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Although the feasibility of randomized trials for investigating the long-term association between oral health and cognitive decline is low, deriving causal inferences from observational data is challenging. We aimed to investigate the association between poor oral status and subjective cognitive complaints (SCC) using fixed-effects model to eliminate the confounding effect of unobserved time-invariant factors.We used data from Japan Gerontological Evaluation Study (JAGES) which was conducted in 2010, 2013, and 2016. β regression coefficients and 95% confidence intervals [CIs] were calculated using fixed-effects models to determine the effect of deteriorating oral status on developing SCC. Onset of SCC was evaluated using the Kihon Checklist-Cognitive function score. Four oral status variables were used: awareness of swallowing difficulty, decline in masticatory function, dry mouth, and number of teeth.We included 13,594 participants (55.8% women) without SCC at baseline. The mean age was 72.4 (standard deviation [SD], 5.1) years for men and 72.4 (SD, 4.9) years for women. Within the 6-year follow-up, 26.6% of men and 24.9% of women developed SCC. The probability of developing SCC was significantly higher when participants acquired swallowing difficulty (β = 0.088; 95% CI, 0.065-0.111 for men and β = 0.077; 95% CI, 0.057-0.097 for women), decline in masticatory function (β = 0.039; 95% CI, 0.021-0.057 for men and β = 0.030; 95% CI, 0.013-0.046 for women), dry mouth (β = 0.026; 95% CI, 0.005-0.048 for men and β = 0.064; 95% CI, 0.045-0.083 for women), and tooth loss (β = 0.043; 95% CI, 0.001-0.085 for men and β = 0.058; 95% CI, 0.015-0.102 for women).The findings suggest that good oral health needs to be maintained to prevent the development of SCC, which increases the risk for future dementia.

Few studies have examined whether maintaining moderate or vigorous physical activity (PA) reduces the risk of low back pain in older people. This study aimed to examine the magnitude of the associations of changes in PA on the risk of low back pain at 4 years of follow-up. We analyzed 4,882 participants in the English Longitudinal Study of Ageing who were initially free from low back pain (mean age, 65.6 ± 8.9 years at baseline). Self-reported PA, which was assessed at wave 6 (2012–2013) and wave 7 (2014–2015), was used as the exposure. The PA of the respondents was categorized into “no PA at all,” “up to moderate PA,” and “up to vigorous PA” groups. Self-reported moderate/severe low back pain assessed at 4 years of follow-up (2016–2017) was used as the outcome. Maintaining moderate (relative risk [RR], 0.59; 95% confidence interval [CI], 0.36–0.99) or vigorous (RR, 0.46; 95% CI, 0.27–0.77) PA at least 1–3 times a month was negatively associated with prevalence of low back pain compared with no PA at all. Interventions for maintaining either moderate or vigorous PA might be beneficial in preventing the incidence of low back pain in the older population. Perspective Perspective: This study examined the magnitude of the association between changes in physical activity over time and the risk of low back pain. The findings suggest that encouraging people to maintain at least moderate physical activity over 2 years is useful for reducing the risk of low back pain at 4 years of follow-up.

The prognostic significance of combining intra-aortic balloon pumping (IABP) with extracorporeal membrane oxygenation (ECMO) for acute myocardial infarction (AMI) patients is still unclear. We investigated whether combining IABP with veno-arterial (VA)-ECMO is associated with a lower risk of short-term mortality.Among 12,093 AMI cases enrolled in the Osaka Acute Coronary Insufficiency Study (OACIS), we identified 519 who were administered VA-ECMO during hospitalization. Among these, 459 received IABP support (IABP group) and 60 cases did not (no-IABP group). The primary endpoint was 30-day all-cause death; the secondary endpoint was major bleeding. Logistic regression analysis using original data was conducted. We also established weighted logistic regression models with inverse probability of treatment weighting (IPTW).Logistic regression analysis revealed that IABP use was significantly associated with a reduced risk of 30-day death in the original data [odds ratio (OR) 0.504, 95% confidence interval (CI) 0.282-0.901, p = 0.021]. After IPTW-adjustment for clinically relevant covariates with the use of IABP, patients receiving VA-ECMO with IABP had a lower risk of 30-day death (OR 0.816, 95% CI 0.746-0.892, p0.001) compared to those without IABP. The incidence of major bleeding was comparable between the groups (IABP 29.0% vs. non-IABP 21.7%, p=0.302). However, the risk of major bleeding was higher in the IABP group after IPTW-adjustment (OR 1.092, 95% CI 1.008-1.184, p=0.032).IABP support for AMI patients with VA-ECMO was significantly associated with reduced risk of short-term mortality, suggesting that the addition of IABP support might contribute to improved survival in AMI patients requiring VA-ECMO.

AIMS/INTRODUCTION Metformin is associated with the risk of gastrointestinal complications, and probiotic Bifidobacterium bifidum G9-1 (BBG9-1) can improve the symptoms of diarrhea. This study aimed to clarify the effects of probiotic BBG9-1 on the gastrointestinal symptoms of type 2 diabetes mellitus patients using metformin. MATERIALS AND METHODS In this open-label single-arm exploratory study, 40 patients (mean age 64.0 ± 9.4 years) were given probiotic BBG9-1 for 10 weeks. Changes in the gastrointestinal symptom rating scale total score, which was the primary end-point, gastrointestinal symptom rating scale subscale scores, glycated hemoglobin levels and gut microbiota after the administration of probiotic BBG9-1 were evaluated by the Student's t-test. RESULTS The gastrointestinal symptom rating scale total score significantly improved (from 2.02 ± 0.51 to 1.59 ± 0.43, change, -0.43 ± 0.49, P

Aim Post‐surgical weight loss influences chemotherapy compliance and may be a risk factor for survival. Intake of an oral elemental nutritional supplement (OENS) can reduce weight loss after gastric cancer (GC) surgery. We assessed whether therapy completion levels would increase in patients receiving postoperative adjuvant chemotherapy in combination with an OENS. Methods This was a multicenter, open‐label, single‐arm, phase II study in GC patients who underwent curative total or distal gastrectomy (TG/DG) and received adjuvant S‐1 chemotherapy. The primary endpoint was the S‐1 completion rate for 1 year with a relative performance (RP) value of ≥70%; secondary endpoints included factors affecting the completion rate of S‐1, RP value after eight S‐1 courses, S‐1 and OENS persistence rates, nutritional index, OENS compliance, and safety. Results In 71 efficacy‐evaluable patients, the S‐1 completion rate was 69.0% (TG, 68.0%; DG, 69.6%) and the RP value was 87.5 (TG, 89.1; DG, 87.5). Over eight treatment courses, median persistence rates were 89.0% for S‐1 and 93.8% for the OENS. The mean OENS compliance was 81.8% at the fourth S‐1 course and 52.9% at the eighth course. The incidence of Grade 3 or 4 adverse events was 27.2%, most commonly neutropenia (12.3%). Conclusions The completion rate of S‐1 for 1 year in patients who could take the OENS exceeded the pre‐defined threshold level. Randomized controlled trials are warranted to confirm the role of OENS in adjuvant chemotherapy., Post‐surgical weight loss influences chemotherapy compliance and may be a risk factor for survival. Intake of an oral elemental nutritional supplement (OENS) can reduce weight loss after gastric cancer (GC) surgery

