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Background and Objective: Tomato seeds are edible seeds unconsciously ingested with the fruit. However, there are few reports regarding the constituents and biological activities of tomato seed extract (TSE). Recently, we found that saponins are major constituents of TSE including lycoperoside H. Previous reports have described that several plant-derived saponins improve skin diseases such as wounds and microangiopathy. Therefore, to discover the effect of TSE on the skin condition, we conducted a clinical trial of TSE (Tomato Seed Extract-P) standardized with lycoperoside H when orally ingested. Methods: The study was performed as a randomized, double-blind, placebo-controlled study. TSE (200 mg daily) containing 1 mg of lycoperoside H was used as the active sample. We enrolled 44 Japanese women who have concerns about facial elasticity and relatively low facial skin elasticity. All subjects were randomly allocated into either the active group (n = 22) or the placebo group (n = 22) using a computerized random-number generator. Capsules containing either the active sample or a placebo were administered for 8 weeks between October 12, 2020, and January 16, 2021. Facial elasticity, specifically the R7 value, was evaluated as the primary outcome. The remaining facial R parameters, upper arm R parameters, and other skin parameters including epidermal moisture, trans epidermal water loss, dermal parameters, and advanced glycation end products (AGEs) parameters were measured at 0, 4, and 8 weeks of ingestion. Blood, urine, and body parameters were also evaluated for safety. Results: Forty-three subjects completed the trial, and the per protocol set comprised 21 subjects in the TSE group and 22 subjects in the placebo group. After ingesting TSE for 8 weeks, the R7 value was significantly higher in the TSE group compared to the placebo group. Furthermore, the change in R7 values from the baseline at 4 and 8 weeks were also higher in the TSE group. Among the secondary outcomes, facial elasticity parameters including R2, R5, R1, and R4 at 4 weeks and facial R5, R1, and R4 and upper arm R2 at 8 weeks were higher in the TSE group. In addition, plasma pentosidine significantly decreased in the TSE group after 8 weeks of ingestion. There were no significant differences in moisture, DermaLab® parameters and AGEs parameters except plasma pentosidine. Laboratory tests revealed no abnormalities suggesting adverse effects of TSE. Conclusions: TSE (200 mg/day) standardized with lycoperoside H improved the facial elasticity parameters. Thus, daily ingestion of TSE was suggested to be beneficial for maintaining the facial skin elasticity. However, the relationship between the reduction of pentosidine and skin elasticity by TSE ingestion should be clarified through further studies. Trial Registration: UMIN-CTR: UMIN000041881. Foundation: Oryza Oil & Fat Chemical Co., Ltd.

As a nation where more than 28% of the total population is 65 years and over, Japan faces multiple ageing-related issues. Among these, dementia dominates the agenda due to its high societal costs. The purpose of this study was to elucidate the state of the current movement to create dementia-friendly communities across Japan, with a focus on the good practices of educational institutions, such as libraries, museums and lifelong learning centers. A case study approach was employed, which involved site visits and interviews with those charged with the development of educational projects to create dementia-friendly communities. The findings of this research suggest that some educational institutions have created dementia-friendly communities through utilizing their existing rich resources and providing approachable, convenient and holistic learning environments. However, current movements have tended to focus on assisting care givers and ordinary citizens through the provision of appropriate information and through opportunities for exchanging ideas and/or anxieties regarding dementia, and no careful attention has been paid to those living with dementia, whose viewpoints tend to be neglected in most current educational provision. Future research should focus on the ways in which different educational institutions can directly contribute to those living with dementia by hearing their voices and defining the meaning of learning for them; the minute process of transformation by deliberately observing the interaction between persons with dementia and others in such institutions through various methodologies; possibilities of learning for all stakeholders regarding persons with dementia, in order to provide more inclusive dementia-friendly communities. Overall, many opportunities still remain uncultivated and diverse individuals could be involved in this process so that the potential of each institution can be more fully developed in the light of current societal needs.

Objectives Plasmalogen, phospholipids with previously shown associations with dementia, has attracted attention as a substance found in some studies to improve cognitive function. The effects of ascidian-derived plasmalogens on cognitive performance improvement were assessed in a randomized, double-blind, placebo-controlled study including Japanese adult volunteers with mild forgetfulness. Methods Participants consumed either the active food containing ascidian-derived plasmalogen (1 mg as plasmalogen) or the placebo food for 12 weeks, and their cognitive performance was assessed by Cognitrax. Participants were randomly allocated into the intervention (ascidian-derived plasmalogen; 8 males, and 17 females; 45.6 ± 11.1 years) or the placebo (9 males, and 15 females; mean age, 46.4 ± 10.8 years) group. Results Compared to the placebo group, the intervention group showed a significant increase score in composite memory (eight weeks: 3.0 ± 16.3 points, 12 weeks: 6.7 ± 17.5 points), which was defined as the sum of verbal and visual memory scores. Conclusions These results indicate the consumption of ascidian-derived plasmalogen maintains and enhances memory function. This study was registered at the University Hospital Medical Information Network Clinical Trial Registry (UMIN-CTR, registry no. UMIN000026297). This study did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.

