Healthy Japanese Volunteers Research Articles

Clinical evaluation of drug-drug interactions between the cytochrome P450 substrates selexipag and clopidogrel in Japanese volunteers.

The strong cytochrome P450 (CYP) 2C8 inhibitor gemfibrozil has been demonstrated to increase the area under the plasma concentration-time curve from 0 to infinity (AUC0-∞ ) of ACT-333679, an active metabolite of selexipag, by 11-fold. Similarly to gemfibrozil, the CYP2C8 inhibitor clopidogrel increased ACT-333679 concentration by 1.9-fold after a single loading dose (300 mg once daily) and 2.7-fold after repeated treatment with the maintenance dose (75 mg once daily) in Europeans. However, the effects of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 have not been fully elucidated in the Japanese population. We investigated the effect of clopidogrel on the pharmacokinetics of selexipag and ACT-333679 in 14 healthy Japanese volunteers. The concomitant administration of clopidogrel with selexipag did not influence the maximum concentration and AUC0-∞ of selexipag, whereas it significantly increased AUC0-∞ of ACT-333679 by approximately 1.90-fold (90% confidence interval 1.69-2.14) without changing the maximum concentration. When selexipag was administered 1 day after clopidogrel was discontinued, the increase in AUC0-∞ of ACT-333679 was 1.37-fold (90% confidence interval 0.93-2.02), suggesting that, although the inhibitory effect of clopidogrel on CYP2C8 was reduced, it persisted for at least 1 day after withdrawal. Our results demonstrated the impact of clopidogrel on the pharmacokinetics of selexipag and its active metabolite and suggested that selexipag should be carefully prescribed with clopidogrel with dose adjustment or reducing the dosing frequency in Japanese clinical settings.

Association between diet-related greenhouse gas emissions and nutrient intake adequacy among Japanese adults.

A growing number of Western studies have been exploring sustainable and healthy dietary patterns that target to reduce diet-related greenhouse gas emissions (GHGE) and to achieve nutritional needs. However, research is limited among Asian populations, where food sources for diet-related GHGE differ from those in Western populations. This study aimed to investigate associations between diet-related GHGE and the prevalence of inadequate nutritional intake. A cross-sectional study was carried out among 392 healthy Japanese volunteers aged 20-69 years. Dietary intake was assessed by four-non-consecutive day diet record. Diet-related GHGE was estimated using the Global Link Input-Output model and adjusted for energy intake by residual method. Prevalence of inadequacy was defined as a percentage of participants with nutrient intake outside the Tentative Dietary Goal for Preventing Lifestyle-Related Disease or below the Estimated Average Requirement defined by the Dietary Reference Intakes (DRIs) for Japanese. The association between diet-related GHGE and the prevalence of inadequacy of the usual intake of each nutrient was examined using logistic regression models. Participants with higher diet-related GHGE had overall better adherence to the DRIs. Intakes of all selected nutrients were positively associated with diet-related GHGE, except for carbohydrate, total fat, and saturated fat. With increasing quartile of diet-related GHGE, the prevalence of inadequacy decreased for protein, dietary fiber, potassium, vitamins A, B-6, and C, thiamin, riboflavin, calcium, magnesium, iron, and zinc, while that for sodium increased. Diets with lower diet-related GHGE did not have better adherence to the DRIs compared to diets with higher diet-related GHGE among Japanese adults. Drastic dietary change or other strategies such as improving the food system would be needed to achieve a sustainable and healthy diet among Japanese.

Influence of Global Spine Sagittal Balance and Spinal Degenerative Changes on Locomotive Syndrome Risk in a Middle-Age and Elderly Community-Living Population.

