Japanese Individuals Research Articles

The Three-Dimensional Criteria of Developmental Dysplasia of the Hip Using the Functional Pelvic Plane Is More Useful Than That Using the Anterior Pelvic Plane.

Background: This retrospective cross-sectional study investigated the cutoff values (COVs) for developmental dysplasia of the hip (DDH) using a three-dimensional (3D) pelvic model reconstructed using computed tomography (CT). We included 107 healthy Japanese participants and 73 patients who had undergone curved periacetabular osteotomy (CPO) for DDH between 2012 and 2017. Methods: The hip CT images were adjusted to the anterior pelvic plane (APP), functional pelvic plane (FPP), sagittal anterior center-edge angle (ACEA), and sagittal posterior center-edge angle (PCEA). The lateral center-edge angle (LCEA), acetabular roof obliquity (ARO), anterior acetabular sector angle (AASA), and posterior acetabular sector angle (PASA) were measured. Receiver operating characteristic (ROC) curves were used to calculate the COVs, and the association between the parameters was analyzed using multiple logistic regression. Results: The ARO (≥10.2°) and LCEA (≤22.2°) were independent influencing factors for the APP, whereas the AASA (≤53.1°) and LCEA (≤24.5°) were independent influencing factors for the FPP. Conclusions: The 3D criteria for the diagnosis of DDH in Japanese individuals can identify DDH with insufficient anterior coverage, which anteroposterior plain radiographs cannot visualize, and can help determine indications for acetabular osteotomy.

Combined effects of blood pressure and glucose status on the risk of chronic kidney disease

This study aimed to assess the combined effects of blood pressure (BP) and glucose status on chronic kidney disease (CKD) incidence in young and middle-aged adults. We examined data from 1,297,341 Japanese individuals aged <60 years (60.1% men; mean age 41.4 ± 9.3 years) with no history of CKD at baseline. The interval-censored Cox proportional hazards model with covariates was used. During a median follow-up period of 2.1 years, new onset CKD (estimated glomerular filtration rate <60 ml/min/1.73 m2 and/or proteinuria) occurred in 80,187 participants. In participants without antihypertensive treatment (AHT), the adjusted hazard ratios (95% confidence interval) per 1-standard deviation, that is, 15 mmHg increase in systolic BP for CKD incidence, were 1.08 (1.07–1.09), 1.12 (1.10–1.13), and 1.15 (1.12–1.18) in normoglycemia, borderline glycemia, and diabetes groups, respectively. These ratios were significantly higher in the borderline glycemia and diabetes groups compared with those in the normoglycemia group (interaction p < 0.0001). The interaction between BP and borderline glycemia was evident when the outcome definition was restricted to proteinuria. In participants under AHT, systolic BP was most strongly associated with CKD risk in the diabetes group, although no significant interaction was observed. High BP and high glucose status may synergistically increase the incidence of CKD. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.This large-scale longitudinal cohort study showed high BP and diabetes synergistically increased the risk of CKD in individuals without AHT. Strict BP management may play an important role in the early prevention of CKD in individuals with worse glucose status within the young and middle-aged population.

Health guidance intervention mitigates the escalation of predicted comprehensive cardiovascular disease risk: Interrupted time series design

IntroductionMetabolic syndrome increases the risk of cardiovascular events. Despite the Japanese healthcare system's efforts in early detection and intervention, particularly through Specific Health Checkup and Guidance programs, research on their effectiveness is limited. This study evaluated the impact of Specific Health Guidance on the predicted risk of atherosclerotic cardiovascular disease (ASCVD) in working-age Japanese individuals. MethodsEmploying an Interrupted Time Series (ITS) design, this study compared the trends in predicted ASCVD risk and each individual risk factor used for the prediction of ASCVD risk before and after intervention in individuals participating in the guidance. ResultsAnalyses based on the ITS design indicated that participation in Specific Health Guidance programs, specifically the intensive level program, mitigates the increase trend of the predicted ASCVD risk. On the other hand, the impact on the trends of individual cardiovascular risk factors was minimal. ConclusionsThe intensive level Specific Health Guidance appeared to reduce the increasing trend in ASCVD risk, emphasizing the importance of comprehensive risk assessment in evaluating health interventions. However, the results are limited owing to the specific demographics and short evaluation period. Further research is necessary to understand the long-term impacts and broader applicability.