A high-throughput screening method for the complexation between metal ions and drugs was established by combining solid-phase extraction (SPE) using a nitrilotriacetic acid (NTA) modified silica spin cartridge with subsequent HPLC analysis. First, a test metal ion solution was passed through the NTA cartridge, then a test drug solution diluted in phosphate buffered saline (pH 7.4) was passed through the metal-chelated NTA cartridge. The complexation behavior between the metal and the drug on the NTA cartridge was evaluated by HPLC quantification of the drug in the SPE eluate. Comprehensive analysis of the complexation behavior between 11 different metal ions and 55 drugs showed that Cu2+, Ni2+, Co2+, Zn2+, Cr3+ and Fe3+ formed complexes with 12, 5, 4, 2, 1 and 1 kinds of drugs, respectively. Bromazepam selectively formed complexes with Cu2+, Ni2+ and Co2+.

This study investigated the effects of proanthocyanidins derived from Acacia (Acacia mearnsii) bark extract in healthy Japanese adult subjects experiencing uncomfortable skin symptoms. All subjects were randomly allocated into two groups (n = 33 each) using a computerized random-number generator. The subjects received either Acacia bark extract tablets or placebo for 8 weeks. Evaluations included water content in the stratum corneum, transepidermal water loss (TEWL), Skindex-16, dermatology life quality index (DLQI), visual analog scale for desire to scratch, and blood tests. At 4 weeks, the symptom/feeling score of DLQI, subjective symptoms related to uncomfortable skin, and the desire to scratch were significantly reduced in the intervention group than in the placebo group. At 8 weeks, the intervention group exhibited significantly lower TEWL on facial skin than that in the placebo group. In conclusion, the intake of Acacia bark extract tablets reduced TEWL and improved dry and uncomfortable skin.

Leadless pacemakers have many advantages for some patients in preventing lead- and pocket-related complications. The traveling of the femoral vein is important in the context of normal approach site choice for leadless pacemakers. In this case, the leadless pacemaker could be successfully implanted without disrupting the inferior vena cava filter by using intravascular ultrasound in a hemodialysis patient with complete atrioventricular block and atrial fibrillation who had obstruction of the bilateral subclavian and right femoral veins, and travel abnormality of the left common iliac vein.

A 56-year-old man presented at a local hospital with nausea, vomiting, epigastric pain, and white stool. CT scan showed hypovascular mass in pancreatic uncinate process and multiple peritoneal nodules. The diagnosis was stage Ⅳ pancreatic cancer(unresectable), and the patient underwent chemotherapy with GEM plus nab-PTX. He also claimed a severe cancer pain at presentation and was prescribed oxycodone 60 mg/day. After 43 months of chemotherapy, the duodenum was obstructed by tumor growth on CT scan, then he underwent duodenal stent placement. He eventually needed a total of 3 duodenal stenting for re-obstruction. He could keep adequate oral intake after the treatment. He also suffered from severe pain by progressed tumor, then underwent celiac plexus block and palliative radiation therapy(20 Gy/5 Fr). Afterwards his cancer pain has been under control. He underwent chemotherapy with FOLFIRINOX for next step. A patient with stage Ⅳ pancreatic cancer may survive for a long period with adequate QOL as a result of multidisciplinary treatment.

Background: Excessive ingestion of fructose can lead to obesity and related diseases. Eucalyptus leaf extract (ELE) contains oenothein B, which inhibits intestinal fructose absorption.Objective: The antiobesity effects of ELE containing oenothein B were evaluated in healthy Japanese whose body mass index (BMI) was ≥ 23 and < 30 kg/m2.Methods: A randomized, placebo-controlled, double-blind, parallel-group study was performed to evaluate the effect of ELE consumption, for 12 weeks at a 3.38 mg/day dose of oenothein B, on the abdominal visceral fat area (VFA) as the primary outcome. Results were compared to those of a placebo group.Results: Of the 721 individuals who underwent screening, 198 were randomly allocated into two groups. A total of 95 subjects in the placebo group and 94 in the intervention group were established as the per-protocol set. VFA in the intervention group significantly decreased compared to that in the placebo group 12 weeks after initiating intervention. This reduction in VFA was considered to have clinical significance. Among the secondary outcomes, VFA, waist circumference, and muscle mass after 8 weeks, as well as body weight and BMI after 12 weeks, were significantly lower in the intervention group compared to the placebo group.Conclusion: ELE containing oenothein B may be effective against obesity and related diseases by reducing VFA levels. Keywords: human trial; Eucalyptus globulus; oenothein B; polyphenol; hydrolyzable tannin; ellagitannin; dietary fructose consumption; dietary survey; Calorie and Nutrition Diary; glucose transporter 5

