Japanese Subjects Research Articles

GWAS Meta-analysis of Kidney Function Traits in Japanese Populations.

Genetic epidemiological evidence for the kidney function traits in East Asian populations, including Japanese, remain still relatively unclarified. Especially, the number of genome-wide association studies (GWASs) for kidney traits reported still remains limited, and the sample size of each independent study is relatively small. Given the genetic variability between ancestries/ethnicities, implementation of GWAS with sufficiently large sample sizes in specific population of Japanese is considered meaningful. We conducted the GWAS meta-analyses of kidney traits by leveraging the GWAS summary data of the representative large genome cohort studies with about 200,000 Japanese participants (n = 202,406 for estimated glomerular filtration rate [eGFR] and n = 200,845 for serum creatinine [SCr]). In the present GWAS meta-analysis, we identified 110 loci with 169 variants significantly associated with eGFR (on chromosomes 1-13 and 15-22; P < 5 × 10-8), whereas we also identified 112 loci with 176 variants significantly associated with SCr (on chromosomes 1-22; P < 5 × 10-8), of which one locus (more than 1 Mb distant from known loci) with one variant (CD36 rs146148222 on chromosome 7) for SCr was considered as the truly novel finding. The present GWAS meta-analysis of the largest genome cohort studies in Japanese subjects provided some original genomic loci associated with kidney function, which may contribute to the possible development of personalized prevention of kidney diseases based on genomic information in the near future.

Equal Despite Different Entitlements? M.C. Piepers’ Ambiguous Conceptualization of Legal Equality (1898)

In ‘Gelijkstelling van Vreemde Oosterlingen met Europeanen’ (‘Legal Equation of Foreign Asians with Europeans’), published in 1898 in Tijdschrift voor Nederlandsch-Indië, the liberal intellectual M.C. Piepers argued against the legal equation of the resident Japanese subjects in the Netherlands Indies with the Europeans. To make such equation happen, Parliament in the Netherlands discussed a change in the Law in order to alter the provisions with respect to the binary colonial distinction between Europeans and all other people in the Netherlands Indies as laid down in article 109 of the ‘colonial constitution’ (‘regeringsreglement’) of 1854. The change was needed for the 1896/1897 trade-agreement between the Netherlandic Empire and Imperial Japan to be implemented. Piepers warned against this ‘surrender’ to Japanese claims, arguing that the change emerged from a wide-spread misunderstanding of the legal and constitutional regulations with respect to legal entitlements in the Netherlands Indies. This article interprets Piepers’ passionate defense of the judicial status quo concerning equality founded on ‘legal’ definitions of difference, as an avant la lettre constitutional ‘apartheid’ argument. Piepers’ view on Netherlands Indies state formation started from a legal pluralism with subjectively defined groups. We will argue how in these subjectivities resonate three levels of power relations around 1900: a) geopolitical; b) national/state/colonial c) individual; with long-living aftermaths. Piepers final line of defending the status quo is the distinction between the just de jure equality in colonial society and the unjustified de facto hierarchical relationships between the different population groups. This very opposition between just laws and unfair practices in colonial governance obscures how the Eurocentrism of European (liberal) legal thought inevitably resulted in racist practice

Sound source locations and their roles in Japanese voiceless "glottal" fricative production.

Although [h] is described as a glottal fricative, it has never been demonstrated whether [h] has its source exclusively at the glottis. In this study, sound source locations and their influence on sound amplitudes were investigated by conducting mechanical experiments and airflow simulations. Vocal tract data of [h] were obtained in three phonemic contexts from two native Japanese subjects using three-dimensional static magnetic resonance imaging (MRI). Acrylic vocal tract replicas were constructed, and the sound was reproduced by supplying airflow to the vocal tracts with adducted or abducted vocal folds. The sound source locations were estimated by solving the Navier-Stokes equations. The results showed that the amplitudes of sounds produced by the vocal tracts with an open glottis were in a similar range (±3 dB) to those with a glottal gap of 3 mm in some contexts. The sound sources in these cases were observed in the pharyngeal cavity or near the soft palate. Similar degrees of oral constrictions were observed in the real-time MRI, indicating that the sound traditionally described as [h] is produced, at least in some contexts, with sound sources of turbulent flow generated by a supralaryngeal constriction of the following vowel.