MRNA expression levels of cytochrome P450 CYP1A2, CYP3A4, and CYP3A5 in the epidermis: a focus on individual differences among Japanese individuals

Various cytochrome P450 enzymes (CYPs) that contribute to drug metabolism are expressed in the skin. However, variation among individuals in CYP expression profiles is not well-understood. To investigate CYPs related to the metabolism of transdermal preparations in Japan, multiple skin tissue specimens of individuals of Japanese descent were prepared, and the mRNA expression levels of CYP1A2, CYP3A4, and CYP3A5 were measured. Associations between the expression patterns of these CYPs and body mass index (BMI) were also investigated. There were considerable individual differences in epidermal CYP1A2 mRNA expression levels, and CYP1A2 showed a weak positive correlation with CYP3A4 mRNA expression levels. In contrast to previous results for other organs, epidermal CYP3A4 mRNA expression levels showed a weak positive correlation with BMI. CYP3A4 in the epidermis may have been locally enhanced as a defence mechanism against xenobiotics in response to impaired barrier function. These differences in mRNA expression in the skin may affect the transdermal absorption of drugs, such as lidocaine and fentanyl, which are metabolised by multiple overlapping CYPs. Our study provides new insights into drug metabolism in the skin. These results are valuable for predicting drug effects and transdermal drug transfer rates in Japanese patients.

Verbal descriptions modulate flavour perception and evaluation of wine: An exploratory study using Riesling and Muscat Bailey A wines

Significant efforts have been made in the wine industry to assist customers in making purchase decisions and enhance their drinking experience by providing verbal descriptions of the complex sensory characteristics of wine. However, the influence of such verbal descriptions on wine flavour perception and evaluation has not been examined. To fill this gap, this exploratory study performed an experiment using white Riesling wine from the 2021 German vintage and red Muscat Bailey A (MBA) wine from the 2019 Japanese vintage. Forty-six Japanese individuals (23 social drinkers and 23 wine experts) participated and were presented with two glasses of Riesling wine and two glasses of MBA wine with different verbal descriptions. One glass of Riesling/MBA wine was served with a description including its distinct aroma descriptor (i.e., a ‘petrol’ note for the Riesling wine and a ‘strawberry candy’ note for the MBA wine). For the other glass, the description did not include the descriptor. The participants were asked to taste the wines and rate their palatability, perceived sweetness intensities, acidity, astringency, alcohol sensation, body, and expensiveness on a 7-point scale. The results demonstrated that the social drinkers rated the Riesling wine with the ‘petrol’ descriptor as heavier-bodied and more expensive compared to the same wine without the descriptor. The wine experts were not as influenced as the social drinkers, but the experts rated the Riesling wine with the ‘petrol’ descriptor as less expensive. In the case of MBA wine with the ‘strawberry candy’ descriptor, the social drinkers rated it as more expensive, whereas the wine experts rated it as more palatable than the same wine without the descriptor. The results indicated that verbal descriptions of wine aroma indeed modulated the flavour perception and evaluation of wine, but the modulation effect varied between social drinkers and wine experts.

High risk of multiple gastric cancers in Japanese individuals with Lynch syndrome.