Background and objective: The fruit of Mauritia flexuosa (moriche palm), which is known as “Aguaje,” has been used for beverages and processed foods. Recently, we found that several methoxyflavans are contained in the fruit and they exhibit estrogenic activities. Therefore, moriche palm extract (MPE) may function as a phytoestrogen and improve the symptoms induced by estrogen deficiency. However, the clinical effects of MPE on females has not yet been reported. We conducted a clinical trial of MPE on undefined complaints related to premenstrual syndrome (PMS) in healthy Japanese females. Methods: This randomized, double-blind, placebo-controlled study examined the effects of MPE (100 mg daily) containing 12.6  g of 5,4'-dihydroxy-7-methoxy-6-methylflavan. Forty-four Japanese women with indefinite complaints in premenstrual and menstrual periods were enrolled in the study. All subjects were randomly allocated into either the MPE (100 mg) group (n=22) or the placebo group (n=22) using a computerized random-number generator. Capsules containing either MPE (100 mg) or placebo were administered for 8 weeks between October and December in 2018. The severity of uncertain complaints and emotional status were evaluated using the Japanese version of the menstrual distress questionnaire (MDQ) as a primary outcome, and Medical Outcomes Study Short-Form 36-Item Health (SF-36) questionnaire at 4 and 8 weeks of ingestion. Blood, urine, and body parameters were also evaluated. Results: Forty-three subjects completed the trial, and the per protocol set comprised 21 subjects in the MPE (100 mg) group and 22 subjects in the placebo group. After ingesting MPE for 4 weeks, arousal in the premenstrual period significantly improved in the MPE (100 mg) group. After 8 weeks, the summary score, water retention, impaired concentration and control during menstrual period significantly improved in the MPE (100 mg) group. Contrarily, among SF-36 domain scores, significant ameliorating effects of MPE were not observed compared with those of the placebo group. Laboratory tests revealed no abnormalities suggesting adverse effects of MPE. Conclusions: MPE (100 mg/day for 8 weeks) improved several indefinite complaint parameters related to mensuration. MPE was suggested to be useful for improving anxiety related to PMS. Keywords: Menstrual distress questionnaire; SF-36 questionnaire; moriche palm; methoxyflavan; indefinite complaint

A 5-year-old girl living in Koriyama, Fukushima Prefecture was admitted in April with cough persisting for 1 month and fever. Chest X-ray showed diffuse ground-glass shadows in both lungs. After treatment with antibiotics, her fever went down on the 2

Background and objective: Chrysanthemum flowers are consumed as fresh condiments, herbal teas, and processed foods in Japan and Taiwan. They contain luteolin as a major polyphenol and are traditionally used for eye care. We previously demonstrated that the ingestion of Chrysanthemum flower extract (CFE) for 1 month reduced serum uric acid levels. However, the findings obtained were considered to be biased because the study was performed by a CFE manufacturer. Therefore, we herein conducted a clinical trial on CFE on a larger scale and examined its effects on purine base absorption from the intestines, which represents an effective approach for reducing serum uric acid levels. Methods: Both studies were performed as randomized, double-blind, placebo-controlled trials and CFE (100 mg) containing 1 mg of luteolin was used as the active sample. We enrolled 44 healthy Japanese men and women with 6.0 to 7.9 mg/dL serum uric acid. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. In the purine base absorption study, CFE was ingested with a purine base-rich diet and serum uric acid levels were measured chronologically. In the 12-week consecutive ingestion study, CFE or placebo was administered between January and April 2021. Serum uric acid levels after 12 weeks were assessed as the primary outcome, and uric acid were measured before and after 4 weeks of the intervention as secondary outcomes. Blood, urine and body parameters were examined to evaluate the safety of CFE. Results: Thirty-nine subjects completed the trial, and the per protocol set comprised 18 and 21 subjects in the active and placebo groups, respectively. In the single dosing study of CFE on subjects loaded by the purine base-rich diet, no significant changes were observed between the CFE and placebo groups. On the other hand, in the 12-week ingestion study, serum uric acid levels were significantly lower in the CFE group than in the placebo group. Laboratory tests revealed no abnormalities to suggest any side effects of CFE.Conclusions: CFE (100 mg/day) containing 1 mg of luteolin reduced serum uric acid levels. CFE may be beneficial for improving hyperurichemia. Trial Registration: UMIN-CTR: UMIN000042327Foundation: The present study was funded by Oryza Oil & Fat Chemical Co., Ltd. Keywords: Chrysanthemum, luteolin, uric acid, purine base

Self-assembled structures of hexa-tert-butyl-hexa-peri-hexabenzocoronene (HB-HBC) on the Si(111)- 3 × 3 -Ag surface have been investigated by low-energy electron diffraction and low-temperature scanning tunneling microscopy (STM). The HB-HBC molecules are assembled into a 21 × 21 − R ± 10 . 9 ∘ structure with respect to the Si(111)- 1 × 1 surface. Although the periodic structure is unchanged as a function of molecular coverage, we find that the orientations and adsorption sites of HB-HBC within the molecular islands are changed at near a full monolayer. At submonolayer coverages, the tert-butyl groups of HB-HBC are adsorbed on both the Si and Ag trimers of the Si(111)-Ag surface, and only on the Si trimers at a full monolayer. This result should be associated with a balance between substrate-molecule and inter-molecule interactions.