Background Studies suggest that fragmented QRS (fQRS) can predict arrhythmic events in various cardiac diseases. However, the association between fQRS recordings on intracardiac electrogram (EGM) and ventricular arrhythmic events remains unknown. Methods We enrolled 51 patients (age, 62 ± 12 years; 40 men) with an implantable cardioverter‐defibrillator (ICD) and structural heart disease and evaluated surface electrocardiogram (ECG) and EGM measurement of fQRS and the association between fQRS and arrhythmic events. Results fQRS was detected on surface ECG and ICD‐EGM in 12 (23.5%) and 15 (29.4%) patients, respectively. fQRS was detected more frequently on ICD‐EGM in patients with fQRS on surface ECG than in patients without fQRS (7/12 [58.3%] vs 8/39 patients [20.5%], P = .01). Appropriate ICD therapies were documented in 16 patients. Among these patients, fQRS was detected more frequently on surface ECG and ICD‐EGM in patients with appropriate ICD therapies (8/16, 50.0%; P = .001 and 11/16, 68.9%; P, We enrolled patients with implantable cardioverter defibrillator (ICD) and structural heart disease and evaluated the surface electrocardiogram (ECG) and intracardiac electrogram (EGM) measurement of fQRS and the association between fQRS and arrhythmic events.Appropriate ICD therapies were significantly higher in patients with fQRS on both surface ECG and ICD EGM than in those without.Surface ECG and ICD‐EGM measurement may help predict ventricular arrhythmic events.

Background: Monocarboxylate transporter 8 (MCT8) deficiency is an X-chromosome-linked neurodevelopmental disorder resulting from impaired thyroid hormone transport across the cell membrane. The diagnosis of MCT8 deficiency is typically delayed owing to the late appearance of signs and symptoms as well as the inability of standard biomarkers of neonatal screening to provide early detection. In this study, we report, for the first time, the ability to detect MCT8 deficiency at birth using dried blood spot (DBS) samples. Methods: We retrospectively measured triiodothyronine (T3), thyroxine (T4), and reverse T3 (rT3) levels in DBS samples obtained at 4–5 days of life from 6 infants with genetically confirmed MCT8 deficiency and from 110 controls. The latter consisted of 58 healthy term neonates obtained at the same time, 16 were stored for more than 1 year before measurement to match samples from the MCT8-deficient infants. Ten DBS samples were collected at day 1 of life and 42 samples were from prematurely born neonates. Measurements were carried out in extract from eight millimeters diameter DBS using liquid chromatography-tandem mass spectrometry. Results: Contrary to characteristic iodothyronine abnormalities of MCT8 deficiency during later life, T3 and T4 values were not discriminatory from those of other study groups. In contrast, rT3 was significantly lower. The T3/rT3 ratio was higher in the DBS samples from the MCT8-deficient infants compared with all other groups with no overlap (p

Background The active hip abduction test (AHAbd) is widely used to evaluate lumbopelvic stability, but the onset of trunk muscle activation during the test in individuals with recurrent low back pain (rLBP) has not been investigated so far. It is important to investigate the pattern of trunk muscle activation during the AHAbd test to provide insight into the interpretation of observation-based assessment results; this may help to create exercise therapy interventions, from a movement control perspective, for people seeking treatment for rLBP. The purpose of this study was to compare the timing of trunk muscle activation between individuals with and without rLBP and to assess potential differences. Methods Seventeen subjects in remission from rLBP and 17 subjects without rLBP were recruited. We performed surface electromyography of the transversus abdominis/internal abdominal oblique, external oblique, erector spinae, and gluteus medius muscles during the AHAbd test on both sides. The onset of trunk muscle activation was calculated relative to the prime mover gluteus medius. The independent-samples t- and Mann-Whitney U tests were used to compare the onset of trunk muscle activation between the two groups. Results The onset of transversus abdominis/internal abdominal oblique activation on the ipsilateral (right AHAbd: −3.0 ± 16.2 vs. 36.3 ± 20.0 msec, left AHAbd: −7.2 ± 18.6 vs. 29.6 ± 44.3 ms) and contralateral sides (right AHAbd: −11.5 ± 13.9 vs. 24.4 ± 32.3 ms, left AHAbd: −10.1 ± 12.5 vs. 23.3 ± 17.2 ms) and erector spinae on the contralateral side (right AHAbd: 76.1 ± 84.9 vs. 183.9 ± 114.6 ms, left AHAbd: 60.7 ± 70.5 vs. 133.9 ± 98.6 ms) occurred significantly later in individuals with rLBP than in individuals without rLBP (p 0.05). Conclusions Our results suggest that individuals with rLBP possess a trunk muscle activation pattern that is different from that of individuals without rLBP. These findings provide an insight into the underlying muscle activation patterns during the AHAbd test for people with rLBP and may support aggressive early intervention for neuromuscular control.

Aims At present, the clinical significance of admission hyperglycaemia in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. This study was designed to evaluate the relationship between admission hyperglycaemia and clinical outcome in HFpEF patients, especially in non‐diabetic patients. Methods and results We enrolled 486 non‐diabetic HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We divided non‐diabetic patients into two groups, an admission hyperglycaemia group whose blood glucose on admission was ≥7.0 mmol/L (148 patients) and a normoglycaemic group whose blood glucose on admission was

Aims The prognostic importance of admission systolic blood pressure (SBP) in heart failure with preserved ejection fraction (HFpEF) is elusive. We aimed to clarify the pathophysiological differences between patients categorized with admission SBP among HFpEF patients. Methods and results We studied 1008 inpatients from PURSUIT‐HFpEF, a multicentre prospective observational registry. We classified patients as having elevated (>140 mmHg), preserved (90–140 mmHg), or low (