Purpose The aim of this study was to describe the characteristics of each locomotive syndrome (LS) risk stage, including global spine sagittal alignment, spinal degenerative changes evident on plain radiographs, low back pain (LBP), muscle strength, and physical ability in middle-aged and elderly people in a health checkup. Methods This study included 211 healthy Japanese volunteers (89 men and 122 women; mean age, 64.0 years) who underwent assessment with both radiographs and Spinal Mouse. Spinal sagittal parameters included thoracic kyphosis angle (TKA), lumbar lordosis angle (LLA), sagittal vertical axis, and spinal inclination angle (SIA). Lumbar disc height (LDH) and lumbar osteophyte formation (LOF) at each level were evaluated as the spinal degenerative changes. The LS assessment comprised three tests: stand-up test, two-step test, and 25-question Geriatric Locomotive Function Scale (GLFS-25). The subjects were divided into three groups (no risk, stage 1 LS, or stage 2 LS) according to LS risk test criteria. The prevalence of LBP was investigated with a visual analogue scale (VAS), and physical performances were also compared among the groups. Results Of the participants, 122 had no risk of LS, 56 had stage 1 LS risk, and 29 had stage 2 LS risk. With increasing LS risk stage, the prevalence of and VAS score for LBP increased significantly, and back muscle strength and physical abilities decreased significantly. The TKA did not differ among the three groups. The LLA decreased gradually with LS risk stage (P = 0.0001). At each level except L1–L2 and L5–S1, LDH decreased gradually with LS risk stage. The prevalence of LOF increased significantly with increasing LS risk stage. The SIA increased significantly with LS risk stage (P = 0.0167). Conclusions Participants with LS had higher prevalence of spinal degeneration, small LLA, and global spinal imbalance by anterior spinal inclination.

P0473LONGITUDINAL CHANGES OF IGA1 O-GLYCOFORM IN IGA NEPHROPATHY

Abstract Background and Aims Elevation of circulatory IgA1 with galactose-deficient (Gd) hinge-region (HR) O-glycans (Gd-IgA1) has been detected in most IgA nephropathy (IgAN) patients based on lectin ELISA. However, new approaches are needed for molecular-level characterization of IgA1 HR glycoform(s) in IgAN. We established a high-throughput method for analysis of IgA1 HR O-glycoforms using liquid chromatography-high-resolution mass spectrometry (LC-HRMS). To identify IgAN-associated IgA1 HR O-glycoforms and to assess their changes after therapy (with or without corticosteroids (CS)), we profiled IgA1 HR glycopeptides from sera collected at two time points (before and after therapy) from Japanese IgAN patients. Method Of the 10 Japanese IgAN patients recruited, 4 received CS treatment (CS group) and 6 have not (non-CS group). Japanese healthy volunteers (HC, n=10) were recruited as controls. Serum IgA1 was purified by affinity chromatography from HC and IgAN patients before and after therapy. After neuraminidase treatment and trypsin digestion, IgA1 HR glycosylation heterogeneity was analyzed by LC-HRMS. The relative abundance (RA, %) for each glycopeptide was calculated as percentage to the total IgA1 HR glycopeptide. The amount of each glycopeptide was then calculated by multiplying serum IgA concentration (mg/dL) by RA. Results Approximately 60% of IgA1 HR O-glycoforms in IgAN patients and HC were Gd O-glycoforms; these glycoforms contained one to three Gd-glycan(s), designated as 1 Gd-glycoform, 2 Gd-glycoform and 3 Gd-glycoform, respectively. In IgAN patients, the RA of non Gd-IgA1 glycoforms was elevated (P=0.002) and correlated with proteinuria (g/gCr) at renal biopsy (P=0.039, R=0.657). The amounts of non Gd- and 1Gd-glycoforms were higher in IgAN patients compared to HC (each P<0.001). After several years of follow up (2.77 years (1.44-3.85)), the RA of non Gd-glycoforms decreased in CS group of IgAN patients (P=0.039) whereas it remained unchanged in the non-CS group (P=0.488). The amount of non Gd-glycoforms exhibited similar trends, i.e., decreased in CS group (P=0.068) whereas it remained unchanged in the non-CS group (P=0.943). Conclusion This study profiled serum IgA1 for IgAN-associated IgA1 HR O-glycoforms at the molecular level and assessed their changes in response to CS vs. non-CS therapy. IgA1 HR O-glycoforms altered by treatment may serve as a biomarker(s) for monitoring patients’ responses to therapy.