Background and objective: The ingestion of plant-derived glucosylceramides (GlcCer) has been reported to contribute to skin barrier function and hydration of the epidermis. b-sitosterol glucoside (BSG) colocalized with GlcCer in the rice hydrophobic fraction has been shown to increase ceramides in the stratum corneum in vitro . Although clinical studies demonstrated that GlcCer reduced transepidermal water loss (TEWL), the contribution of BSG to epidermal dehydration when applied with GlcCer remains unknown. Therefore, we herein conducted a clinical trial on the effects of a rice-derived mixed fraction of GlcCer and BSG (Oryza Ceramide ® ) on TEWL and other skin parameters. Methods: A randomized, double-blind, placebo-controlled study design was used. Oryza Ceramide ® (type PCD, 40 mg daily) containing 1.2 mg of GlcCer and 40 mg of BSG was used as the active sample. We enrolled 44 healthy Japanese women with epidermal dehydration. All subjects were randomly allocated to an active group (n=22) or placebo group (n=22) using a computerized random number generator. Capsules containing the active sample or placebo were administered for 12 weeks between August and December 2020. Cheek TEWL after 12 weeks was assessed as the primary outcome, and TEWL on a different part of the skin and various skin parameters, including epidermal moisture, pigmentation, pores, and elasticity, were measured before and after 4, 8, and 12 weeks of the intervention. Blood, urine, and body parameters were also examined to evaluate safety. Results: Forty-four subjects completed the trial, and the per protocol set comprised 22 each in the active and placebo groups. Cheek TEWL significantly reduced after the Oryza Ceramide ® intervention for 4 and 12 weeks. Among the secondary outcomes examined, lip moisture (12 weeks) and visible pore number (4 weeks) were improved by Oryza Ceramide ® . Laboratory tests revealed no abnormalities to suggest any adverse effects of Oryza Ceramide ® . Conclusions: Oryza Ceramide ® (40 mg/day) consisting of GlcCer and BSG improved facial TEWL, lip moisture, and visible pores, and these effects may be attributed to increases in epidermal ceramides. The combination of rice GlcCer and BSG appears to be beneficial for improving facial skin conditions. Trial Registration : UMIN-CTR: UMIN000041295 Foundation : The study was funded by Oryza Oil & Fat Chemical Co., Ltd. and Aichi Prefectural Subsidies for Research and Development of Creative Products in 2020. Keywords: rice; glucosylceramide; β -sitosterol glucoside; trans epidermal water loss; pore

Heart failure often presents with prognosis-relevant impaired renal function. To investigate whether the chronic activation of guanylate cyclase-A (GC-A) protects both heart and kidney, we examined the effects of TDT, a neprilysin (NEP)-resistant natriuretic peptide (NP) derivative, on cardiac and renal dysfunction in Dahl salt-sensitive hypertensive (DS) rats. Pretreatment with NEP or NEP inhibitor did not influence GC-A activation by TDT both in vitro and in vivo, resulting in a long-acting profile of TDT compared with native human atrial NP (hANP). The repeated administration of TDT to DS rats suppressed the progress of cardiac hypertrophy, systolic/diastolic dysfunction, and proteinuria in a dose-dependent manner. Compared with vehicle and hANP, salt diet-induced podocyte injury was reduced by TDT, as analyzed by urinary podocalyxin concentration, renal expression of nephrin mRNA, and glomerular expression of desmin protein. Since glomerular TRPC6 plays detrimental roles in podocyte homeostasis, we examined the renal expression of TRPC6 in DS rats and found that salt diet upregulated the expression of TRPC6. Importantly, TRPC6 induction was significantly decreased in TDT-treated rats, compared with vehicle and hANP. Consistently, in primary-culture podocytes from DS rats, TDT inhibited ATP-induced calcium influx, similar to TRPC inhibitor SKF96365. Finally, TDT-mediated protection of podocytes was abolished by protein kinase G inhibitor KT5823. In conclusion, TDT treatment attenuated heart and kidney dysfunction, accompanied by podocyte protection through inhibition of TRPC6. Thus, long-acting NPs could be a new avenue for treatment of heart failure.