Aims The impacts of high density lipoprotein cholesterol (HDL‐C) as an anti‐inflammatory and C reactive protein (CRP) as inflammatory properties on the pathogenesis of heart failure were reported. At present, the clinical significance of the HDL‐C/CRP ratio in heart failure with preserved ejection fraction (HFpEF) patients remains unknown. Methods and results We examined the data on 796 consecutive HFpEF (left ventricular ejection fraction ≥50%) patients hospitalized due to acute decompensated heart failure from the PURSUIT‐HFpEF registry, a prospective, multicentre observational study. We calculated the HDL/CRP ratios and evaluated the relationship between the values and clinical outcomes, including degree of cardiac function. The mean follow‐up duration was 420 ± 346 days. All‐cause death occurred in 118 patients, of which 51 were cardiac deaths. HDL/CRP ≤ 4.05 was independently and significantly associated with all‐cause death (odds ratio = 1.84, 95% CI: 1.06–3.20, P = 0.023), and HDL/CRP ≤ 3.14 was associated with cardiac death by multivariate Cox proportional hazard analysis (odds ratio = 2.86, 95% CI: 1.36–6.01, P = 0.003). HDL‐C/CRP ratio significantly correlated with the product of the left atrial volume and left ventricular mass index as well as the tricuspid annular plane systolic excursion by multiple regression analysis (standardized beta‐coefficient = −0.085, P = 0.034 and standardized beta‐coefficient = 0.081, P = 0.044, respectively). Conclusions HDL‐C/CRP ratio was a useful marker for predicting all‐cause death and cardiac death and correlated with left ventricular diastolic function and right ventricular systolic function in HFpEF patients.

Background Depression is a major health problem among older adults, for which previous studies have suggested tooth loss as a risk factor. This study examined the mediating effect of oral function and orofacial appearance in the relationship between tooth loss and depression. Methods This three-year follow-up longitudinal study was based on a self-reported questionnaire targeting community-dwelling older adults aged ≥65 years. We used the incidence of depressive symptoms during follow-up as the outcome, the number of remaining teeth (≥20/≤19) as the exposure, and the deterioration of oral function and orofacial appearance (speaking, smiling, and eating) as mediators. We fitted the logistic regression model including confounders and calculated the natural indirect effect (NIE), natural direct effect, and the proportion mediated (PM) by the deterioration of oral functions by applying the causal mediation analysis framework. Results The mean age of the 8,875 participants was 72.7 years (1SD=5.5) and 48.0% were male. Depressive symptoms developed during follow-up in 11.5% of the participants (n=1,024). The incidence for those with ≤19 and ≥20 remaining teeth was 13.1% and 9.2%, respectively. Total effect of fewer remaining teeth (≤19) on depressive symptoms was OR=1.30 (95%CI=1.12–1.51). Difficulty in speaking (NIE OR=1.03, 95%CI=1.00–1.06, PM=12.4%), problems in smiling (NIE OR=1.04, 95%CI=1.01–1.07, PM=16.9%), and difficulty in chewing (NIE OR=1.05, 95%CI=1.02–1.09, PM=21.9%) significantly mediated the relationship. Limitation Selection bias due to dropout. Conclusion Deterioration of oral function and orofacial appearance were mediating factors of the mechanism for the relationship between tooth loss and the incidence of depressive symptoms.

Objectives To evaluate whether the long-term usage of mirabegron, which was reported to have potential side effects on male reproductive organs in animal studies, was harmful to spermatogenesis in human testis. Methods Thirty consecutive patients with spinal cord injury (20-48 years old) who performed clean intermittent catheterization were involved in this study. Ten patients were treated with mirabegron (50 mg/d) for more than 2 years and refrained from using an antimuscarinic agent due to the side effects of constipation and dry mouth. Twenty patients were treated with neither anticholinergic agents nor mirabegron. All underwent conventional testicular sperm extraction. The sperm recovery rate and histopathologic findings of the retrieved testicular tissue were compared between both groups. Results We found no difference in the sperm recovery rate (P = .083) between both groups. Spinal cord injury patients treated with mirabegron had better spermatogenesis than those not treated with mirabegron (P Conclusions From these data, we conclude that the therapeutic dose of mirabegron had no harmful effect on spermatogenesis in spinal cord injury patients of reproductive age.

The native tricuspid leaflets are sometimes preserved with tricuspid valve replacement to prevent atrioventricular block or maintain right ventricular function. However, after a tricuspid valve replacement using bioprosthetic valve, a rare complication involving adhesion of the pannus formation to the prosthetic valve may occur. We report the case of a 48-year-old woman who underwent a third tricuspid valve replacement with a bioprosthetic valve for severe tricuspid regurgitation 2.5 years after the redo tricuspid valve replacement.

Background Primary neuroendocrine tumors of the gallbladder (GB-NETs) are rare, accounting for 0.5% of all NETs and 2.1% of all gallbladder cancers. Among GB-NETs, mixed neuroendocrine–non-neuroendocrine neoplasms of the gallbladder (GB-MiNENs) are extremely rare. Case presentation We present the case of a 66-year-old woman who was referred to us for the management of a gallbladder tumor (incidentally found during abdominal ultrasonography indicated for gallbladder stones). The patient had no history of abdominal pain or fever, and the findings on a physical examination were unremarkable. Blood tests showed normal levels of tumor markers. Imaging studies revealed a mass of approximately 10 mm in diameter (with no invasion of the gallbladder bed) located at the fundus of the gallbladder. A gallbladder cancer was suspected. Therefore, an open whole-layer cholecystectomy with regional lymph nodes dissection was performed. The postoperative course was uneventful, and she was discharged on postoperative day 6. Pathological findings showed GB-MiNENs with invasion of the subserosal layer and no lymph node invasion (classified T2aN0M0 pStage IIA according to the Union for International Cancer Control, 8th edition staging system). Analysis of the neuroendocrine markers revealed positive chromogranin A and synaptophysin, and a Ki-67 index above 95%. Fourteen months after the operation, a local recurrence was detected, and she was referred to another hospital for chemotherapy. Conclusions GB-MiNENs are extremely aggressive tumors despite their tumor size. Optimal therapy should be chosen for each patient.

Introduction Pigment epithelium-derived factor (PEDF) may play a role in cardiometabolic disorders. The aim of this study was to investigate which biochemical and clinical parameters are independently associated with serum PEDF levels in patients with type 2 diabetes mellitus (T2DM). Methods We performed a cross-sectional analysis of 124 patients with T2DM who underwent continuous glucose monitoring (CGM) and blood chemistry analysis, including the diacron-reactive oxygen metabolites (d-ROMs) test and serum PEDF measurement (study 1). Then we investigated whether the changes in the studied biochemical and clinical parameters after 24 weeks of treatment (Δparameters) with anti-hyperglycemic agents, including sodium-glucose cotransporter 2 inhibitors, glucagon-like peptide 1 receptor agonists, and/or insulin and anti-hypertensive drugs and statins, were independently correlated with change in PEDF (ΔPEDF) in 52 of the patients with T2DM for whom there was sufficient serum samples to perform the post-treatment analysis (study 2). Serum levels of PEDF were measured with an enzyme-linked immunosorbent assay. CGM metrics were calculated on days 2 and 3. Oxidative stress was evaluated using the d-ROMs test. Results Body mass index (BMI), triglycerides, fasting C-peptide, mean amplitude of glycemic excursions (MAGE), urinary albumin-to-creatinine ratio (UACR), and d-ROMs were positively associated with serum PEDF level, and high-density lipoprotein cholesterol (HDL-C) and estimated glomerular filtration rate (eGFR) were inversely associated with serum PEDF level. Because these parameters were correlated with each other, multivariate stepwise analysis was performed: eGFR, HDL-C, BMI, MAGE, and UACR remained significant (R2 = 0.452). Furthermore, ΔMAGE and Δd-ROMs were positively correlated with ΔPEDF in study 2. Conclusions The results of this study suggest that MAGE may be independently correlated with elevations in serum PEDF level in patients with T2DM.