Lynch syndrome (LS) is a dominantly inherited syndrome characterized by an increased risk for LS associated tumors such as colorectal cancer (CRC) and gastric cancer (GC). However, the clinical benefit of surveillance for GC remains unclear while it has already been recommended for CRC. This study aimed to elucidate the clinical features of GC in Japanese individuals with LS, and the risk of developing multiple GCs to build regional-tailored surveillance programs in LS patients with GC. Data on Japanese individuals with LS were retrospectively collected from a single institution. The clinical features of GC, including the cumulative risk of multiple GCs, were analyzed. Among 96 individuals with LS (MLH1/MSH2/MSH6, 75:20:1), 32 GC lesions were detected in 15 individuals with LS (male/female, 11:4). The median age at initial GC diagnosis was 52.7 y (range: 28-71). Histological examination revealed a predominance of intestinal type (19/24: 87.5%). Moreover, the majority of the GC lesions (82%) were determined to have high-frequency of microsatellite instability. The cumulative risk of individuals with LS developing GC at 70 y was 31.3% (MLH1 36.1%, MSH2 18.0%). Notably, the cumulative risk of individuals with LS developing metachronous and/or synchronous GCs at 0, 10 and 20 y after initial diagnosis of GC was 26.7%, 40.7%, and 59.4%, respectively. Due to a higher risk of developing multiple GCs, intensive surveillance might be especially recommended for Japanese individuals with LS associated initial GC.

Genetic diversity among the present Japanese population: evidence from genotyping of human cell lines established in Japan

Japan is often assumed to have a highly homogeneous ethnic population, because it is an island country. This is evident in human cell lines collected from cell banks; however, these genotypes have not been thoroughly characterized. To examine the population genotypes of human cell lines established in Japan, we conducted SNP genotyping on 57 noncancerous cell lines and 43 lung cancer cell lines. Analysis of biogeographic ancestry revealed that 58 cell lines had non-admixed Japanese genotypes, 21 cell lines had an admixture of Japanese and East Asian genotypes, and the remaining 21 cell lines had East Asian genotypes. The proportion of non-admixed Japanese genotypes was similar between lung cancer and noncancerous cell lines, suggesting that patients in Japan may not exclusively have Japanese genotypes. This could influence the incidence of inherited diseases and should be taken into account in personalized medicine tailored to genetic background. The genetic makeup of the present-day Japanese population cannot be fully explained by the ancestral Jomon and Yayoi lineages. Instead, it is necessary to consider a certain level of genetic admixture between Japanese and neighboring Asian populations. Our study revealed genetic variation among human cell lines derived from Japanese individuals, reflecting the diversity present within the Japanese population.

Association between predicted fat mass, predicted lean mass, predicted percent fat and type 2 diabetes mellitus in Japanese adults: a retrospective study.

Type 2 diabetes mellitus (T2DM) is known to have obesity as a risk factor. Body mass index cannot distinguish between lean mass and fat mass. We aimed to examine the association between predicted fat mass, predicted lean mass, predicted percent fat and risk of T2DM in Japanese adults. We also explored whether these three new parameters could predict T2DM better than other obesity markers. This present study is a secondary data analysis. The study enrolled 20,944 Japanese individuals who participated in the NAGALA medical assessment program between 2004 and 2015. 15,453 participants who are eligible and have complete information were included to our analysis. Through the use of Kaplan-Meier curve, restricted cubic spline and univariate and multivariate Cox regression analysis, the relationship between predicted fat mass, predicted lean mass, predicted percent fat and T2DM risk was examined. The area under the curve method was used to assess the differences between these markers of obesity. A total of 373 cases of T2DM occurred over a median time of 5.4 years. In the male group, we found a U-shaped connection between predicted fat mass, predicted lean mass, and T2DM onset (p value, non-linearity < 0.05). A linear relationship was found between predicted percent fat and T2DM onset. The linear relationship was also found in the female group for predicted fat mass, and predicted percent fat. And for women, predicted lean mass was not an independent predictor. The area under the curve (AUC) for predicted fat mass, predicted lean mass, predicted percent fat in men was 0.673 (95%CI: 0.639 ~ 0.707), 0.598 (95%CI: 0.561 ~ 0.635), 0.715 (95%CI: 0.684 ~ 0.745), respectively. In males, WHtR was the strongest predictor (AUC 0.7151, 95%CI: 0.684 ~ 0.746), followed by predicted percent fat (AUC 0.7150, 95%CI: 0.684 ~ 0.745). In the females, WHtR was also the strongest predictor (AUC 0.758, 95%CI: 0.703 ~ 0.813), followed by body mass index (AUC 0.757, 95%CI: 0.704 ~ 0.811) and predicted percent fat (AUC 0.742, 95%CI: 0.687 ~ 0.798). Predicted fat mass, predicted lean mass, predicted percent fat were strongly connected with an increased risk for developing T2DM in Japanese, particularly in males. WHtR and predicted percent fat had a slightly better discrimination than other common obesity indicators in males. In the females, predicted fat mass and predicted percent fat were associated with T2DM risk, WHtR and body mass index had the slightly higher predictive power.

