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.

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.

Anti-ß2-glycoprotein I/HLA-DR Antibody and Adverse Obstetric Outcomes.

Anti-ß2-glycoprotein I/HLA-DR (anti-ß2GPI/HLA-DR) antibody has been reported to be associated with antiphospholipid syndrome and recurrent pregnancy loss (RPL). We conducted a prospective multicenter cross-sectional study aimed at evaluating whether the anti-ß2GPI/HLA-DR antibody is associated with adverse obstetric outcomes and RPL. From 2019 to 2021, serum anti-ß2GPI/HLA-DR antibody levels (normal, <73.3 U) were measured in 462 women with RPL, 124 with fetal growth restriction (FGR), 138 with hypertensive disorders of pregnancy (HDP), 71 with preterm delivery before 34 gestational weeks (preterm delivery (PD) ≤ 34 GWs), and 488 control women who experienced normal delivery, by flow cytometry analysis. The adjusted odds ratios (aORs) of anti-ß2GPI/HLA-DR antibody positivity for adverse obstetric outcomes and RPL were evaluated on the basis of comparisons between the control and each patient group, using multivariable logistic regression analysis. The following were the positivity rates for the anti-ß2GPI/HLA-DR antibody in the patient and control groups: RPL, 16.9%; FGR, 15.3%; HDP, 17.4%; PD ≤ 34 GWs, 11.3%; and the control, 5.5%. It was demonstrated that anti-ß2GPI/HLA-DR antibody positivity was a significant risk factor for RPL (aOR, 3.3 [95% confidence interval {CI} 1.9-5.6], p < 0.001), FGR (2.7 [1.3-5.3], p < 0.01), and HDP (2.7 [1.4-5.3], p < 0.01) although not for PD ≤ 34 GWs. For the first time, our study demonstrated that the anti-ß2GPI/HLA-DR antibody is involved in the pathophysiology underlying FGR and HDP, as well as RPL.

Effect of Novel Stratified Lipid Risk by "LDL-Window" and Flow-Mediated Dilation on the Prognosis of Coronary Artery Disease Using the FMD-J Study A Data.

BACKGROUND: Elevated levels of triglyceride (TG) and non-high-density lipoprotein cholesterol (non-HDL-C) are regarded as a residual lipid risk in low-density lipoprotein cholesterol (LDL-C)-lowering therapy. This study investigated the association between lipid risk stratified by TG and non-HDL-C and the prognosis of patients with coronary artery disease (CAD), and the association between stratified lipid risk and flow-mediated dilatation (FMD) index.Methods and Results: The 624 CAD patients enrolled in flow-mediated dilation (FMD)-J study A were divided into 4 groups: low-risk group (n=413) with TG <150 mg/dL and non-HDL-C <170 mg/dL; hyper-TG group (n=180) with TG ≥150 mg/dL and non-HDL-C <170 mg/dL; hyper-non-HDL group (n=12) with TG <150 mg/dL and non-HDL-C ≥170 mg/dL; and high-risk group (n=19) with TG ≥150 mg/dL and non-HDL-C ≥170 mg/dL. Comparison of the groups showed the cumulative incidence of a 3-point major adverse cardiovascular event (MACE) was different and highest in the high-risk group in all the patients (P=0.009), and in patients with a FMD index ≥7.0% (P=0.021), but not in those with a FMD index <7.0%. Multivariable regression analysis showed that high lipid risk (P=0.019) and FMD <7.0% (P=0.040) were independently correlated with the incidence of a 3-point MACE. CONCLUSIONS: Novel stratification of lipid risk, simply using TG and non-HDL-C levels, combined with FMD measurement, is useful for predicting cardiovascular outcomes in patients with CAD.

Trends in Lifestyle-related Diseases and Their Risk Factors After the Fukushima Daiichi Nuclear Power Plant Accident: Results of the Comprehensive Health Check in the Fukushima Health Management Survey.