Construction of new polygon mesh-type phantoms based on adult Japanese voxel phantoms.

To construct adult Japanese phantoms applicable to individual exposure dose assessments, we created adult Japanese polygon mesh-type male (JPM) and female (JPF) phantoms through modification of the adult Japanese voxel phantoms, JM-103 (male) and JF-103 (female). The body sizes and masses of organs, tissues, and organ contents in JPM and JPF were adjusted to the Japanese averages, except for those unimportant for radiation protection or risks. The JPM and JPF data were converted to tetrahedral mesh-type data and incorporated into the Particle and Heavy Ion Transport code System (PHITS) for dose calculations. The dosimetric characteristics of the JPM and JPF phantoms were validated by calculating their effective doses in the anterior-posterior geometry for the external irradiation of photons with energies of 0.01-20 MeV and compared with those of JM-103 and JF-103 or the reference values given in ICRP Publication 116. The results confirmed no problems applying JPM and JPF to dose assessments in adult Japanese subjects. Furthermore, it was found that JPM and JPF can also accurately calculate the absorbed doses for entire organs and high radiosensitive cell regions with thin, small, and complicated structures.

Comparison of Magnetic Resonance Imaging Features Between Programmed Cell Death 1/Programmed Cell Death Ligand 1 Inhibitor-Induced Hypopituitarism and Idiopathic Hypopituitarism in Japanese Subjects

Comparison of Magnetic Resonance Imaging Features Between Programmed Cell Death 1/Programmed Cell Death Ligand 1 Inhibitor-Induced Hypopituitarism and Idiopathic Hypopituitarism in Japanese Subjects

Simultaneous Genotyping of Three SNVs, rs5471, rs5472, and rs2000999 Involved in Serum Haptoglobin Levels by Fluorescent Probe-Based Melting Curve Analysis.

Haptoglobin (Hp) is a hemoglobin-binding acute-phase serum protein. Several single nucleotide variations (SNVs) within the Hp gene (HP) or Hp-related protein gene (HPR), such as rs5471 (A>C) and rs5472 (A>G) in HP promoter region and rs2000999 (G>A) in intron 2 of HRP, are suggested to correlate with the serum Hp levels. To determine these three SNVs simultaneously, a genotyping assay based on duplex dual-labeled fluorescent probes was developed. The method was then validated by analyzing genomic DNA from 121 Ghanaian and two Japanese subjects who had been previously genotyped for rs5471, rs5472, and rs2000999. Both rs5471 and rs5472 could be determined as haplotypes with a single FAM-labeled fluorescent probe, and rs2000999 could be genotyped with a HEX-labeled fluorescent probe. The results obtained with the present method were consistent with the previous results except for those of three Ghanaian subjects. All three subjects appear to have multiple HPR copy number variants characteristic of African populations, which may have led to incorrect results during previous genotyping. This method allows us to genotype these three SNVs in a relatively large number of samples, especially in African populations where rs5471 is uniquely distributed.

Obicetrapib as an Adjunct to Stable Statin Therapy in Japanese Subjects: Results from a Randomized Phase 2 Trial.

Obicetrapib is a highly selective cholesteryl ester transfer protein (CETP) inhibitor shown to reduce low-density lipoprotein cholesterol (LDL-C) and apolipoprotein B (apoB), when taken as monotherapy and in combination with ezetimibe on a background of statins, in clinical trials predominantly conducted in Northern European/Caucasian participants. We characterized the efficacy, safety, and tolerability of obicetrapib within an Asian-Pacific region population. This double-blind, randomized, phase 2 trial examined obicetrapib 2.5, 5, and 10 mg/d, compared with placebo, for 8 weeks as an adjunct to stable statin therapy (atorvastatin 10 or 20 mg/d or rosuvastatin 5 or 10 mg/d) in Japanese men and women who had not achieved 2022 Japan Atherosclerosis Society Guidelines and had LDL-C ＞70 mg/dL or non-high-density lipoprotein cholesterol (non-HDL-C) ＞100 mg/dL and triglycerides (TG) ＜400 mg/dL. Endpoints included LDL-C, non-HDL-C, HDL-C, very low-density lipoprotein cholesterol, apolipoproteins, TG, steady state pharmacokinetics (PK) in obicetrapib arms, safety, and tolerability. In the 102 randomized subjects (mean age 64.8 y, 71.6% male), obicetrapib significantly lowered median LDL-C, apoB, and non-HDL-C, and raised HDL-C at all doses; responses in the obicetrapib 10 mg group were -45.8%, -29.7%, -37.0%, and +159%, respectively (all p＜0.0001 vs. placebo). The PK profile demonstrated near complete elimination of drug by 4 weeks. Obicetrapib was well tolerated and there were no adverse safety signals. All doses of obicetrapib taken as an adjunct to stable statin therapy significantly lowered atherogenic lipoprotein lipid parameters, showed near complete elimination of drug by 4 weeks, and were safe and well tolerated in a Japanese population, similar to previous studies of obicetrapib conducted in predominantly Caucasian participants.