Deciphering metabolic dysfunction-associated steatotic liver disease: insights from predictive modeling and clustering analysis.

New nomenclature of steatotic liver disease (SLD) including metabolic dysfunction-associated SLD (MASLD), MASLD and increased alcohol intake (MetALD), and alcohol-associated liver disease (ALD) has recently been proposed. We investigated clustering analyses to decipher the complex landscape of SLD pathologies including the former nomenclature of nonalcoholic fatty liver disease (NAFLD) and metabolic dysfunction-associated fatty liver disease (MAFLD). Japanese individuals who received annual health checkups including abdominal ultrasonography (n=15 788, men/women: 10 250/5538, mean age: 49years) were recruited. The numbers of individuals with SLD, MASLD, MetALD, ALD, NAFLD, and MAFLD were 5603 (35.5%), 4227 (26.8%), 795 (5.0%), 324 (2.1%), 3982 (25.8%), and 4946 (31.3%), respectively. Clustering analyses using t-distributed stochastic neighbor embedding and K-means to visually represent interconnections in SLDs uncovered five cluster formations. MASLD and NAFLD mainly shared three clusters including (i) low alcohol intake with relatively low-grade obesity; (ii) obesity with dyslipidemia; and (iii) dysfunction of glucose metabolism. Both MetALD and ALD displayed one distinct cluster intertwined with alcohol consumption. MAFLD widely shared all of the five clusters. In machine learning-based analyses using algorithms of random forest and extreme gradient boosting and receiver operating characteristic curve analyses, fatty liver index (FLI), calculated by body mass index, waist circumference, and levels of γ-glutamyl transferase and triglycerides, was selected as a useful feature for SLDs. The new nomenclature of SLDs is useful for obtaining a better understanding of liver pathologies and for providing valuable insights into predictive factors and the dynamic interplay of diseases. FLI may be a noninvasive predictive marker for detection of SLDs.

Heterogeneity in the effect of type 2 diabetes on dementia incidence in a diverse cohort of Asian American and non-Latino White older adults.

Dementia incidence is lower among Asian Americans than among Whites, despite higher prevalence of type 2 diabetes, a well-known dementia risk factor. Determinants of dementia, including type 2 diabetes, have rarely been studied in Asian Americans. We followed 4846 Chinese, 4129 Filipino, 2784 Japanese, 820 South Asian, and 123 360 non-Latino White members of a California-based integrated health-care delivery system from 2002 to 2020. We estimated dementia incidence rates by race/ethnicity and type 2 diabetes status, and we fitted Cox proportional hazards and Aalen additive hazards models for the effect of type 2 diabetes (assessed 5years before baseline) on age of dementia diagnosis, controlling for sex/gender, educational attainment, nativity, height, race/ethnicity, and a race/ethnicity × diabetes interaction. Type 2 diabetes was associated with higher dementia incidence in Whites (hazard ratio [HR] = 1.46; 95% CI, 1.40-1.52). Compared with Whites, the estimated effect of diabetes was larger in South Asians (HR = 2.26; 95% CI, 1.48-3.44), slightly smaller in Chinese (HR = 1.32; 95% CI, 1.08-1.62) and Filipino (HR = 1.31; 95% CI, 1.08-1.60) individuals, and similar in Japanese individuals (HR = 1.44; 95% CI, 1.15-1.81). Heterogeneity in this association across Asian subgroups may be related to type 2 diabetes severity. Understanding this heterogeneity may inform prevention strategies to prevent dementia for all racial and ethnic groups.