Implication of core beliefs about negative-self in neuroticism

Objective: Core beliefs about negative-self are beliefs about self-deficiencies in basic aspects of human adaptation. Meanwhile, neuroticism is a personality trait characterised by negative emotionality, i.e., a tendency to react to stress with negative emotions. The present study tested the hypothesis that core beliefs about negative-self are implicated in neuroticism.Methods: The subjects were 309 Japanese healthy volunteers. Core beliefs about negative-self were evaluated by the Brief Core Schema Scales, and neuroticism was evaluated by the NEO Personality Inventory-Revised.Results: In both multiple regression analysis and structural equation modelling, higher neuroticism was strongly predicted by higher levels of core beliefs about negative-self.Limitations: The present study cannot determine the causal relationship between core beliefs about negative-self and neuroticism, because of its cross sectional design.Conclusions: The present study suggests that core beliefs about negative-self are deeply implicated in neuroticism.Key PointsImplication of core beliefs about negative-self in neuroticism was examined.Neuroticism was predicted by higher levels of these core beliefs.These core beliefs may be involved in negative emotionality of neuroticism.

Interrelation Between Increased BDNF Gene Methylation and High Sociotropy, a Personality Vulnerability Factor in Cognitive Model of Depression.

PurposeIt is suggested that increased methylation of the brain-derived neurotrophic factor (BDNF) gene is involved in the pathogenesis of depression, while sociotropy and autonomy are proposed as personality vulnerability factors in cognitive model of depression. We examined the interrelation between BDNF gene methylation and sociotropy or autonomy, with taking into account the previously reported deleterious effect of parental overprotection on sociotropy.Materials and MethodsThe participants consisted of 90 healthy Japanese volunteers. Methylation levels of the BDNF gene in peripheral blood were quantified by bisulfite pyrosequencing. Sociotropy and autonomy were assessed by the Sociotropy-Autonomy Scale, and perceived parental protection was evaluated by the Parental Bonding Instrument.ResultsIn Pearson’s correlation analysis, there was a positive correlation between methylation levels of the BDNF gene and sociotropy scores (p<0.05) but not autonomy scores, and a positive correlation between maternal protection scores and sociotropy scores (p<0.05). In structural equation modeling, two models were proposed; the first one is that hypermethylation of the BDNF gene and maternal overprotection independently contribute to high sociotropy, and the second one is that maternal overprotection contributes to high sociotropy which then leads to hypermethylation of the BDNF gene.ConclusionThe present study suggests an interrelation between increased BDNF gene methylation and high sociotropy.

Intake of Alpha-Linolenic Acid-Rich Perilla frutescens Leaf Powder Decreases Home Blood Pressure and Serum Oxidized Low-Density Lipoprotein in Japanese Adults.

Oxidized low-density lipoprotein (Ox-LDL) is known to be highly atherogenic. Thus, decreasing the blood levels of Ox-LDL through dietary means is an important approach to reduce cardiovascular events in high-risk individuals. In this randomized placebo-controlled human interventional trial, we aimed to evaluate whether Perilla frutescens leaf powder (PLP) ameliorates Ox-LDL and home blood pressure, along with its biological antioxidant potential. Healthy Japanese volunteers aged 30–60 years (n = 60) were randomized to PLP and placebo groups. The PLP group consumed PLP dried using a microwave under reduced pressure, and the placebo group consumed pectin fiber daily for 6 months. Home blood pressure, serum biochemical parameters, and fatty acid profiles of erythrocyte plasma membranes were analyzed. Plasma Ox-LDL levels significantly decreased in the PLP group but not in the placebo group. Mean changes in the biological antioxidant potential and alpha-linolenic acid levels in the erythrocyte plasma membrane were significantly increased in the PLP group than in the placebo group. In subjects with prehypertension (systolic blood pressure [SBP] ≥ 120 mmHg), the mean reduction in morning or nocturnal SBP was significantly greater in the PLP group than in the placebo group. Thus, PLP intake may be an effective intervention to prevent cardiovascular diseases.

Twelve-month Studies on Perilla Oil Intake in Japanese Adults-Possible Supplement for Mental Health.

Perilla oil (PO), rich in α-linolenic acid (LNA, C18:3, ω-3), is increasingly alleged to have numerous health benefits in humans. However, the current reports detailing the effects of PO on human mental health are not adequate. Therefore, in the current investigation we compared the effects of PO or placebo treatment on the mental condition of healthy adult Japanese volunteers. At baseline and after 12 months of treatment, mental health condition was assessed using the Zung Self-Rating Depression Scale (SDS) and Apathy Scale, and serum biochemical parameters were determined. From baseline to 12 months of intervention, both SDS depression and apathy scores improved significantly in the PO-administered group. Compared to those of control group, serum norepinephrine and serotonin levels after 12 months decreased in the PO-administered group. The enhanced mental state observed in PO-subjects was accompanied by LNA level increases in erythrocyte plasma membranes. Our data demonstrate that PO intake enhances blood LNA levels and may maintain healthy mental conditions in adult subjects.