Three-Dimensional Geometry Values and Clinical Determinants for the Annulus of the Tricuspid Valve in a Japanese Population.

The tricuspid annulus (TA) is the primary target of tricuspid valve (TV) surgery for tricuspid regurgitation (TR). However, the reference values for TA geometry in the Japanese population is currently unavailable. We aimed to elucidate the geometric reference values of the TA in Japanese individuals using 3-dimensional (3D) echocardiography.We conducted a prospective study using transthoracic 3D echocardiography on 142 healthy Japanese subjects aged between 20 and 79 years. The tricuspid geometric parameters in the late-diastole and the mid-systole were analyzed using custom 3D software (Realview™).After excluding 46 subjects with poor images, data from 96 subjects (67.6%) were analyzed. TA area and circumference showed strong correlations with body surface area (BSA) (P < 0.001 for all), while some of these parameters exhibited weak correlations with age. Gender differences in TV geometry were assessed across 3 age groups: 20-39 years (42 subjects), 40-59 years (28 subjects), and 60-79 years (26 subjects). In the youngest subjects (20-39 years), males had a significantly larger TA area and smaller anterior-posterior and medial-lateral diameters (P < 0.001 for all), even after adjusting for BSA, indicating gender differences of TA geometry. These differences diminished with age.We present reference values for TA geometry by age and gender in a Japanese cohort. BSA may be a suitable metric for indexing the TA parameters. While age-related changes in TA parameters may not be significant, gender differences, particularly in younger individuals, persist even after adjusting for BSA.

Development of a method for the imputation of the multi-allelic serotonin-transporter-linked polymorphic region (5-HTTLPR) in the Japanese population.

Serotonin-transporter-linked polymorphic region (5-HTTLPR), a variable number of tandem repeats in the promoter region of serotonin transporter gene, is classified into short (S) and long (L) alleles. Initial case-control association studies claiming the risks of the S allele in depression and anxiety were not completely supported by recent studies. However, most studies, especially those on East Asian populations, have overlooked the complexity of 5-HTTLPR, which involves multiple different alleles with distinct functional properties. To address this issue, distinguishing multiple 5-HTTLPR alleles is essential. Here, using the 5-HTTLPR genotypes previously determined by exhaustive Sanger sequencing of approximately 1,500 Japanese subjects and their comprehensive SNP data, we constructed a method for 5-HTTLPR genotype imputation. We identified 28 tag SNPs for the imputation of four major 5-HTTLPR alleles, which collectively account for 97.6% of 5-HTTLPR alleles in the Japanese population. Our imputation method, achieved an accuracy of 0.872 in cross-validation, will contribute to association analysis of 5-HTTLPR in the Japanese subjects.