Age estimation using postmortem computed tomography-based Hounsfield unit values of the palate and mandibular condyle and the Eichner classification

Age estimation is important in forensic investigations of unidentified human remains. This study assessed the correlation between age and Hounsfield unit (HU) values of the palate and mandibular condyle based on postmortem computed tomography (CT) and analyzed the influence of occlusal support in developing an age estimation method for Japanese individuals, including older adults.The sample consisted of a training dataset (357 cadavers) and a validation dataset (300 cadavers) that underwent postmortem CT.Three measurements were selected: the respective HU values of the palate and mandibular condyle and the Eichner classification. The correlation coefficients between age and HU values were also evaluated. Multiple stepwise regression analysis was performed to evaluate the significance of four parameters (sex, respective HU values of the palate and mandibular condyle, and the Eichner classification) for age estimation and to determine the best age estimation formula. In the validation tests, inaccuracy and bias were calculated for the groups aged ≥65 or <65 years.Significant correlations between age and HU values of the palate and mandibular condyle were observed, regardless of sex. In multiple stepwise regression analysis, all variables except sex were significantly correlated with age. The age estimation formula from the regression analysis was useful, and the validation test exhibited high accuracy, especially in older adults.The HU values of the palate and mandibular condyle and the Eichner classification are useful for age estimation in Japanese individuals.

Comparative effects of sodium-glucose cotransporter 2 inhibitors versus dipeptidyl peptidase-4 inhibitors on kidney function decline in Japanese individuals with type 2 diabetes.

Limited direct comparative studies exist in terms of the effects of sodium-glucose cotransporter 2 inhibitors (SGLT2is) and dipeptidyl peptidase-4 inhibitors (DPP4is) on the kidney outcomes in Japanese individuals with type 2 diabetes. This retrospective cohort study included 561 Japanese adults with type 2 diabetes, who were newly prescribed either an SGLT2i or a DPP4i and had an eGFR≥30mL/min/1.73m2. The cohort comprised 207 women and 354 men, with a mean (± standard deviation) age of 63 (± 12) years. The exposure and outcome were SGLT2i or DPP4i initiation and eGFR slope during the overall follow-up period, restricted to participants who were followed for ≥2years. We adopted the on-treatment analysis. Analysis of covariance was used to compare the adjusted eGFR slope between the two groups, incorporating 10 variables at baseline. During the median follow-up period of 3.4years, least square mean (95% CI) eGFR slopes were -1.91 (-2.15, -1.67) and -1.12 (-1.58, -0.67) mL/min/1.73m2/year in individuals treated with a DPP4i (n=460) and an SGLT2i (n=101), respectively, demonstrating statistical significance (p=0.002). The robustness of this finding was strengthened by sensitivity analyses. This study provides potential evidence of the superiority of SGLT2is over DPP4is in slowing kidney function decline in Japanese adults with type 2 diabetes and eGFR≥30mL/min/1.73m2.

Regulatory role of Prunus mume DAM6 on lipid body accumulation and phytohormone metabolism in the dormant vegetative meristem.

Bud dormancy is a crucial process in the annual growth cycle of woody perennials. In Rosaceae fruit tree species, DORMANCY-ASSOCIATED MADS-box (DAM) transcription factor genes regulating bud dormancy have been identified, but their molecular roles in meristematic tissues have not been thoroughly characterized. In this study, molecular and physiological analyses of transgenic apple plants overexpressing the Japanese apricot DAM6 gene (PmDAM6) and Japanese apricot cultivars and F1 individuals with contrasting dormancy characteristics revealed the metabolic pathways controlled by PmDAM6. Our transcriptome analysis and transmission electron microscopy examination demonstrated that PmDAM6 promotes the accumulation of lipid bodies and inhibits cell division in the dormant vegetative meristem by down-regulating the expression of lipid catabolism genes (GDSL ESTERASE/LIPASE and OIL BODY LIPASE) and CYCLIN genes, respectively. Our findings also indicate PmDAM6 promotes abscisic acid (ABA) accumulation and decreases cytokinin (CTK) accumulation in vegetative buds by up-regulating the expression of the ABA biosynthesis gene ARABIDOPSIS ALDEHYDE OXIDASE and the CTK catabolism gene CYTOKININ DEHYDROGENASE, while also down-regulating the expression of the CTK biosynthesis genes ISOPENTENYL TRANSFERASE (IPT) and CYP735A. Additionally, PmDAM6 modulates gibberellin (GA) metabolism by up-regulating GA2-OXIDASE expression and down-regulating GA3-OXIDASE expression. Furthermore, PmDAM6 may also indirectly promote lipid accumulation and restrict cell division by limiting the accumulation of CTK and GA in buds. In conclusion, using our valuable genetic platform, we clarified how PmDAM6 modifies diverse cellular processes, including lipid catabolism, phytohormone (ABA, CTK, and GA) biosynthesis and catabolism, and cell division, in the dormant vegetative meristem.

