An Image Turing Test on Realistic Gastroscopy Images Generated by Using the Progressive Growing of Generative Adversarial Networks.

Generative adversarial networks (GAN) in medicine are valuable techniques for augmenting unbalanced rare data, anomaly detection, and avoiding patient privacy issues. However, there were limits to generating high-quality endoscopic images with various characteristics, such as peristalsis, viewpoints, light sources, and mucous patterns. This study used the progressive growing of GAN (PGGAN) within the normal distribution dataset to confirm the ability to generate high-quality gastrointestinal images and investigated what barriers PGGAN has to generate endoscopic images. We trained the PGGAN with 107,060 gastroscopy images from 4165 normal patients to generate highly realistic 5122 pixel-sized images. For the evaluation, visual Turing tests were conducted on 100 real and 100 synthetic images to distinguish the authenticity of images by 19 endoscopists. The endoscopists were divided into three groups based on their years of clinical experience for subgroup analysis. The overall accuracy, sensitivity, and specificity of the 19 endoscopist groups were 61.3%, 70.3%, and 52.4%, respectively. The mean accuracy of the three endoscopist groups was 62.4 [Group I], 59.8 [Group II], and 59.1% [Group III], which was not considered a significant difference. There were no statistically significant differences in the location of the stomach. However, the real images with the anatomical landmark pylorus had higher detection sensitivity. The images generated by PGGAN showed highly realistic depictions that were difficult to distinguish, regardless of their expertise as endoscopists. However, it was necessary to establish GANs that could better represent the rugal folds and mucous membrane texture.

Factors of influenza vaccine inoculation and non-inoculation behavior of community-dwelling residents in Japan: Suggestions for vaccine policy and public health ethics after COVID-19.

The aim of this study is to provide basic information that contributes to vaccine inoculation policy after COVID-19. We used the secondary data of the influenza vaccine inoculation behavior survey for community-dwelling adults conducted in 2011, before the COVID-19 pandemic, but after the 2009 novel influenza A (H1N1) pdm 09 pandemic. All factors such as socio-demographic characteristics, health-related behaviors, family environment, physical and social environment, and area of residence were adjusted, and factors related to vaccine inoculation behavior were analyzed. Those living with pregnant women had a significantly higher odds ratio of inoculation; this was self-evident in that those people considered infection to their family. Regarding the social environment, those aged 20-64 years with a significantly higher adjusted odds ratio of inoculation were those with "at least five people with which they interacted in the neighborhood". This result can be interpreted in two ways relating to altruism in Japan. Finally, we indicated the importance of learning from the past, including the case of 2009.

Use of Dietary Supplements among Japanese Female Nursing Professionals.

The use of dietary supplements has become a common way to maintain good health. This study evaluated the status of supplement use and supplement user characteristics among participants from the Japan Nurses' Health Study, which comprised a cohort of Japanese female nursing professionals. A questionnaire survey covering the use of vitamins and supplements was conducted. Supplements were classified according to their constituents and formulations. Logistic regression analyses were performed to determine the characteristics of supplement users. Results were as follows. There were 4,017 supplement users (34.4% of 11,665 valid answers). The supplement types used were: vitamins (n=2,655), minerals (n=1,121), amino acids and proteins (n=139), botanical products (n=714), animal by-products (n=849), herbal medicines (n=152), nutritional drinks (n=19), others (n=117), and unclassified supplements (n=320). Logistic regression analyses showed that supplement use was significantly associated with age and body mass index, and there were significantly higher proportions of supplement users among pregnant women, black tea drinkers, soy milk consumers, and lactobacillus beverage drinkers. In conclusion, the overall percentage of supplement users was 34.4%. A high prevalence of supplement use was observed among older, non-obese, and pregnant participants, and those who paid more attention to their health. The prevalence of supplement users was significantly higher among those who habitually drank black tea, soy milk, and lactobacillus beverages, suggesting participants used supplements to maintain their health or prevent diseases based on high health consciousness.

Complaints of reduced cognitive functioning during perimenopause: a cross-sectional analysis of the Japan Nurses' Health Study.