A randomized phase I study of the safety and pharmacokinetics of BI 1291583 in healthy Japanese male subjects

AimsBronchiectasis patients face an unmet need for treatment options that reduce inflammation. Cathepsin C inhibition is expected to achieve this by reducing the activation of neutrophil‐derived serine proteases. Here, we present safety and pharmacokinetic (PK) data from a Phase I trial evaluating the novel cathepsin C inhibitor BI 1291583 in healthy Japanese male subjects.MethodsThis randomized, double‐blind, placebo‐controlled, parallel‐group study investigated BI 1291583 in healthy Japanese male subjects (jRCT2071210111) and consisted of a single‐rising‐dose (SRD) part and a multiple‐dose (MD) part. The primary endpoint was the percentage of subjects with drug‐related treatment‐emergent adverse events (AEs). Secondary PK endpoints (SRD: AUC0‐∞ and Cmax; MD: AUCτ,1 and Cmax,1 after first dose and AUCτ,ss and Cmax,ss after last dose), as well as further safety and PK endpoints, were also assessed.ResultsOverall, 36 subjects (n = 24 for SRD part; n = 12 for MD part) entered this Phase I trial. BI 1291583 was safe and well tolerated across the doses tested. All AEs were of mild intensity, with no drug‐related treatment‐emergent AEs, deaths, serious AEs or AEs of special interest reported in either part of the trial. Following both SRD and MD administration, BI 1291583 was readily absorbed, and PK was supraproportional over the doses assessed.ConclusionThe results show that BI 1291583 has an appropriate benefit–risk ratio for Japanese patients, with no safety or exposure concerns at the doses studied. Japanese patients with bronchiectasis can be safely integrated into future global clinical trials of BI 1291583, with no dose adjustment required.

The Need for Separate Testing with Acetylcholine for the Assessment of Endothelial Dysfunction and Coronary Artery Spasm.

Intracoronary acetylcholine (ACH) testing is clinically useful to diagnose the presence of the coronary vasomotor disorders coronary endothelial dysfunction and coronary epicardial/microvascular spasm. In Western countries, continuous intracoronary injection of ACH for 2-3 minutes without a pacemaker is the usual method, while rapid injection of ACH for 20-30 seconds with a pacemaker is the traditional procedure in Japan. Coronary microvascular spasm is often observed in Western populations, whereas coronary epicardial spasm is frequently seen in Japanese subjects. Methodological differences between Western and Japanese protocols may lead to the opposite prevalence of coronary vasomotor disorders. This article discusses the optimal method for diagnosing endothelial dysfunction and epicardial/microvascular spasm based on previous reports, and compares intracoronary ACH testing performed by Western cardiologists with that by Japanese physicians.

Association of Prepregnancy Cardiometabolic Factors With Gestational Diabetes Among Asian Populations in the United States

BackgroundAsian individuals are among the highest immigrant group to the United States and at particularly high risk of gestational diabetes, which is associated with long-term maternal cardiovascular disease. Limited data are available on the association of prepregnancy cardiometabolic risk factors with gestational diabetes among Asian American subjects. ObjectivesThis study sought to determine the association of prepregnancy hypertension and body mass index (BMI) among Asian ancestry subgroups and by maternal nativity. MethodsUsing data from the National Vital Statistics System from 2016 to 2019, the prevalence of gestational diabetes, stratified according to prepregnancy hypertension and obesity, was examined according to maternal race. Predicted probability of gestational diabetes with continuous BMI was calculated across Asian ancestry subgroups and by maternal nativity. ResultsAmong 13.3 million pregnancies, gestational diabetes occurred in 6.5%. Asian subjects had the highest prevalence (12.3%). Among those with prepregnancy hypertension, Asian subjects had the highest prevalence (29.3%). Across the range of BMI (18-42 kg/m2), Asian subjects had the highest predicted probability. There was substantial heterogeneity across Asian ancestry subgroups between the association of BMI with gestational diabetes, with highest probability among Japanese and Korean American subjects at BMI >23 kg/m2. Predicted probability of gestational diabetes was higher for mothers born outside the United States among all Asian subgroups, except for Japanese American subjects. ConclusionsAsian American individuals have the highest prevalence of gestational diabetes at any BMI and with hypertension. Substantial variation in risk is present across Asian subgroups. Findings suggest a need for more tailored screening and intervention for gestational diabetes among Asian American subjects, with a specific focus on risk for individuals born outside the United States.

Suppressive Effect of Apple Juice Intake on Urinary Excretion of Ascorbic Acid: Unblinded Randomized Crossover Study in Healthy Japanese Subjects.