Residents were forced to evacuate owing to the radiation released after the Fukushima Nuclear Power Plant (NPP) accident following the Great East Japan Earthquake on 11/03/2021; thus, their lifestyles drastically changed. The Comprehensive Health Check (CHC) of the Fukushima Health Management Survey (FHMS) was performed to evaluate health statuses and prevent lifestyle-related diseases in evacuation area residents. The first part of the CHC survey is a retrospective analysis of pre- and post-disaster data on health check-ups of evacuation area residents. The second part is a cross-sectional, prospective analysis of post-disaster (fiscal year (FY) 2011-2017) data on health check-ups. Subjects were men and women living in 13 municipalities in areas surrounding the NPP in Fukushima Prefecture. Post-disaster (FY 2011-2012) overweight, hypertension, dyslipidemia, diabetes mellitus, metabolic syndrome, liver dysfunction, hyperuricemia, polycythemia and atrial fibrillation cases increased from the pre-disaster (FY 2008-2010) levels. This tendency was strongest among residents who were forced to evacuate. Proportion of overweight people remained unchanged, the prevalence of liver dysfunction decreased and the proportion of people with treated hypertension and dyslipidemia increased during FY 2011-2017. Meanwhile, the prevalence of diabetes mellitus and mean levels of HbA1c increased. Furthermore, Evacuees showed higher risks of diabetes mellitus, dyslipidemia, chronic kidney diseases and liver dysfunction than non-evacuees. Therefore, residents in the evacuation area, especially evacuees, are at high risk of developing lifestyle-related diseases, especially cardiovascular diseases; therefore, it is necessary to observe health statuses and implement measures to prevent lifestyle-related diseases.

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.

The vaccination status and adverse effects of COVID-19 vaccine among pregnant women in Japan in 2021.

To investigate the vaccination status and adverse reactions to the COVID-19 vaccine among pregnant women in Japan, we conducted an online questionnaire survey from October 5 to November 22, 2021. The number of participants in the online survey was 6576. Of the participants, 4840 (73.6%) were vaccinated twice, and 557 (8.5%) were vaccinated once. A total of 1179 (17.9%) responders had never been vaccinated against COVID-19. The most frequent adverse reaction was local pain at the injection site. The incidence of local adverse reactions was almost identical after the first and the second vaccinations, while systemic reactions, such as fever and fatigue/malaise, and adverse reactions outside the vaccination site such as headache and arthralgia, were more frequent after the second vaccination than after the first vaccination. Regarding the obstetrical complications, uterine tension and/or contraction was observed in 1.65% of the pregnant women after the first vaccination and in 2.98% after the second vaccination, and uterine pain appeared in 1.06% of the pregnant women after the second vaccination. However, serious symptoms, such as hemorrhage, decreased fetal movement, edema, increased blood pressure, and amniorrhexis, were seen in less than 1% of vaccinated women after both the first and second vaccinations. This study clarified the characteristics of vaccination, adverse reactions, and obstetrical symptoms in pregnant women in Japan who had the COVID-19 vaccine up to the second dose. As a booster vaccination is currently underway, further study is needed to improve the management of pregnant women during the current pandemic.

Characteristics of Emergency Neurological Patients Who Were Transported by Helicopter Emergency Medical Services in Tochigi, Japan.

In Japan, reports on the association of individual characteristics, and geographical distance and time with clinical outcomes for neurological emergencies involving helicopter emergency medical services (HEMS) are scarce. Using Tochigi HEMS data (2010-2018), we assessed the characteristics of 1,170 emergency neurological patients (e.g., stroke, neurotrauma, and seizure) at the base hospital, which covered 58% of all HEMS patients in the prefecture. After initial treatment in the emergency room, emergency physicians confirmed the clinical outcomes of each patient compared to those at the incident sites (recovery/non-recovery). We calculated the geographic distance from the base hospital to each incident site, and estimated and adjusted odds ratios (aOR) and 95% confidence intervals (CI) for non-recovery against distance. The mean distance between the incident site and base hospital was 22.0 ± 11.7 km, and 77.4% of patients recovered following initial treatment. Two peak age groups were observed among emergency neurological diseases, including seizures in patients who were aged < 5 years and stroke and neurotrauma in patients who were aged 70-80 years. The percentages of stroke, traumatic head and brain injury, and seizure were 35.8%, 29.2%, and 22.8%, respectively. The incidence of stroke (aOR = 11.8, 95% CI 6.86-20.3) and neurotrauma (aOR = 4.86, 95% CI 2.78-8.51) independently predicted a poor prognosis. However, no significant association was observed with the distance from the base hospital. Therefore, in the Tochigi prefecture, geographical disparities may not affect the short-term prognosis of patients with neurological emergencies who were transported by HEMS.