Purpose This study was designed to evaluate the efficacy and safety of a compound supplement containing glucosamine (GS), chondroitin sulfate (CS), and five bioactive ingredients for improvement of knee osteoarthritis (OA). Methods Sixteen volunteers aged ≥40 years with knee pain and without ambulant treatment participated in a 6-week randomized, double-blind, placebo-controlled study. They were assigned to the dietary supplement or placebo groups (n = 8, respectively) and ingested six capsules twice daily. The OA symptoms of each subject were determined in pre- and post-treatment periods using a visual analog scale for pain (VAS pain) and four Japanese Knee Osteoarthritis Measure (JKOM) subscales ("joint stiffness," "daily living," "social activities," and "general health condition"). For safety and biomarker assessments, blood and urine samples were tested. Results In the treatment group, the subjective symptoms of VAS pain and three JKOM subscale scores except for "social activities" were significantly improved compared to pre-treatment. Among them, the pattern of change in "joint stiffness" and total JKOM scores showed a significant difference between groups (p = 0.008 and 0.041, respectively). The serum level of interleukin-6, a systemic inflammation biomarker, was significantly decreased in the treatment group after 6 weeks (p = 0.019), whereas the level remained stable in the placebo group (p = 0.690). Diagnostic urine and hematological parameters revealed no serious adverse differences following dietary supplementation over the 6-week study. Conclusion These findings suggest that the compound supplementation of functional food ingredients has potential as an adjunctive and safe therapy for knee OA.

Background: Complete heart block (CHB) is a serious complication of cardiac sarcoidosis (CS) which requires pacemaker implantation. Some patients recover from CHB after steroid therapy. Aims and Objectives: To investigate whether cardiac imaging features including echocardiography (Echo), 18F-fluoro-2-deoxyglucose positron emission tomography (FDG-PET), cardiac magnetic resonance imaging (CMR) or cardiac CT could predict recovery of CHB. Methods: Seventeen CS patients newly diagnosed with CHB who received steroid therapy were included. The presence of basal thinning of the interventricular septum (IVS) on Echo was evaluated. Focal myocardial FDG uptake on FDG-PET and delayed enhancement (DE) on CMR or CT were considered to be positive. The extent of the DE was classified into “none or mild fibrosis = less than one layer of the 3 myocardial layers” or “moderate or severe fibrosis = greater than 2 layers of the 3 myocardial layers”. Results: Six patients (35%) recovered from CHB and the remaining 11 patients (65%) did not. Six patients with recovery; no patients (0%) had basal thinning of the IVS (p = 0.02 vs without recovery), and 6 patients showed none or mild fibrosis of the basal IVS (p Conclusion: When Echo did not show basal thinning of the IVS and CMR or CT showed none or mild fibrosis of the basal IVS, the patients may recover from CHB.

The cytological diagnosis of hepatocellular adenoma (HCA) is difficult since it is a very rare tumor and lacks characteristic cytological features. We have just reported a case of inflammatory HCA that displayed an unusual histological pattern (Clin J Gastroenterol 8:426–434, 2015). A touch cytology smear sample was obtained from the surgical specimen, and it also exhibited very unique features. A 56-year-old male underwent partial hepatectomy for an inflammatory HCA (diameter: 1.4 cm) in the right posterior lobe of the liver. The cytological sample displayed a characteristic two-cell pattern. One type of cells contained thick cytoplasm, a high nucleus/cytoplasmic (N/C) ratio, and well-defined cytoplasmic borders. The other type demonstrated small pyknotic nuclei and a lower N/C ratio. The immunohistochemical staining pattern of the histological specimen suggested that the latter cells might have been undergoing apoptosis. We report a case of inflammatory HCA with characteristic features. To diagnose this type of variant, it is important to recognize the unique pattern described in this study. Diagn. Cytopathol. 2016. © 2016 Wiley Periodicals, Inc.

This study was aimed to investigate the capacity of a standardized root water extract of Eurycoma longifolia (Tongkat Ali, TA), Physta® to modulate human immunity in a middle-aged Japanese population. This randomized, double-blind, placebo-controlled, parallel study was conducted for 4 weeks. Eighty-four of 126 subjects had relatively lower scores according to Scoring of Immunological Vigor (SIV) screening. Subjects were instructed to ingest either 200 mg/day of TA or rice powder as a placebo for 4 weeks [TA and Placebo (P) groups] and to visit a clinic in Tokyo twice (weeks 0 and 4). SIV, immunological grade, immunological age, and other immune parameters were measured. Eighty-three subjects completed the study; 40 in the TA group and 41 in the P group were statistically analyzed, whereas two were excluded from the analyses. At week 4, the SIV and immunological grade were significantly higher in the TA group than those in P group (p

