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Background: To our knowledge, no nationwide epidemiological study of myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) has been conducted. Objective: We examined the epidemiology and clinical features of MOGAD in Japan. Methods: We distributed questionnaires on the clinical characteristics of patients with MOGAD to neurology, pediatric-neurology, and neuro-ophthalmology facilities throughout Japan. Results: In total, 887 patients were identified. The estimated number of total and newly diagnosed MOGAD patients was 1,695 [95% confidence interval (CI): 1483–1907] and 487 (95% CI: 414–560), respectively. The estimated prevalence and incidence were 1.34/100,000 (95% CI: 1.18–1.51) and 0.39/100,000 (95% CI: 0.32–0.44), respectively. The median age at onset was 28 years (range: 0–84 years). At onset, optic neuritis was present in approximately 40% of patients, irrespective of the onset age. Acute disseminated encephalomyelitis was more frequent in younger patients, whereas brainstem encephalitis, encephalitis, and myelitis were more frequent in elderly patients. Immunotherapy was highly effective. Conclusion: The prevalence and incidence rates of MOGAD in Japan are similar to those in other countries. Notable characteristics such as the preferential occurrence of acute disseminated encephalomyelitis in children exist; however, general characteristics including symptoms and treatment response are common irrespective of the onset age.

Background: Inflammation is thought to be a risk factor for kidney disease. However, whether inflammatory status is either a cause or an outcome of chronic kidney disease remains controversial. We aimed to investigate the causal relationship between high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) using Mendelian randomization (MR) approaches. Methods: A total of 10,521 participants of the Japan Multi-institutional Collaborative Cohort Study was analyzed in this study. We used two-sample MR approaches (the inverse-variance weighted (IVW), the weighted median (WM), and the MR-Egger method) to estimate the effect of genetically determined hs-CRP on kidney function. We selected four and three hs-CRP associated single nucleotide polymorphisms (SNPs) as two instrumental variables (IV): IVCRP and IVAsian, based on SNPs previously identified in European and Asian populations. IVCRP and IVAsian explained 3.4% and 3.9% of the variation in hs-CRP, respectively. Results: Using the IVCRP, genetically determined hs-CRP was not significantly associated with eGFR in the IVW and the WM methods (estimate per 1 unit increase in ln(hs-CRP), 0.000; 95% confidence interval [CI], −0.019 to 0.020 and −0.003; 95% CI, −0.019 to 0.014, respectively). For IVAsian, we found similar results using the IVW and the WM methods (estimate, 0.005; 95% CI, −0.020 to 0.010 and −0.004; 95% CI, −0.020 to 0.012, respectively). The MR-Egger method also showed no causal relationships between hs-CRP and eGFR (IVCRP: −0.008; 95% CI, −0.058 to 0.042; IVAsian: 0.001; 95% CI, −0.036 to 0.036). Conclusion: Our two-sample MR analyses with different IVs did not support a causal effect of hs-CRP on eGFR.

Background: Mid-regional pro-adrenomedullin (MR-proADM) is a novel biomarker for cognitive decline based on its association with cerebral small vessel disease (SVD). Cerebral microbleeds (MBs) are characteristic of SVD; however, a direct association between MR-proADM and MBs has not been explored. Objective: We aimed to examine whether circulating levels of MR-proADM are associated with the identification of MBs by brain magnetic resonance imaging (MRI) and whether this association could be linked with cognitive impairment. Methods: In total, 214 participants (mean age: 75.9 years) without history of cerebral infarction or dementia were prospectively enrolled. All participants underwent brain MRI, higher cognitive function testing, blood biochemistry evaluation, lifestyle examination, and blood MR-proADM measurement using a time-resolved amplified cryptate emission technology assay. For between-group comparisons, the participants were divided into two groups according to whether their levels of MR-proADM were normal (

Objective Poor sleep quality, such as nocturnal arousal and sleep inefficiency, is associated with frailty and sarcopenia. Herein, we evaluated the relationship between poor sleep quality and locomotive syndrome (LS), a motor organ dysfunction common among community-dwelling middle-aged and older women. Methods Participants comprised 2246 Japanese middle-aged and older women. LS was classified into stages LS-1, LS-2, and LS-3 (from least to most severe) according to the results of the stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale. Sleep quality was assessed using the Pittsburgh Sleep Quality Index. Results The Pittsburgh Sleep Quality Index scores were significantly higher in the LS group than that in the non-LS group (P Conclusions Poor sleep quality was independently associated with LS among community-dwelling middle-aged and older women. As the stage of LS progressed, the proportion of women with poor sleep quality increased significantly.

