Consumption of OLL1073R-1 yogurt improves psychological quality of life in women healthcare workers: secondary analysis of a randomized controlled trial.

BACKGROUND: We conducted a randomized controlled trial to investigate the effects of consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 in women healthcare workers. In a previous study we used these data to investigate hypothesized preventive effects against flu, however any effects on improving mental quality of life were not analyzed at that time. In the present study, we focus on that aspect. METHODS: The participants (961 women; mainly nurses, aged 20-71 years) were randomly allocated to either the yogurt group (n = 479) or the control group (n = 482). Participants in the yogurt group drank 112 mL of OLL1073R-1 yogurt for 16 weeks, while those in the control group did not consume any yogurt. All participants were prohibited from consuming other yogurt or fermented dairy products during the study period. The participants answered the Pittsburgh Sleep Quality Index (PSQI), Short Form-8 Health Survey (SF-8), and Gastrointestinal Symptom Rating Scale (GSRS) questionnaires at baseline and after 16 weeks. RESULTS: The PSQI score showed significant improvement after the intake of yogurt (p < 0.01). SF-8 results showed significant intervention effects in the General Health and Vitality scores (p = 0.02 and p = 0.01, respectively). In other subscales of SF-8, we did not observe significant effects of the yogurt. In the GSRS, daily intake of yogurt exerted a preventive effect on constipation (p = 0.03). CONCLUSIONS: Consumption of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 enhances subjective psychological quality of life by improving quality of sleep and gastrointestinal condition among women healthcare workers.

Continence Status and Presence of Pressure Skin Injury among Special Elderly Nursing Home Residents in Japan: A Nationwide Cross-Sectional Survey.

Urinary and fecal incontinence as well as skin pressure injury are common healthcare problems in nursing homes; however, the prevalence and related risk factors were not well understood in the Japanese special elderly nursing home settings. We surveyed the prevalence of urinary, fecal and double incontinence, and skin pressure injury among the elderly living in special elderly nursing homes in Japan. A nationwide cross-sectional epidemiological survey was conducted with a total of 4881 residents. The prevalence of urinary, fecal and double incontinence was 82.9%, 68.9% and 64.9%, respectively. Skin pressure injury was found in 283 residents (283/4881, 5.8%). Age, Care-Needs level, loss of voiding desire, and fecal incontinence were significant risk factors for urinary incontinence. Residential period, Care-Needs level, loss of voiding and defecation desires, and urinary incontinence were significant risk factors for fecal incontinence. Only male sex was a significant risk factor for skin pressure injury. Our study revealed continence status and the prevalence of pressure skin injury among older adult residents who receive end-of-life care in special elderly nursing homes in Japan. Further studies should be conducted to examine whether recovery of urinary and fecal sensations improves continence status.

[The association between alcohol consumption and Mild Cognitive Impairment: the Toon Health Study].

AIM: The effects of alcohol consumption on Mild Cognitive Impairment (MCI) among the Japanese population had not been fully examined. Therefore, the objective of this study was to examine the association between alcohol consumption and MCI among the Japanese elderly population. METHODS: In total, 421 men and 700 women aged 60-84 years participated in this cross-sectional study. Alcohol consumption was estimated according to frequency and amount of major alcoholic beverages (i.e., beer, Japanese sake, shochu, and wine) consumed by each individual using a self-administered questionnaire. MCI was assessed using the Japanese version of the Montreal Cognitive Assessment. Multivariable odds ratio (OR) and 95% confidence intervals (CIs) of MCI according to alcohol consumption were calculated using logistic models. We further analyzed the associations of the major alcoholic beverages with MCI. RESULTS: The prevalence of MCI was 50.4% among the male participants and 31.4% among the females. A positive association between alcohol consumption and MCI was observed in men, but not in women. The multivariable OR (95% CI) of MCI for ≥ 2 go (46 g ethanol) /day vs. non-drinkers was 1.78 (0.93-3.40, p for trend = 0.045) in men and for ≥ 1 go (23 g ethanol) /day was 0.96 (0.39-2.38, p for trend = 0.92) in women, respectively. We also observed an association between shochu consumption and MCI in men, whereby the multivariable OR (95% CI) of MCI for each 1 go increment was 1.57 (1.18-2.07). CONCLUSION: Our findings suggest that alcohol consumption in moderation may contribute to the prevention of MCI development in men.