Ascorbic acid is essential for human health. As this vitamin is water-soluble, it cannot be stored in the body for a long time and is easily excreted in urine; therefore, it is necessary to ingest it in sufficient amounts every day. The fact that apples retain ascorbic acid in human bodies are known; however, this has not been experimentally demonstrated/documented. In this study, to clarify the effect of apple juice ingestion on the urinary excretion of ascorbic acid, we compared urinary ascorbic acid excretion in healthy women administered ascorbic acid alone or with apple juice. The experimental design was an unblinded randomized crossover study. Subjects ingested ascorbic acid in apple juice or ascorbic acid with water. Urine was collected after ingestion, and urinary ascorbic acid was measured. When ascorbic acid was ingested with apple juice, urinary excretion of ascorbic acid was significantly suppressed compared to when ascorbic acid was ingested alone. This suggests that apple juice intake can help retain ascorbic acid in the body.

Prevention of Age-Related-Increases in the Risks of Incident Functional Disability and Dementia by Home-Delivered Functional Dairy Product Consumption in Japanese Older Adults.

Dairy products formulated with bioactives are widely distributed in Japan, but it remains to be clear whether a regular consumption of these products would help reduce the risks of incidental functional disability and dementia in older adults. This study aimed to investigate Japanese subjects aged ≥65 y (n=629) that routinely consumed three functional dairy products, a calcium-enriched milk supplemented with Bifidobacterium longum BB536, a yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed Lacticaseibacillus paracasei MCC1849, and a drinkable yogurt supplemented with lactoferrin, B. longum BB536 and heat-killed L. paracasei MCC1849, through a home delivery service. Intake frequency and intake duration of these functional dairy products were compared with the risk scores of incident functional disability and dementia, developed by the Japan Gerontological Evaluation Study. In the participants aged <75 y, the incident functional disability risk was significantly maintained or decreased in the participants with the long intake duration level compared with the short intake duration level (OR, 95% CI: 0.48, 0.25-0.93). In the participants aged ≥75 y, the dementia risk was significantly maintained or decreased in the participants with the high intake frequency level compared with the low intake frequency level (OR, 95% CI: 0.46, 0.22-0.95). A high intake frequency or long term duration of these functional dairy products may be effective in preventing an aging-related increase in the risks of incident functional disability and dementia in older adults, but this warrants further investigation using different products containing different bioactives.

Pharmacokinetics, safety, and efficacy of daridorexant in Japanese subjects: Results from phase 1 and 2 studies.

Daridorexant is a dual orexin receptor antagonist for the treatment of insomnia. We report results from the first two randomised, double-blind clinical studies of daridorexant in Japanese subjects. In the Phase 1 study, daridorexant (10, 25, 50 mg) or placebo were administered in the morning for 4 days in 24 young (mean age 26.9 years) and 24 older (mean age 69.7 years) healthy Japanese adults. Daridorexant reached a peak plasma concentration within 1.0 h across every dose and age group. For all doses, the mean plasma concentration of daridorexant showed a similar change between the age groups. Exposure parameters increased dose-dependently with minimal/no accumulation upon repeated dosing. The terminal half-life was ~8 h. In the Phase 2, four-period, four-way crossover study, 47 Japanese subjects (mean age 50.4 years) with insomnia disorder were randomised to receive four treatments (daridorexant 10, 25, 50 mg, placebo) during four treatment periods, each consisting of two treatment nights (5-12 day washout between treatment periods). Subjects continued their fourth treatment for 12 further days. A statistically significant dose-response relationship (multiple-comparison procedure-modelling, p < 0.0001) was found in the reduction of polysomnography-measured wake after sleep onset (WASO; primary endpoint) and latency to persistent sleep (secondary endpoint) from baseline to days 1/2. Statistically significant dose-response relationships were also observed for secondary subjective endpoints from baseline to days 1/2 (sWASO, latency to sleep onset). All daridorexant doses were well tolerated, with no treatment discontinuations and no next-morning residual effects. These results supported further investigation of daridorexant in Japanese patients with insomnia disorder.

Metabolic dysfunction-associated steatotic liver disease (SLD) and alcohol-associated liver disease, but not SLD without metabolic dysfunction, are independently associated with new onset of chronic kidney disease during a 10-year follow-up period.