Cardiac hemangioma is relatively rare, accounting for approximately 1-3% of all primary heart tumors. This benign tumor may be an incidental lesion, but can also cause arrhythmias, pericardial effusion, congestive heart failure or outflow obstruction. We report a rare case with exophytic cardiac hemangioma arising from the right ventricle. Echocardiography showed an approximately 40 mm round protruding mass on the anterior wall of the right ventricle. Cardiovascular magnetic resonance demonstrated isointense and hyperintense signals on T1- and T2-weighted images, respectively. These imaging studies suggested a pericardial cyst. Perioperative findings indicated a globular, exophytic mass, vascular in nature, arising from the right ventricle. The lesion was resected directly, and the space left by defect in the right ventricular wall was covered with a bovine pericardial patch. Cardiac hemangiomas are generally endoluminal tumors, but we must keep in mind that the differential diagnoses include various pericardial lesions by medical images.

Cabozantinib (CAB) is a receptor tyrosine kinase inhibitor with activity against MET, VEGFR2, and AXL, among others. This drug is considered to exert excellent antitumor effects by inhibiting these targets simultaneously. Significant improvement in the primary endpoint (overall survival or PFS) were observed in patients on CAB in comparison with controls in a phase-III study in patients with renal cell carcinoma, progressed after treatment with anti-angiogenic agents, and in another phase-III study in patients with previously treated, advanced hepatocellular carcinoma. These results led to the approval of CAB in Japan in 2020 as a therapeutic agent for unresectable or metastatic renal cell carcinoma and unresectable hepatocellular carcinoma progressed after cancer chemotherapy, under the trade name of CABOMETYX® (20 mg, and 60 mg tablets). It has been suggested that CAB may modulate the immune system in favor of antitumor immunity and combined use with PD-1 checkpoint inhibitors may exert a synergistic effect. In a phase-III study that examined the efficacy of combination therapy with CAB and nivolumab in treatment-naive patients with advanced renal cell carcinoma, progression-free survival was significantly increased in patients on combination therapy over patients on sunitinib monotherapy. Three global phase-III clinical studies of combination therapy with atezolizumab and CAB in patients with non-small cell lung cancer, castration-resistant prostate cancer, and renal cell carcinoma, are in progress to confirm the efficacy of CAB.

Introduction Metachromatic leukodystrophy (MLD) refers to leukodystrophy caused by the accumulation of sulfatide from arylsulfatase A (ARSA) gene mutations. Sulfatide also accumulates in various organs, including the peripheral nerves, kidney, and gallbladder. Proliferative changes in the gallbladder have been reported in several patients, while gallbladder cancer is reported in only two adult MLD cases. We report what is likely the first pediatric case of MLD with gallbladder cancer. Case report The patient was a 5-year-old girl diagnosed with MLD using head magnetic resonance imaging and detecting a homozygous mutation of c.302G>A (p.Gly101Asp) in ARSA. Abdominal bloating was observed at the age of 4 years; CT revealed a giant tumor in the gallbladder and massive ascites. Cholecystectomy was performed and pathological examination revealed adenocarcinoma. Measurement of serum sulfatide revealed increased levels compared to the average healthy range. Discussion Rapidly increased ascites and large polyps which are reported as risk factors for cancer were characteristic in our MLD case. When such lesions are detected, they should be removed immediately because of the possibility of cancer, even in a pediatric patient.

Chondroid lipoma (CL) in the oral cavity is relatively rare. Here, we report a case of CL arising from the tongue. A 51-year-old man with a painless soft tissue swelling on the left tongue was referred to our department for detailed examination and treatment. As no metastatic lesions were found at other sites, CL was suspected. Subsequently, we performed tumor resection under general anesthesia. Histological findings revealed mature adipocytes and small, round vacuolar cells against the background of the myxoid and chondroid matrix. Immunohistochemical staining showed that these adipocytes and vacuolar cells were positive for S-100. Furthermore, the myxoid and chondroid matrix were stained blue with Alcian blue staining, and acidic mucopolysaccharides were identified. Therefore, we diagnosed this tumor as a CL. The patient was alive without recurrence or metastasis 14 months after surgery. CL is an extremely rare benign adipose tumor that should be carefully differentiated from liposarcoma and myxoid liposarcoma to avoid overtreatment.

Severe acute respiratory syndrome coronavirus 2 rapid antigen detection (RAD) test kits are widely used as primary screening test in Japan because rapid diagnosis of coronavirus disease 2019 (COVID-19) is critical for infection control. We report cases with RAD test false-positive results in a ward for patients with disabilities. RAD tests potentially evoke hospital operational risk. It is desirable that performing PCR test appropriately when patients admitted to a medical treatment ward with COVID-19 symptoms instead of RAD test.

INTRODUCTION In laparoscopic surgery, surgical instruments are inserted from a trocar to the target organ in a blind fashion, which carries a risk of organ injury. To clarify the risks associated with surgical instrument insertion, we measured grip strength and pushing/pressing force during surgical instrument insertion in laparoscopic surgery. METHODS Using forceps with sensors inside a trocar, 10 urologists performed a laparoscopic procedure in pigs, in which they were asked to touch the abdominal wall. The surgeons closed their eyes during the procedure and stopped moving the forceps when they felt them come into contact with the abdominal wall. They were ordered to grip the forceps strongly or softly and to move them rapidly or slowly during the procedure. Grip strength and the pushing/pressing force when the forceps hit the abdominal wall were measured and analyzed. RESULTS The mean pushing/pressing force when the surgeons gripped the forceps strongly and moved them rapidly (strong/rapid), strongly/slowly, softly/rapidly, and softly/slowly were 2.8, 2.0, 1.7, and 1.1 N, respectively. The pushing/pressing force was significantly greater when the surgeons gripped the forceps strongly, regardless of the forceps speed (P

Excessive intake of fat causes accumulation of fat in liver, leading to non-alcoholic fatty liver disease (NAFLD). High-fat diet (HFD) upregulates the expression of Factor D, a complement pathway component, in the liver of mice. However, the functions of Factor D in liver are not well known. Therefore, the current study investigated the relationship between Factor D and hepatic lipid accumulation using CRISPR/Cas9-mediated Factor D knockout (FD-KO) mice. Factor D deficiency downregulated expression of genes related to fatty acid uptake and de novo lipogenesis in the liver. Furthermore, Factor D deficiency reduced the expression of inflammatory factors (Tnf and Ccl2) and fibrosis markers and decreased accumulation of F4/80-positive macrophages. These data suggest that the Factor D deficiency improved hepatic lipid accumulation and hepatic inflammation in HFD-fed mice.