Background: Heart Rhythm Society (HRS) consensus statement recommends that patients with biopsy-proven extracardiac sarcoidosis (extra-CS) should be screened for CS with an electrocardiogram (ECG) and echocardiogram (Echo). However, there have been lack of studies investigating prevalence of CS in patients with normal ECG and Echo. Aims and objectives: To investigate prevalence and explore characteristics among these patients. Methods: We studied 94 consecutive biopsy proven extra-CS patients. All patients underwent F-18 fluorodeoxyglucose positron emission tomography (FDG-PET) and cardiac MRI for the evaluation of CS. Patients were categorized into 2 groups according to the ECG and Echo findings as normal or abnormal of either or both ECG or Echo. The Japanese Ministry of Health and Welfare (JMHW) criteria 2015 were used as the standard for the diagnosis of CS. Results: Among the 94 patients, 28 (30%) were normal and 66 (70%) were abnormal group. The prevalence of CS was as follows; 6/28 (21%) for normal, 39/66 (59%) for abnormal (p=0.0006). Of these 6 patients from normal group, FDG-PET and/or cardiac MRI showed that 1 patient had multiple organ involvement (lung, skin, stomach, bone and heart), 3 patients had cardiac involvement in the RV papillary muscle, inferior or lateral wall of the LV, 1 patient had small subendocardial lesions in the mid segments of the anteroseptal and inferior walls, and 1 had relatively lower LVEF for his age. Conclusions: The prevalence of CS exceeds 20% in extra-CS patients even with normal ECG and Echo. Physicians should keep in mind such an unrecognized population and risk of underdiagnosis of CS.

Background: Decompression sickness (DCS) is a rare condition that is often difficult to diagnose in deep-sea divers. Because of this, prevention and early diagnosis are important. In this case-control study, we examined the risk and preventive factors associated with DCS. Methods: Our original questionnaire survey was conducted among 269 recreational divers in Okinawa. Divers who were diagnosed with DCS by a physician (n = 94) were compared with healthy recreational divers (n = 175). The questionnaire consisted of 30 items and included a dive profile. Odds ratios and multiple logistic regression analysis were used to estimate the relative risk of DCS. Results: Logistic regression analysis revealed the following risk factors for DCS: a past history of DCS, drinking alcohol the evening before diving, indicating decompression stops, cold exposure after the dive, and maximum depth. Preventive factors included hydration before the dive, deep stops, safety stops and using nitrox gas. The results were reliable according to the Hosmer-Lemeshow and omnibus tests. Conclusion: We identified certain risk factors, together with their relative risks, for DCS. These risk factors may facilitate prevention of DCS among Okinawa divers.

Summary Background Some natural substances may affect the expression of microRNAs (miRNAs) in humans. However, it is unclear whether this effect can be induced by the ingestion of whole foods containing these natural substances. Objective We investigated whether ingestion of the whole food FFC® Pairogen affects the expression of miRNAs in humans. Design This was a pilot study and part of a randomized controlled trial. Four subjects ingested the test material daily for 8 weeks (three times 180 ml bottles a day, morning, noon and evening; a total of 540 ml per day). The study did not include control subjects. Results Several miRNAs showed differential expression. The expression of two miRNAs, hsa-let-7c and hsa-miR-92a-2-5p, changed in three of the four subjects, who had lower concentration of serum total antioxidant status. The expression of hsa-let-7c increased and that of hsa-miR-92a-2-5p decreased. Conclusions The expression of hsa-let-7c and hsa-miR-92a-2-5p has been linked with lung cancer manifestation. The increased expression of hsa-let-7c and the decreased expression of hsa-miR-92a-2-5p suggest possible oncogene suppressive functions of these miRNAs. The ingestion of FFC® Pairogen may have a positive effect on cancer prevention.

Background: Although activated partial prothrombin time (aPTT) has often been used as a biomarker for evaluating the safety of dabigatran use in patients with non-valvular atrial fibrillation (NVAF), the optimal frequency of aPTT measurements is unclear. This study aimed to identify the frequency distribution of aPTT measurements in clinical practice and its clinical significance. Methods: This was a retrospective cooperative study conducted in 2 sites. All NVAF patients who underwent aPTT measurements before and after dabigatran treatment were included (n=380). The patients were divided into 2 groups according to the frequency of aPTT measurements during the first 3 months after drug prescription: Group A: infrequent group with only 1 measurement; and Group B: frequent group with ≥2 measurements. The clinical characteristics and outcomes were compared between the groups. Results: The frequency of aPTT measurements in the 3 months after dabigatran initiation varied: 240 patients underwent 1 measurement (Group A), and the remaining 140 patients underwent repeated measurements (Group B). There were significant differences in age and creatinine clearance (Ccr) between the groups (Group A vs. Group B: age 64.0±11.7 vs. 67.0±11.1 years, p=0.01; Ccr 83.8±30.3 vs.76.7±31.1 mL/min, p=0.03). During the mean follow-up period of 310 days, there were no significant differences in the discontinuation rate and incidence of bleeding (17% vs. 15% and 5% vs. 3%, respectively; both not significant). In Group B, the aPTT rarely increased beyond twice the upper normal limit within the 3 months (2.1%), although the correlation between the initial and subsequent aPTT measurements was low (r=0.366). Conclusions: In this retrospective study, the frequency of aPTT measurements after dabigatran initiation might have been dependent on patient characteristics. However, frequent aPTT measurements did not lead to a reduction in adverse clinical events.