The physical and mental burden on obstetricians and gynecologists during the COVID-19 pandemic: A September 2020 questionnaire study.

AIM: The aim of this study was to clarify the physical and mental burden of the COIVD-19 pandemic on obstetricians and gynecologists in Japan and to identify factors that increase the burden of their psychological stress. METHODS: A web-based questionnaire was sent to obstetricians and gynecologists in Japan via email and social media to collect voluntary responses. This survey was conducted from September 1 to 30, 2020. RESULTS: A total of 852 valid responses were included in the analysis; 76% (644) of the physicians felt that the COVID-19 pandemic caused them physical and mental stress equal to or greater than the most severe disaster they had ever experienced. Physicians who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients (odds ratio (OR) 1.571, p = 0.012). Physicians experienced great stress to the point of wearing heavy personal protective equipment during routine vaginal deliveries by mothers with no COVID-19 symptoms. This trend was markedly pronounced for physicians working in regions with fewer cases of COVID-19 infection. CONCLUSIONS: Obstetricians and gynecologists who reported high mental and physical stress were more likely to be in areas with high numbers of infected patients. One potential reason for this may be that they were required to wear more personal protective equipment than necessary. Infection control methods that ensure the safety of obstetricians and gynecologists while not causing unnecessary physical or psychological stress are needed.

Psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 pandemic.

AIM: To evaluate psychological stress among pregnant and puerperal women in Japan during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: In this cross-sectional study, we recruited pregnant women and puerperal women who delivered between January and September 2020 in Japan, using an online questionnaire. Participants were divided into low, middle, and high groups according to the degree of the epidemic in their region of residence. Related factors were analyzed using the chi-squared test. The relationship between COVID-19 epidemic regions and depression risks and anxiety using the Edinburgh Postnatal Depression Scale (EPDS) and Kessler 6 scale (K6) was evaluated using a univariate and multivariable logistic regression model. RESULTS: Overall, 7775 cases, including 4798 pregnant and 2977 puerperal women, were analyzed. The prevalence of high EPDS and K6 scores was significantly increased in pregnant women in the high than those in the low epidemic regions (EPDS: adjusted odds ratio [aOR] 1.453, 95% confidence interval [CI] 1.205-1.753; K6: aOR 1.601, 95% CI 1.338-1.918). There was no difference in EPDS score, but the prevalence of high K6 scores was significantly increased in puerperal women in the high than those in the low epidemic regions (aOR 1.342, 95% CI 1.066-1.690). Further, restriction on going to their hometown for delivery increased the prevalence of high EPDS scores among pregnant (aOR 1.663, 95% CI 1.296-2.133) and puerperal women (aOR 1.604, 95% CI 1.006-2.557). CONCLUSIONS: Decreased support due to the COVID-19 pandemic affected the psychological status of pregnant and puerperal women; hence, investing medical resources in their healthcare essential.

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.

Influence of post-disaster evacuation on incidence of hyperuricemia in residents of Fukushima Prefecture: the Fukushima Health Management Survey.

AIM: After the Great East Japan Earthquake, over 160,000 residents in Fukushima Prefecture were forced to evacuate the area around the Fukushima Daiichi power plant following nuclear accident there. Health problems in these evacuees have since become a major issue. We have examined the association between evacuation and incidence of hyperuricemia among residents in Fukushima. METHODS: We conducted a cohort study of residents aged 40-90 years without hyperuricemia at the time of the Fukushima disaster. Among 8173 residents who met the inclusion criteria before the disaster, 4789 residents (men: 1971, women: 2818; follow-up duration: 1.38 years; and follow-up rate: 58.6%) remained available for follow-up examinations at the end of March 2013. The main endpoint was incidence of hyperuricemia, defined by the Japanese committee guidelines, using local health data from before and after the disaster. We divided participants by evacuation status and compared outcomes between groups. Using a logistic regression model, we estimated the odds ratio for incidence of hyperuricemia, adjusting for potential confounders, age, gender, waist circumference, physical activity, and alcohol consumption. RESULTS: Incidence of hyperuricemia was higher in evacuees (men 10.1%; women 1.1%) than in non-evacuees (men 7.4%, women 1.0%). Evacuees had higher body mass index, waist circumference, triglycerides, LDL-cholesterol, fasting plasma glucose, HbA1c, and lower HDL-cholesterol after the disaster than non-evacuees. We found that evacuation was associated with incidence of hyperuricemia (adjusted odds ratio: 1.38; 95% confidence interval: 1.03-1.86). CONCLUSION: This is the first study to demonstrate an association between evacuation after a disaster and increased incidence of hyperuricemia.