The inclination of the femoral medial posterior condyle was almost vertical and that of the lateral was tilted medially.

The purpose of this study was to three-dimensionally analyse the size and shape of the femoral posterior condyles of the normal knee. A total of 62 healthy Japanese volunteers (37 males and 25 females) providing a sample of 124 normal knee joints, who had no knee-related symptoms and no history of major trauma, underwent computed tomography scans of the bilateral femur and tibia. Three-dimensional digital models of the femur were constructed from computed tomography data using visualisation and modelling software. The following parameters were evaluated: (1) the radii of the posterior condyles approximated to spheres and (2) the inclination angle of the posterior condyles in the coronal plane of the femoral coordinate system. The radii of the medial and lateral condyles approximated to spheres were 17.0 ± 1.6 and 17.1 ± 1.8mm, respectively and were not different. The inclination angles of the medial and lateral condyles in the coronal plane were - 0.6° ± 4.6° and 9.7° ± 5.7°, respectively. The medial condyle was almost vertical, whereas the lateral one was medially tilted. This study found an asymmetrical inclination between medial and lateral condyles. This may be related to the asymmetrical motion of the knee, which is known as medial pivot motion. This finding provides valuable morphological information and may be useful for implant designs for total knee arthroplasty. IV.

Randomised trial of acid inhibition by vonoprazan 10/20 mg once daily vs rabeprazole 10/20 mg twice daily in healthy Japanese volunteers (SAMURAI pH study).

Vonoprazan (V), a potassium-competitive acid blocker, has a more durable acid-inhibitory effect as compared with standard-dose proton pump inhibitors (PPIs) but has not been compared with 2-4 times higher daily PPI doses administered in two divided doses. To evaluate the acid-inhibitory effect of V 10/20mg once-daily (OD; V10/V20) vs rabeprazole (R) 10/20mg twice-daily (BID; R20/R40) in healthy Japanese volunteers. This multicentre, randomised, open-label, two-period, crossover study compared V10 or V20 vs R20, or V20 vs R40 using three cohorts of 10 healthy Japanese adults. Within each cohort, subjects were randomised to receive V or R for 7days and, following a washout period≥7days, the other treatment for 7days. On day 6 of each period, 24-hours multichannel gastric impedance-pH monitoring was performed. Percent times pH≥3, ≥4 and≥5 (pH 3, 4 and 5 holding time ratios [HTRs]) in 24hours were evaluated as primary pharmacodynamic endpoints. Acid-inhibitory effect (24-hours pH 3 HTR) of V20 was greater than those of R20 (91.0% vs 65.3%; P=.0049) and R40 (98.5% vs 85.9%; P=.0073). Similar results were obtained for 24-hours pH 4 and 5 HTRs. V20 also achieved greater nocturnal pH 4 (91.5% vs 73.2%; P=.0319) and 5 HTRs (78.8% vs 62.2%; P=.0325) as compared with R40. One subject (20%) developed diarrhoea while receiving R40 which was considered treatment-related. Compared with 2-4 times the standard daily dose of R, V20 exerts a more potent and durable acid-inhibitory effect. Trial identifier: UMIN000022198 (www.umin.ac.jp/ctr/index.htm).

A Study to Assess the Effect AZD4831 in Japanese and Chinese Healthy Volunteers

A Study to Assess the Effect AZD4831 in Japanese and Chinese Healthy Volunteers

Differences of lumbopelvic sagittal parameters among community-dwelling middle-age and elderly individuals: Relations with locomotor physical function