Pyrroloquinoline quinone (PQQ) is a water-soluble quinone compound that has a strong anti-oxidant capacity. A previous study in rats fed a PQQ-depleted diet showed that elevated levels of serum triglyceride (TG) decreased after PQQ supplementation. However, there is only one study reporting the effects of PQQ on serum lipid levels, such as those of TG and cholesterol, in humans. In this study, the effects of PQQ disodium salt (BioPQQ™) on serum TG and cholesterol levels in humans after 6 and 12 wk of treatment at an oral dosage of 20 mg/d were examined. This trial was conducted according to a randomized, placebo-controlled, double-blinded protocol. A total of 29 healthy Japanese adults, ranging from 40 to 57 y old, with normal to moderately high TG levels (110-300 mg/dL) as measured by a recent blood examination, were included in this study. In eleven volunteers out of 29, serum low-density lipoprotein cholesterol (LDL-chol) levels at baseline were high (≥140 mg/dL). After 12 wk, the mean serum TG levels had not changed; however, a marginally significant decrease in the mean LDL-chol (from 136.1 to 127.0 mg/dL) was observed in the PQQ group. In the stratification analysis of the high LDL-chol subgroup (baseline LDL-chol level ≥140 mg/dL), the mean LDL-chol levels decreased significantly from the baseline values in the PQQ group compared to the placebo group. Our study findings suggest that PQQ suppressed the LDL-chol level, which is an important finding, because a high level of this lipid is a risk factor for various lifestyle-related diseases.

This volume examines the mutual images formed between Japan and Germany from the mid-nineteenth to early twenty-first centuries. Exploring previously untapped historical sources, the contributions by seventeen leading scholars create a more nuanced picture of Japanese-German relations.

Lying on one of the world’s most seismologically active areas, Japan has been affected by frequent natural disasters. In fact, many lessons have been learned after each occurrence of a horrible event from the ancient times up to the present, which have been implemented in order to avoid and/or reduce the degree to which the country is affected by such disasters. Yet, until the recent years, these lessons tended to be diffused within local communities only and thus remained within a narrow and closed society. However, the Great East Japan Earthquake in March 2011, one of the most serious catastrophes of the last 1000 years, has gradually been changing this tendency and has prompted a wide variety of new learning styles. One of the most conspicuous features of this is the enhancement of mutual learning at various levels and through different methods between those who were the most seriously affected and those who, no matter how near or far from the affected area they live, are worried about future disasters of this kind which have been predicted. Thus the recent disaster has had positive impacts on learning about disaster prevention among the nationwide population, generating a variety of new approaches. This paper intends to illustrate some good examples of new trends in learning about disaster prevention and indicate how the nation has been transferring the experience of catastrophes into effective learning.

Background It is well-known that health education programs carried out in the work place are useful for employees' health promotion. However, the effectiveness of group health education programs for workers as a population approach is unclear. Objective The purpose of this study was to examine the effectiveness of a group health education program in the workplace, and to investigate educational methods which support workers modifying their health behaviors. Methods A total of 289 workers who received a group health education program in the manufacturing industry (mean age, 42.1 ± 11.3 years old; 175 males and 114 females) were enrolled in this study. The group health education program was carried out to educate the subjects about periodontitis, oral health actions and lifestyle behaviors to prevent oral diseases. Participants were required to fill out a self-administered questionnaire which included information about oral health knowledge, oral health actions, lifestyle behaviors and symptoms of periodontitis before, immediately after and one month after the education. We used McNemar's test for the paired comparison of questionnaire responses. The relation between acquiring knowledge about periodontitis and subjects' modification of oral health action, behavior modification and symptoms of periodontitis were examined using the chi-squared test. The relationships of knowledge retention about periodontitis, the modification of the oral health actions and lifestyle behaviors (i.e., cigarette smoking, alcohol drinking and eating between meals), were examined with participants' characteristics (i.e., age, gender and occupational category) using Fisher's exact test. Results Knowledge about periodontitis significantly improved immediately after receiving the health education, and this effect of education was evident one month later. However, not all of the knowledge was sufficiently retained one month after the education session. The proportion of participants undertaking desirable oral health actions significantly increased one month after the education, whereas lifestyle behaviors did not alter. The modification of oral health actions improved periodontitis-related symptoms, however, no relationship was found between knowledge acquisition and behavior modification. The characteristics of the participants did not influence knowledge retention about periodontitis or modification of oral health actions. Conclusions Our group health education program was appropriate and effective at providing knowledge about periodontitis and at modifying oral health actions. We should identify factors that obstruct workers behavior modification, and eliminate them to improve health behaviors.