The effects of OLL1073R-1 yogurt intake on influenza incidence and immunological markers among women healthcare workers: a randomized controlled trial.

Probiotics have been expected to enhance human immune function. The aim of this study was to evaluate the effects of dietary intake of yogurt fermented with Lactobacillus delbrueckii ssp. bulgaricus OLL1073R-1 (OLL1073R-1) on the prevention of influenza during winter and on the activation of immunological markers among women healthcare workers. 961 women aged 20-71 years were randomly assigned to either the yogurt group (n = 479) or the control group (n = 482). Participants in the yogurt group consumed a 112 mL yogurt drink fermented with OLL1073R-1 every day for 16 weeks, whereas those in the control group consumed no yogurt during this period. All participants were instructed not to consume any other kinds of yogurt or fermented dairy products throughout this trial. The cumulative incidence rate of influenza was measured, and immunological markers were examined at the baseline and after 16 weeks. No significant difference in the incidence rate of influenza was found between the two groups (cumulative incidence rates of flu: yogurt 7.5% and control 7.7%). Natural killer (NK) cell activity did not show a significant intervention effect (p = 0.11), whereas the intervention effect on serum interferon gamma (IFN-γ) production was significant (p = 0.03). Other immunological markers did not show significant intervention effects. Consumption of OLL1073R-1 yogurt did not show a significant preventive effect against influenza or a significant enhancement in NK cell activity. However, intake of this yogurt showed an increase in IFN-γ production.

Factors related to the urination methods of elderly people with incontinence who require at-home nursing care.

OBJECTIVE: This study aimed to elucidate the urination status among elderly people with incontinence who require at-home nursing care as well as the status of their family caregivers, and to identify the factors related to their urination methods. METHODS: In the present study, questionnaires were distributed to 101 elderly subjects (n=101) and their caregivers. RESULTS: The most prevalent urination method was the collaboration of toilet and adult diapers (69, 68.8%).There was a significantly larger number of patients who used a toilet <4 times and who had a "moderate" amount of incontinence and patients who used toilet 4-8 times and had a "slight" amount of incontinence (p<0.05). We performed a multivariate logistic regression analysis using the stepwise method. We used 8 items from the responses of the elderly subjects and their caregivers that were identified as being independently associated with the urination method using the chi-squared test (or Fisher's exact probability test), with the urination method as the dependent variable. Among elderly people, the ability to use a toilet properly (p=0.004) and independent mobility (p=0.028) strongly influenced their use of a toilet for urination. Among caregivers, the influencing factor was not thinking that they have to use the toilet even though they are unable to urinate (p=0.027). CONCLUSION: The use of a toilet for urination by elderly people was influenced by their physical functions and by the caregivers' attitudes toward excretion-related nursing care. When providing urination assistance, it is important for caregivers to maintain the physical functions of the elderly by providing support when necessary. It is also important to assess the bladder function by, methods such, as measuring the amount of residual urine and cooperate with a physician.

Thymic neuroendocrine tumour in multiple endocrine neoplasia type 1: female patients are not rare exceptions.

OBJECTIVE: Thymic neuroendocrine tumour (Th-NET) occurs in 2-5% of patients with MEN1 and has high malignant potency accompanying recurrence and distant metastasis. While Th-NET is recognized to develop predominantly in men and heavy smokers, a number of female patients have been reported in the literature. The objective of this study is to clarify the clinical features of MEN1 patients with Th-NET using database analysis. DESIGN/PATIENTS: Clinical data of patients with Th-NET were extracted and analysed from a recently constructed database of Japanese MEN1 patients. RESULTS: Among 560 registered cases, Th-NET was seen in 28 (5·0%) patients. Of note, 36% of patients (10/28) were women; only one patient among those was a smoker and another six patients were non-smokers. Age at diagnosis of Th-NET and MEN1, tumour size, prevalence of other MEN1-related tumours did not differ between male and female patients, and 10-year survival probability was 0·271 ± 0·106. CONCLUSIONS: Although the prevalence of Th-NET in women (3·2%) is significantly lower than that in men (7·6%), a considerable proportion of female patients develop Th-NET. Given that Th-NET is a major determinant of life expectancy of patients, our results alert clinicians who treat patients with MEN1 that surveillance of Th-NET is essential even for female patients without a smoking habit.

