Effects of rhamnose consumption on bone mineral density in healthy postmenopausal women: a randomised, placebo-controlled, double-blind, parallel-group pilot study.

Preventing the decrease in bone mineral density (BMD) is significant for postmenopausal women. We previously discovered that rhamnose, a deoxy monosaccharide used as a food additive, could suppress bone resorption; however, studies confirming this effect in postmenopausal women are lacking. Therefore, this pilot study aimed to explore whether rhamnose could help maintain BMD via bone resorption suppression in postmenopausal women. The participants consumed either 1.0 or 0.5 g/day of rhamnose or placebo for 24 weeks, and BMD (lumbar spine and femur) and bone turnover markers were measured. After 24 weeks, the group consuming rhamnose 1.0 g/day exhibited a significantly higher BMD of the lumbar spine than the placebo group. Furthermore, the levels of tartrate-resistant acid phosphatase 5b, a bone resorption marker, were significantly lower in both rhamnose groups. These results indicated that rhamnose might contribute to the maintenance of BMD by suppressing bone resorption in healthy postmenopausal women (UMIN000046570).

[A CHILD CASE OF EGOMA (PERILLA FRUTESCENS) ALLERGY DUE TO SCHOOL LUNCH, PROBABLY CAUSED BY PERCUTANEOUS SENSITIZATION].

Herein, we report the case of a 7-year-old girl with a history of atopic dermatitis because of infancy. Her grandfather grew Egoma (Perilla frutescens), and her family frequently consumed food items prepared using Egoma; however, she never consumed them because she did not enjoy these food items; she experienced vomiting, facial swelling, and oral discomfort upon ingesting Egoma during school lunch for the first time. Her food oral challenge test was positive, as well as a skin-prick test with sesame powder. Egoma antigen protein was extracted and reacted with patient serum by immunoblotting, which detected a positive band of approximately 26kDa. She was brought up in an environment with high exposure to Egoma; hence, she most likely developed an allergy to Egoma because of percutaneous sensitization. This is the first time an Egoma allergen analysis has been conducted in Japan, and we consider it to be a valuable case.

Host-parasite relationships between seabirds and the haemadipsid leech Chtonobdella palmyrae (Annelida: Clitellata) inhabiting oceanic islands in the Pacific Ocean.

The duognathous haemadipsid leeches of the genus Chtonobdella show a trans-oceanic distribution throughout the Indo-Pacific region. Although passive long-distance dispersal (LDD) of Chtonobdella leeches by birds has been suggested, little is known about the host-parasite relationships between avian hosts and Chtonobdella leeches. In the current study, we investigated Chtonobdella leech infestations of the eyes and other mucus membranes of migratory procellariiform seabirds, Pterodroma hypoleuca and Oceanodroma tristrami, captured at six locations in the Bonin Islands, Honshu and Okinawa Island, Japan. Analyses of the partial sequences of 18S rRNA, 28S rRNA, and mitochondrial cytochrome c oxidase subunit I (COI) and morphological examination of the specimens demonstrated that the Chtonobdella leeches belonged to Chtonobdella palmyrae, which is indigenous to Palmyra Atoll in the Northern Line Islands. A dominant COI sequence type was observed in samples from all six sites; therefore, C. palmyrae almost surely dispersed approximately 1000 km by infesting the eyes and mucus membranes of procellariiform seabirds. The host-parasite relationships between procellariiform seabirds and C. palmyrae provide explicit evidence of the LDD of duognathous haemadipsid leeches. The taxonomic status of Haemadipsa zeylanica ivosimae from the Volcano Islands is also briefly discussed.

[SUMMER-TYPE HYPERSENSITIVITY PNEUMONITIS CAUSED BY A HUMIDIFIER INDUCED IN SPRING, IN A 5-YEAR-OLD GIRL LIVING IN FUKUSHIMA-A CASE REPORT].

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 2nd day, and her cough subsided gradually. She was discharged on the 7th day, but her symptoms relapsed on the 8th day. Due to her worsening symptoms, she was readmitted on the 16th day. Chest CT scans showed enhancement of interstitial density. Serum anti-Trichosporon asahii antibody was positive. Her symptoms rapidly improved on a steroid regimen, and she was discharged on the 23th day. She was diagnosed as having summer-type hypersensitivity pneumonitis (SHP). She was instructed not to use a moldy humidifier and not to go to her grandmother's 57 years old wooden house. She has had no symptom after discharge. However, suspected mold was not found at her grandmother's house, and a provocation test there was negative. The HLA typing of the patient showed HLA-DQ8, which was previously described as SHP-sensitive.

[Multidisciplinary Treatment Aids Long-Term Stage â £ Pancreatic Cancer Survival-A Case Report].

