Neighbourhood relationships moderate the positive association between family caregiver burden and psychological distress in Japanese adults: a cross-sectional study.

OBJECTIVES: Family caregiver burden is associated with higher psychological distress. However, little is known about the impact of neighbourhood relationships on caregivers' psychological distress. We examined whether neighbourhood relationships of caregivers moderate the association between family caregiver burden and psychological distress. STUDY DESIGN: This was a cross-sectional study. METHODS: We recruited 5321 Japanese adults who participated in the Japan Multi-Institutional Collaborative Cohort Study in the Okazaki area between 2013 and 2017. Participants completed self-reported questionnaires to measure psychological distress (Kessler 6: K6), subjective caregiver burden, and neighbourhood relationships. We performed a multivariable linear regression analysis in which caregiver burden was designated as an independent variable and the K6 score as a dependent variable, adjusting for demographics. The interaction term between caregiver burden and neighbourhood relationships was also included in the analysis. RESULTS: Data from a total of 5069 participants were included (mean age [standard deviation]: 63.1 years [10.3 years]; 2226 [43.9%] female). Caregiver burden was significantly and positively associated with psychological distress (compared with no burden, mild burden: ß = 0.24, P = 0.197; severe burden: ß = 0.60, P < 0.01; P for trend < 0.01). There was a significant negative interaction effect of caregiver burden × neighbourhood relationship on psychological distress (severe burden × good neighbourhood relationship: ß = -3.29, P < 0.01). CONCLUSIONS: A higher caregiver burden was associated with higher psychological distress, and neighbourhood relationships moderated this association. Our findings suggest that good neighbourhood relationships can buffer caregiving-associated psychological distress.

Accuracy of self-reported height, weight and waist circumference in a Japanese sample.

Objective: Inconsistent results have been found in prior studies investigating the accuracy of self-reported waist circumference, and no study has investigated the validity of self-reported waist circumference among Japanese individuals. This study used the diagnostic standard of metabolic syndrome to assess the accuracy of individual's self-reported height, weight and waist circumference in a Japanese sample. Methods: Study participants included 7,443 Japanese men and women aged 35-79 years. They participated in a cohort study's baseline survey between 2007 and 2011. Participants' height, weight and waist circumference were measured, and their body mass index was calculated. Self-reported values were collected through a questionnaire before the examination. Results: Strong correlations between measured and self-reported values for height, weight and body mass index were detected. The correlation was lowest for waist circumference (men, 0.87; women, 0.73). Men significantly overestimated their waist circumference (mean difference, 0.8 cm), whereas women significantly underestimated theirs (mean difference, 5.1 cm). The sensitivity of self-reported waist circumference using the cut-off value of metabolic syndrome was 0.83 for men and 0.57 for women. Conclusions: Due to systematic and random errors, the accuracy of self-reported waist circumference was low. Therefore, waist circumference should be measured without relying on self-reported values, particularly in the case of women.

Liver-related safety assessment of green tea extracts in humans: a systematic review of randomized controlled trials.

There remain liver-related safety concerns, regarding potential hepatotoxicity in humans, induced by green tea intake, despite being supposedly beneficial. Although many randomized controlled trials (RCTs) of green tea extracts have been reported in the literature, the systematic reviews published to date were only based on subjective assessment of case reports. To more objectively examine the liver-related safety of green tea intake, we conducted a systematic review of published RCTs. A systematic literature search was conducted using three databases (PubMed, EMBASE and Cochrane Central Register of Controlled Trials) in December 2013 to identify RCTs of green tea extracts. Data on liver-related adverse events, including laboratory test abnormalities, were abstracted from the identified articles. Methodological quality of RCTs was assessed. After excluding duplicates, 561 titles and abstracts and 119 full-text articles were screened, and finally 34 trials were identified. Of these, liver-related adverse events were reported in four trials; these adverse events involved seven subjects (eight events) in the green tea intervention group and one subject (one event) in the control group. The summary odds ratio, estimated using a meta-analysis method for sparse event data, for intervention compared with placebo was 2.1 (95% confidence interval: 0.5-9.8). The few events reported in both groups were elevations of liver enzymes. Most were mild, and no serious liver-related adverse events were reported. Results of this review, although not conclusive, suggest that liver-related adverse events after intake of green tea extracts are expected to be rare.