Age, initial dose and dose increase are independent risk factors for symptomatic vertebral fractures in glucocorticoid-treated male patients.

OBJECTIVE: The incidence and risk factors for symptomatic vertebral fracture were analyzed in glucocorticoid-treated male patients. METHODS: This was an observational cohort study at Shimoshizu National Hospital in Japan. Analyzed were 161 male patients newly treated with high-dose glucocorticoid (≥20 mg/day prednisolone equivalent) (initial age: 53.5±16.9, initial glucocorticoid dose: 38.9±12.9 mg/day (0.66±0.23 mg/kg/day), follow-up time: 70.4±52.5 months) and 33 male patients with no glucocorticoid (initial age: 52.7±13.0, follow-up time: 76.4±62.7 months). The vertebral fracture was determined by x-rays. RESULTS: Symptomatic vertebral fractures occurred more frequently in the high-dose glucocorticoid group (21.1%) than in the no glucocorticoid group (3.0%). Using Cox model, the adjusted hazard ratio (HR) for the high-dose glucocorticoid group was 8.16 (95% confidence interval: 1.09-60.86) relative to the no glucocorticoid control group. In the high-dose glucocorticoid group, Kaplan-Meier analyses demonstrated that the incidence of fractures in the patients with glucocorticoid dose increase was significantly higher in comparison with those with no glucocorticoid dose increase. Cox model demonstrated that the risk was independently higher in every 10-year increment of initial age with HR 1.58 (1.18-2.13), in every 10 mg increment of initial dose of prednisolone with HR 2.03 (1.43-2.88), in every dose increase of glucocorticoid increase with HR 3.63 (2.04-6.46), and with each 1-gram decrease of cumulative dose of glucocorticoid with HR 0.88 (0.84-0.93). CONCLUSION: In male patients, high-dose glucocorticoid causes a significantly high prevalence of symptomatic vertebral fractures, and the independent risk factors are age, initial glucocorticoid dose, glucocorticoid dose increase, and decrease of cumulative glucocorticoid dose.

Incidence of symptomatic vertebral fractures in women of childbearing age newly treated with high-dose glucocorticoid.

BACKGROUND: The treatment and prevention of glucocorticoid (GC)-induced osteoporosis have been controversial in premenopausal women during their childbearing years. OBJECTIVE: This study assessed the incidence and risk factors for symptomatic vertebral fracture in women of childbearing age newly treated with high-dose GC. METHODS: An observational cohort study was conducted at the rheumatic center of Shimoshizu National Hospital in Chiba, Japan, from 1986 to 2006. The prevalence of symptomatic vertebral fractures, as determined by x-rays, was assessed in premenopausal (aged <50 years) women with collagen vascular disease newly treated with high-dose GC (> or =20 mg/d prednisolone equivalent) compared with their counterparts who did not receive GC. Differences in the incidences of vertebral fractures were compared between groups by the Kaplan-Meier method and evaluated by the log-rank test. Hazard ratios (HRs) with 95% CIs were estimated using the Cox proportional hazards regression model. RESULTS: A total of 373 women were assessed: 292 patients in the high-dose GC treatment group (mean [SD] initial age, 32.4 [8.2] years; initial dose, 43.8 [14.9] mg/d; follow-up time, 124.2 [75.4] months) and 81 patients in the non-GC control group (initial age, 39.3 [7.8] years; follow-up time, 106.5 [79.7] months). Symptomatic vertebral fractures occurred more frequently in the high-dose GC group (11.3%) than in the non-GC group (1.2%). Using the Cox model, the adjusted HR for the high-dose GC group was 13.96 (95% CI, 1.87-104.22) relative to the non-GC group. In the high-dose GC group, Kaplan-Meier analyses revealed that the incidence of fractures in women in their forties was significantly higher in comparison with those in their twenties (P < 0.001) and thirties (P < 0.05), and that the incidence of fractures in those who consumed alcohol (>80 g/wk of pure alcohol) was significantly higher than in those who did not (P < 0.05). The Cox model also revealed that the risk was independently higher with every 10-year increment of initial age (HR = 2.27; 95% CI, 1.46-3.53), with every GC dose increase (HR = 2.28; 95% CI, 1.58-3.31), and with each 1-gram decrease of cumulative GC dose (HR = 0.95; 95% CI, 0.93-0.98). CONCLUSIONS: In this study, high-dose GC use was associated with a significantly high prevalence of symptomatic vertebral fractures in premenopausal women with collagen vascular disease during their childbearing years. However, the fracture risk was relatively low in women of childbearing age, especially those in their twenties and thirties during the early years of treatment.

cAMP activation by PACAP/VIP stimulates IL-6 release and inhibits osteoblastic differentiation through VPAC2 receptor in osteoblastic MC3T3 cells.