Streptococcus mutans, a major cariogenic bacterium, expressing the collagen-binding protein Cnm induces cerebrovascular inflammation, resulting in the impairment of blood brain barrier integrity followed by cerebral bleeding. We here examined the association of Cnm-positive S. mutans with cerebral microbleeds (CMBs) in acute stroke patients selected from a single-center registry database. Of 428 patients who received oral bacterial examinations among 3154 stroke patients, 326 patients who harbored S. mutans were identified. After excluding four patients without imaging data, we compared 72 patients with Cnm-positive S. mutans and 250 with Cnm-negative S. mutans. Deep, lobar and infratentorial CMBs were observed in 46 (63.9%), 36 (50.0%), 25 (34.7%) patients with Cnm-positive S. mutans and 144 (57.6%), 114 (45.6%), 101 (40.4%) with Cnm-negative S. mutans. Possession of Cnm-positive S. mutans was related to higher numbers of both deep and lobar, but not infratentorial, CMBs (risk ratios 1.57 [1.07‒2.30], deep; 5.44 [2.50‒11.85], lobar). Statistical significance persisted after adjusting for age, sex, hypertension, stroke type, National Institutes of Health Stroke Scale score, and cerebral amyloid angiopathy (risk ratios 1.61 [1.14‒2.27], deep; 5.14 [2.78‒9.51], lobar). Our study indicated that reduction of Cnm-positive S. mutans may serve as a therapeutic approach for improving the prognosis of stroke patients.

There are many reports on the risk of falls in older adults but none regarding the risk among middle-aged people. We aimed to determine fall risk factors among middle-aged women. The participants comprised 1421 women aged 40 to 64 years; anthropometric and other measurements were obtained, and lifestyle factors were examined using a self-administered questionnaire. The participants were categorized into two groups (No-fall and Fall/Almost-fall) based on their questionnaire responses. The No-fall and Fall/Almost-fall groups comprised 1114 and 307 participants, respectively. Body mass index, abdominal circumference measurements, and prevalence of dyslipidemia were significantly higher in the Fall/Almost-fall group. Additionally, those in the Fall/Almost-fall group had a shorter two-step test, experienced difficulty performing the 40 cm single-leg sit-to-stand test, and had higher 25-question Geriatric Locomotive Function Scale (GLFS-25) scores than those in the No-fall group. The results of the adjusted logistic regression analysis indicated that physical activity, higher GLFS-25 scores, and sedentary time of more than seven hours were all risk factors for falling or almost falling. Longer sedentary time is a new risk factor for falls among middle-aged women. It is necessary for people to be concerned with their sedentary behavior, such as by reducing or interrupting continuous sedentary time.

Reperfusion therapy has improved the outcomes of ischemic stroke but also emphasized the importance of ischemic penumbra. However, blood biomarkers are currently unavailable for this region. Adrenomedullin (ADM) is a neuroprotective peptide, secreted in a compensatory response to brain ischemia. We thus investigated whether an increase in mid-regional pro-ADM (MR-proADM), a stable peptide fragment of the ADM precursor, could act as a biomarker by predicting the ischemic penumbra in hyperacute ischemic stroke (HAIS). We prospectively enrolled consecutive HAIS patients (n = 119; median age, 77 years; male, 59.7%) admitted to our institutes from July 2017 to March 2019 and evaluated plasma MR-proADM levels within 4.5 h of onset. MR-proADM levels in HAIS were compared to healthy controls (n = 1298; median age, 58 years; male, 33.2%) in the Japan Multi-Institutional Collaborative Cohort Study from 2013 to 2017. Furthermore, we evaluated whether MR-proADM levels were associated with the penumbra estimated by clinical-diffusion mismatch (CDM) (National Institute of Health Stroke Scale [NIHSS] ≥8, diffusion ischemic core volume ≤25 ml), or magnetic resonance angiography-diffusion-weighted imaging mismatch (MDM) (NIHSS ≥5, a proximal vessel occlusion with core volume ≤25 ml, or a proximal vessel stenosis/distal vessel occlusion with core volume ≤15 ml). In a case-control study, multivariate logistic analysis showed a significant association between HAIS and MR-proADM ≥0.54 nmol/L (adjusted odds ratio, 7.92 [95% CI, 4.17-15.02], p 0.001). Though MR-proADM levels in HAIS did not correlate with the ischemic core volume (r