High-dose chemotherapy for high-risk retinoblastoma: clinical course and outcome of 14 cases in the National Cancer Center, Japan.

The prognosis of high-risk retinoblastoma (RB) with extraocular disease, relapse, or invasion of the cut end of the optic nerve is extremely poor. Following the discontinuation of thiotepa production in Japan, BU- and melphalan (Mel)-based regimens have been used, followed by the standard treatment for neuroblastoma. This study retrospectively analyzed 14 high-risk RB patients who underwent high-dose chemotherapy (HDC) and hematopoietic SCT; 8 received a BU/Mel conditioning regimen and 6 received other regimens. The disease status at HDC was relapse in 8 patients and extraocular involvement in 5. All patients received peripheral blood stem cell infusion >1.5 × 10(6)/kg. Engraftment occurred within a median of 11 days (BU/Mel: 10-13, others: 9-13). Primary toxicities included mucositis (⩾grade 3) in 9 patients (4 with BU/Mel, 5 with others). Veno-occlusive disease (VOD) occurred in two 1-year-old patients in the BU/Mel group. There were no treatment-related deaths. Of 4 (2 with BU/Mel, 2 with others) patients with central nervous system (CNS) relapse after HDC, 3 died. In conclusion, the BU/Mel regimen may be feasible for high-risk RB under careful monitoring for VOD, particularly in younger patients. CNS relapse associated with a lethal prognosis occurred after all regimens; therefore, further evaluation of HDC efficacy for high-risk RB is required.

Changes in microtubule-related proteins and autophagy in long-term vitamin E-deficient mice.

Vitamin E deficiency induces neuronal dysfunction and while oxidative stress is likely to be involved in mediating this process, the detailed mechanisms remain to be elucidated. Previously, we found axonal degeneration in the hippocampal CA1 region in vitamin E-deficient mice of 6 months of age (long-term). However, 3 month-old (short-term) vitamin E-deficient mice did not exhibit axonal degeneration in same region. In order to characterize the mechanisms involved in axonal degeneration in long-term vitamin E-deficient mice, we examined changes in microtubule-related proteins. Long-term vitamin E-deficiency led to significantly increased expression of the phosphorylated form of collapsin response mediator protein (CRMP)-2 compared to short-term deficiency. It is well known that CRMP-2 plays a crucial role in the maintenance of neurite function. Similarly, long-term vitamin E-deficiency significantly decreased the expression of silent mating type information regulation (SIRT)-2 mRNA compared to short-term deficiency. SIRT-2 belongs to a family of class III histone deacetylases (HDACs) and functions in the deacetylation of tubulins. Furthermore, the expression of microtubule-associated protein light chain (MAP-LC)3-2, which is a key autophagy protein was significantly higher in the short-term vitamin E-deficiency than the long-term deficiency. These results indicate that the mechanisms of axonal injury in long-term vitamin E-deficient mice are related to dysfunction in microtubules assembly via alterations in microtubule-related proteins and autophagy.

Enhancement of intestinal immune function in mice by ß-D-glucan from aureobasidium pullulans ADK-34.

ß-Glucans, glucose polymers that are the main constituents of the outer cell walls of micro-organisms such as fungi and yeast, are known to play an immunostimulatory role. We prepared ß-glucan (ß-(1-3),(1-6)-D-glucan) from an edible cultured fungus through fermentation techniques using a strain of Aureobasidium pullulans ADK-34. The purity of this ß-glucan preparation (AP-FBG) was demonstrated to be high through various instrumental analyses. We then examined the effects of AP-FBG on intestinal immune systems. We prepared Peyer's patch (PP) cells and measured interleukin (IL)-5, IL-6, and IgA production in culture media with AP-FBG. We found that both cytokines and IgA increased; furthermore, IL-6 secreted by PP dendritic cells (PPDCs) cultured in the presence of AP-FBG significantly increased. We tested IgA production after oral administration of AP-FBG for 2 weeks and found that AP-FBG tended to promote the production of IgA in the small intestine. Interestingly, we observed a significant increase in IgA production in the small intestines of mice treated with cyclophosphamide (CY; an immunosuppressant) after oral administration of AP-FBG diet compared with CY-treated and control diet mice. Production of IL-6 and IgA by PP cells and IL-6 production by PPDCs in AP-FBG-fed and CY-treated mice also increased. These results demonstrate that AP-FBG has the ability to activate PPDC and induce IL-6 production and IgA secretion in PP cells. These abilities were more clearly expressed when AP-FBG was orally administered in a CY-induced immunosuppressed condition. Therefore, AP-FBG may be a useful ingredient for preparing functional foods with immunomodulatory activities.