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.

Impact of Acacia bark extract tablets on the skin of healthy humans: a randomized, double-blind, placebo-controlled study.

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.

A case-control questionnaire survey of decompression sickness risk in Okinawa divers.

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.

Sustained Activation of Guanylate Cyclase-A with TDT, a Natriuretic Peptide Derivative, Exhibits Cardiorenal Protection in Dahl Salt-Sensitive Hypertensive Rats.

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.

Silent Cerebral Ischemic Lesions After Catheter Ablation of Atrial Fibrillation in Patients on 5 Types of Periprocedural Oral Anticoagulation　- Predictors of Diffusion-Weighted Imaging-Positive Lesions and Follow-up Magnetic Resonance Imaging.

BACKGROUND: The aim of this study was to identify the predictors of silent cerebral ischemic lesions (SCIL) after catheter ablation of atrial fibrillation (AF) and to determine whether SCIL develop into cerebral infarcts in patients with 5 types of oral anticoagulants (OAC). METHODS AND RESULTS: We retrospectively studied 286 consecutive patients (median, 67 years; 208 male; paroxysmal/persistent/long-standing persistent AF [LSP-AF], 147/90/49) who received periprocedural OAC and underwent MRI after the procedure. Warfarin (n=46) was continued, while dabigatran (n=47), rivaroxaban (n=89), apixaban (n=87), and edoxaban (n=17) were discontinued on the day of the procedure. I.v. heparin was infused to maintain an activated clotting time of 300-350 s during the procedure. Fifty-eight SCIL in 40 patients (14.0%) were identified on diffusion-weighted MRI. On multivariate logistic analysis, LSP-AF and dabigatran use were significant positive predictors of SCIL (OR, 2.912 and 2.287; P=0.006 and 0.042, respectively). Among 34 patients with 49 SCIL undergoing follow-up MRI, 45 (91.8%) of the lesions disappeared and 4 lesions developed into chronic cerebral infarcts. The SCIL with development into infarcts had a larger lesion diameter than those without (median, 6.55 mm vs. 4.2 mm; P=0.002). CONCLUSIONS: LSP-AF and dabigatran use were independent risk factors for post-ablation SCIL in patients with uninterrupted warfarin and interrupted non-vitamin K antagonist OAC, but the majority of SCIL disappeared.

Immunomodulation in Middle-Aged Humans Via the Ingestion of Physta® Standardized Root Water Extract of Eurycoma longifolia Jack--A Randomized, Double-Blind, Placebo-Controlled, Parallel Study.

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 < 0.05). The numbers of total, naïve, and CD4(+) T cells were also higher in the TA group than those in P group (p < 0.05). No severe adverse events were observed. The results suggest that ingestion of the root water extract of TA (Physta®) enhances comprehensive immunity in both middle-aged men and women. This study is registered in UMIN-CTR (UMIN000011753).

[Feasibility Study of a One-Day Educational Program to Train Advance Care Planning Facilitators(ACPFs)in Regional Areas].

Promoting advance care planning in regional areas is important. Education For Implementing End-of-Life Discussion(EFIELD) is a two-day educational program for Advance Care Planning Facilitators(ACPFs)developed by the National Center for Geriatrics and Gerontology. Unfortunately, some trainers experience difficulties implementing the content of the program, and some trainees feel the program is too long for implementation in many regional areas. The purpose of the research is to clarify the feasibility of ACPFs education using a one-day program in regional areas. The methods involved documenting the process of a one-day program from implementation to evaluation from May of 2015 to March of 2016 and then evaluating the effectiveness of the program 3 months after the implementation using meeting minutes from 7 local hospitals. The results indicated a need for 5 steps from program implementation to evaluation as well as 5 categories for final evaluation. The most important finding is that E-FIELD challenged trainers to shorten and simplify their expressions in order to teach the content more efficiently. The second finding is that Group for Promoting Advance Care Planning & End Of Life Discussion in Chita(GACPEL) activities encouraged ACPimplementation within each hospital. The limitations of this research are related to small regional areas. In conclusion, a one-day regional ACPFs educational program is feasible.

Clot retraction is mediated by factor XIII-dependent fibrin-αIIbß3-myosin axis in platelet sphingomyelin-rich membrane rafts.