Salivary duct carcinoma (SDC) that occurs in the oral cavity in the minor salivary glands is relatively rare. Here, we report a case of SDC arising from the buccal minor salivary glands. An 83-year-old man with a mass in the right buccal mucosa was referred to our department for detailed examination and treatment. As no metastatic lesions were found at other sites, SDC was suspected, and cT4aN0M0: Stage IVa was diagnosed in the right buccal mucosa. Subsequently, we performed tracheostomy, tumor resection, mandibular resection, reconstruction with a pectoralis major flap, and split-thickness skin graft under general anesthesia. Histological findings revealed formation of small alveolar clusters in the tumor with invasive proliferation in the surrounding tissue; keratinization was unclear. The findings indicated a glandular malignancy. Histologically, the tumor cells were strongly positive for HER2, AR, and GCDFP-15. Therefore, we diagnosed this tumor as an SDC. The patient is alive without recurrence or metastasis 29 months after surgery. As SDC is rare, especially in the minor salivary glands, the prognosis is poor, and the treatment not established. Hence, studies of accumulated cases are necessary for establishing adequate treatment for SDC of the head and neck region.

Objective: Remodeling of the extracellular matrix plays a vital role in cardiovascular diseases. Using a mouse model of postnatal ascending aortic aneurysms (termed Fbln4 SMKO ), we have reported that abnormal mechanosensing led to aneurysm formation in Fbln4 SMKO with an upregulation of the mechanosensitive transcription factor, Egr1 (Early growth response 1). However, the role of Egr1 and its upstream regulator(s) in the initiation of aneurysm development and their relationship to an aneurysmal microenvironment are unknown. Approach and Results: To investigate the contribution of Egr1 in the aneurysm development, we deleted Egr1 in Fbln4 SMKO mice and generated double knockout mice ( DKO , Fbln4 SMKO ; Egr1 −/− ). Aneurysms were prevented in DKO mice (42.8%) and Fbln4 SMKO ; Egr1 +/− mice (26%). Ingenuity Pathway Analysis identified PAR1 (protease-activated receptor 1) as a potential Egr1 upstream gene. Protein and transcript levels of PAR1 were highly increased in Fbln4 SMKO aortas at postnatal day 1 before aneurysm formed, together with active thrombin and MMP (matrix metalloproteinase)-9, both of which serve as a PAR1 activator. Concordantly, protein levels of PAR1, Egr1, and thrombin were significantly increased in human thoracic aortic aneurysms. In vitro cyclic stretch assays (1.0 Hz, 20% strain, 8 hours) using mouse primary vascular smooth muscle cells induced marked expression of PAR1 and secretion of prothrombin in response to mechanical stretch. Thrombin was sufficient to induce Egr1 expression in a PAR1-dependent manner. Conclusions: We propose that thrombin, MMP-9, and mechanical stimuli in the Fbln4 SMKO aorta activate PAR1, leading to the upregulation of Egr1 and initiation of ascending aortic aneurysms.

BackgroundVariants in the type IV collagen gene (COL4A1/2) cause early-onset cerebrovascular diseases. Most individuals are diagnosed postnatally, and the prenatal features of individuals with COL4A1/2 variants remain unclear.MethodsWe examined COL4A1/2 in 218 individuals with suspected COL4A1/2-related brain defects. Among those arising from COL4A1/2 variants, we focused on individuals showing prenatal abnormal ultrasound findings and validated their prenatal and postnatal clinical features in detail.ResultsPathogenic COL4A1/2 variants were detected in 56 individuals (n=56/218, 25.7%) showing porencephaly (n=29), schizencephaly (n=12) and others (n=15). Thirty-four variants occurred de novo (n=34/56, 60.7%). Foetal information was available in 47 of 56 individuals, 32 of whom (n=32/47, 68.1%) had one or more foetal abnormalities. The median gestational age at the detection of initial prenatal abnormal features was 31 weeks of gestation. Only 14 individuals had specific prenatal findings that were strongly suggestive of features associated with COL4A1/2 variants. Foetal ventriculomegaly was the most common initial feature (n=20/32, 62.5%). Posterior fossa abnormalities, including Dandy-Walker malformation, were observed prenatally in four individuals. Regarding extrabrain features, foetal growth restriction was present in 16 individuals, including eight individuals with comorbid ventriculomegaly.ConclusionsPrenatal observation of ventriculomegaly with comorbid foetal growth restriction should prompt a thorough ultrasound examination and COL4A1/2 gene testing should be considered when pathogenic variants are strongly suspected.

A 23-year-old man was admitted to our hospital with a huge pelvic tumor. MRI showed a tumor mixed with a solid component and polycystic cyst with maximum diameter of about 20 cm. Percutaneous tumor needle biopsy was performed and diagnosis was Ewing sarcoma. At that time, operation is extremely difficult, so the neoadjuvant chemotherapy with ifosfamide, etoposide, Adriamycin, and vincristine were administered. After 6 courses, MRI showed tumor reduction to maximum diameter of 10 cm. We planned tumor resection with total cystectomy for radical resection, but we also tried to preserve bladder considering the young age and quality of life. Although the bladder was partially resected, tumor resection was succeeded without removing surrounding organs. Histopathological examination revealed viable cells remained, but more than 95% was disappeared and the surgical margins were negative. Here we report a case of extra skeletal Ewing sarcoma in the retroperitoneum that was treated with chemotherapy and surgery without scarifying surrounding organs.

Purpose Cryptorchidism is one of the most common causes of non‐obstructive azoospermia (NOA) in adulthood. Even if early orchidopexy is performed to preserve fertility potential, some patients still suffer from azoospermia. Fertility potential is significantly lower in bilateral than unilateral cryptorchidism. The aims of this study were to identify clinical parameters that predict the likely success of sperm recovery by microscopic testicular sperm extraction (micro‐TESE) and also the likely outcome of intracytoplasmic sperm injection using sperm from NOA patients who submitted to bilateral orchidopexy. Methods Fifty‐two NOA patients with a history of bilateral cryptorchidism underwent micro‐TESE. The following clinical parameters were evaluated as predictive factors for successful sperm recovery: age at micro‐TESE; age at orchidopexy; period from orchidopexy to micro‐TESE; luteinizing hormone (LH); follicle‐stimulating hormone (FSH); testosterone; average testicular volume; and body mass index. Results In the successful sperm retrieval group, average testicular volume was significantly greater, while serum LH and FSH, and body mass index were significantly lower. In a multivariate analysis, average testicular volume was positively correlated with successful sperm recovery. Conclusion Our results indicate that testicular volume in NOA patients with bilateral cryptorchidism is a predictor for successful sperm recovery.