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.

Influence of post-disaster evacuation on childhood obesity and hyperlipidemia.

BACKGROUND: The objectives of this study were to determine the longer-term trends in childhood obesity and hyperlipidemia among residents of Fukushima Prefecture 5 years after the Great East Japan Earthquake. METHODS: We evaluated the changes in height, weight, body mass index (BMI) standard deviation score (BMI-SDS), low-density lipoprotein-cholesterol (LDL-CHO), high-density lipoprotein-cholesterol (HDL-CHO), and triglyceride (TG) in residents aged 7-15 years who had lived in the evacuation zone between 2011 and 2015. RESULTS: (i) the mean BMI SDS in all residents in 2011 was 0.113, and the mean BMI-SDS in all residents gradually decreased from 2011 to 2015; (ii) serum LDL-CHO levels and TG levels in all residents with a BMI value â‰§ 2SD in 2011 were higher than those in residents with a BMI value <2SD; (iii) the frequency of residents with an LDL-CHO level ≥ 140 mg/dl in 2012, 2013, and 2014 did not decrease in comparison with that in 2011, whereas the frequency of residents with an LDL-CHO level of  ≥ 140 mg/dl in 2015 was lower than that in 2011. The frequency of residents with a TG level ≥ 120 mg/dl increased over the 5 years. CONCLUSIONS: These results suggest that a number of pediatric residents suffered from obesity and hyperlipidemia. Furthermore, the long-term observation indicated an improvement in obesity, although the improvement in lipid abnormalities was delayed compared with that in obesity. Thus, it is necessary to continue with health checks for these residents with obesity and/or hyperlipidemia.

Survey on the use of personal protective equipment and COVID-19 testing of pregnant women in Japan.

AIM: To clarify the status of personal protective equipment (PPE) and coronavirus disease 2019 (COVID-19) tests for pregnant women, we conducted an urgent survey. METHODS: The survey was conducted online from April 27 to May 1, 2020. Questionnaires were sent to core facilities and affiliated hospitals of the obstetrics and gynecology training program and to hospitals of the national perinatal medical liaison council. RESULTS: A total of 296 institutions participated in our survey; however, 2 institutions were excluded. Full PPE was used by doctors in 7.1% of facilities and by midwives in 6.8%. Our study also determined that around 65.0% of facilities for doctors and 73.5% of facilities for midwives used PPE beyond the "standard gown or apron, surgical mask, goggles or face shield" during labor of asymptomatic women. N95 masks were running out of stock at 6.5% of the facilities and goggles and face shields at 2.7%. Disposable N95 masks and goggles or face shields were re-used after re-sterilization in 12% and 14% of facilities, respectively. Polymerase chain reaction (PCR) testing of asymptomatic patients was performed for 9% of vaginal deliveries, 14% of planned cesarean sections and 17% of emergency cesarean sections. The number of PCR tests for obstetrics and gynecology per a week ranged from zero to five in 92% of facilities. CONCLUSION: The shortage of PPE in Japan is alarming. Sufficient stockpiling of PPE is necessary to prevent unnecessary disruptions in medical care. Appropriate guidelines for PPE usage and COVID-19 testing of pregnant women at delivery are needed in Japan.

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.

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.

High Hematocrit Levels Are Associated with Risk of Cardiovascular Mortality among Middle-Aged Japanese Women: The Ibaraki Prefectural Health Study (IPHS).