Membrane rafts are spatially and functionally heterogenous in the cell membrane. We observed that lysenin-positive sphingomyelin (SM)-rich rafts are identified histochemically in the central region of adhered platelets where fibrin and myosin are colocalized on activation by thrombin. The clot retraction of SM-depleted platelets from SM synthase knockout mouse was delayed significantly, suggesting that platelet SM-rich rafts are involved in clot retraction. We found that fibrin converted by thrombin translocated immediately in platelet detergent-resistant membrane (DRM) rafts but that from Glanzmann's thrombasthenic platelets failed. The fibrinogen γ-chain C-terminal (residues 144-411) fusion protein translocated to platelet DRM rafts on thrombin activation, but its mutant that was replaced by A398A399 at factor XIII crosslinking sites (Q398Q399) was inhibited. Furthermore, fibrin translocation to DRM rafts was impaired in factor XIII A subunit-deficient mouse platelets, which show impaired clot retraction. In the cytoplasm, myosin translocated concomitantly with fibrin translocation into the DRM raft of thrombin-stimulated platelets. Furthermore, the disruption of SM-rich rafts by methyl-ß-cyclodextrin impaired myosin activation and clot retraction. Thus, we propose that clot retraction takes place in SM-rich rafts where a fibrin-αIIbß3-myosin complex is formed as a primary axis to promote platelet contraction.

A case-control study evaluating relative risk factors for decompression sickness: a research report.

BACKGROUND: Factors contributing to the pathogenesis of decompression sickness (DCS) in divers have been described in many studies. However, relative importance of these factors has not been reported. METHODS: In this case-control study, we compared the diving profiles of divers experiencing DCS with those of a control group. The DCS group comprised 35 recreational scuba divers who were diagnosed by physicians as having DCS. The control group consisted of 324 apparently healthy recreational divers. All divers conducted their dives from 2009 to 2011. The questionnaire consisted of 33 items about an individual's diving profile, physical condition and activities before, during and just after the dive. To simplify dive parameters, the dive site was limited to Izu Osezaki. Odds ratios and multiple logistic regression were used for the analysis. RESULTS: Odds ratios revealed several items as dive and health factors associated with DCS. The major items were as follows: shortness of breath after heavy exercise during the dive (OR = 12.12), dehydration (OR = 10.63), and maximum dive depth > 30 msw (OR = 7.18). Results of logistic regression were similar to those by odds ratio analysis. CONCLUSION: We assessed the relative weights of the surveyed dive and health factors associated with DCS. Because results of several factors conflict with previous studies, future studies are needed.

Insulin resistance assessed by short insulin tolerance test and its association with obesity and insulin resistance-related parameters in humans: A pilot randomized trial.

The aim of this study was to examine the association of insulin resistance (evaluated by the short insulin tolerance test [SITT]) with parameters related to obesity and insulin resistance. We prospectively recruited controls and patients with type 2 diabetes mellitus (T2DM), subjected them to the SITT, and calculated the K indices of the intravenous insulin tolerance test (KITT(iv)) and the subcutaneous insulin tolerance test (KITT(sc)). We compared KITT(iv) results between the volunteers and patients and examined its correlation with KITT(sc). We also examined the association of KITT(iv) with obesity, insulin resistance-related parameters, and the insulin dose required for glycemic control. A total of 24 participants (seven controls and 17 patients with T2DM) were studied. The mean KITT(iv) was significantly lower in patients with T2DM than in the controls (2.5%±2.1% vs. 4.5%±1.8%). In all participants, KITT(iv) was significantly correlated with the homeostasis model assessment for insulin resistance (HOMA-IR) values (r = -0.601, p<0.05) but not with KITT(sc) (p = 0.62). KITT(iv) was correlated positively with the serum adiponectin concentration, but negatively with the visceral fat area and serum concentrations of tumor necrosis factor-α and branched-chain amino acids. In patients with T2DM, KITT(iv) and HOMA-IR values were significantly correlated with the total insulin dose required for glycemic control. Insulin resistance evaluated using KITT(iv) was correlated with the HOMA-IR values, but not with the resistance evaluated using KITT(sc). The degree of insulin resistance was associated with biomarkers, such as adiponectin, tumor necrosis factor-α, branched-chain amino acids, the visceral fat area, and the dose of insulin required for glycemic control.

Involvement of gangliosides in the process of Cbp/PAG phosphorylation by Lyn in developing cerebellar growth cones.

