Lifestyle habits associated with nocturnal urination frequency: The Nagahama study.

BACKGROUND: Nocturia is a risk factor for poor quality of life and increased mortality. This study was aimed to clarifying dietary habits, eating behaviors, and sleep characteristics associated with nocturia to identify modifiable lifestyle factors for nocturia. METHODS: This cross-sectional study included 5683 community residents (64.5 ± 7.7 years old). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. The frequency of food intake, unfavorable eating behaviors, and sleep characteristics that may have influence on salt intake and wasting were obtained using a structured questionnaire. RESULTS: The frequency of nocturnal urination was increased with age (ß = .312, P < .001). Other basic factors associated with the frequency were the male sex (ß = .090), hypertension (ß = .038), sleep apnea (ß = .030), B-type natriuretic peptide level (ß = .089), and spot urine sodium excretion (ß = -.058). Dietary factors independently associated with nocturnal urination frequency were coffee (≥1 time/day: ß = -.059, P < .001) and green vegetable consumption (≥1 time/week: ß = -.042, P = .001), whereas habitual intake of dairy products, miso soup, and alcohol were not associated with urination frequency. Later bedtime was inversely associated with nocturnal urination frequency independent of sleep duration (before 23:00: ß = -.096; before 24:00: ß = -.225; after midnight: ß = -.240; all P < .001). CONCLUSION: Coffee and green vegetable consumption and later bedtime but not sleep duration are lifestyle factors associated with nocturnal urination frequency.

Total synthesis of (-)-cinatrin C1 based on an In(OTf)3-catalyzed Conia-Ene reaction.

The stereocontrolled total synthesis of (-)-cinatrin C1, a phospholipase A2 inhibitor, has been accomplished. The key feature includes the stereoselective construction of the highly substituted tetrahydrofuran core by In(OTf)3-catalyzed Conia-ene reaction of the oxygen-tethered acetylenic malonic ester followed by dihydroxylation with concomitant lactonization.

Treatment strategy for pediatric giant mucinous cystadenoma: A case report.

Because of their rarity, the treatment strategy for pediatric ovarian epithelial tumors is controversial, especially for a giant cystadenoma. We report the largest mucinous cystadenoma (MCA) case in the pediatric literature thus far. A 12-year-old girl had abdominal distention and visited our hospital. She had a multilocular cyst with some protuberance on the inside and high values of CA 19-9 and CA-125. We diagnosed her with a left MCA and performed a left oophorectomy. The tumor was the stage IA borderline malignant MCA and weighed 11.8 kg. Five years have passed, the patient has not experienced recurrence or metastasis. The resection of giant tumors can affect respiration and circulation. However, pre- or intra-operative drainage may lead to dissemination and adhesion. When we treat pediatric giant ovarian epithelial tumors, we must understand the findings that suggest the possibility of malignancy to decide appropriately as to whether drainage should be performed.

Association of the spot urine sodium-to-potassium ratio with blood pressure is independent of urinary Na and K levels: The Nagahama study.

The sodium-to-potassium ratio (Na/K) of a urine sample is a simple index of salt loading. To practically use Na/K, we aimed to determine whether the Na/K value affects blood pressure (BP) at any age, irrespective of urinary Na and K levels. We analyzed a dataset of the general population (the Nagahama study), including baseline and second-visit measurements performed 5 years after the baseline. Spot urine samples were used for Na/K assessments. A total of 18,505 observations were analyzed using a linear mixed model, including the measurement term as a random effect. Urinary Na/K values showed a positive association with BP. When the highest quartile of Na/K was further divided by the urinary Na/creatinine (Cre) and K/Cre levels, the high-Na/Cre (3.58) and high-K/Cre (0.75) (Na/K = 4.80) groups, as well as the low Na/Cre (1.23) and low-K/Cre (0.26) (Na/K = 4.87) groups, exhibited similar effects on systolic BP (6.82 mmHg [95% CI: 5.72-7.92] and 6.63 mmHg [95% CI: 5.35-7.91], respectively). A similar association was observed in other Na/K quartiles. The positive association of Na/K and Na/Cre with BP was steeper in the older groups, while the inverse association of K/Cre was predominant in the younger population. The results of the multivariate analysis identified interaction terms between age and Na/K, Na/Cre and K/Cre as significant determinants for SBP. The positive association of urinary Na/K with BP was independent of the urinary Na and K levels. The association between Na/K and BP may not be uniform across ages by decade.