Objectives Previous studies have shown the association between liver fibrosis and albuminuria. However, the effect of liver fibrosis on change in albuminuria is unclear. Thus, we investigated the effect of liver fibrosis on change in albuminuria in patients with type 2 diabetes. Methods In this retrospective cohort study, we assessed 105 patients with type 2 diabetes concomitant with nonalcoholic fatty disease. A change in urinary albumin excretion (UAE) was defined as follows: change in UAE=(logarithm [UAE+1] at follow-up examination minus logarithm [UAE+1] at baseline examination) / follow-up duration (1 year in this study). Elastography was performed to assess controlled attenuation parameter (dB/m) and liver stiffness measurement (LSM; kPa) values. Results Mean (standard deviation) data were as follows: age, 63.3 (12.1) years; body mass index, 25.4 (4.3) kg/m2; controlled attenuation parameter, 273.1 (53.0) dB/m; and LSM, 6.2 (3.4) kPa. Median UAE value (interquartile range) was 16 (6 to 43) mg/g creatinine. LSM was associated with changes in UAE (r=0.27, p=0.005). Multiple regression analysis demonstrated that LSM was associated with change in UAE (β=0.28, p=0.015) after adjusting for sex, age, duration of diabetes, smoking status, exercise habits, glycated hemoglobin, body mass index, estimated glomerular filtration rate, systolic blood pressure, logarithm (UAE+1) at baseline examination, use of renin‒angiotensin system inhibitors, new use of sodium glucose cotransporter-2 inhibitors and glucagon-like peptide-1 and controlled attenuation parameter. Conclusions Liver stiffness is an independent risk factor for the progression of albuminuria in patients with type 2 diabetes.

Planned caesarean delivery (CD) did not significantly decrease or increase the risk of fetal or neonatal death or serious neonatal morbidity in twin pregnancy between 32 0/7 and 38 6/7 weeks of gestation, with the first twin in the vertex presentation. As prevalence rises for the second twin, emergency CD is necessary for delivery of the second twin after vaginal delivery of the first twin. Waiting after 38 weeks' gestation essentially requires close fetal and maternal surveillance to identify if those pregnancies may benefit to extend a gestational period. It is important to construct a system in which an emergency CD can be performed anytime. The caesarean section does not change in even multifetal pregnancy. Each step after laparotomy has few tips: (1) because the uterus strongly leans to the right, image the uterine rotation. To avoid thick vessels on the uterine lateral wall, perform long U-shaped incision using a scissor. 2) Ensure not to rupture the membrane of the second twin before delivery of the first twin. (3) Check the presentation of the second twin before rupture of that fetus's membrane. The second twin tends to change the presentation. If the upper uterine segment will clamp down and entrap the second twin, a vertical uterine incision is performed without hesitation. Women with multifetal pregnancy are at increased risk of postpartum hemorrhage (PPH). Mainly PPH is caused by uterine atony. Oxytocin should be prepared before starting the CD. All bleeding may not be recognized in the operation field. Do not lose the timing of blood transfusion.

Nivolumab is part of the standard therapy for mRCC. Although deep and long-lasting responses are seen in some patients, the benefit of treatment is limited to some patients and the majority of patients will experience disease progression. PD-L1 is still under evaluation as a predictive biomarker and there is an urgent need to establish biomarkers for the treatment of nivolumab. Here, we investigate C-reactive protein (CRP) at 1 month after treatment of nivolumab as a target to predict the response of patients with metastatic renal cell carcinoma (mRCC) to nivolumab.After approval of the study by our institutional review board, 64 patients with mRCC who underwent nivolumab treatment at Kanagawa Cancer Center and Yokohama City University Hospital were enrolled. The patient characteristics, blood examination data at start of nivolumab treatment and 1 month after treatment, response to treatment and progression-free survival (PFS) were evaluated. Tumour responses were assessed according to both the Response Evaluation Criteria in Solid Tumors (RECIST) 1.1 and the immune RECIST (iRECIST) criteria. Moreover, in 12 patients who agreed to an additional blood examination, several serum inflammatory factors were investigated and their correlation with CRP level was examined.The median follow-up was 8.3 months (range 0.2-29.8 months). The median PFS period was 4.5 months and the median immune-PFS (iPFS) period was 5.3 months. RECIST 1.1 criteria underestimated the benefits of nivolumab in four (6.4%) cases. Multivariate analyses showed that an Eastern Cooperative Oncology Group performance status (≥ 2) at start of treatment and CRP level at 1 month after treatment (≥ 1.5 mg/dL) were independent risk factors for a poor iPFS of nivolumab. The CRP level at baseline was not an independent prognostic factor for iPFS. When compared with the responder group (iCR + iPR + iSD), the non-responder group (iPD) had a significantly higher CRP levels at 1 month after treatment (p 0.001). In the responder group, there was significant decrease in the CRP level after nivolumab treatment when compared with the baseline (p = 0.002), whereas there was a significant increase in the non-responder group (p = 0.019). Even patients with high baseline CRP (≥ 1.5 mg/dL) obtained good iPFS if CRP was decreased ( 1.5 mg/dL) 1 month after treatment. In addition, the classification of Glasgow prognostic score (GPS), which is a cumulative prognostic score based on CRP and albumin, was a significant predictor for iPFS. A strong correlation (|r| 0.7) with CRP level at 1 month after treatment was seen for sCD163, IL-34, MMP-1, MMP-2, osteopontin, sTNF-R1 and sTNF-R2. Of these, MMP-1 and MMP-2 were not correlated at baseline.Our results indicated that the CRP level at 1 month after treatment with nivolumab appears to be a promising predictive biomarker for response to nivolumab treatment in patients with mRCC. It is clinically useful to be able to predict the effect within a short period. Further prospective trials are needed to prove these preliminary findings.