The association of gangliosides with specific proteins in the central nervous system was examined by coimmunoprecipitation with an anti-ganglioside antibody. The monoclonal antibody to the ganglioside GD3 (R24) immunoprecipitated the Csk (C-terminal src kinase)-binding protein (Cbp). Sucrose density gradient analysis showed that Cbp of rat cerebellum was detected in detergent-resistant membrane (DRM) raft fractions. R24 treatment of the rat primary cerebellar cultures induced Lyn activation and tyrosine phosphorylation of Cbp. Treatment with anti-ganglioside GD1b antibody also induced tyrosine phosphorylation. Furthermore, over-expressions of Lyn and Cbp in Chinese hamster ovary (CHO) cells resulted in tyrosine 314 phosphorylation of Cbp, which indicates that Cbp is a substrate for Lyn. Immunoblotting analysis showed that the active form of Lyn and the Tyr314-phosphorylated form of Cbp were highly accumulated in the DRM raft fraction prepared from the developing cerebellum compared with the DRM raft fraction of the adult one. In addition, Lyn and the Tyr314-phosphorylated Cbp were highly concentrated in the growth cone fraction prepared from the developing cerebellum. Immunoelectron microscopy showed that Cbp and GAP-43, a growth cone marker, are localized in the same vesicles of the growth cone fraction. These results suggest that Cbp functionally associates with gangliosides on growth cone rafts in developing cerebella.

Contribution of hly homologs to the hemolytic activity of Prevotella intermedia.

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.

Underdiagnosis of cardiac sarcoidosis by ECG and echocardiography in cases of extracardiac sarcoidosis.

Background: Although screening with 12-lead electrocardiography and transthoracic echocardiography for cardiac involvement has been recommended for patients with biopsy-proven extracardiac sarcoidosis, cardiac sarcoidosis has been reported even in patients with normal electrocardiography and echocardiography findings. We investigated the prevalence and characteristics of these patient cohorts. Methods: We studied 112 consecutive patients (age, 55±17 years, 64% females) with biopsy-proven extracardiac sarcoidosis who had undergone 18F-fluorodeoxyglucose positron emission tomography and cardiac magnetic resonance imaging for cardiac sarcoidosis evaluation. The patients were categorised as those showing normal findings both in electrocardiography and transthoracic echocardiography (normal group) and those showing abnormal findings in one or both examinations (abnormal group). Results: 33 (29%) and 79 (71%) patients were categorised into the normal and abnormal groups, respectively, of which 6 (18%) and 43 (54%) patients, respectively, were diagnosed with cardiac sarcoidosis (p<0.01). Of these six patients in the normal group, two with multiple-organ sarcoidosis showed clinical deterioration of cardiac involvement and required steroid therapy; three with small cardiac involvement showed natural remission over follow-up assessments; and one underwent steroid therapy and showed an improvement in the left ventricular ejection fraction to within normal limits. Conclusions: The prevalence of cardiac sarcoidosis in patients with biopsy-proven extracardiac sarcoidosis and normal electrocardiography and transthoracic echocardiography findings was ∼20%. Electrocardiography and transthoracic echocardiography may not detect cardiac sarcoidosis in patients without conduction and morphological abnormalities. However, some of these patients may subsequently show clinically manifested cardiac sarcoidosis. Physicians should be mindful of this population.

Ganglioside GD3 monoclonal antibody-induced paxillin tyrosine phosphorylation and filamentous actin assembly in cerebellar growth cones.

We have demonstrated that antibody to ganglioside GD3 (R24) immunoprecipitates src-family tyrosine kinase Lyn from primary cerebellar granule cells and R24 treatment of the intact cells induces Lyn activation and rapid tyrosine phosphorylation of several substrates, suggesting the functional association of ganglioside GD3 with Lyn. In this study, R24 treatment of primary cerebellar granule cells enhances phosphorylation of paxillin at tyrosine residue 118 and induces filamentous actin assembly and neurite outgrowth. R24 treatment of cerebellar growth cone membrane fraction induces prominent tyrosine phosphorylation of 68 kDa protein which comigrates with phosphopaxillin at tyrosine residue 118. Tyrosine phosphorylation of paxillin is known to regulate actin cytoskeleton-dependent changes in cell morphology. Signal transduction by ganglioside GD3 is involved in growth cone morphology via tyrosine phosphorylation of paxillin.

miRNA profiling of bilateral rat hippocampal CA3 by deep sequencing.

MicroRNAs (miRNAs) have been demonstrated to be potent post-trascriptional modulators of protein expression. miRNA expression was profiled in the left and right dorsal hippocampal CA3 of mature rats by high-throughput deep sequencing. Among the sequenced and cross-mapped small RNAs, 88% belonged to the miRNAs annotated in the miRBase 15 database. Nearly half of the small RNAs belonged to the let-7 family miRNA. Seven percent of the sequenced small RNAs were not annotated in miRBase 15. Bioinformatic analysis of the unannotated small RNA sequences suggested seventeen novel miRNA candidates with relatively high expression levels (>100 tags per million). The left:right expression ratios were similar for all highly expressed miRNAs with less than 10% differences. These results provide a basic idea of the relative expression strengths of known and unknown miRNAs in the dorsal hippocampal CA3.