Identification of lactose ureide, a urea derivative of lactose, in milk and milk products.

With the widespread consumption of milk, the complete characterization of the constituents of milk and milk products is important in terms of functionality and safety. In this study, a novel nonreducing carbohydrate was separated from powdered skim milk and was identified using electron spray ionization-mass spectrometry (m/z 385.1[M + H(+)]), ¹H, ¹³C, ¹H¹H-correlation spectroscopy, and heteronuclear single quantum-nuclear magnetic resonance spectra. The carbohydrate was identified as a lactose derivative of urea, N-carbamoyl-o-ß-D-galactopyranosyl-(1-4)-D-glucopyranosylamine (lactose ureide, LU). For the HPLC analysis of LU in milk and milk products, benzoylated LU, hepta-o-benzoyl lactose ureide (melting point 137-139°C; m/z 1,113 [M + H⁺]; wavelength of maximum absorption, λ(max), 229 nm; molar extinction coefficient, ε, 8.1037 × 107), was used as a standard. The crude nonreducing carbohydrate fraction from raw milk, thermally processed milk, and milk products such as powdered milks were directly benzoylated and subjected to HPLC analysis using an octadecylsilyl column to determine the quantity of LU. The content of LU in 10% solutions of powdered skim milk and powdered infant formula (5.0±1.1 and 4.9±1.5 mg/L, respectively) were almost 3-fold higher than that of UHT milk (1.6±0.5 mg/L) and higher than that of low-temperature, long-time-processed (pasteurized at 65°C for 30 min) milk (1.2±0.3 mg/L) and the fresh raw milk sample (0.3±0.1 mg/L). A time-course of the LU content in raw milk during heating at 110°C revealed that LU increased with time. From these results, it is likely that LU is formed by the Maillard-type reaction between the lactose and urea in milk and milk products. Because the concentration of LU in milk increased with the degree of processing heat treatment, it could serve as an indicator of the thermal deterioration of milk. Although it is known that the human intestine is unable to digest LU, the gastrointestinal bacteria in human subjects are able to digest and utilize urea nitrogen in formation of essential amino acids that are available to the host human. These findings suggest that LU in milk might have a functional role in human health.

Blood pressure and urine output during the first 120 h of life in infants born at less than 29 weeks' gestation related to umbilical cord milking.

OBJECTIVE: To investigate the effects of umbilical cord milking on cardiopulmonary adaptation in very low birth weight infants. PATIENTS AND METHODS: This study was the secondary analysis of a randomised control study of the effect of umbilical cord milking in premature infants. Forty singleton infants born between 24 and 28 weeks' gestation were randomly assigned to groups in which the umbilical cord was clamped either immediately after birth (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Blood pressure, heart rate, urine output, fluid intake, and ventilatory index values in both groups were measured during the first 120 h after birth. RESULTS: There were no significant differences in gestational age or birth weight between the two groups. The initial haemoglobin value was higher in the milked group (mean (SD) 16.5 (1.4) g/dl in the milked vs 14.1 (1.6) g/dl in the control; p<0.01). During the first 12 h, blood pressure was significantly higher in the milked group. Urine output in the milked group was higher than that in the control group during the first 72 h. There were no significant differences in heart rate, water intake, or ventilatory index values between the groups. CONCLUSION: Umbilical cord milking may facilitate early stabilisation of both blood pressure and urine output in very low birth weight infants.

