRT monotherapy. The incidence of acute adverse events was the primary endpoint. Dose-limiting toxicities (DLTs) were defined as grade ≥3 skin, gastrointestinal tract, or urologic adverse events. Based on the eligibility criteria, 8 patients with primary RCC, including 3 medically inoperable patients and 5 patients with tumors >4 cm, were enrolled. Of the 8 patients, 5 were treated with 66 Gy (relative biological effectiveness [RBE]), and subsequently, the dose was escalated to 72 Gy (RBE) for the remaining 3 patients. The median follow-up time was 43.1 months. No DLTs were observed at any dose level though the end of follow-up. Although 1 patient died of pneumonia 3 months after CIRT, which was determined to be unrelated to CIRT, no grade 3 or higher adverse events were observed, and both local control and cancer-specific survival rates were 100%. In conclusion, the safety and efficacy of CIRT hypofractionation using 12-fractions for the treatment of eligible RCC patients, including those with inoperable or tumor size >4 cm, were confirmed in this prospective trial, and a recommended dose of 72 Gy (RBE) was established.

Reduced aqueous humour ascorbic-acid concentration in women with smaller anterior chamber depth.

Short anterior chamber depth (ACD) is considered a risk factor of endothelial-cell loss after phacoemulsification. However, whether it is an independent risk factor or not remains controversial. We investigated the relationship between ascorbic acid (AA) concentrations in the aqueous humour (AqH) and ACD. We analysed 165 AqH samples of 97 patients (42 men and 55 women) who underwent small incision cataract surgery. AqH and plasma AA concentrations were measured using a high-performance liquid chromatography - electrochemical detection method. Patient characteristics were compared between and within the sexes. As a result, age and ACD were significantly correlated with AqH AA concentrations (r = -0.206, P = 0.045; r = 0.339, P < 0.001) only in women. Moreover, plasma AA concentrations were significantly correlated with AqH AA concentrations (r = 0.420, P < 0.001; r = 0.316, P = 0.002) both in men and women. After adjusting for confounding factors (age and plasma AA concentrations), ACD was significantly and positively correlated with AqH AA concentrations (partial.r = 0.275, P = 0.009) only in women. In conclusion, AqH AA concentrations were reduced in women with smaller ACD. This may suggest that women with short ACD could be more susceptible to oxidative damage.