BACKGROUND: Many women experience various symptoms during the period of menopausal transition, including complaints of reduced cognitive functioning. However, these complaints are not necessarily recognized as core menopausal symptoms. In this study, we sought to characterize subjective complaints of reduced cognitive functioning by analyzing cross-sectional data from the Japan Nurses' Health Study (JNHS). METHODS: The JNHS 4-year follow-up questionnaire containing a 21-item climacteric symptom checklist, which included a question about "poor memory or forgetfulness", was mailed between 2005 and 2011 to all JNHS participants, regardless of their age at the time of the survey. We estimated the prevalence of slight and severe complaints in 5-year age-groups. We used principal component analysis to explore the underlying factors among the 21 symptoms during the menopausal transition period in women aged 45-54 years at the time of the survey. We also examined risk factors for complaints using multivariable modified Poisson regression analysis. RESULTS: In total, 12,507 women responded to the 4-year survey. The mean age at the time of the 4-year survey was 46.5 years (range 27-82). "Poor memory or forgetfulness" showed a peak prevalence of 81.7% (severe 27.9%; slight 53.8%) at 50-54 years, and gradually decreased after 55 years. Principal component analysis indicated that "poor memory or forgetfulness" belonged to somatic symptoms and was close to psychological symptoms in women aged 45-54 years. In women aged 45-54 years, the complaint was also significantly associated with hot flashes and sweats. Multivariable modified Poisson regression analysis showed that menopausal status (uncertain and postmenopausal), less sleep (sleep of < 5 h and sleep of 5- < 6 h), night-shift work, and severe vasomotor symptoms (VMS) were significantly associated with the prevalence of severe complaints of reduced cognitive functioning in women aged 45-54 years. CONCLUSIONS: We found that prevalence of "poor memory or forgetfulness" was highest during the menopausal transition period and among perimenopausal women. This subjective complaint was associated with somatic, psychological complaints and VMS. It may be useful for women with cognitive problems in the transition period to consider management of comorbid menopausal symptoms.

Long-Term Outcomes of Secondary Nasal Tip Plasty After Degradation of a Polycaprolactone (PCL) Mesh.

BACKGROUND: In secondary nasal tip plasty, it is often difficult to harvest appropriate septal extension grafts for sufficient tip projection. Therefore, studies using numerous alloplastic materials in rhinoplasty have been reported. This study aimed to evaluate the nasal tip change over time after tip plasty using a PCL mesh. METHODS: We conducted a retrospective study of 86 Asian patients who received secondary tip plasty by septal extension grafting with a PCL mesh as a batten graft. Patient demographics and surgical outcomes were examined. The outcome variables were nasolabial angle, nasofrontal angle and Goode ratio. Measurements were performed with photographs obtained at short-term (postoperative 4-6 months) and long-term (more than postoperative 24 months) follow-ups. Aesthetic outcomes and safety were assessed using the Global Aesthetic Improvement Scale. RESULTS: Among 86 patients, 56 had a long-term follow-up. The mean age was 33.33 years, and the male-to-female ratio was 17.44:82.56. The nasolabial and nasofrontal angles did not change significantly between the short-term and long-term follow-ups. The Goode ratio, which is a useful tool to evaluate nasal projection, was decreased by 5.00%. Nevertheless, all patients were satisfied, and the long-term aesthetic outcomes were improved in 54 (96.4%) patients. There were two cases (2.33%) of complications, including one infection and one case of PCL-mesh protrusion. CONCLUSIONS: The present study demonstrated the usefulness and safety of PCL meshes when used in septal extension grafts as batten grafts. Although biodegradation seems to affect the nasal projection, PCL is still useful in secondary tip plasty along with other alloplastic materials. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Hypertensive disorders of pregnancy increase the risk of future menopausal hot flashes in Japanese women: results from the Japan Nurses' Health Study.