Background: Obesity is a reported risk factor for various health problems. Genome-wide association studies (GWASs) have identified numerous independent loci associated with body mass index (BMI). However, most of these have been focused on Europeans, and little evidence is available on the genetic effects across the life course of other ethnicities. Methods: We conducted a cross-sectional study to examine the associations of 282 GWAS-identified single nucleotide polymorphisms with three BMI-related traits, current BMI, BMI at 20 years old (BMI at 20), and change in BMI (BMI change), among 11,586 Japanese individuals enrolled in the Japan Multi-Institutional Collaborative Cohort study. Associations were examined using multivariable linear regression models. Results: We found a significant association (P < 0.05/282 = 1.77 × 10−4) between BMI and 11 polymorphisms in or near FTO, BDNF, TMEM18, HS6ST3, and BORCS7. The trend was similar between current BMI and BMI change, but differed from that of the BMI at 20. Among the significant variants, those on FTO were associated with all BMI traits, whereas those on TMEM18 and HS6SR3 were only associated with BMI at 20. The association of FTO loci with BMI remained, even after additional adjustment for dietary energy intake. Conclusions: Previously reported BMI-associated loci discovered in Europeans were also identified in the Japanese population. Additionally, our results suggest that the effects of each loci on BMI may vary across the life course and that this variation may be caused by the differential effects of individual genes on BMI via different pathways.

Differences in individual eating habits may be influenced by genetic factors, in addition to cultural, social or environmental factors. Previous studies suggested that genetic variants within sweet taste receptor genes family were associated with sweet taste perception and the intake of sweet foods. The aim of this study was to conduct a genome-wide association study (GWAS) to find genetic variations that affect confection consumption in a Japanese population. We analysed GWAS data on confection consumption using 14 073 participants from the Japan Multi-Institutional Collaborative Cohort study. We used a semi-quantitative FFQ to estimate food intake that was validated previously. Association of the imputed variants with confection consumption was performed by linear regression analysis with adjustments for age, sex, total energy intake and principal component analysis components 1–3. Furthermore, the analysis was repeated adjusting for alcohol intake (g/d) in addition to the above-described variables. We found 418 SNP located in 12q24 that were associated with confection consumption. SNP with the ten lowest P-values were located on nine genes including at the BRAP, ACAD10 and aldehyde dehydrogenase 2 regions on 12q24.12-13. After adjustment for alcohol intake, no variant was associated with confections intake with genome-wide significance. In conclusion, we found a significant number of SNP located on 12q24 genes that were associated with confections intake before adjustment for alcohol intake. However, all of them lost statistical significance after adjustment for alcohol intake.

There are few studies examining the association between homocysteine (Hcy) level and the risk of hypertension with consideration for folate and vitamin B12 as related to Hcy level. We simultaneously examined the associations of plasma levels of Hcy, folate, and vitamin B12, and dietary folate intake with the prevalence of hypertension. Participants included 1046 men and 1033 women (mean age ± standard deviation: 56.0 ± 8.9 years) in the Japan Multi-Institutional Collaborative Cohort Study. Dietary folate intake was estimated using a validated food frequency questionnaire. Hypertension was defined based on measured blood pressure and use of antihypertensive medication. A total of 734 participants (35.3%) had hypertension. Multivariate-adjusted odds ratios of hypertension for the highest quartile group of Hcy were 2.36 (95% CI 1.41–3.96) in men and 1.86 (95% CI 1.11–3.11) in women, as compared with the lowest group (P for trend = 0.014 and 0.005, respectively). Dietary folate intake was not correlated with hypertension in both men and women (P for trend = 0.099 and 0.703, respectively). Plasma vitamin B12 was positively associated with hypertension only in women (P for trend = 0.027). Plasma Hcy level was positively linked with hypertension after controlling for covariates, including folate and vitamin B12.

Background The process of birth causes stress for neonates, but additional stressors for sick neonates are a matter of concern. As analysis of heart-rate variability (HRV), which reflects autonomic activity, has demonstrated that low-frequency (LF) activity reflects overall autonomic activity, high-frequency (HF) activity reflects parasympathetic activity, and the LF/HF ratio reflects sympathetic activity, HRV has been clinically applied as a non-invasive index of physical stress. In this study, we evaluated whether HRV is useful as a stress index for neonates by analyzing it in comparison with their salivary cortisol level. Methods We measured the salivary cortisol level and HRV in 12 healthy neonates and 37 neonates born during between 2014 and 2016 and admitted to the neonatal intensive care unit. These examinations were performed at birth and after approximately 1 week. The changes in parameters with time were examined. Results The LF and HF values in both groups exhibited significant negative correlations with the salivary cortisol level. In those admitted to the neonatal intensive care unit, the LF and HF values were correlated with gestational age and height. In the healthy neonates, a reduced salivary cortisol level and increase in the LF and HF values were observed approximately 1 week after birth compared with the values at birth, whereas the LF/HF ratio was not correlated with the salivary cortisol level and did not change over time. Conclusions The LF and HF values were significantly correlated with the cortisol level, suggesting their usefulness as physiological indices of stress in clinical neonatal care.