Development of a Scale to Measure Tolerance Toward Diverse Others1

AbstractOpportunities to interact with people from different cultures and languages have increased as society has become more globalized. Hence, it has become increasingly important for people living in today's international society to accept and try to build trusting relationships with those who may perceive the world differently. This study aimed to develop a scale to measure people's tolerant attitudes toward diverse others (hereafter, tolerance toward diverse others). Furthermore, after confirming the newly developed scale's reliability and validity, we used it to examine its associations with general trust and cultural interdependent self‐construal. Albeit exploratively, we then discuss the relationships among these variables. Our results showed that scores on the newly developed Tolerance of Diverse Others Scale were positively correlated with scores on the General Trust Scale and also with scores on tolerance‐related items in the World Values Survey. Furthermore, the harmony‐seeking aspect of cultural interdependent self‐construal was positively correlated with tolerance toward diverse others, while the rejection‐avoidance aspect was negatively correlated, although the positive correlation between harmony seeking and rejection avoidance was shown. We discuss what the results suggest about Japanese individuals' perceptions of diverse others.

Exploring the Impact of the COVID-19 Pandemic on Twitter in Japan: Qualitative Analysis of Disrupted Plans and Consequences.

Despite being a pandemic, the impact of the spread of COVID-19 extends beyond public health, influencing areas such as the economy, education, work style, and social relationships. Research studies that document public opinions and estimate the long-term potential impact after the pandemic can be of value to the field. This study aims to uncover and track concerns in Japan throughout the COVID-19 pandemic by analyzing Japanese individuals' self-disclosure of disruptions to their life plans on social media. This approach offers alternative evidence for identifying concerns that may require further attention for individuals living in Japan. We extracted 300,778 tweets using the query phrase Corona-no-sei ("due to COVID-19," "because of COVID-19," or "considering COVID-19"), enabling us to identify the activities and life plans disrupted by the pandemic. The correlation between the number of tweets and COVID-19 cases was analyzed, along with an examination of frequently co-occurring words. The top 20 nouns, verbs, and noun plus verb pairs co-occurring with Corona no-sei were extracted. The top 5 keywords were graduation ceremony, cancel, school, work, and event. The top 5 verbs were disappear, go, rest, can go, and end. Our findings indicate that education emerged as the top concern when the Japanese government announced the first state of emergency. We also observed a sudden surge in anxiety about material shortages such as toilet paper. As the pandemic persisted and more states of emergency were declared, we noticed a shift toward long-term concerns, including careers, social relationships, and education. Our study incorporated machine learning techniques for disease monitoring through the use of tweet data, allowing the identification of underlying concerns (eg, disrupted education and work conditions) throughout the 3 stages of Japanese government emergency announcements. The comparison with COVID-19 case numbers provides valuable insights into the short- and long-term societal impacts, emphasizing the importance of considering citizens' perspectives in policy-making and supporting those affected by the pandemic, particularly in the context of Japanese government decision-making.