Frequent nocturnal urination in older men is associated with arterial stiffness: The Nagahama study.

Nocturia in older adults has been reported to be a risk factor for cardiovascular outcomes, and the stiffening of large arteries might be an underlying mechanism. To clarify the possible association between nocturia and arterial stiffness, we analyzed a dataset from the Japanese general population. Study participants consisted of 5928 community residents (mean age: 60.0 ± 11.8 years). The frequency of nocturnal urination was recorded for 1 week using a sleep diary. Arterial stiffness was assessed by brachial-to-ankle pulse wave velocity (baPWV). Sleep blood pressure was measured automatically at 0000, 0200, and 0400 hours by wearing a cuff on the upper arm during sleep. The mean baPWV was 1278 ± 227 cm/s. The frequency of nocturnal urination showed a linear positive association with baPWV (P < 0.001). The association between a sleep diary-based nocturnal urination frequency > 1.5 times/night (corresponding to a ≥ 2 times/night frequency obtained by the questionnaire) and baPWV remained significant after adjusting for major covariates, including office blood pressure (ß = 0.051, P < 0.001) and sleep blood pressure (ß = 0.040, P < 0.001). This association was more prominent in men (ß = 0.069, P < 0.001) than in women (ß = 0.023, P = 0.013), particularly in older (ß = 0.068, P = 0.006) compared with younger (ß = 0.029, P = 0.270) men. Frequent nocturnal urination was independently associated with baPWV in older men. Nocturia may be a marker for cardiovascular disease risks that cannot be assessed by conventional risk factors such as blood pressure.

Association between sleep disturbance and nocturnal blood pressure profiles by a linear mixed model analysis: the Nagahama study.

OBJECTIVES: We aimed to analyze associations of sleep disturbance, including sleep disordered breathing, sleep fragmentation, and sleep efficiency, with abnormal nocturnal blood pressure (BP) profiles that may be risk factors for adverse cardiovascular outcomes. METHODS: The study included 5854 community residents with 20,725 multi-day measurements. Sleep fragmentation and efficiency were evaluated using a wrist-worn activity monitor. Sleep disordered breathing was assessed using the 3% oxygen desaturation index corrected for actigraphy-determined sleep duration. A timer-equipped standard cuff-oscillometric device was used for home and sleep BP monitoring. RESULTS: Mean nocturnal systolic BP (SBP) change was -8.6 ± 9.7% (-11.1 ± 12.6 mmHg), and inter-day correlation coefficient of the nocturnal SBP change was 0.443. Results of a linear mixed model analysis using daily measured values identified lower sleep efficiency (coefficient = -0.130, p < 0.001) as a determinant for decreased nocturnal SBP dipping beyond the interday variations of these parameters. Number of nocturnal urinations was another strong determinant (coefficient = 1.191, p < 0.001), although the association of sleep efficiency was independent of nocturnal urination, awake SBP, and sleep disordered breathing (coefficient = -0.102, p < 0.001). Sleep efficiency was also independently associated with sleep SBP level (coefficient = -0.138, p < 0.001). Estimated differences in nocturnal SBP dipping and sleep SBP level as a function of the degree of sleep efficiency (less than 80%) reached 1.63% (1.09-2.17%) and 2.16 mmHg (1.49-2.82%), respectively. CONCLUSION: More attention should be paid to sleep efficiency as a factor in maintaining circadian BP rhythm.

Association of weak hip abduction strength with nocturia in older women: The Nagahama study.