In Japan, heart disease and cerebrovascular disease were the second and fourth leading cause of death, respectively in 2014. Hematocrit, the ratio of the red blood cells to the total volume of blood is known to play a role in cardiovascular diseases. However, the relationship between elevated hematocrit and the risk of cardiovascular disease based on sex has not been examined in Asian countries. We analyzed data from the Ibaraki Prefectural Health Study, a community-based large cohort study, which included 87,533 individuals, aged 40 to 79 years living in 38 municipalities of the Ibaraki Prefecture, who had completed an annual health checkup in 1993, and were followed until 2013. The hematocrit levels of the subjects were categorized into 5 quintiles (Q1-Q5), and hazard ratios for cause-specific mortality were calculated using the Cox proportional hazards regression models. Age and other cardiovascular risk factors were the covariates in the study. During the follow-up for a mean of 17.9 years, 1,207 deaths (615 men and 592 women) due to acute myocardial infarction (AMI) were reported in this population. The p values for the trend in the Q3-Q5 groups were 0.661 for men and 0.020 for women. Additionally, these values were significant in younger (40 to 59 years) women but not in older (60 to 79 years) women. This study is the first one to demonstrate an association between high hematocrit level and risk of AMI mortality in younger Japanese women, but not in men and older women.

Determination of the origin of oral squamous cell carcinoma by microarray analysis: Squamous epithelium or minor salivary gland?

More than 90% of oral cancers are histopathologically squamous cell carcinomas (SCCs). According to clinical behavior and histopathological features, we hypothesize that oral SCC can originate from either oral squamous epithelium or minor salivary glands. Here, we examined whether some oral SCCs originate from minor salivary glands, and investigated whether these tumors show particularly aggressive biological behavior. The mRNA expression profiles of samples obtained from six patients with oral floor SCC (five men, one woman; mean age, 62.7 years) were analyzed using a microarray containing 32,878 probes. The six samples were divided into two groups by clustering of expression levels of 845 probes differentially expressed in normal oral squamous epithelium and normal salivary glands. The expression profile in four cases was similar to that of normal oral squamous epithelium, and in two cases was similar to that of normal salivary glands. Furthermore, we identified nine genes that reveal the origin of the oral SCC. Subsequently, we examined the expression levels of these nine marker genes by reverse transcriptase-polymerase chain reaction to determine the origin of 66 oral SCCs. Twelve of the 66 oral SCCs were considered to originate from minor salivary glands, and these tumors showed high metastatic potential (p = 0.044, Chi-square test). Furthermore, SCC derived from minor salivary glands showed a poor event-free survival rate (p = 0.017, Kaplan-Meier analysis). In conclusion, determination of the origin of oral SCC is helpful in planning treatment for patients with oral SCC.

Updated long-term outcomes after carbon-ion radiotherapy for primary renal cell carcinoma.

Long-term oncological outcomes for primary renal cell carcinoma (RCC) treated with carbon-ion radiotherapy (CIRT) are poorly understood. Patients with primary RCC were treated with 12 or 16-fraction CIRT at The Hospital of the National Institute of Radiological Sciences outside of clinical trials. Outcome data were pooled and retrospectively analyzed for toxicity, local control, and disease-free, cancer-specific, and overall survival. From 1997 to 2014, 19 RCC patients (11 with T1aN0M0, 4 with T1bN0M0, and 4 with inoperable advanced stage [T4N0M0, T3aN1M0, and T1aN0M1]) were treated with CIRT and followed up for a median of 6.6 (range, 0.7-16.5) years; 9 of these patients were inoperable because of comorbidities or advanced-stage disease. Diagnoses were confirmed by imaging in 11 patients and by biopsy in the remaining 8. In 4 of 5 patients with definitive renal comorbidities, including diabetic nephropathy, sclerotic kidney or solitary kidney pre-CIRT progressed to grade 4 chronic kidney disease (CKD). In contrast, the remaining 14 patients without definitive renal comorbidities did not progress to grade 3 or higher CKD. Furthermore, although 1 case of grade 4 dermatitis was observed, there were no other grade 3 or higher non-renal adverse events. Local control rate, and disease-free, cancer-specific, and overall survival rates at 5 years of all 19 patients were 94.1%, 68.9%, 100%, and 89.2%, respectively. This updated retrospective analysis based on long-term follow-up data suggests that CIRT is a safe treatment for primary RCC patients without definitive renal comorbidities pre-CIRT, and yield favorable treatment outcomes, even in inoperable cases.