This study aims to establish radiographic parameters of lumbopelvic sagittal alignment, gender related differences, and age-related changes in a middle-aged community, to investigate whether age-related changes of lumbopelvic alignment reflect the risk of locomotive syndrome (LS). This study included 448 healthy Japanese volunteers who attended a basic health checkup supported by the local government. The subjects (184 males and 264 females, mean age: 62.7 years) were grouped according to their age by decade. Sagittal lumbopelvic parameters were collected by lateral spine radiographs including lumbar lordosis (L1–S1, LL), lower lumbar lordosis (L4–S1, LLL), pelvic incidence (PI), pelvic tilt (PT) and sacral slope (SS). The three tests (stand-up test, two-step test, and 25-question geriatric locomotive function scale [GLFS-25]) composing the LS risk test were performed. LL was significantly lower in males than in the females. A significant decrease of LL and LLL was observed from 60 s to 70 s in the females. PI did not markedly change with aging in either gender but was lower in males. A remarkable increase of PT was seen from 60 s to 70 s in the females. SS did not markedly change with aging and was lower in males in all decades. The prevalence of LS risk in males and females increased gradually with age and was greater in females in any decade. 70 s females with LS risk had significantly lower LL and higher PT compared to them without LS risk. Radiographic parameters of lumbopelvic sagittal alignment were established in community-dwelling middle-age and elderly individuals.

Draft Genome Sequences of Bifidobacterium animalis Consecutively Isolated from Healthy Japanese Individuals.

Bifidobacterium species are well recognized as probiotics and colonized in various parts of the human body. Here, we report the draft genome sequences of Bifidobacterium animalis isolated from two healthy Japanese volunteers, one of which was sampled twice before and after a 10-year interval. A core genome phylogeny analysis indicated that the strains isolated from the same volunteer were closely related. This paper is the first report of multiple draft genome sequences of B. animalis independently isolated from the same individual and provides insight into the probiotic potential of a member of this species.

Determination of the Kinetic Parameters for 123I Uptake by the Thyroid, Thyroid Weights, and Thyroid Volumes in Present-day Healthy Japanese Volunteers.

The purpose of this study was to evaluate the kinetic parameters that determine the uptake rate of radioiodide in the thyroid over 24 h after administration and to estimate thyroid volumes/masses of present-day Japanese. Methods: We determined the thyroid uptake rate of I in healthy male Japanese after oral administration (4.5-8.0 MBq) without iodine restriction. Masses of thyroid glands were collected in 2012-2016 during autopsies of 7,651 male and 3,331 female subjects. Volumes of thyroid glands were estimated by ultrasonography and magnetic resonance imaging in 52 male subjects. Results: The thyroid uptake rate of I for 24 h was 16.1 ± 5.4%. Kinetic model analysis was conducted to obtain the clearances (L h) for thyroid uptake and urinary excretion of I (0.499 ± 0.258 and 2.10 ± 0.39 L h, respectively). The masses of thyroid glands were on average 19.8 g (95% confidence interval of 18.3-19.5 g) and 15.5 g (95% confidence interval of 14.7-16.2 g) in male and female subjects aged 19-52 y, respectively. Volumes of thyroid glands estimated by ultrasonography and magnetic resonance imaging were 17.5 ± 5.2 and 14.2 ± 5.3 mL, respectively. In healthy Japanese, there has been no significant change for at least 50 y in the thyroid uptake of radioiodide over 24 h or in its kinetic parameters. These Japanese-specific kinetic parameters will allow quantitative estimation of the radiation exposure from the Fukushima accident and its variance during the individual's evacuation from or stay in Fukushima.

Phase 1 study of crisaborole in Japanese healthy volunteers and patients with atopic dermatitis.

Crisaborole ointment, 2%, is a non-steroidal phosphodiesterase 4 inhibitor for the treatment of mild to moderate atopic dermatitis (AD). This parallel-cohort, phase 1 study was conducted to investigate skin irritation potential and safety of crisaborole in healthy Japanese adults (cohort 1) and the safety and pharmacokinetic profile of crisaborole and metabolites AN7602 and AN8323 in Japanese adults with mild to moderate AD (cohort 2). In cohort 1, 20 healthy volunteers received single applications of crisaborole and vehicle simultaneously on separate locations under 48-h occlusion. In cohort 2, 12 patients with mild to moderate AD received crisaborole (n=10) or vehicle (n=2) twice daily for 8days. Skin irritation and safety were assessed in cohort 1. Pharmacokinetics and safety were assessed in cohort 2. Skin irritation index (scale 0-400) was 40.0 for crisaborole and 5.0 for vehicle. No treatment-emergent adverse events (TEAE) were reported in cohort 1. The most common TEAE in the crisaborole group in cohort 2 were application site irritation (n=7) and application site pain (n=4). Crisaborole was rapidly absorbed, with limited systemic exposure between days 1 and 8 that was comparable with that seen in US-based participants in previous trials. Crisaborole had higher skin irritation than vehicle under occlusion in healthy Japanese adults and had an acceptable safety profile in Japanese adults with mild to moderate AD.