AIM: Nocturia is a common phenomenon in older individuals, and is associated with poor quality of life. Nocturia is a multifactorial disorder, wherein the frailty of skeletal muscles, particularly muscle weakness in the lower trunk and hip regions, might be a risk factor in women. We analyzed a dataset of the general Japanese population to clarify the hypothesis. METHODS: Study participants included 1207 older women (mean age 67.4 ± 5.2 years). The frequency of nocturnal urination was assessed using a sleep diary for 1 week, and associations with lower muscle strength, skeletal muscle index, sarcopenia and physical performance (one-leg standing time and Timed Up and Go test) were investigated. RESULTS: The frequency of nocturnal urination more than one voiding per night was 28.1%; this frequency was inversely associated with hip abduction strength quartiles (Q1: 37.0, Q2: 30.5, Q3: 25.1 and Q4: 19.9%, P < 0.001). When a sleep diary-based nocturnal urination frequency >1.5 times/night (corresponding to a ≥2 times/night frequency obtained by questionnaire) was considered as nocturia, logistic regression analysis adjusted for major covariates identified hip abduction strength as an independent inverse determinant of nocturia (odds ratio 0.75, 95% CI 0.52-0.90, P = 0.002). In contrast, no significant association was observed with knee extension (P = 0.322) and hip flexion (P = 0.603) strengths. Physical performance, skeletal muscle index and sarcopenia did not show significant associations with nocturia. CONCLUSIONS: Weak hip abduction strength might be a factor associated with nocturnal urination frequency in older women. Geriatr Gerontol Int 2019; 19: 1010-1016.

Bright-light exposure during daytime sleeping affects nocturnal melatonin secretion after simulated night work.

The guidelines for night and shift workers recommend that after night work, they should sleep in a dark environment during the daytime. However, staying in a dark environment during the daytime reduces nocturnal melatonin secretion and delays its onset. Daytime bright-light exposure after night work is important for melatonin synthesis the subsequent night and for maintaining the circadian rhythms. However, it is not clear whether daytime sleeping after night work should be in a dim- or a bright-light environment for maintaining melatonin secretion. The aim of this study, therefore, was to evaluate the effect of bright-light exposure during daytime sleeping on nocturnal melatonin secretion after simulated night work. Twelve healthy male subjects, aged 24.8 ± 4.6 (mean ± SD), participated in 3-day sessions under two experimental conditions, bright light or dim light, in a random order. On the first day, the subjects entered the experimental room at 16:00 and saliva samples were collected every hour between 18:00 and 00:00 under dim-light conditions. Between 00:00 and 08:00, they participated in tasks that simulated night work. At 10:00 the next morning, they slept for 6 hours under either a bright-light condition (>3000 lx) or a dim-light condition (<50 lx). In the evening, saliva samples were collected as on the first day. The saliva samples were analyzed for melatonin concentration. Activity and sleep times were recorded by a wrist device worn throughout the experiment. In the statistical analysis, the time courses of melatonin concentration were compared between the two conditions by three-way repeated measurements ANOVA (light condition, day and time of day). The change in dim light melatonin onset (ΔDLMO) between the first and second days, and daytime and nocturnal sleep parameters after the simulated night work were compared between the light conditions using paired t-tests. The ANOVA results indicated a significant interaction (light condition and3 day) (p = .006). Post hoc tests indicated that in the dim-light condition, the melatonin concentration was significantly lower on the second day than on the first day (p = .046); however, in the bright-light condition, there was no significant difference in the melatonin concentration between the days (p = .560). There was a significant difference in ΔDLMO between the conditions (p = .015): DLMO after sleeping was advanced by 11.1 ± 17.4 min under bright-light conditions but delayed for 7.2 ± 13.6 min after sleeping under dim-light conditions. No significant differences were found in any sleep parameter. Our study demonstrated that daytime sleeping under bright-light conditions after night work could not reduce late evening melatonin secretion until midnight or delay the phase of melatonin secretion without decreasing the quality of the daytime sleeping. Thus, these results suggested that, to enhance melatonin secretion and to maintain their conventional sleep-wake cycle, after night work, shift workers should sleep during the daytime under bright-light conditions rather than dim-light conditions.

Day-to-Day Home Blood Pressure Variability and Orthostatic Hypotension: The Nagahama Study.