OBJECTIVE: We aimed to investigate whether hypertensive disorders of pregnancy (HDP) are associated with problematic hot flashes in Japanese women. METHODS: In this study, we included participants in the Japan Nurses' Health Study who were women aged 41 to 55 years at baseline, parous, and completed a 4-year follow-up questionnaire. The main outcome was self-reported problematic hot flashes. At the 4-year follow-up survey, we investigated hot flashes using the Climacteric Symptom Checklist for Japanese Women, which was developed by a subcommittee of the Japan Society of Obstetrics and Gynecology. RESULTS: At the baseline survey, of the 4,627 women included in the analysis, 610 (13.2%) reported a history of HDP. At the 4-year follow-up survey, 394 women (8.5%) reported problematic hot flashes, 529 (11.4%) were diagnosed with premenopausal hypertension, and 2,389 (51.5%) were postmenopausal. Multivariable logistic regression analysis revealed a multivariable-adjusted odds ratio (95% confidence interval) of problematic hot flashes for women with a history of HDP of 1.42 (1.04-1.94), compared with women without this history. Among women without premenopausal hypertension, the odds ratio increased to 1.55 (1.10-2.19) among women with HDP as compared with those without these disorders. CONCLUSIONS: In this prospective study, we found that women with a history of HDP have a significantly increased risk of problematic hot flashes, compared with their counterparts without a history of HDP.

Predictive Role of Endoscopic Surveillance after Total Gastrectomy with R0 Resection for Gastric Cancer.

BACKGROUND: Endoscopic surveillance after total gastrectomy (TG) for gastric cancer is routinely performed to detect tumor recurrence and postoperative adverse events. However, the reports on the clinical benefits of endoscopic surveillance are ambiguous. We investigated the clinical benefit of endoscopic surveillance after TG for gastric cancer. METHODS: We analyzed 848 patients who underwent TG with R0 resection for gastric cancer between 2011 and 2012 (380 early gastric cancer and 468 advanced gastric cancer) and underwent regular postoperative surveillance with endoscopy and abdominopelvic computed tomography (CT) with contrast. RESULTS: Median follow-up periods were 58 months for both endoscopy (range, 3-96) and abdominopelvic CT (range, 1-96). Tumor recurrence occurred in 167 patients (19.7%), of whom seven (4.2%) were locoregional recurrences in the peri-anastomotic area (n = 5) or regional gastric lymph nodes (n = 2). Whereas the peri-anastomotic recurrences were detected by both endoscopy and abdominopelvic CT, regional lymph node recurrences were only detected by abdominopelvic CT. Out of the 23 events of postoperative adverse events, the majority (87%) were detected by radiologic examinations; three events of benign strictures in the anastomotic site were detected only by endoscopy. CONCLUSION: Endoscopic surveillance did not have a significant role in detecting locoregional tumor recurrence and postoperative adverse events after TG with R0 resection for gastric cancer. Routine endoscopic surveillance after TG may be considered optional and performed according to the capacities of each clinical setting.

Forehead Reduction Surgery via an Anterior Hairline Pretrichial Incision in Asians: A Review of 641 Cases.

BACKGROUND: Forehead reduction is gaining in popularity, as facial proportions that include shorter upper and lower thirds are currently more aesthetically pleasing. In this first large-scale study, we present an analysis of several important aspects of surgical design and postoperative complications associated with forehead reduction performed via a pretrichial skin excision. METHODS: Patients who underwent surgery from 2006 to 2018 were reviewed retrospectively. Data included the amount of skin excised, postoperative complications experienced during the first three months, and forehead length measured 2 years postoperatively. Objective outcomes reported by three independent surgeons and subjective satisfaction reported by patients at three months postoperatively were evaluated on 5-point Likert scales that addressed both postoperative scarring and overall aesthetics. RESULTS: A total of 641 patients underwent forehead reduction surgery. The average lengths of the skin excisions were 16.64 mm, 15.36 mm, and 15.33 mm from regions at the center and at the left and right mid-pupillary lines, respectively. Long-term follow-up of 85 patients revealed forehead lengthening that exceeded the initial postoperative measurements by 2.44 mm (15.04%), 1.98 mm (11.53%), and 2.51 mm (15.8%) at the left, center, and right, respectively. Means (standard deviation [SD]) for subjective and objective measures of postoperative scarring were 1.32 (0.49) and 1.78 (0.66), respectively. The means (SD) for subjective and objective postoperative aesthetic scores were 4.38 (0.47) and 3.98 (0.39), respectively. CONCLUSIONS: Forehead reduction surgery via a pretrichial skin excision is a straightforward procedure that is easy to perform, has few complications, and result in high rates of patient satisfaction. LEVEL OF EVIDENCE IV: This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .

Machine learning approach for differentiating cytomegalovirus esophagitis from herpes simplex virus esophagitis.

The endoscopic features between herpes simplex virus (HSV) and cytomegalovirus (CMV) esophagitis overlap significantly, and hence the differential diagnosis between HSV and CMV esophagitis is sometimes difficult. Therefore, we developed a machine-learning-based classifier to discriminate between CMV and HSV esophagitis. We analyzed 87 patients with HSV esophagitis and 63 patients with CMV esophagitis and developed a machine-learning-based artificial intelligence (AI) system using a total of 666 endoscopic images with HSV esophagitis and 416 endoscopic images with CMV esophagitis. In the five repeated five-fold cross-validations based on the hue-saturation-brightness color model, logistic regression with a least absolute shrinkage and selection operation showed the best performance (sensitivity, specificity, positive predictive value, negative predictive value, accuracy, and area under the receiver operating characteristic curve: 100%, 100%, 100%, 100%, 100%, and 1.0, respectively). Previous history of transplantation was included in classifiers as a clinical factor; the lower the performance of these classifiers, the greater the effect of including this clinical factor. Our machine-learning-based AI system for differential diagnosis between HSV and CMV esophagitis showed high accuracy, which could help clinicians with diagnoses.

The Clinical Significance of Anastomotic Ulcers After Ileocolic Resection to Predict Postoperative Recurrence of Crohn's Disease.

BACKGROUND: The Rutgeerts score is used to predict postoperative recurrence in CD patients after ileocolic resection and is primarily based on endoscopic findings at the neoterminal ileum. However, the optimal assessment of anastomotic ulcers (AUs) remains subject to debate. AIMS: We aimed to investigate the association between anastomotic ulcers (AUs) and endoscopic recurrence in postoperative Crohn's disease (CD) patients. METHODS: This single-center retrospective study, conducted between 2000 and 2016, evaluated postoperative CD patients with endoscopic remission at the first ileocolonoscopy within 1 year after ileocolic resection and those who underwent subsequent ileocolonoscopic follow-up. The study outcome was the clinical significance of AUs in predicting endoscopic recurrence. RESULTS: Among 116 patients who were in endoscopic remission defined as the RS of i0 to i1 at the index postoperative ileocolonoscopy, 84.5% (98/116) underwent subsequent ileocolonoscopies. During the median 30.0 months (interquartile range, 21.3-53.3) of follow-up after the first ileocolonoscopy, 56.1% (55/98) of patients showed endoscopic recurrence. Furthermore, 65.8% (48/73) with AUs and 75.5% (40/53) with major AUs, defined as either an ulcer occupying ≥ 1/4 of the circumference, ≥ 3 ulcers confined to anastomotic ring, or any ulcers extending to the ileocolonic mucosa, showed endoscopic recurrence. On multivariable analysis, AUs (adjusted hazard ratio [aHR], 4.33; 95% confidence interval [CI], 1.87-10.0; P < 0.001) and major AUs (aHR, 3.64; 95% CI, 1.95-79; P < 0.001) were associated with endoscopic recurrence. CONCLUSIONS: AUs are associated with a significantly high risk of endoscopic recurrence in postoperative CD patients who are in endoscopic remission.

A case of eosinophilic cholangiopathy mimicking cholangiocarcinoma.

Eosinophilic cholangiopathy is an uncommon etiology of biliary stenosis, which is characterized by eosinophilic infiltration. Clinically, it is difficult to distinguish eosinophilic cholangiopathy from other causes of obstructive cholangiopathy before pathologic confirmation. We report a case of eosinophilic cholangiopathy. A 30-year-old male patient complained of right upper quadrant abdominal pain. Magnetic resonance cholangiopancreatography showed distended gallbladder and multifocal bile duct strictures with diffuse wall thickening. His bilirubin level increased continuously even after endoscopic retrograde cholangiopancreatography. He underwent laparoscopic cholecystectomy for cholecystitis and pathology of resected gallbladder revealed marked eosinophilic infiltration with no malignant component. His pain improved after cholecystectomy and multifocal bile duct strictures with wall thickening were rapidly improved after steroid therapy.

Association Between Reproductive Life Span and Incident Nonfatal Cardiovascular Disease: A Pooled Analysis of Individual Patient Data From 12 Studies.