Changes of mental stress biomarkers in ultramarathon.

We investigated the possible influence of an exhaustive physical exercise on mental stress biomarkers (serotonin, tryptophan, and beta-endorphin) along with dopamine, noradrenaline and free fatty acids in an ultramarathon race in which 45 km was run on the first day and 90 km on the second. We obtained serum samples at 6 different time points during and after the race from 18 Japanese male runners who completed the marathon. Overall changes of serum serotonin and tryptophan concentrations were statistically significant according to ANOVA for repeated measurements (p < 0.05). Serum serotonin levels elevated rapidly on the first day with the post hoc Tukey's test. Tryptophan concentrations inversely decreased during the race, possibly because of utilization for synthesis of serotonin. Levels of beta-endorphin appeared to increase on the first and second days, but were not statistically significant. In conclusion, serum serotonin, tryptophan and beta-endorphin appeared to be used for mental stress markers in physical exercise.

Umbilical cord milking reduces the need for red cell transfusions and improves neonatal adaptation in infants born at less than 29 weeks' gestation: a randomised controlled trial.

OBJECTIVE: To investigate the effects of umbilical cord milking on the need for red blood cell (RBC) transfusion and morbidity in very preterm infants. PATIENTS AND METHODS: 40 singleton infants born between 24 and 28 weeks' gestation were randomly assigned to receive umbilical cord clamped either immediately (control group, n = 20) or after umbilical cord milking (milked group, n = 20). Primary outcome measures were the probability of not needing transfusion, determined by Kaplan-Meier analysis, and the total number of RBC transfusions. Secondary outcome variables were haemoglobin value and blood pressure at admission. RESULTS: There were no significant differences in gestational age and birth weight between the two groups. The milked group was more likely not to have needed red cell transfusion (p = 0.02) and had a decreased number (mean (SD)) of RBC transfusions (milked group 1.7 (3.0) vs controls 4.0 (4.2); p = 0.02). The initial mean (SD) haemoglobin value was higher in the milked group (165 (14) g/l) than in the controls (141 (16) g/l); p<0.01). Mean (SD) blood pressure at admission was significantly higher in the milked group (34 (9) mm Hg) than in the controls 28 (8) mm Hg; p = 0.03). There was no significant difference in mortality between the groups. The milked group had a shorter duration of ventilation or supplemental oxygen than the control group. CONCLUSION: Milking the umbilical cord is a safe procedure, reducing the need for RBC transfusions, and the need for circulatory and respiratory support in very preterm infants.

A multidisciplinary treatment strategy that includes high-dose chemotherapy for metastatic retinoblastoma without CNS involvement.

The prognosis of patients with metastatic retinoblastoma is poor with conventional chemotherapy and radiation. Since retinoblastoma is highly chemosensitive, dose-escalation of chemotherapeutic agents with stem cell support should be promising. We report our experience with high-dose chemotherapy (HDC) and autologous stem cell transplantation (SCT) in patients with metastatic retinoblastoma. Five patients with metastatic retinoblastoma underwent HDC with autologous SCT following conventional chemotherapy and local radiation therapy. Stem cells (bone marrow in four and peripheral blood stem cells in one) were collected after marrow involvement was cleared. Melphalan was a key drug in all patients, and was administered in combination with other agents such as cisplatin, cyclophosphamide, carboplatin or thiotepa. Three patients are currently alive disease-free at 113, 107 and 38 months, respectively, from the time of SCT. They had no central nervous system (CNS) involvement. The two patients who died of disease had CNS involvement. No long-term sequelae of HDC have been noted. Our treatment strategy using HDC appears to be effective for treating metastatic retinoblastoma without CNS involvement.

Effects of milk products fermented by Bifidobacterium longum on blood lipids in rats and healthy adult male volunteers.