BACKGROUND: The aim of this study is to clarify associations between orthostatic blood pressure (BP) change, as well as possible physiological factors, and day-to-day home BP variability, a promising risk factor for cardiovascular outcomes. METHODS: Study participants were 6,465 community residents (age 58.3 years). Home BP was measured every morning and evening for 7 days. Orthostatic BP was calculated as the maximum difference between BP measured while sitting and remeasured after 1 and 3 minutes standing. RESULTS: Frequency of individuals who showed orthostatic BP decline was as follows: systolic BP (SBP) change ≥-20 mm Hg: 2.6%, ≥-10 mm Hg: 14.1%. These subgroups showed larger home SBP variability (average real variability: 11.3 ± 5.3, 8.7 ± 3.9 mm Hg) when compared with orthostatic normotensives (7.6 ± 3.7 mm Hg) (all P < 0.001). Multiple linear regression analysis adjusted for major covariates, including seated BP, identified orthostatic BP drop as an independent determinant for morning BP variability (≥-20 mm Hg: ß = 0.037, P = 0.003; ≥-10 mm Hg: ß = 0.026, P = 0.036) but not for evening BP variability. Carotid hypertrophy was significantly associated with home BP variability (morning: ß = 0.052, P = 0.001; evening: ß = 0.065, P < 0.001) and showed a U-shaped association with orthostatic BP change. Plasma B-type natriuretic peptide level, a previously suggested factor for BP variability, did not show significant association with morning and evening BP variability. CONCLUSION: Orthostatic BP decline was significantly associated with morning BP variability. Large artery atherosclerosis was a common risk factor.

Seasonal variation in nocturnal home blood pressure fall: the Nagahama study.

Abnormalities in circadian blood pressure (BP) variation have been suggested to be associated with cardiovascular diseases and mortality. Factors affecting this variability need to be clarified to precisely evaluate the risk of circadian BP abnormalities. Given the seasonal differences in casual BP, it was hypothesized that nocturnal BP may also differ by season. Here, we aimed to clarify the seasonality of circadian BP variation, as well as the factors associated with this seasonality, in a large-scale general population (n = 4780). This is a cross-sectional study based on multiday BP values measured in the evening, during sleep, and in the morning. Measurements were taken at home using an automatic cuff-oscillometric device. The sleeping period was objectively defined by actigraphy. The nocturnal systolic BP fall was significantly less in individuals whose BP was measured during the summer season (summer, -5.8 ± 7.8%; middle (spring or autumn), -8.2 ± 7.5%; winter, -11.0 ± 7.7%; p < 0.001), resulting in higher frequencies of riser (summer, 19.9; middle, 12.8; winter, 7.8%) and non-dipper (summer, 51.4; middle, 46.3; winter, 37.0%) patterns in the summer season (p < 0.001). The results of linear regression analysis identified the middle (ß = 0.154, p < 0.001) and summer season (ß = 0.261, p < 0.001) as strong positive determinants for decreasing the nocturnal SBP fall. No seasonality was observed in day-to-day variability of the dipping pattern (Kendall's coefficient: winter, 0.527; middle, 0.539; summer, 0.515). The nocturnal BP fall was largely different by season, with a higher frequency of riser and non-dipper patterns in the summer. The seasonality might not be due to the seasonal difference in day-to-day variability of nocturnal BP changes.

Nocturia and increase in nocturnal blood pressure: the Nagahama study.

OBJECTIVE: Abnormalities in circadian blood pressure (BP) variation, particularly increase in nocturnal BP, have been reported to be risk factors for cardiovascular disease, although the factors associated with BP abnormalities are not fully understood. This study aimed to clarify possible associations of sleep characteristics, including sleep fragmentation, sleep disordered breathing, and nocturia, with sleep BP by simultaneous multiday measurements. METHODS: A cross-sectional study evaluated 5959 community participants having home-measured data on nocturnal BP change (sleep BP - awaking BP), sleep characteristics, and sleep disordered breathing. Sleep characteristics including the fragmentation index were assessed using wrist-wearable actigraphy, whereas sleep disordered breathing was assessed by 3% oxygen desaturation index obtained using a finger-type monitor. The number of nocturnal urinations was recorded in a sleep diary. RESULTS: Mean nocturnal SBP change was -8.5 ±â€Š7.9%. A 3% oxygen desaturation index was associated with the BP change independently of the basic covariates (ß = 0.051, P = 0.001), although the association became insignificant (P = 0.196) after adjusting the fragmentation index (ß = 0.105, P < 0.001). The association of the fragmentation index was also insignificant (P = 0.153) after adjusting measurement season (middle season: ß = 0.163, P < 0.001; summer season: ß = 0.249, P < 0.001). In contrast, the frequency of urination showed strong and independent association (ß = 0.140, P < 0.001), with smaller nocturnal BP drop in participants with frequent urination. CONCLUSION: Subjective sleep estimates and frequent nocturnal urination may represent a potential risk for circadian BP abnormalities.