Importance: Early menarche and early menopause are associated with increased risk of cardiovascular disease (CVD) in midlife, but little is known about the association between reproductive life span and the risk of CVD. Objective: To investigate the association between the length of reproductive life span and risk of incident CVD events, while also considering the timing of menarche and menopause. Design, Setting, and Participants: Individual-level data were pooled from 12 studies participating in the International Collaboration for a Life Course Approach to Reproductive Health and Chronic Disease Events consortium. Women provided complete information on the timing of menarche and menopause, nonfatal CVD events, and covariates. Cox proportional hazards models were used to estimate hazard ratios and 95% CIs, adjusted for covariates. The association between reproductive life span and CVD was adjusted for age at menarche and age at menopause separately. Analysis began March 2018 and ended December 2019. Exposures: Reproductive life span was calculated by subtracting age at menarche from age at menopause and categorized as younger than 30, 30 to 32, 33 to 35, 36 to 38 (reference group), 39 to 41, 42 to 44, and 45 years or older. Main Outcomes and Measures: First nonfatal CVD event, including coronary heart disease and stroke events. Results: A total of 307 855 women were included. Overall, the mean (SD) ages at menarche, menopause, and reproductive life span were 13.0 (1.5) years, 50.2 (4.4) years, and 37.2 (4.6) years, respectively. Pooled analyses showed that women with a very short reproductive life span (<30 years) were at 1.71 (95% CI, 1.58-1.84) times higher risk of incident CVD events than women with a reproductive life span of 36 to 38 years after adjustment for covariates. This association remained unchanged when adjusted for age at menarche but was attenuated to 1.26 (95% CI, 1.09-1.46) when adjusted for age at menopause. There was a significant interaction between reproductive life span and age at menarche associated with CVD risk (P < .001). Women who had both short reproductive life span (<33 years) and early menarche (age ≤11 years) had the highest risk of CVD (hazard ratio, 2.06; 95% CI, 1.76-2.41) compared with those with a reproductive life span of 36 to 38 years and menarche at age 13 years. Conclusions and Relevance: Short reproductive life span was associated with an increased risk of nonfatal CVD events in midlife, and the risk was significantly higher for women with early age at menarche.

One-step immunoassay without washing steps for influenza A virus detection using ISFET.

A one-step immunoassay for influenza A virus detection was developed using two different microbeads and a filter-inserted bottle. Two bead types with diameters of 15 (capture bead) and 3 (detection bead) µm were prepared to specifically detect influenza A virus. Anti-influenza A virus antibodies were coated on both bead types, whereas urease was immobilized only on the detection bead. An influenza A-positive sample could form a sandwich complex with the capture and detection beads; this complex would not pass through the filter, which had a controlled pore size. As the detection bead was used at a limiting concentration, it would be prevented from crossing the filter; thus, it would further react with the substrate urea and consequently increase the pH. An influenza A-negative sample would fail to form the sandwich complex in the presence of the capture and detection beads. Accordingly, the detection bead would pass through the filter into the urea buffer and increase the pH. The pH change in the urease reaction could be quantitatively measured by an indicator such as phenol red or using ion-selective field-effect transistor (ISFET). This one-step immunoassay was used for the detection of influenza A virus in real samples. The receiver operating characteristic (ROC) plot analysis showed an area under the curve (AUC) value of 0.931; the sensitivity and specificity of the assay was 80% and 90%, respectively, at a cutoff value of 0.9986. These results demonstrate that the one-step immunoassay could increase the sensitivity of influenza A virus detection in real samples.

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data.

BACKGROUND: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease. METHODS: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause). FINDINGS: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1·55, 95% CI 1·38-1·73; p<0·0001), early menopause (age 40-44 years; 1·30, 1·22-1·39; p<0·0001), and relatively early menopause (age 45-49 years; 1·12, 1·07-1·18; p<0·0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0·0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1·88, 1·62-2·20; p<0·0001) and early menopause (1·40, 1·27-1·54; p<0·0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older. INTERPRETATION: Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as an important factor in risk stratification of cardiovascular disease for women. FUNDING: Australian National Health and Medical Research Council.