ObjectivesGenome-wide meta-analyses of clinically defined gout were performed to identify subtype-specific susceptibility loci. Evaluation using selection pressure analysis with these loci was also conducted to investigate genetic risks characteristic of the Japanese population over the last 2000–3000 years.MethodsTwo genome-wide association studies (GWASs) of 3053 clinically defined gout cases and 4554 controls from Japanese males were performed using the Japonica Array and Illumina Array platforms. About 7.2 million single-nucleotide polymorphisms were meta-analysed after imputation. Patients were then divided into four clinical subtypes (the renal underexcretion type, renal overload type, combined type and normal type), and meta-analyses were conducted in the same manner. Selection pressure analyses using singleton density score were also performed on each subtype.ResultsIn addition to the eight loci we reported previously, two novel loci, PIBF1 and ACSM2B, were identified at a genome-wide significance level (p–8) from a GWAS meta-analysis of all gout patients, and other two novel intergenic loci, CD2-PTGFRN and SLC28A3-NTRK2, from normal type gout patients. Subtype-dependent patterns of Manhattan plots were observed with subtype GWASs of gout patients, indicating that these subtype-specific loci suggest differences in pathophysiology along patients’ gout subtypes. Selection pressure analysis revealed significant enrichment of selection pressure on ABCG2 in addition to ALDH2 loci for all subtypes except for normal type gout.ConclusionsOur findings on subtype GWAS meta-analyses and selection pressure analysis of gout will assist elucidation of the subtype-dependent molecular targets and evolutionary involvement among genotype, phenotype and subtype-specific tailor-made medicine/prevention of gout and hyperuricaemia.

Few studies have investigated the interactions between HDL-C-related SNPs identified by genome-wide association (GWA) study and physical activity (PA) on HDL-C. First, we conducted a sex-stratified GWA study in a discovery sample (2,231 men and 2,431 women) and replication sample (2,599 men and 3,109 women) to identify SNPs influencing log-transformed HDL-C in Japanese participants in the baseline survey of the Japan Multi-Institutional Collaborative Cohort Study. We also replicated previously reported HDL-C-related SNPs in a combined (discovery plus replication) sample (4,830 men and 5,540 women). We then analyzed the interactions of the HDL-C-related SNPs with PA on HDL-C. The sex-stratified GWA analyses identified 11 and 10 HDL-C-related SNPs in men and women as targets for an interaction analysis. Among these, only one interaction of ABCA1 rs1883025 with PA was statistically significant in men, after Bonferroni correction [P-interaction = 0.001 (α = 0.05/21 = 0.002)]. The per-major-allele (C allele) increase in log-transformed HDL-C was lost in men with low PA (β = 0.008) compared with those with medium (β = 0.032) or high PA (β = 0.034). These findings suggest that the benefit of carrying a C allele of ABCA1 rs1883025 on enhancing HDL-C may be attenuated in inactive men.

Aims/Introduction Osteoporosis is known to be intimately related to sympathetic nerve activity. We examined the relationship of plasma leptin with cortical and trabecular bone components in patients with type 2 diabetes mellitus. Materials and Methods The present cross‐sectional study included 182 type 2 diabetes mellitus patients (93 men, 89 women). Cortical thickness (CoTh) and trabecular bone mineral density (BMD) were determined at the 5.5% distal radius using an LD‐100 ultrasonic bone densitometry device. Plasma leptin along with physical and laboratory measurements was simultaneously determined. Results Plasma leptin, but not body mass index (BMI), was inversely correlated with CoTh (ρ = −0.487, P, The pathophysiology of reduced cortical thickness in patients with type 2 diabetes mellitus remains unclear. We determined plasma leptin and also cortical thickness with an LD‐100 device in 192 type 2 diabetes mellitus patients. Plasma leptin was inversely associated with cortical thickness, independent of body mass index and waist‐to‐hip ratio, suggesting that hyperleptinemia due to obesity might contribute to cortical porosis in type 2 diabetes mellitus patients.