The effects of milk products fermented by Bifidobacterium longum strain BL1, a probiotic strain, on blood lipids in rats and humans were studied. Rats were fed a cholesterol-enriched experimental diet, supplemented with lyophilized powders of 1) acid milk (control), 2) milk fermented with a mixed culture of ordinary yogurt starters composed of Streptococcus thermophilus and Lactobacillus delbrueckii subsp. bulgaricus (SL), and 3) bifidobacterium milk fermented with the probiotic B. longum strain BL1, respectively. The bifidobacterium milk feeding brought about significant lowering of the serum concentrations of total cholesterol, low-density lipoprotein cholesterol, and triglycerides, in comparison with the control, while no change in high-density lipoprotein cholesterol concentration was observed. On the other hand, supplementation with SL milk resulted in only slight, nonsignificant decreases in serum lipid concentrations in comparison with the control. In the human study, 32 subjects with serum total cholesterol ranging from 220 to 280 mg/dl were randomly assigned to two treatments: 1) intake of a low-fat drinking yogurt prepared with ordinary yogurt starters composed of S. thermophilus and L. delbrueckii subsp. bulgaricus (P-group) and 2) intake of a low-fat drinking yogurt prepared with the two ordinary yogurt starters plus B. longum strain BL1 (B-group). After intake for 4 wk at 3 x 100 ml/day, reduction of serum total cholesterol was observed in approximately half of the B-group subjects; a particularly significant decrease in serum total cholesterol was found among subjects with moderate hypercholesterolemia (serum total cholesterol > 240 mg/dl). However, the serum lipid concentrations in the P-group subjects were almost stable during the experimental periods. The present results indicate the potential of the probiotic B. longum strain BL1 in serum lipid improvement.

Hypocholesterolemic effect of Lactobacillus gasseri SBT0270 in rats fed a cholesterol-enriched diet.

The effects of administration of Lactobacillus gasseri SBT0270 on serum lipids and bile acids, faecal bile acids and microflora were estimated in hypercholesterolemic rats. An effective dose of strain SBT0270 to exert its hypocholesterolemic effect was 10(9) viable cells/d. The dose of 10(9) cells/d did not affect the faecal coliform counts, but the number of faecal lactobacilli in rats fed this dose was significantly higher than that in the control group observed at the end of feeding period. Hypocholesterolemic effect of Lb. gasseri SBT0270 was attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation and to enhance the excretion of acidic steroids in faeces of hypercholesterolemic rats.

Effect of administration of Lactobacillus gasseri on serum lipids and fecal steroids in hypercholesterolemic rats.

The effects of milk and nonfermented milks produced from Lactobacillus gasseri on serum lipids and total bile acids and fecal steroids and microflora were estimated in rats fed cholesterol-enriched diets. Lactobacilli decreased and coliforms increased in feces of the control group; however, the concentrations of fecal lactobacilli remained unchanged when rats were fed nonfermented milks. Fecal coliforms in rats receiving milk and nonfermented milk produced from L. gasseri SBT0270 increased, while rats receiving nonfermented milk produced from L. gasseri SBT0274 had lower fecal coliform count than did the control group. Only NFM-A significantly reduced serum total cholesterol and low-density lipoprotein (LDL) cholesterol, and bile acids. High-density lipoprotein (HDL) cholesterol was significantly decreased when rats were given milk and nonfermented milks. Milk and NFM-A lowered serum triglycerides levels. Milk and nonfermented milks did not affect the total neutral steroids, but higher levels of acidic steroid were detected in the feces than the control group. The results showed that the hypocholesterolemic effect of L. gasseri SBT0270 was attributed to its ability to suppress the reabsorption of bile acids into the enterohepatic circulation and to enhance the excretion of acidic steroids in feces of hypercholesterolemic rats.

Immediate effect of Lactobacillus acidophilus on the intestinal flora and fecal enzymes of rats and the in vitro inhibition of Escherichia coli in coculture.