The 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 aimed to elucidate the relationship between each category of SLD and chronic kidney disease (CKD). We investigated the effects of various SLDs on the development of CKD, defined as estimated glomerular filtration rate (eGFR)<60mL/min/1.73m2 or positive for urinary protein, during a 10-year period in 12138 Japanese subjects (men/women, 7984/4154; mean age, 48years) who received annual health examinations including abdominal ultrasonography. The prevalences of SLD without metabolic dysfunction (SLD-MD[-]), MASLD, MetALD, and ALD were 1.7%, 26.3%, 4.9%, and 1.9%, respectively. During the follow-up period, 1963 subjects (16.2%) (men/women, 1374 [17.2%]/589 [14.2%]) had new onset of CKD. Multivariable Cox proportional hazard model analyses after adjustment of age, sex, eGFR, current smoking habit, diabetes mellitus, hypertension, and dyslipidemia showed that the hazard ratios (HR [95% confidence interval]) for the development of CKD in subjects with MASLD (1.20 [1.08-1.33], p=0.001) and those with ALD (1.41 [1.05-1.88], p=0.022), but not those with MetALD (1.11 [0.90-1.36], p=0.332), were significantly higher than the HR in subjects with non-SLD. Interestingly, subjects with SLD-MD[-] had a significantly lower HR (0.61 [0.39-0.96], p=0.034) than that in subjects with non-SLD. The addition of the novel classification of SLDs into traditional risk factors for the development of CKD significantly improved the discriminatory capacity. MASLD and ALD, but not SLD-MD[-], are independently associated with the development of CKD.

Asymptomatic Intracranial Artery Stenosis/Occlusion in Heterozygous Familial Hypercholesterolemia: Its Frequency and Implications for Cerebrovascular and Cardiovascular Events.

The atherogenic characteristics of heterozygous familial hypercholesterolemia (HeFH) increase the risk of premature atherosclerotic cardiovascular disease including not only coronary artery disease but ischemic stroke. Asymptomatic intracranial artery stenosis/occlusion (IASO) is a major cause of ischemic stroke, but it has not yet been fully characterized in patients with HeFH. This study analyzed 147 clinically diagnosed subjects with HeFH who underwent magnetic resonance imaging/magnetic resonance angiography imaging for evaluation of IASO (≥50% diameter stenosis). Major adverse cerebrovascular and cardiovascular events (cardiac death, ischemic stroke, and acute coronary syndrome) were compared in patients with HeFH with and without asymptomatic IASO. Asymptomatic IASO was observed in 13.6% of patients with HeFH. The untreated low-density lipoprotein cholesterol level (240±95 versus 244±75 mg/dL; P=0.67) did not differ between the 2 groups. Despite the use of lipid-lowering therapies (statin, P=0.71; high-intensity statin, P=0.81; ezetimibe, P=0.33; proprotein convertase subxilisin/kexin type 9 inhibitor, P=0.39; low-density lipoprotein apheresis, P=0.14), on-treatment low-density lipoprotein cholesterol level in patients with both HeFH and IASO was still suboptimally controlled (97±62 versus 105±50 mg/dL; P=0.17), accompanied by a higher triglyceride level (median, 109 versus 79 mg/dL; P=0.001). During the 12.4-year observational period (interquartile range, 6.2-24.6 years), asymptomatic IASO exhibited a 4.04-fold greater likelihood of experiencing a major adverse cardiovascular event (95% CI, 1.71-9.55; P=0.001) in patients with HeFH. This increased risk of a major adverse cardiovascular event was consistently observed in a multivariate Cox proportional hazards model adjusting clinical characteristics (hazard ratio, 4.32 [95% CI, 1.71-10.9]; P=0.002). A total of 13.6% of Japanese subjects with HeFH presented with asymptomatic IASO. Despite lipid-lowering therapies, patients with both HeFH and IASO more likely had elevated risk of cerebrovascular and cardiovascular events. Our findings highlight asymptomatic IASO as a phenotypic feature of HeFH-related atherosclerosis, which ultimately affects future outcomes.

Efficacy and Safety of Oral Administration of Wine Lees Extract (WLE)-Derived Ceramides and Glucosylceramides in Enhancing Skin Barrier Function: A Randomized, Double-Blind, Placebo-Controlled Study.