Does risk aversion affect individuals’ interests and actions in angel investing? Empirical evidence from Japan

This study explores individuals’ interests and actions in angel investing. Using a sample of Japanese individuals who are interested and engage in general investing obtained from original survey data, we examine whether risk aversion and subjective time discounting are associated with angel investing. To provide a clear picture of potential and actual angel investors, we classify individuals’ attitudes toward angel investing into “no interest,” “interest only,” and “action.” By estimating the marginal effects of risk aversion on angel investment, we find that individuals’ risk aversion is negatively associated with their angel investment actions; that is, individuals with a higher degree of risk aversion are less likely to engage in angel investing. We also find that wealthy individuals are more likely to engage in angel investing. Moreover, among individuals with entrepreneurial experience, subjective time discounting is positively associated with their angel investment actions, suggesting that entrepreneurs with higher subjective time discounting are more likely to engage in angel investing.

Associations of hypertension and/or diabetes and the risk of dementia according to participation in social activities from an age-specific community-based cohort study (the NISSIN Project)

AimThis study investigated the association between participation in social activities and incident dementia among physically and socially independent older adults with or without diseases (hypertension and/or diabetes mellitus) in a Japanese age-specific cohort (the NISSIN Project). MethodsWe conducted a prospective cohort study of 1,856 Japanese individuals (953 men and 903 women) aged 64/65 years. Information on medical status, demographics, and lifestyle characteristics was collected using a baseline questionnaire and health checkup (2000–2005). Incident dementia were confirmed among these received long-term care certifications using the nationally standardized dementia scale proposed by the Ministry of Health, Labor, and Welfare. A competing risk model was used to calculate hazard ratios (HRs) and 95 % confidence intervals (CIs) for dementia incidence. We treated the censored cases of death as competing events. ResultsDuring a median of 16.0 years of follow-up, incident dementia occurred in 332 participants. The presence of diseases and nonparticipation in social activities were associated with a significantly higher risk of incident dementia (HR 1.65; 95 % CI 1.21–2.26) after adjusting for potential confounders compared with participants without diseases and those who participated in social activities. ConclusionsIn this age-specific cohort study, participants with diseases and those who did not participate in social activities were more likely to have incident dementia than those without diseases and those who participated in social activities. For older people with hypertension and/or diabetes mellitus, engaging in social activities could be a beneficial strategy for reducing the risk of developing dementia.

Oral SSTR5 Antagonist SCO-240 for Growth Hormone Stimulation: A Phase I Single-Dose Study in Healthy Individuals.

Somatostatin inhibits endocrine and exocrine secretion in various tissues by acting on five somatostatin receptor subtypes (SSTR1-5). The clinical effects of SSTR5 antagonism remain unknown. Herein, we evaluated the effects of SCO-240, an oral SSTR5 antagonist, in healthy individuals. This randomized, single-center, double-blind, placebo-controlled, phase I study included healthy Japanese and White individuals. The effects of ascending single oral doses of SCO-240 were evaluated in healthy individuals. The main outcome measures were safety, tolerability, pharmacokinetics, and pharmacodynamics (gallbladder contractions and levels of serum insulin and plasma glucagon-like peptide-1 (GLP-1)). The levels of pituitary hormones were evaluated in our exploratory analysis. The results indicated that SCO-240 was safe and well-tolerated at all tested doses. Oral SCO-240 was readily absorbed, with its systemic exposure increasing in a dose-dependent manner. The median time to maximum concentration and mean terminal half-life of SCO-240 were 3-4 and 10.2-12.6 hours, respectively, in the ascending dose section. No clinically meaningful changes in SCO-240 pharmacokinetic profiles were observed between fed and fasted or between Japanese and White individuals. No increase in gallbladder contractions or levels of insulin and GLP-1 were detected. SCO-240 induced robust growth hormone (GH) secretion without altering the levels of other pituitary hormones. In conclusion, the study is the first to demonstrate that SSTR5 antagonism stimulates GH secretion in humans. SCO-240 was safe and well-tolerated and exhibited once-daily oral dosing potential. The robust effects of SCO-240 on GH secretion suggest that it may be a treatment option for GH-related disorders.

Milk-based culture of Penicillium camemberti and its component oleamide affect cognitive function in healthy elderly Japanese individuals: a multi-arm randomized, double-blind, placebo-controlled study.