BackgroundThere was no nationwide epidemiological study of Lambert-Eaton myasthenic syndrome (LEMS) in Japan; therefore, we conducted a nationwide survey.MethodsFor the first survey, we sent survey sheets to randomly selected medical departments (n=7545) to obtain the number of LEMS who visited medical departments between 1 January 2017 and 31 December 2017. For the second survey, we sent survey sheets to the corresponding medical departments to obtain clinical information on LEMS.ResultsWe received 2708 responses (recovery rate: 35.9%) to the first survey. We estimated the number of LEMS as 348 (95% CI 247 to 449). The prevalence was 2.7 (95% CI 1.9 to 3.5) in 1 000 000 population. As a result of the second survey, we obtained 30 case records of 16 men and 14 women. Fourteen patients (46.7%) had a tumour, and 10 out of 14 tumours were small-cell lung carcinoma (71.4%). There was a predominance of men in the LEMS with tumour (paraneoplastic LEMS, P-LEMS) (n=11, 78.6%) and women in the LEMS without tumour (a primary autoimmune form of LEMS, AI-LEMS) (n=11, 68.8%) (p=0.0136). The onset age (mean (SD)) for the P-LEMS was 67.1 (9.0), and that for AI-LEMS was 57.8 (11.2) years old (p=0.0103). The disease duration (median) for P-LEMS was 2 years, and for AI-LEMS was 7.5 years (p=0.0134).ConclusionsThe prevalence of LEMS in Japan is similar to that in other countries. There are predominances of men in P-LEMS and women in AI-LEMS.

Background: Adrenomedullin (AM), an endogenous peptide, is secreted in response to cerebral ischemia, contributing to neuroprotection by exerting anti-inflammatory and vasodilatory effects. Although previous studies showed elevated levels of mid-regional fragment of pro-AM (MR-proAM), a stable marker of AM, predict unfavorable outcome in acute ischemic stroke (AIS), the role of the biomarker remains to be determined. Methods: Firstly, plasma MR-proAM levels were measured in consecutively enrolled patients with AIS within 4.5 hours of the onset and compared with those of healthy controls. Propensity score was used to match the baseline difference. Secondly, variables associated with the increased MR-proAM levels were evaluated in AIS. Finally, it was determined whether MR-proAM levels are associated with a large penumbra which was defined as ICA/M1 occlusion with NIH stroke scale ≥ 6 and ischemic core volume ≤ 50 ml calculated by the RAPID software. Results: MR-proAM levels in AIS (n = 122; median age, 77 years; male, 59%; median NIHSS 6.5) were higher (median 0.68 vs. 0.42 nmol/L, p < 0.001) compared with controls (n = 1298; median age, 58 years; male, 33%). The difference remained after matching of baseline (p=0.004). In patients with AIS, MR-proAM levels were correlated with NIHSS (r = 0.367, p < 0.001) and eGFR (r = -0.527, p < 0.001). MR-proAM levels did not correlate with ischemic core volume (r = 0.065, p = 0.478), but significantly increased in AIS patients with cardioembolic stroke (CES) (n = 53) (0.80 vs. 0.59 nmol/L, p < 0.001) and ICA/M1 occlusion (n = 40) (0.78 vs. 0.63 nmol/L, p = 0.048). Interestingly, MR-proAM levels were higher (0.85 vs. 0.62, p < 0.001) in AIS patients with a large penumbra (n = 24) compared to those without (n = 98), and the difference remained after adjustment of baseline factors (OR [95% confidence interval], 1.43 [1.10-2.02], p = 0.004). Conclusions: MR-proAM levels increase in patients with AIS, especially in those with large vessel occlusion and clinical imaging mismatch. MR-proAM is a potential biomarker for ischemic penumbra.

Background Bone mass was recently reported to be related to skeletal muscle mass in humans, and a decrease in cortical bone is a risk factor for osteoporosis. Since circulating myostatin is a factor that primarily controls muscle metabolism, this study examined the role of myostatin in blood in bone mass-skeletal muscle mass interactions. Methods The subjects were 375 middle-aged community residents with no history of osteoporosis or sarcopenia who participated in a health check-up. The subjects were divided into those with low cortical bone thickness (LCT) or low cancellous bone density (LBD) and those with normal values (NCT/NBD). Bone metabolism markers (BAP, TRACP-5b, etc.), skeletal muscle mass, serum myostatin levels, and lifestyle, were then compared between the groups. Results The percentage of diabetic participants and blood HbA1c, TRACP-5b, and myostatin levels were significantly higher, and the frequency of physical activity, skeletal muscle mass, grip strength, and leg strength were significantly lower in the LCT group than in the NCT group. The odds ratio of high myostatin in the LCT group compared with the NCT group was significant (2.26) even after adjusting for related factors. Significant differences were observed in the same items between the LBD and NBD groups as between the LCT and NCT groups, with no significant differences in skeletal muscle mass and serum myostatin levels. The serum myostatin level was significantly negatively correlated with cortical bone thickness and skeletal muscle mass. Conclusions Myostatin may regulate bone-skeletal muscle interactions and serve as a surrogate marker of cortical bone metabolism. Key messages The interaction between bone and skeletal muscle is reported to be important for preserving the activity of bone and muscle metabolism. Herein, we report for the first time that myostatin may regulate bone-skeletal muscle interactions and serve as a surrogate marker of cortical bone metabolism in adults.