Our search for plant-derived ceramides from sustainable sources led to the discovery of ceramides and glucosylceramides in wine lees. This study evaluated the efficacy and safety of wine lees extract (WLE)-derived ceramides and glucosylceramides in enhancing skin barrier function. A randomized, double-blind, placebo-controlled study was conducted with 30 healthy Japanese subjects aged 20-64. Subjects were allocated to receive either the WLE-derived ceramides and glucosylceramides (test group) or placebo for 12 weeks. The primary outcome was transepidermal water loss (TEWL), and secondary outcomes included skin hydration, visual analog scale (VAS) of itching sensation, and the Japanese Skindex-29. One participant withdrew for personal reasons, resulting in 29 subjects for data analysis (placebo n = 15; test n = 14). The test group showed a tendency of lower TEWL compared to the placebo after 8 weeks (p = 0.07). Furthermore, after 12 weeks of administration, the test group had significantly lower TEWL than the placebo (p = 0.04). On the other hand, no significant differences were observed in the secondary outcome parameters. No adverse events related to the supplements were reported. Oral supplementation of WLE-derived ceramides and glucosylceramides is a prominent and safe approach to enhancing skin barrier function and health. (UMIN000050422).

Sequential Sampling of the Gastrointestinal Tract to Characterize the Entire Digestive Microbiome in Japanese Subjects.

The gastrointestinal (GI) tract harbors trillions of microorganisms known to influence human health and disease, and next-generation sequencing (NGS) now enables the in-depth analysis of their diversity and functions. Although a significant amount of research has been conducted on the GI microbiome, comprehensive metagenomic datasets covering the entire tract are scarce due to cost and technical challenges. Despite the widespread use of fecal samples, integrated datasets encompassing the entire digestive process, beginning at the mouth and ending with feces, are lacking. With this study, we aimed to fill this gap by analyzing the complete metagenome of the GI tract, providing insights into the dynamics of the microbiota and potential therapeutic avenues. In this study, we delved into the complex world of the GI microbiota, which we examined in five healthy Japanese subjects. While samples from the whole GI flora and fecal samples provided sufficient bacteria, samples obtained from the stomach and duodenum posed a challenge. Using a principal coordinate analysis (PCoA), clear clustering patterns were identified; these revealed significant diversity in the duodenum. Although this study was limited by its small sample size, the flora in the overall GI tract showed unwavering consistency, while the duodenum exhibited unprecedented phylogenetic diversity. A visual heat map illustrates the discrepancy in abundance, with Fusobacteria and Bacilli dominating the upper GI tract and Clostridia and Bacteroidia dominating the fecal samples. Negativicutes and Actinobacteria were found throughout the digestive tract. This study demonstrates that it is possible to continuously collect microbiome samples throughout the human digestive tract. These findings not only shed light on the complexity of GI microbiota but also provide a basis for future research.

Upper eyelid morphology and age-related changes in Japanese and Chinese females.

Many consumers use cosmetic eye products to counteract age-related changes in appearance. Measurements of eyelid shape in Asian women have been reported in the frontal view or 45-degree profile only. The aim of this study was to describe morphological characteristics of the upper eyelid in Japanese and Chinese females from the frontal and profile aspects and examine morphological changes with age. Standardized digital photographs of 772 Japanese and 346 Chinese women (15-79 years of age) were acquired in frontal and 90-degree profile aspects. Eleven upper eyelid parameters (e.g., width, length, depth, aperture, and curvature) were measured using image analysis to determine age-related changes and compare by ethnicity. Eyelid width, area between eyebrow and eyelid, and eyelid curvature were comparable for both ethnicities under age 40, but the aging effect was more pronounced in Chinese subjects. Eyelid height, depth, and upper eyelid aperture angle were also comparable for both ethnicities under age 40, but the aging effect was more evident in Japanese subjects. Upper eyelid incline angle, eye orientation, and upper eyelid protrusion angle changed comparably with age for both ethnicities. No prominent age-related changes were evident for eyelid length or area between eyebrow and eye with the eye closed. Upper eyelid morphology changes with age in Japanese and Chinese females, starting around 40 years of age. Ethnic differences are limited in younger age groups but become more prominent with age. The findings suggest that aging affects some upper eyelid features earlier than others.