The in vitro role of Lactobacillus acidophilus was investigated to explore the potential to inhibit coliforms. A threefold concentrated cell-free extract from L. acidophilus SBT2074 could efficiently inhibit most of the tested Gram-positive and Gram-negative bacteria. Among the three strains of L. acidophilus, SBT2062, SBT2071, and SBT2074, only L. acidophilus SBT2074 showed this inhibitory property. These three strains were also tested in coculture with Escherichia coli 3544 in skim milk medium. The fermentation could result in complete inhibition of E. coli in 36 h. Short-term administration of L. acidophilus SBT2074 in rats with and without E. coli resulted in significant inhibition of coliforms and anaerobes. The E. coli infected rats regained the normal flora in the presence of lactic acid bacteria. The fecal enzyme beta-glucuronidase activity was also decreased significantly when L. acidophilus SBT2074 was administered and was related to the decreased number of bacteria in the intestinal tract. The analysis of the small intestinal contents showed that the concentrations of coliforms in the duodenum, jejunum, and the ileum were significantly reduced by the administration of lactic acid bacteria. The effects are seen in a short period, suggesting that L. acidophilus SBT2074 fermentate may have clinical application for people suffering from gastrointestinal distress caused by coliforms.

Effect of administration of fermented milk containing whey protein concentrate to rats and healthy men on serum lipids and blood pressure.

The effect of fermented milk supplemented with whey protein concentrate on the serum lipid level of rats was investigated. The serum total cholesterol level for the group fed fermented milk with both Lactobacillus casei TMC0409 and Streptococcus thermophilus TMC 1543 was significantly lower than that of the control group (P<0.05) in rats. Furthermore, the effect of the longterm intake of this fermented milk on the serum lipid level of twenty healthy adult men was investigated. During the 8-wk study, the volunteers consumed 200 ml of fermented milk or placebo in the morning and evening. Blood samples were drawn for analysis three times, just before taking the experimental diet, and after 4 wk and 8 wk of consumption. After 8 wk, the high density lipoprotein cholesterol level for the fermented milk group showed a significant rise after 4 wk (P<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The triglyceride level for the fermented milk group lowered significantly after 4 wk (<0.05), whereas that of the placebo group showed no change even after 4 wk (P>0.05). The atherogenic index [(total cholesterol - high density lipoprotein cholesterol)/high-density lipoprotein cholesterol] for the fermented milk group decreased significantly from 4.24 to 3.52 (P<0.05). The systolic blood pressure lowered significantly by the intake of fermented milk (P<0.05) On the other hand, such effect was not observed in the placebo group (P>0.05). These results indicate potential of the development of fermented milk with multiple therapeutic effects.

Bile tolerance, taurocholate deconjugation, and binding of cholesterol by Lactobacillus gasseri strains.

Bile tolerance, deconjugation of sodium taurocholate, and the cholesterol-binding ability of 28 strains of Lactobacillus gasseri were examined. There was significant variation among strains in growth in media containing bile and also variation in the ability to bind cholesterol. Cultures grown for 12 h at 37 degrees C bound significantly more cholesterol than did cells from a 48-h incubation. Variation among strains in the ability to deconjugate sodium taurocholate was not significantly different. Maximal deconjugation of sodium taurocholate was achieved with the cells during the stationary phase of growth (12 h). Statistical analysis showed no significant correlation between bile tolerance and sodium taurocholate deconjugation, bile tolerance and cholesterol-binding ability, or sodium taurocholate deconjugation and cholesterol-binding ability.

Viability of Lactobacillus gasseri and its cholesterol-binding and antimutagenic activities during subsequent refrigerated storage in nonfermented milk.

The effect storage at 4 degrees C on the viability of Lactobacillus gasseri and its sodium taurocholate-deconjugating and cholesterol-binding abilities as well as desmutagenic activity was investigated. Unfermented milks containing L. gasseri strains SBT0274 and SBT0270 at 10(9) cfu/ml were prepared using 10% skim milk. Total and bile-tolerant lactobacilli for strains SBT0274 and SBT0270 generally decreased after 14 d of storage at 4 degrees C; however, viable cells of these strains were still at 10(8) cfu/ml after 28 d of storage. The amounts of cholic acid released and of cholesterol bound by strains SBT0274 and SBT0270 declined over time, especially at 21 d of storage. Antimutagenic activity of unfermented milk made from both strains was attributed to the bacterial cells, and the activity was stable during storage at 4 degrees C for 28 d.