The polyunsaturated fatty acid (PUFA) elongase, ELOVL5, is upregulated in breast cancer (BC) vs. adjacent normal tissue. We performed a comprehensive lipid metabolomic analysis of serum using high-resolution accurate mass spectrometry from two case-control studies that included non-BC, BC subjects pre-surgery, and BC subjects one-month post-surgery to determine if the metabolic signatures of over-active fatty acid elongation and other lipid changes could be detected in BC vs. non-BC subjects: study 1 (n = 48: non-BC, n = 69: pre-surgery BC), study 2 (blinded validation: n = 121: non-BC, n = 62: pre-surgery BC, n = 31: one month post-surgery). The ratio of the ELOVL5 precursor, linoleic acid (18:2) to a non-ELOVL5 precursor, oleic acid (18:1) was evaluated in multiple lipid pools (phosphatidylethanolamine (PtdEtn), phosphatidylcholine (PtdCho), lyso-PtdCho, and free fatty acids). This ratio was lower in pre-surgery BC subjects in all pools in both studies (p &lt, 0.001). At one-month post-surgery, the 18:2/18:1 ratios increased vs. pre-surgery and were no longer different from non-BC subjects (p &gt, 0.05 expect for lyso-PtdCho). In contrast to the elongation biomarkers, docosahexaenoic acid (22:6n-3) containing ethanolamine plasmalogen (EtnPls) species were observed to be further decreased in BC subjects one-month post-surgery vs. pre-surgery levels (p &lt, 0.001). These results are consistent with the hypothesis that ELOVL5 is upregulated in BC tissue, which would result in the selective depletion of 18:2 vs. 18:1 containing lipid species. Surgical removal of the tumor removes the overactive ELOVL5 effect on serum lipids. In contrast, the low EtnPls levels do not appear to be caused by BC tumor activity and may be pre-existent and a possible risk factor for BC. These results indicate that it may be possible to screen for both breast cancer risk and breast cancer activity using a simple blood test.

Background Helicobacter pylori (H. pylori) colonize the stomach and are considered an etiological agent of gastric cancer. The oral cavity is a transmission route to the stomach, but the exact site of colonization has not yet been explicated. Our study investigated the association between H. pylori infection and presence in oral samples. Methods Dental pulp, supragingival plaque, and saliva from 192 patients visiting the Dentistry’s outpatient clinic were collected for testing. The H. pylori ureA gene was identified via Nested PCR. Urine anti-H. pylori antibody test was utilized to detect infection. Results Twenty-five subjects were found to be antibody-positive. PCR analysis of dental pulp revealed that 23 subjects possessed the ureA gene. Twenty-one subjects were positive for both antibodies and genes in dental pulp. PCR testing revealed that 2 subjects were positive in dental plaque but negative for saliva. The subjects positive for H. pylori in dental pulp expressed clinical signs of severe dental caries. Conclusions H. pylori infected subjects expressed H. pylori in samples from the oral cavity. The main reservoir for infection within the oral cavity was determined to be dental pulp. Moreover, H. pylori are likely transmitted from dental caries to the root canal.

The fluctuation of hemoglobin A1c (HbA1c) and changes in health habits over time was not considered in previous studies. The aim of this study was to evaluate the time-sequenced association between malignancy incidence and HbA1c with a longitudinal study design using repeated measurements of HbA1c. A retrospective longitudinal study was conducted at a large teaching hospital in Tokyo, Japan, from 2005 to 2016. All participants who underwent voluntary health check-ups at the hospital were included. Our outcomes were the development of malignancy. We compared these outcomes using HbA1c categories. Longitudinal analyses were conducted with a mixed effects model in which time-dependent HbA1c measurements were applied to consider fluctuations in HbA1c levels, adjusted for covariates. A total of 77,385 nondiabetic participants were included in the study; the mean age was 44.7 and 49.4% of participants were male. During a median follow-up of 1588 (interquartile range 730–2946) days, 4506 (5.8%) participants developed malignancies. The relationship between future malignancies and HbA1c was U-shaped; both the lower HbA1c groups (OR 1.31, 95% CI 1.17–1.46 for