A proper reference metabolic equivalent value to assess physical activity intensity in Japanese female nurses.

BACKGROUND: Various questionnaires have been developed to assess physical activity, but only a few simple questionnaires are suitable for self-administration in large groups of midlife working women. This study examined the usefulness of the Japan Nurses' Health Study (JNHS) questionnaire for self-administered physical activity surveys. METHODS: The JNHS physical activity questionnaire consisted of items covering seven degrees of intensity. The metabolic equivalents (METs) for the physical activity intensity of the questionnaire were estimated from energy expenditure as measured by a uniaxial accelerometer with the Markov Chain Monte Carlo (MCMC) simulation. The estimated METs were then assigned to the JNHS baseline survey data, and the total energy expenditure (TEE) and the time spent performing ≥3 METs hour of physical activity, called moderate to vigorous intensity physical activity (MVPA), were calculated. RESULTS: For working situations, application of the MCMC simulation resulted in estimated reference values of 1.2 METs for "sitting work", 1.6 METs for "standing work", 1.8 METs for "walking work", and 4.5 METs for "heavy work". For non-working situations, the estimated values were 1.1 METs for sedentary time, 2.4 METs for "moderate physical activity", 4.4 METs for "vigorous physical activity", and 9.4 METs for "very vigorous physical activity". When these estimated METs were used, the mean TEE/day was 1808 kcal. This corresponded to - 3.0% of the TEE/day generated by the accelerometer. These estimated MET values showed similar results as a previous study measuring activity using the doubly-labeled water method. The number of hours per week of MVPA significantly decreased with age, which is also consistent with previous findings. CONCLUSIONS: Estimated reference MET values in this study were similar to those in previous studies of Japanese women. The JNHS questionnaire is therefore useful for epidemiological surveys of midlife working women because it assigns estimated MET values as physical activity intensities.

Mortality inequalities by occupational class among men in Japan, South Korea and eight European countries: a national register-based study, 1990-2015.

BACKGROUND: We compared mortality inequalities by occupational class in Japan and South Korea with those in European countries, in order to determine whether patterns are similar. METHODS: National register-based data from Japan, South Korea and eight European countries (Finland, Denmark, England/Wales, France, Switzerland, Italy (Turin), Estonia, Lithuania) covering the period between 1990 and 2015 were collected and harmonised. We calculated age-standardised all-cause and cause-specific mortality among men aged 35-64 by occupational class and measured the magnitude of inequality with rate differences, rate ratios and the average inter-group difference. RESULTS: Clear gradients in mortality were found in all European countries throughout the study period: manual workers had 1.6-2.5 times higher mortality than upper non-manual workers. However, in the most recent time-period, upper non-manual workers had higher mortality than manual workers in Japan and South Korea. This pattern emerged as a result of a rise in mortality among the upper non-manual group in Japan during the late 1990s, and in South Korea during the late 2000s, due to rising mortality from cancer and external causes (including suicide), in addition to strong mortality declines among lower non-manual and manual workers. CONCLUSION: Patterns of mortality by occupational class are remarkably different between European countries and Japan and South Korea. The recently observed patterns in the latter two countries may be related to a larger impact on the higher occupational classes of the economic crisis of the late 1990s and the late 2000s, respectively, and show that a high socioeconomic position does not guarantee better health.

The association of urinary estrogen levels with urinary isoflavone levels: Difference between premenopausal women and postmenopausal women.

Results of studies on the associations of soy food intake with urinary estrogen levels in premenopausal women and in postmenopausal women have been inconsistent. We examined the associations of urinary isoflavone levels as well as soy food intake with estrone (E1) and estradiol (E2) in pre- and postmenopausal women. In addition, we compared the levels of isoflavones, E1 and E2 across current hormone users such as those receiving hormone replacement therapy and those using oral contraceptives and non-users among both pre- and postmenopausal women. Urinary levels of isoflavones, E1 and E2 in 498 women (36 hormone users and 462 non-users) were analyzed. Premenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, but there were no significant associations between E1 and E2 levels and urinary isoflavone levels. Levels of E1 and E2 in hormone users were significantly lower than those in hormone non-users among premenopausal women, but levels of E1 and E2 in hormone users were significantly higher than those in hormone non-users among postmenopausal women. Postmenopausal women with a higher frequency of soy food intake had higher urinary isoflavone levels, and postmenopausal women with high urinary isoflavone levels had significantly higher E1 and E2 levels. In conclusion, the associations of urinary isoflavone levels with urinary estrogen levels differed with menopausal status. Urinary levels of E1 and E2 were high in postmenopausal women with high urinary isoflavone levels but not in premenopausal women with high urinary isoflavone levels.