Dairy products and fermented foods have a reported association with maintained cognitive function. Camembert cheese, a dairy product fermented by the white mold Penicillium camemberti, has also been shown to enhance cognitive function in vivo. Oleamide, derived from the fermentation of the white mold, is a candidate for an active component, and expected to improve both cognitive function and sleep conditions. Thus, this study investigated whether the milk-based culture of white mold (MCW), and oleamide, could improve cognitive function and sleep state clinically. A multi-arm randomized, double-blind, placebo-controlled trial was conducted in Tokyo, Japan. 60 healthy Japanese individuals aged 50-75 who were aware of their cognitive decline were randomly and equally divided into three groups of 20 participants using computer-generated random numbers. Participants took either MCW (equivalent to 60 μg/day of oleamide), 60 μg/day of oleamide, or placebo capsules for 12 weeks. Serum BDNF, cognitive function by Cognitrax as primary and MCI Screen as secondary outcome, and sleep status using the Japanese version of the Pittsburgh Sleep Quality Index (PSQI-J) were assessed before and after intervention. The participants, outcome assessors and analysts, and research assistants were blinded to the group assignment. Of the 60 participants, 58 completed the study and were analyzed. No adverse events related to test foods were observed. The placebo group showed a negative rate of change in serum BDNF (-10.5% ± 19.7%), whereas the MCW and oleamide groups showed positive changes (2.0% ± 27.1% and 1.3% ± 13.5%, respectively). Cognitrax scores increased after 12 weeks in all groups. Conversely, the MPI score of the MCI Screen demonstrated a significant improvement in the MCW and oleamide groups compared to the placebo group (p = 0.013 and p < 0.001, respectively). The subscales, immediate free recall and delayed free recall, also significantly increased in them compared to the placebo group. Although PSQI-J revealed no significant differences among groups, the MCW and oleamide groups showed significant improvement after intervention in overall score, subjective sleep quality, and sleep latency. Our results suggest that MCW and its component, oleamide, are safe and contribute to maintaining cognitive functions, particularly short-term and working memory, and improving sleep state. Clinical trial registration: https://center6.umin.ac.jp/cgi-open-bin/ctr/ctr_view.cgi?recptno=R000054792, identifier UMIN-CTR UMIN000048084.

Heterogeneous Association of Tooth Loss with Functional Limitations

Tooth loss is prevalent in older adults and associated with functional capacity decline. Studies on the susceptibility of some individuals to the effects of tooth loss are lacking. This study aimed to investigate the heterogeneity of the association between tooth loss and higher-level functional capacity in older Japanese individuals employing a machine learning approach. This is a prospective cohort study using the data of adults aged ≥65 y in Japan (N = 16,553). Higher-level functional capacity, comprising instrumental independence, intellectual activity, and social role, was evaluated using the Tokyo Metropolitan Institute of Gerontology Index of Competence (TMIG-IC). The scale ranged from 0 (lowest function) to 13 (highest function). Doubly robust targeted maximum likelihood estimation was used to estimate the population-average association between tooth loss (having <20 natural teeth) and TMIG-IC total score after 6 y. The heterogeneity of the association was evaluated by estimating conditional average treatment effects (CATEs) using the causal forest algorithm. The result showed that tooth loss was statistically significantly associated with lower TMIG-IC total scores (population-average effect: −0.14; 95% confidence interval, −0.18 to −0.09). The causal forest analysis revealed the heterogeneous associations between tooth loss and lower TMIG-IC total score after 6 y (median of estimated CATEs = −0.13; interquartile range = 0.12). The high-impact subgroup (i.e., individuals with estimated CATEs of the bottom 10%) were significantly more likely to be older and male, had a lower socioeconomic status, did not have a partner, and had poor health conditions compared with the low-impact subgroup (i.e., individuals with estimated CATEs of the top 10%). This study found that heterogeneity exists in the association between tooth loss and lower scores on functional capacity. Implementing tooth loss prevention policy and clinical measures, especially among vulnerable subpopulations significantly affected by tooth loss, may reduce its burden more effectively.