Chronic kidney disease (CKD) is a public health problem worldwide including Japan. Recent genome-wide association studies have discovered CKD susceptibility variants. We developed a genetic risk score (GRS) based on CKD-associated variants and assessed a possibility that the GRS can improve the discrimination capability for the prevalence of CKD in a Japanese population. The present study consists of 11 283 participants randomly selected from 12 Japan Multi-Institutional Collaborative Cohort Study sites. Individual GRS was constructed combining 18 single-nucleotide polymorphisms identified in a Japanese population. Participants with eGFR

Background Patients with idiopathic normal-pressure hydrocephalus (iNPH) are typically older adults with multiple comorbidities that are associated with a reduction in the efficacy of iNPH treatment via cerebrospinal fluid (CSF) shunt placement. Objective The present study aimed to investigate the effectiveness of CSF shunt for iNPH using data from a nationwide epidemiological survey in Japan. Methods We examined 1,423 patients (581 women) aged ≥60 years (median age [25%-75%]: 77 [73-80] years) who were diagnosed with iNPH following a hospital visit in 2012. Patients who experienced an improvement of at least one modified Rankin Scale (mRS) grade after the CSF shunt were classified as "improvement" while the remaining patients were classified as "non-improvement." The efficacy of the shunt intervention (n = 842) was analyzed using a binomial logistic regression analysis. Results An analysis of risk factors associated with shunt placement in patients with mRS grade 2 revealed an association between comorbid chronic ischemic lesions (odds ratio [OR], 2.28; 95% confidence interval [CI], 1.11-4.67; p = 0.025) and cervical spondylosis (OR, 3.62; 95% CI, 1.15-11.34; p = 0.027). Patients with mRS grade 3 at study entry had an association with comorbid Alzheimer's disease (OR, 3.02; 95% CI, 1.44-6.31; p = 0.003). Conclusions The results presented here showed that any age-related risk is minimal and should not be cause for rejection of surgical treatment options. Clinical decisions regarding CSF shunt should be individualized to each patient, with adequate consideration of the relative risks and benefits, including maximizing a healthy life expectancy.

OBJECTIVEThe gold standard for the diagnosis of idiopathic normal pressure hydrocephalus (iNPH) is the CSF removal test. For elderly patients, however, a less invasive diagnostic method is required. On MRI, high-convexity tightness was reported to be an important finding for the diagnosis of iNPH. On SPECT, patients with iNPH often show hyperperfusion of the high-convexity area. The authors tested 2 hypotheses regarding the SPECT finding: 1) it is relative hyperperfusion reflecting the increased gray matter density of the convexity, and 2) it is useful for the diagnosis of iNPH. The authors termed the SPECT finding the convexity apparent hyperperfusion (CAPPAH) sign.METHODSTwo clinical studies were conducted. In study 1, SPECT was performed for 20 patients suspected of having iNPH, and regional cerebral blood flow (rCBF) of the high-convexity area was examined using quantitative analysis. Clinical differences between patients with the CAPPAH sign (CAP) and those without it (NCAP) were also compared. In study 2, the CAPPAH sign was retrospectively assessed in 30 patients with iNPH and 19 healthy controls using SPECT images and 3D stereotactic surface projection.RESULTSIn study 1, rCBF of the high-convexity area of the CAP group was calculated as 35.2–43.7 ml/min/100 g, which is not higher than normal values of rCBF determined by SPECT. The NCAP group showed lower cognitive function and weaker responses to the removal of CSF than the CAP group. In study 2, the CAPPAH sign was positive only in patients with iNPH (24/30) and not in controls (sensitivity 80%, specificity 100%). The coincidence rate between tight high convexity on MRI and the CAPPAH sign was very high (28/30).CONCLUSIONSPatients with iNPH showed hyperperfusion of the high-convexity area on SPECT; however, the presence of the CAPPAH sign did not indicate real hyperperfusion of rCBF in the high-convexity area. The authors speculated that patients with iNPH without the CAPPAH sign, despite showing tight high convexity on MRI, might have comorbidities such as Alzheimer’s disease.