The neuropeptide pituitary adenylate cyclase-activating polypeptide (PACAP), a member of the glucagon/vasoactive intestinal peptide (VIP) superfamily, stimulates cyclic AMP accumulation initiating a variety of biological processes such as: neurotropic actions, immune and pituitary function, learning and memory, catecholamine biosynthesis and regulation of cardiopulmonary function. Both osteoclasts and osteoblasts have been shown to express receptors for PACAP/VIP implicated in their role in bone metabolism. To further understand the role of PACAP/VIP family in controlling bone metabolism, we investigated differentiation model of MC3T3-E1 cells, an osteoblastic cell line derived from mouse calvaria. Quantitative RT-PCR analysis demonstrated that MC3T3-E1 cells expressed only VPAC2 receptor and its expression was upregulated during osteoblastic differentiation, whereas VPAC1 and PAC1 receptors were not expressed. Consistent with expression of receptor subtype, both PACAP and VIP stimulate cAMP accumulation in a time- and dose-dependent manner with the similar potency in undifferentiated and differentiated cells, while Maxadilan, a specific agonist for PAC1-R, did not. Furthermore, downregulation of VPAC2-R by siRNA completely blocked cAMP response mediated by PACAP and VIP. Importantly, PACAP/VIP as well as forskolin markedly suppressed the induction of alkaline phosphatase mRNA upon differentiation and the pretreatment with 2',5'-dideoxyadenosine, a cAMP inhibitor, restored its inhibitory effect of PACAP. We also found that PACAP and VIP stimulated IL-6 release, a stimulator of bone resorption, and VPAC2-R silencing inhibited IL-6 production. Thus, PACAP/VIP can activate adenylate cyclase response and regulate IL-6 release through VPAC2 receptor with profound functional consequences for the inhibition of osteoblastic differentiation in MC3T3-E1 cells.

Vasopressin responders have a high prevalence of hypertension and insulin resistance in spite of a lower secretion of cortisol in subclinical Cushing's syndrome.

The hyper-responsiveness of plasma cortisol to vasopressin has been reported in patients with ACTH-independent bilateral macronodular adrenocortical hyperplasia (AIMAH) and in certain cases of Cushing's adenomas with overexpression of V1a receptors in the adrenal gland. We previously reported a high prevalence of the adrenal hyper-responsiveness of plasma cortisol to vasopressin (vasopressin responders) in Japanese patients with Cushing's syndrome (CS), in which vasopressin responders had low autonomous cortisol secretion and were diagnosed as having subclinical CS. In the present study, we aimed to evaluate the pathophysiological significance of vasopressin responsiveness in patients with subclinical CS in terms of hormonal secretion and metabolic abnormalities. We compared 14 vasopressin responders and 13 non-responders with subclinical CS, admitted to Chiba University Hospital between 1999 and 2007. Among these patients, the vasopressin responders were found to have lower plasma cortisol levels than non-responders at midnight (P<0.05) and in the morning following overnight dexamethasone suppression at 1 mg (P<0.05). On the other hand, they showed a significantly higher frequency of hypertensive complications than non-responders. In addition, according to 75g-OGTT the vasopressin responders had significantly higher levels of plasma insulin at 60 min than the non-responders, and their cortisol response to vasopressin had a significantly positive association with HOMA-IR (r=0.671, P<0.05). A high expression level of V1a receptor mRNAs was observed in the resected adrenal glands of vasopressin responders with AIMAH and unilateral adenomas. Though vasopressin responders with subclinical CS had lower autonomous cortisol secretion, they had a high prevalence of hypertension, in which insulin resistance was closely correlated with cortisol response to vasopressin.

A possible association between aldosterone response to vasopressin and circadian change of aldosterone in the patients with aldosterone-producing adenoma.