We hypothesized that the baseline FRAX score and previous falls would predict the incidence of sarcopenia in community-dwelling older adults who received medical check-ups. The FRAX score (hazard ratio [HR] = 1.087, 95% CI 1.014–1.167) and previous falls (HR = 5.181, 95% CI 1.002–26.777) were determined to be independent risk factors for the incidence of sarcopenia. This prospective study was performed to elucidate the prevalence and incidence of sarcopenia in community-dwelling older adults who received medical check-ups, and to determine whether FRAX score and fall history predict the incidence of sarcopenia. Participants were recruited from a group of individuals who had registered for an annual town-sponsored medical check-up. Study inclusion criteria were aged older than 60 years, living independently, and ability to walk without assistance. Individuals who received nursing care were excluded from the study. A total of 426 residential participants were analyzed. Demographic information, fall history of the previous year, and FRAX score without bone mineral density were assessed. The assessment for sarcopenia was based on the recommendations of the Asian Working Group for Sarcopenia. The final sample for the assessment of sarcopenia incidence comprised 258 participants. The mean follow-up time was 2.92 years. The rate of sarcopenia was 1.06 cases per 100 person-years at risk. The Cox multivariate logistic regression model in our analysis was adjusted for age, gender, muscle mass, and covariates and showed that the FRAX score (HR = 1.087, 95% CI 1.014–1.167) and recent history of falls (HR = 5.181, 95% CI 1.002–26.777) were independent risk factors for the incidence of sarcopenia. FRAX and history of falling can be a simple screening tool to raise awareness of the prevention of osteoporosis and sarcopenia in clinical settings.

To investigate the role of microRNA (miRNA) in muscle atrophy, we performed microarray analysis of miRNA expression in skeletal muscles of Sham, orchiectomized (ORX) mice, and ORX mice treated with androgen and identified that the expression of miR-23b-3p in ORX mice was significantly higher than that in Sham mice (P = 0.007); however, miR-23b-3p expression in ORX mice treated with androgen was lower (P = 0.001). We also investigated the mechanism by which overexpression or knockdown of miR-23b-3p influences the expression of myosin heavy chain, muscle protein synthesis, ATP activity, and glucose uptake in C2C12 myotube cells. Moreover, we examined the serum miR-23b-3p levels among male subjects with type 2 diabetes and whether the serum miR-23b-3p levels could be a biomarker for muscle atrophy. The overexpression of miR-23b-3p in C2C12 myotube cells significantly upregulated the expression of myosin heavy chain, protein synthesis, ATP activity, and glucose uptake. Reporter assays raised a possible direct post-transcriptional regulation involving miR-23b-3p and the 3′-UTR of PTEN mRNA. Among subjects with type 2 diabetes, serum miR-23b-3p levels in the subjects with decreased muscle mass were significantly higher compared to the levels in the subjects without. Our results indicate that miR-23b-3p downregulates the expression of PTEN in myotube cells and induces the growth of myosin heavy chain. In addition, the serum level of miR-23b-3p can be used as a diagnostic marker for muscle atrophy.

Background The pathogenesis of acute encephalopathy (AE) remains unclear, and a biomarker has not been identified. Methods Levels of 49 cytokines and chemokines, including osteopontin (OPN), were measured in serum and cerebrospinal fluid (CSF) of children with AE (n = 17) or febrile convulsion (FC; n = 8; control group). The AE group included acute necrotizing encephalopathy (n = 1), acute encephalopathy with biphasic seizures and late reduced diffusion (AESD; n = 3), clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS; n = 4), and unclassified acute encephalopathy (UCAE; n = 9) that does not meet the criteria of syndrome classification. Five individuals with AE had neurological sequelae or death (poor prognosis), whereas 12 were alive without neurological sequelae (good prognosis). Results The CSF:serum ratios of OPN, CC chemokine ligand (CCL)4, and interleukin (IL)-10 were significantly higher in AE than in FC. The CSF levels of macrophage inhibitory factor (MIF) and leukemia inhibitory factor (LIF) were significantly higher in the poor-prognosis group than in the good-prognosis group. The CSF:serum ratios of OPN were significantly higher in AESD and in MERS than in FC. The CSF:serum ratios of MIF and OPN were higher in MERS than in UCAE or FC. Conclusion Our results suggest that microglia-related cytokines and chemokines such as OPN, MIF, and LIF could be novel biomarkers of AE, in addition to the previously reported IL-10 and CCL4, and that MIF and LIF may be markers of poor prognosis.

Healthcare for the increasing senior population is a significant challenge. To address this problem, the use of healthcare robot is increasingly being recognized to have strong potential in addressing older adult and psychiatric patients' healthcare and welfare needs. The purpose of this preliminary study is to evaluate the changes in the autonomic nervous activity of an elderly patient with schizophrenia during upper limb range of motion (ROM) exercises led by Pepper (SoftBank Robotics) with the application program of Care Prevention Gymnastics Exercises (Pepper-CPGE) made by Xing Company in Japan. A Pepper-CPGE-led three-minute radio gymnastics program (Radio Exercises #1, consisted of three types of exercises) and instructions were developed. The normal aging 69-year old schizophrenic subject followed instructions from Pepper throughout the intervention. Electrocardiography (ECG) records, heart rate, acceleration score, and ROM exercises of upper limb were collected and analyzed using the GSM's Bonaly Light instrument and Image-J analysis. (1) The high-frequency (HF) (indicative of parasympathetic nervous activity), and low-frequency (LF)/HF ratio (indicative of sympathetic nerve activity) were increased in reference from the baseline data before the exercise stretching the chest. (2) The momentum decreased as the ROM of shoulder joint flexion declined. Declines in both parasympathetic and sympathetic nervous activity were observed. Also, (3) when the exercise "bend the body forward" was performed, the HF and LF/HF also decreased. Evaluation of robot-based rehabilitation exercise program effectiveness by the ROM exercises image analysis and autonomic nervous activity is essential for the futurist programming of ROM exercise among patients with schizophrenia.

This study aimed that we were classification of physical activity in patients with heart failure categorized as New York Heart Association (NYHA) class I or II. We were a survey using a researcher- administered questionnaire, SF-8, the Specific Activity Scale (SAS), and the Scale to Measure Self-Care Behavior of Patients with Heart Disease. We included 70 patients who were treated in the Department of Cardiovascular Medicine at Hospital A. Regarding patient characteristics and clinical information after the cluster analysis, there were significant differences in the NYHA class (p = 0.001), BNP level (p = 0.012), self-management of medication adherence (p = 0.000), and exercise habits (p = 0.005). We summarized characteristics of each group as follows : Group A showed high tolerance to physical activity and near-perfect self-management; Group B showed moderate tolerance to physical activity but was not willing to commit to daily exercise and self-management; and Group C showed low tolerance to physical activity and often requested others to handle medication management. We needed that tolerance to physical activity and proposals for tailored instruction according to patient conditions, and needed that instructions tailored to the characteristics of heart failure patients in groups A-C. J. Med. Invest. 67 : 124-133, February, 2020.