Impact of sleep characteristics and obesity on diabetes and hypertension across genders and menopausal status: the Nagahama study.

Study Objectives: The individual prevalence of sleep-disordered breathing (SDB), short sleep duration, and obesity is high and increasing. The study aimed to investigate potential associations between SDB, objective sleep duration, obesity, diabetes and hypertension across genders, and the effect of pre- or post-menopausal status. Methods: A cross-sectional study evaluated 7051 community participants with wrist actigraphy for a week, and nocturnal oximetry ≥ 2 nights. SDB was assessed by 3 per cent oxygen desaturation index (ODI) corrected for sleep duration obtained from wrist actigraphy. Moderate-to-severe SDB was defined as ODI3% levels ≥ 15 per hour. Results: Both logODI3% and body mass index showed independent negative associations with sleep duration (ß = -0.16, p < 0.001 and ß = -0.07, p < 0.001, respectively). Moderate-to-severe SDB (men/premenopausal women/postmenopausal women; 23.7/1.5/9.5%, respectively) was associated with a higher risk of diabetes in premenopausal women (OR 28.1; 95%CI 6.35-124.6; p < 0.001) and postmenopausal women (OR 3.25; 95%CI 1.94-5.46; p < 0.001), but not in men (OR 1.47; 95%CI 0.90-2.40; p = 0.119). Moderate-to-severe SDB was associated with a higher risk of hypertension in men (OR 3.11; 95%CI 2.23-4.33; p < 0.001), premenopausal women (OR 3.88; 95%CI 1.42-10.6; p = 0.008), and postmenopausal women (OR 1.96; 95%CI 1.46-2.63; p < 0.001). Short sleep duration was not associated with diabetes or hypertension. The associations of obesity with diabetes or hypertension were indirectly mediated by SDB (24.0% and 21.5%, respectively), with possible sex differences emerging (men/women; 15.3/27.8% and 27.0/16.9%, respectively). Conclusions: Notwithstanding the cross-sectional design, SDB and obesity, but not short sleep duration, were independently associated with diabetes and hypertension, with gender and menopausal status-related differences in risk emerging.

Can tryptophan supplement intake at breakfast enhance melatonin secretion at night?

BACKGROUND: Tryptophan (TRP) is an essential amino acid, and it has been suggested that TRP intake at breakfast combined with daytime bright light exposure can increase nocturnal melatonin secretion. However, the mechanisms involved are not yet clear. The aim of this study was to examine the effect of TRP supplement intake at breakfast on nocturnal melatonin secretion under different daytime light intensities in humans. METHOD: Twelve subjects (aged 21.3 ± 3.0 years, mean ± standard deviation) participated in a random order in experimental sessions lasting 3 days under four conditions in a laboratory setting. The four conditions were TRP*Bright, Placebo*Bright, TRP*Dim, and Placebo*Dim. A TRP capsule (1000 mg) or a placebo starch capsule (1000 mg) were taken at breakfast. In addition, during the daytime (07:00-18:00), the subjects were asked to stay under different light intensities: >5000 lx (bright) or <50 lx (dim). Saliva samples were collected for measuring the concentration of melatonin. The time courses of melatonin concentration and dim light melatonin onset (DLMO) were compared among the four conditions using repeated measurements analysis of variance (ANOVA). RESULT: Nocturnal melatonin concentrations in the bright light condition tended to be higher than in the dim light condition (main effect of light: p = .099). Moreover, in the bright light condition, the change in DLMO between baseline and after the intervention was significantly higher than that in the dim light condition (main effect of light: p <.001). However, the ANOVA results indicated no significant effect of TRP intake on melatonin secretion. CONCLUSION: Our findings indicated that intake of 1000 mg of TRP at breakfast on 1 day did not change nocturnal melatonin secretion, even though TRP is the precursor of melatonin. In contrast, daytime bright light exposure increased nocturnal melatonin secretion and advanced the phase of melatonin onset. Therefore, TRP supplementation, unlike exposure to daytime bright light, does not acutely affect biological rhythm and sleep in humans. TRIAL REGISTRATION: UMIN Clinical Trial Registry: UMIN000024121.