Vasopressin was reported to stimulate secretion of both cortisol and aldosterone through eutopic V1a receptors in adrenal gland. Recently, adrenal hyper-responsiveness of plasma cortisol to vasopressin with eutopic overexpession of V1a receptors has been reported in Cushing's syndrome, such as a majority of cases of ACTH-independent macronodular adrenal hyperplasia and some cases of Cushing's adenomas. There were a few reports regarding the aldosterone response to vasopressin in aldosterone-producing adenoma. The aim of our study was to investigate the aldosterone response to vasopressin and its pathophysiological roles in the patients with aldosterone-producing adenoma. Vasopressin-loading test was performed in 10 patients with aldosterone-producing adenoma, and in 16 patients with non-functioning adrenal tumors. The roles of the aldosterone response to vasopressin were analyzed in terms of hormonal secretion and the expression of V1a receptor mRNA on the operated adrenal gland in aldosterone-producing adenoma. We found that (1) a varying aldosterone response to vasopressin was observed, (2) absolute response of plasma aldosterone in aldosterone-producing adenoma was significantly higher than that in non-functioning tumor, (3) aldosterone response rate to vasopressin was significantly and negatively correlated with the decline rate (%) in plasma aldosterone from morning to evening in aldosterone-producing adenoma, (4) V1a receptor mRNA was expressed at various values in aldosterone-producing adenoma, and (5) surgical removal of aldosterone-producing adenoma eliminated the aldosterone response to vasopressin observed in patients with aldosterone-producing adenoma. These findings indicated that vasopressin might be involved in the coordination of aldosterone secretion through eutopic expression of V1a receptor in aldosterone-producing adenoma.

Isoprenoid-independent pathway is involved in apoptosis induced by risedronate, a bisphosphonate, in which Bim plays a critical role in breast cancer cell line MCF-7.

Bisphosphonates cause apoptosis to various types of cancer cells including breast cancer. Inhibition of the mevalonate pathway was reported to be involved in the apoptosis induced by bisphosphonates, but its precise mechanism has not been unveiled. In the present study, we investigated the molecular mechanism of risedronate, a bisphosphonate, in the apoptosis of the breast cancer cell line MCF-7 in comparison with that of cerivastatin, an HMG CoA reductase inhibitor (statin), since statin has been known to induce apoptosis through an isoprenoid-dependent pathway in these cells. We found that i) risedronate induced MCF-7 cells into apoptosis in a manner similar to cerivastatin with the activation of caspase-9 followed by caspase-6 and -7, that ii) bisphosphonate-induced apoptosis was significantly, but not fully, recovered by the addition of GGOH, an isoprenoid, which completely rescued in case of cerivastatin-induced apoptosis, that iii) risedronate induced G2 arrest with the induction of Bim (BH3-only protein), but that statin induced G1 arrest without it, and that iv) the down-regulation of Bim protein by siRNA significantly attenuated the risedronate-induced apoptosis. These data clearly indicate that both isoprenoid-dependent and -independent pathways might be involved in the apoptosis induced by bisphosphonate, and Bim might be a critical component for the isoprenoid-independent apoptotic pathway.

Effect of fenofibrate on uric acid metabolism in Japanese hyperlipidemic patients.

Forty Type IIb or IV hyperlipidemic patients (serum triglyceride concentrations were higher than 150 mg/dl) were treated with fenofibrate (300 mg/day) for 12 weeks. Lipid profile and uric acid metabolism were evaluated before and after the treatment; the serum concentrations of total cholesterol and triglyceride respectively decreased from 224 +/- 41.9 mg/dl to 199 +/- 35.2 mg/dl and from 205 +/- 71.7 mg/dl to 134 +/- 67.5 mg/dl (p < 0.001). The uric acid concentrations in the serum also significantly decreased from 7.0 +/- 1.58 mg/dl to 5.2 +/- 1.57 mg/dl (p < 0.001). Fenofibrate treatment did not cause any change in the serum xanthine and hypoxanthine concentrations. Instead the urinary concentrations of uric acid decreased from 7.0 +/- 1.58 mg/dl to 5.2 +/- 1.57 mg/dl (p < 0.01), while the clearance ratio of uric acid and creatinin increased from 6.1 +/- 2.56 to 9.9 +/- 3.87 (p = 0.02) by the fenofibrate treatment. Fenofibrate decreases uric acid concentrations in the serum not as a result of inhibition of uric acid production but by increasing the urinary excretion of uric acid.