Objective To study the updated prevalence and clinical features of myasthenia gravis (MG) in Japan during 2017. Methods We sent survey sheets to the randomly selected medical departments (number = 7,545). First, we asked the number of MG patients who visited medical departments from January 1, 2017, to December 31, 2017. Then, we sent the second survey sheet to the medical departments that answered the first survey to obtain the clinical information of patients who received MG diagnosis between January 1, 2015, and December 31, 2017. Results The received answer to the first survey were 2,708 (recovery rate: 35.9%). After all, the prevalence of the 100,000 population was estimated as 23.1 (95%CI: 20.5–25.6). As a result of the second survey, we obtained 1,464 case records. After checking the duplications and lacking data, we utilized 1,195 data for further analysis. The median [interquartile range (IQR)] from the onset age of total patients was 59 (43–70) years old. The male-female ratio was 1: 1.15. The onset age [median (IQR)] for female patients was 58 (40–72) years old, and that for male patients was 60 (49–69) years old (Wilcoxon-Mann-Whitney test, p = 0.0299). We divided patients into four categories: 1) anti-acetylcholine receptor antibody (AChRAb) (+) thymoma (Tm) (-), 2) AChRAb(+)Tm(+), 3) anti-muscle-specific kinase antibody (MuSKAb) (+), and AChRAb(-)MuSKAb(-) (double negative; DN). The onset age [median (IQR)] of AChRAb(+)Tm(-) was 64 (48–73) years old, and AChRb(+)Tm(+) was 55 (45–66), MuSKAb(+) was 49 (36–64), DN was 47 (35–60) year old. The multivariate logistic regression analysis using sex, initial symptoms, repetitive nerve stimulation test (RNST), and edrophonium test revealed that sex, ocular symptoms, bulbar symptoms, and RNST were factors to distinguish each category. The myasthenia gravis activities of daily living profile at the severest state were significantly higher in MuSKAb(+). MuSKAb(+) frequently received prednisolone, tacrolimus plasmapheresis, and intravenous immunoglobulin; however, they received less acetylcholine esterase inhibitor. 99.2% of AChRAb(+)Tm(+) and 15.4% of AChRAb(+)Tm(-) received thymectomy. MuSKAb(+) did not receive thymectomy, and only 5.7% of DN received thymectomy. The prognosis was favorable in all categories. Conclusion Our result revealed that the prevalence of Japanese MG doubled from the previous study using the same survey method in 2006. We also found that the onset age shifted to the elderly, and the male-female ratio reached almost even. Classification in four categories; AChRAb(+)Tm(-), AChRAb(+)Tm(+), MuSKAb(+), and DN, well describe the specific clinical features of each category and differences in therapeutic approaches.

Prostate cancer is emerging as a significant global public health burden. The incidence and prevalence of prostate cancer has increased in Japan, as westernized lifestyles become more popular. Recent advances in genetic epidemiology, including genome-wide association studies (GWASs), have identified considerable numbers of human genetic factors associated with diseases. Several GWASs have reported significant loci associated with serum prostate-specific antigen (PSA) levels. One GWAS, which was based on classic GWAS microarray measurements, has been reported for Japanese so far. In the present study, we conducted a GWAS of serum PSA using 1000Genomes imputed GWAS data (n =1,216) from the Japan Multi-Institutional Collaborative Cohort (J-MICC) Study, to detect candidate novel genetic loci that influence serum PSA levels in Japanese. The association of SNPs/genetic variants with serum PSA as a continuous variable was tested using the linear Wald test. SNP rs10000006 in SGMS2 (sphingomyelin synthase 2) on chromosome 4 had genome-wide significance (P

Secular changes in the incidence rate of hip fractures were estimated to vary by fracture type, i.e., femoral neck or trochanteric fractures, age, and sex, in urban or rural areas in Kyoto Prefecture, Japan from 2008 to 2017. PURPOSE Our survey in Kyoto Prefecture from 2008 to 2017 showed that the incidence rate of femoral neck fractures is generally increasing. We investigated the differences between urban and rural areas in the changes of the incidence rate over time of femoral neck and trochanteric fractures during the same period. METHODS Patients aged 65 years and above who sustained hip fractures between 2008 and 2017 and were treated at one of the participating 11 hospitals were included. The ratio of sick beds for acute-term care at the investigated hospitals to total number of beds in the urban area was 16.5% (1863/11,158) and 30.6% (1863/5623) in the rural area. The change in incidence rate was estimated utilizing the population according to the national census conducted in 2010 and 2015. RESULTS There were 3559 and 6474 hip fractures in the urban and rural areas, respectively. Femoral neck fractures were 1936 (54.4%) and 2813 (43.5%) in each area. The increase of the population-adjusted numbers was marked by neck fractures in males, in both areas. In women, there was a significant increase in femoral neck fractures in the urban area in those aged 85 years and over. For trochanteric fractures, a significant increase was only found in women aged 65 to 74 years in the rural area. CONCLUSION A regional difference in the secular changes in incidence rate of hip fractures was found in women, not in men, mostly because neck fractures in women increased in the over 85 group in the urban area.