Draft Genome Sequences of Enterococcus faecalis Strains Isolated from Healthy Japanese Individuals.

Enterococcus faecalis is a common commensal of the intestines of humans and other mammals but is also a frequent cause of serious ailments. Here, we report 14 draft genome sequences of strains of Enterococcus faecalis, a normal inhabitant and Gram-positive bacterium that was isolated from 7 healthy Japanese volunteers.

P031 Systematic-analysis of injection-site pain from administration of subcutaneous adalimumab biosimilar FKB327 versus the adalimumab reference product humira via different methods

BACKGROUND: FKB327 is a proposed biosimilar of the adalimumab reference product (RP). Several studies in both healthy volunteers and patients with active rheumatoid arthritis (RA) were undertaken, the results of which have been reported elsewhere. The formulation excipients of the biosimilar product differ from that of the RP, and different injection-site pain with subcutaneous injection has been reported. The current meta-analysis examines pooled data from these studies in relation to the amount of injection-site pain resulting from using prefilled syringes (PFS) versus auto-injectors (AI) versus regular syringes (RS) and the proposed biosimilar, FKB327, versus the RP. METHODS: Data from 4 studies, FKB327-001, -002, -003, and -004, were pooled in an effort to compare injection-site pain upon subcutaneous administration of FKB327 versus the RP (citrate-containing formulation of the RP (40 mg/0.8 mL). Study FKB327-001, in healthy volunteers (n = 180), involved a single subcutaneous dose of either FKB327 or the RP. Study FKB327-004 was a similar study in healthy Japanese volunteers (n = 130). Study FKB327-002 was a randomized (FKB327 with RS or the RP), double-blind, multiple-dose study in patients with active RA. This was followed by Study FKB327-003, in which patients were rerandomized to receive either FKB327-PFS or the RP in the randomization phase, followed by an open-label extension phase of the study, in which AI was introduced. As patients were continued on treatment or switched during the course of the FKB327-002 and -003 studies, the injection-site pain was assessed at the first dosing occasion of FKB327 or the RP (n = 691). Data from all 4 studies were examined by meta-analysis of the visual analog scale (VAS) using a 100-mm horizontal scale for FKB327 versus the RP and for comparison of AI, PFS, and RS. RESULTS: Data were analyzed from a total of 2007 assessments in 1,001 subjects. A linear mixed model of the VAS in mm for the RP versus FKB327 across all 4 studies showed a 12.6-point improvement in the score for FKB327 versus the RP (95% confidence interval [CI], –14.3 to –10.8; P &lt; 0.001). For the AI and PFS used for FKB327 administration, AI showed a 1.7-point improvement in VAS compared with PFS (95% CI, –3.3 to –0.1; P = 0.035). Gender, age, body weight, and population (healthy subject or patient) were not identified for differences in injection-site pain. CONCLUSION(S): FKB327 showed a significant advantage in terms of injection-site pain compared with the RP, as well as lack of inferiority for both AI and PFS versus RS.

Healthy human serum N-glycan profiling reveals the influence of ethnic variation on the identified cancer-relevant glycan biomarkers.