The cytological diagnosis of hepatocellular adenoma (HCA) is difficult since it is a very rare tumor and lacks characteristic cytological features. We have just reported a case of inflammatory HCA that displayed an unusual histological pattern (Clin J Gastroenterol 8:426-434, 2015). A touch cytology smear sample was obtained from the surgical specimen, and it also exhibited very unique features. A 56-year-old male underwent partial hepatectomy for an inflammatory HCA (diameter: 1.4 cm) in the right posterior lobe of the liver. The cytological sample displayed a characteristic two-cell pattern. One type of cells contained thick cytoplasm, a high nucleus/cytoplasmic (N/C) ratio, and well-defined cytoplasmic borders. The other type demonstrated small pyknotic nuclei and a lower N/C ratio. The immunohistochemical staining pattern of the histological specimen suggested that the latter cells might have been undergoing apoptosis. We report a case of inflammatory HCA with characteristic features. To diagnose this type of variant, it is important to recognize the unique pattern described in this study. Diagn. Cytopathol. 2016;44:1074-1077. © 2016 Wiley Periodicals, Inc.

Prevotella intermedia is a periodontal pathogen that requires iron for its growth. Although this organism has hemolytic activity, the precise nature of its hemolytic substances and their associated hemolytic actions are yet to be fully determined. In the present study, we identified and characterized several putative hly genes in P. intermedia ATCC25611 which appear to encode hemolysins. Six hly genes (hlyA, B, C, D, E, and hlyI) of P. intermedia were identified by comparing their nucleotide sequences to those of known hly genes of Bacteroides fragilis NCTC9343. The hlyA-E, and hlyI genes were overexpressed individually in the non-hemolytic Escherichia coli strain JW5181 and examined its contribution to the hemolytic activity on sheep blood agar plates. E. coli cells expressing the hlyA and hlyI genes exhibited hemolytic activity under anaerobic conditions. On the other hand, only E. coli cells stably expressing the hlyA gene were able to lyse the red blood cells when cultured under aerobic conditions. In addition, expression of the hlyA and hlyI genes was significantly upregulated in the presence of red blood cells. Furthermore, we found that the growth of P. intermedia was similar in an iron-limited medium supplemented with either red blood cells or heme. Taken together, our results indicate that the hlyA and hlyI genes of P. intermedia encode putative hemolysins that appear to be involved in the lysis of red blood cells, and suggest that these hemolysins might play important roles in the iron-dependent growth of this organism.

The Tokyo sky tree is supported by the pile group foundation using under-reamed diaphragm-wall-type piles with different sizes. This report describes the outline of the foundation design, the evaluation method in design of the effect of pile group and the analytical results of FEM. The results of this study are shown as follows: (1) The pile group efficiency is 0.58, 0.49 and 0.68 - 0.73 respectively under pushing, pulling and lateral load. (2) In case of the lateral loading, the pile group efficiency changed according to the direction of the load and the position of the piles.

In this paper, the piled raft foundation is supported with thin cement treated soil layer below the raft and various length of friction piles. The part of this raft has a possibility of rising to the surface by over-turning moment of the tall building during a big earthquake. The authors present the outline of designing the foundation, the comparative studies on estimated settlements and measured results, and the analysis results of the lateral resistance of the piled raft which considered the rising zone of the raft from the surface.

We encountered a 60-year-old woman with remarkably elevated thyroid-stimulating hormone (TSH) level as measured by electrochemiluminescent immunoassay (ECLIA), but with no specific symptoms, and with normal levels of free T3 and free T4. We performed the following investigations: polyethylene glycol (PEG) precipitation test, human antimouse IgG antibody (HAMA) interference test, and 3 additional TSH measurements by chemiluminescent immunoassay (CLIA). We then performed 2 gel filtration chromatography (GFC) procedures; one was at pH 7.2, and the other was at pH 3.0. Although the recovery of TSH shown by the PEG precipitation test was 4% which was extremely low, no HAMA interference was observed. Moreover, 3 CLIA instruments also showed various high values. The first GFC showed that the main peak of TSH immunoreactivity by ECLIA was located at a slightly larger molecular weight position than that of IgG. By the second GFC, the sample from the peak fraction of the first GFC showed that the TSH peak disappeared completely at the previous retention time but newly appeared at the same retention time as the TSH monomer. Protein G-Agarose gel removed the majority of the TSH complex. In conclusion, the majority of TSH in her serum was macro-TSH; TSH and anti- TSH IgG autoantibody complex. We should keep the possibility of macro-TSH in mind in cases with unexpectedly high TSH values, especially in autoimmune thyroidal disorders.