Step Counts of Middle-Aged and Elderly Adults for 10 Months Before and After the Release of Pokémon GO in Yokohama, Japan.

BACKGROUND: Smartphones have been integrated into our society and are expected to serve as tools to improve health outcomes. In the summer of 2016, Pokémon GO, a location-based augmented reality game for smartphones was released; it attracted attention from the perspective of health, especially with its potential to increase physical activity (PA). A few studies have compared objectively measured step counts before and after the release of the game; however, they were conducted over a short study period and evaluated only young people. OBJECTIVE: The objective of this study was to confirm whether there was a difference in step counts between middle-aged and elderly players and nonplayers before and after the release of Pokémon GO. METHODS: A total of 46 players and 184 nonplayers aged ≥40 years were matched for sex, age group, and PA level; they were respondents to a questionnaire randomly sent to citizens who were given free pedometers by Yokohama city. Their play status was identified through the questionnaire. To investigate the change in step counts before and after the release of Pokémon GO according to play status, a 2-way repeated-measures analysis of variance was performed. Step counts 1 month before the release of the game were compared with those 8 months after the release. In addition, subgroup analyses according to sex, age group, PA level, and subjective health status were performed. RESULTS: The mean ages of players and nonplayers were 56.5 (SD 9.9) years and 57.3 (SD 9.6) years, respectively, and the mean baseline step counts of players and nonplayers were 7641.8 (SD 2754.5) and 7903.3 (SD 2674.7), respectively. There was no significant difference in the age and baseline step counts according to a t test (2-tailed). In the analysis of all samples, the interaction between play status and time effect was significant for 3 of 8 months after release. In the subgroup analyses, the interaction was significant for 3 months in men, 7 months in the 55-64-year-old group, 2 months in workers, 4 months in the active group in PA level, and 2 months in participants with subjectively good health. The interaction was significant for only 1 month, at most, in other subgroups. CONCLUSIONS: The present study confirmed a difference in step counts between players and nonplayers before and after the release of Pokémon GO. According to our analysis, step counts were higher until 7 months after the release. The player group maintained their step counts in winter, despite the decrease in step counts of nonplayers. In subgroup analyses, players were more likely to be men, aged <55 years, workers, active, and subjectively in good health.

Premenopausal cardiovascular disease and age at natural menopause: a pooled analysis of over 170,000 women.

Early menopause is associated with an increased risk of subsequent cardiovascular disease (CVD). Few studies have investigated the converse. We examined whether premenopausal CVD events are associated with early age at menopause. We pooled the individual data of 177,131 women from nine studies. We used multinomial logistic regression models to estimate multivariable relative risk ratios (RRR) and 95% confidence intervals (CI) for the associations between age at onset of premenopausal CVD events-including coronary heart disease (CHD) and stroke-and age at natural menopause. Altogether 1561 (0.9%) premenopausal participants reported CVD events (including 1130 CHD and 469 stroke) at a mean age of 41.3 years. Compared with women without any premenopausal CVD events, women who experienced a first CVD event before age 35 years had a twofold risk of menopause before age 45 years (early menopause); adjusted RRR (95% CI) of 1.92 (1.17, 3.14) for any CVD, 1.86 (1.01, 3.43) for CHD and 2.17 (1.43, 3.30) for stroke. Women who experienced a first premenopausal CVD event after age 40 years underwent a natural menopause at the expected age (around 51 years). These associations were robust to adjustment for smoking status, BMI, educational level, race/ethnicity, age at menarche, parity, hypertension and family history of CVD. For premenopausal women, a first CVD event before age 35 years is associated with a doubling of the risk of an early menopause, while a first CVD event occurred after 35 years indicates a normal menopause at around 51 years. Shared genetic and environmental factors (such as smoking), as well as compromised vasculature following CVD events, may contribute to this outcome.