BackgroundMost glycomics studies have focused on understanding disease mechanisms and proposing serum markers for various diseases, yet the influence of ethnic variation on the identified glyco-biomarker remains poorly addressed. This study aimed to investigate the inter-ethnic serum N-glycan variation among US origin control, Japanese, Indian, and Ethiopian healthy volunteers.MethodsHuman serum from 54 healthy subjects of various ethnicity and 11 Japanese hepatocellular carcinoma (HCC) patients were included in the study. We employed a comprehensive glycoblotting-assisted MALDI-TOF/MS-based quantitative analysis of serum N-glycome and fluorescence HPLC-based quantification of sialic acid species. Data representing serum N-glycan or sialic acid levels were compared among the ethnic groups using SPSS software.ResultsTotal of 51 N-glycans released from whole serum glycoproteins could be reproducibly quantified within which 33 glycoforms were detected in all ethnicities. The remaining N-glycans were detected weakly but exclusively either in the Ethiopians (13 glycans) or in all the other ethnic groups (5 glycans). Highest abundance (p < 0.001) of high mannose, core-fucosylated, hyperbranched/hypersialylated N-glycans was demonstrated in Ethiopians. In contrast, only one glycan (m/z 2118) significantly differed among all ethnicities being highest in Indians and lowest in Ethiopians. Glycan abundance trend in Ethiopians was generally close to that of Japanese HCC patients. Glycotyping analysis further revealed ethnic-based disparities mainly in the branched and sialylated structures. Surprisingly, some of the glycoforms greatly elevated in the Ethiopian subjects have been identified as serum biomarkers of various cancers. Sialic acid level was significantly increased primarily in Ethiopians, compared to the other ethnicities.ConclusionThe study revealed ethnic-specific differences in healthy human serum N-glycome with highest abundance of most glycoforms in the Ethiopian ethnicity. The results strongly emphasized the need to consider ethnicity matching for accurate glyco-biomarker identification. Further large-scale study employing various ethnic compositions is needed to verify the current result.

Pharmacokinetic Study of Compound K in Japanese Subjects After Ingestion of Panax ginseng Fermented by Lactobacillus paracasei A221 Reveals Significant Increase of Absorption into Blood.

Compound K (CK) is a metabolite of a saponin in Panax ginseng, formed from ginsenoside, a triterpenoid glycoside, by human intestinal bacteria. Lactobacillus paracasei A221 isolated from fermented food can hydrolyze (deglycosylate) the main ginsenoside, ginsenoside Rb1, and generate CK. However, the pharmacokinetics of L. paracasei A221 fermented ginseng (FG) and nonfermented ginseng (NFG) have not been investigated so far. The aim of this study was to investigate the pharmacokinetics of CK after oral administration of single doses of FG and NFG in healthy Japanese adults. An open-label, randomized, single-dose, two-period, crossover study was conducted in 12 Japanese healthy volunteers (five men and seven women, aged 40-60 years). All subjects were equally allocated into two groups and administered tablets containing FG or NFG. Until 24 h after the administration, blood samples were sequentially collected, plasma concentrations of CK were measured, and the pharmacokinetic parameters were calculated. We also expected restoration of decreased testosterone level as one of the beneficial effects of FG and measured plasma total testosterone concentrations in male volunteers. The means of Tmax, Cmax, and area under the concentration-time curve (AUC) were significantly different between the two groups. In the FG group, AUC0-12h (ng h/mL) and AUC0-24h (ng h/mL) were, respectively, 58.3- and 17.5-fold higher than those in the NFG group. Moreover, mean testosterone concentration in the FG group significantly increased 24 h after administration. These results showed that the main ginsenoside metabolite of ginseng, CK, produced by L. paracasei A221 has potential utility in health maintenance in healthy middle-aged and old Japanese adults.

Utilization of Facial Image Analysis Technology for Blink Detection: A Validation Study.

The assessment of anterior eye diseases and the understanding of psychological functions of blinking can benefit greatly from a validated blinking detection technology. In this work, we proposed an algorithm based on facial recognition built on current video processing technologies to automatically filter and analyze blinking movements. We compared electrooculography (EOG), the gold standard of blinking measurement, with manual video tape recording counting (mVTRc) and our proposed automated video tape recording analysis (aVTRa) in both static and dynamic conditions to validate our aVTRa method. We measured blinking in both static condition, where the subject was sitting still with chin fixed on the table, and dynamic condition, where the subject's face was not fixed and natural communication was taking place between the subject and interviewer. We defined concordance of blinks between measurement methods as having less than 50 ms difference between eyes opening and closing. The subjects consisted of seven healthy Japanese volunteers (3 male, four female) without significant eye disease with average age of 31.4±7.2. The concordance of EOG vs. aVTRa, EOG vs. mVTRc, and aVTRa vs. mVTRc (average±SD) were found to be 92.2±10.8%, 85.0±16.5%, and 99.6±1.0% in static conditions and 32.6±31.0%, 28.0±24.2%, and 98.5±2.7% in dynamic conditions, respectively. In static conditions, we have found a high blink concordance rate between the proposed aVTRa versus EOG, and confirmed the validity of aVTRa in both static and dynamic conditions.