Background: The TROFEO trial demonstrated that febuxostat causes greater and more rapid reduction of serum uric acid (s-UA) than topiroxostat. We compared these drugs in patients with chronic kidney disease (CKD) by sub-analysis of the TROFEO trial. Methods: This sub-analysis targeted patients with an estimated glomerular filtration rate (eGFR) ≤60 mL/min/1.73 m2. The primary endpoint was the s-UA level. Secondary endpoints included creatinine, eGFR, urinary albumin, cystatin-C, oxidized low-density lipoprotein (Ox-LDL), eicosapentaenoic acid/arachidonic acid ratio, lipid biomarkers, high-sensitivity C-reactive protein, and B-type natriuretic peptide (BNP). Results: There was no significant difference of s-UA between the two groups either before or after treatment. However, s-UA did not exceed 6.0 mg/dL in febuxostat group during the study period, but it exceeded this level in seven patients from topiroxostat group, with the number being significantly higher in topiroxostat group. Serum creatinine (s-Cr) and eGFR were significantly better after 6 months of febuxostat treatment compared with topiroxostat Cystatin-C was significantly lower after 6 months of febuxostat treatment compared with topiroxostat. The Ox-LDL was significantly lower after 3 and 6 months of febuxostat treatment compared with topiroxostat. Conclusion: Febuxostat had stronger renoprotective and antioxidant effects than topiroxostat in patients with hyperuricemia and CKD.

Pregnant women with obesity are at increased risk of parturition dysfunction; however, the biological mechanism has remained unknown. We hypothesized that molecules circulating in the serum of pregnant women with obesity may induce the aberrant expression of contraction-associated proteins (CAPs), leading to insufficient uterine contractions. This study aimed to investigate the effects of maternal serum on CAPs expression by human uterine smooth muscle cells (UtSMCs) and elucidate the influence of maternal obesity. Blood samples were collected from singleton pregnant women at 36-41 weeks of gestation before the onset of labor. UtSMCs were incubated in the serum, and the mRNA expressions of PTGFR, OXTR, GJA1, and PTGS2 were examined by RT-PCR. Progranulin (PGRN) is a circulating glycoprotein associated with insulin resistance characterized by the accumulation of visceral fat. The serum PGRN levels of the samples were measured by ELISA. After incubated with PGRN (100-1,000 ng/mL), mRNA expression of PTGFR, OXTR, and GJA1 and protein expression of CX43 were examined by RT-PCR and western blotting, respectively. The mRNA expressions of PTGFR, OXTR, and GJA1 showed significantly negative correlations with gestational weight gain (GWG). Serum PGRN levels showed a significantly positive correlation with GWG. High levels of PGRN suppressed the mRNA expression of GJA1 and the protein expression of CX43. The change in maternal serum induced by GWG suppressed the CAPs expression by UtSMCs. PGRN is one of the factors in the serum responsible for inhibiting the expression of CX43.

Metformin is associated with risks of gastrointestinal complications in patients with type 2 diabetes. In contrast, probiotic Bifidobacterium bifidum G9-1 (BBG9-1) could improve the symptoms of diarrhea caused by metformin in animal models. Thus, the primary outcome of this study will be the effect of the probiotic BBG9-1 on gastrointestinal symptoms, including diarrhea, in patients with type 2 diabetes who use metformin. This open-label, single-arm, and exploratory study will examine 40 patients with type 2 diabetes who use metformin and have symptoms of constipation or diarrhea. After the baseline examination (objective 1), patients will be administered probiotic BBG9-1 for 10 ± 2 weeks. Then, examinations will be performed (objective 2). The primary outcome will be changes in the symptoms of constipation or diarrhea from objective 1 to objective 2. Secondary outcomes will include changes in gut microbiota, and correlations between changes in fecal properties and biomarkers, including HbA1c level and body mass index. This is the first study to investigate the effect of probiotic BBG9-1 on the change in the symptom of constipation or diarrhea in patients with type 2 diabetes who use metformin.

Oral diseases produce enormous productivity loss. However, epidemiological evidence of work stress and tooth loss is scarce. The aim of this study was to examine the association of work stress, according to effort–reward imbalance (ERI), with tooth loss. We conducted a cross-sectional study using data obtained between 2010 and 2011 in Japan. This study included 1,195 employees aged 25–50 years old (response rate=32%). The dependent variable was self-reported tooth loss (having or not). The independent variable was a dichotomized ERI ratio (>1.4 and ≤1.4). Age, sex, sociodemographic variables, work-related factors, and health-related variables were adjusted. Psychological distress was used as a potential mediator. We also examined an additive interaction between support from supervisors and ERI. The median age was 37, and 48% were women. After adjusting for the covariates, ERI was still associated with tooth loss (prevalence ratio=1.20 [95% confidence interval=1.01, 1.42] from Poisson regression models with a robust error variance). Psychological distress partially explained the association, and support from supervisors significantly attenuated the association. In conclusion, high ERI ratio was still associated with an increased risk of tooth loss among working adults.

We have previously reported that the creatinine (Cre) to cystatin C (CysC) ratio is associated with height-adjusted skeletal muscle mass index (SMI). However, weight-adjusted SMI is reported to be a more useful marker of insulin sensitivity than height-adjusted SMI. Thus, we hypothesized that the creatinine to (cystatin C × body weight [BW]) relationship (Cre/[CysC × BW]) might be associated with weight-adjusted SMI. In this cross-sectional study of 169 males and 132 females, a body composition analyzer was used and the weight-adjusted SMI was calculated as (absolute muscle mass [kg]/BW [kg]) × 100. The cut-off of low muscle mass was defined as weight-adjusted SMI

Objectives: Although inequalities in dental implant use based on educational level have been reported, no study has used income as a proxy for the socioeconomic status. We examined: (i) income inequalities in implant use; and (ii) whether income or education has a stronger association with implant use in elder Japanese. Methods: In 2016, a self-reported questionnaire was mailed to participants aged 65 years or older living across Japan as part of the ongoing Japan Gerontological Evaluation Study. We used data from 84,718 respondents having 19 or fewer teeth. After multiple imputation, multi-level logistic regression estimated the association of dental implant use with equivalised income level and years of formal education. Confounders were age, sex, and density of dental clinics in the residential area. Results: 3.1% of respondents had dental implants. Percentages of dental implant use among the lowest (≤ 9 years) and highest (≥ 13 years) educational groups were 1.8 and 5.1, respectively, and among the lowest (0 < 12.2 ‘1,000 USD/year’) and highest (≥ 59.4 ‘1,000 USD/year’) income groups were 1.7 and 10.4, respectively. A fully adjusted model revealed that both income and education were independently associated with dental implant use. Odds ratios for implant use in the highest education and income groups were 2.13 [95% CI = 1.94–2.35] and 4.85 [95% CI = 3.78–6.22] compared with the lowest education and income groups, respectively. From a model with standardised variables, income showed slightly stronger association than education. Conclusion: This study reveals a public health problem that even those with the highest education but low income might have limited accessibility to dental implant services.