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Background: Cold exposure induces lower urinary tract symptoms, including nocturia. Cold-induced detrusor overactivity can be alleviated by increasing skin temperature in rats. However, no study has shown an association between passive heating via hot-water bathing and nocturia among humans.Methods: We included 1,051 Japanese community-dwelling older adults (mean age: 71.7 years) in this cross-sectional study from 2010 to 2014. The number of nocturnal voids was recorded in a self-administered urination diary. Nocturia was defined as ≥2 nocturnal voids. We evaluated bathing conditions in the participants’ houses.Results: Hot-water bathing (n = 888) was associated with a lower prevalence of nocturia than no bathing (n = 163), independent of potential confounders, including age, sex, obesity, income, physical activity, diabetes, medication (diuretics, nondiuretic antihypertensives, and hypnotics), depressive symptoms, indoor/outdoor temperature, and day length (odds ratio [OR] 0.68; 95% confidence interval [CI], 0.48–0.97; P = 0.035). Compared with the quartile group with the longest bath-to-bed interval (range: 161–576 min), the second and third quartile groups (range: 61–100 and 101–160 min, respectively) were associated with a lower prevalence of nocturia, after adjusting for water temperature and bathing duration besides the same covariates (OR 0.60; 95% CI, 0.38–0.96; P = 0.031 and OR 0.59; 95% CI, 0.37–0.94; P = 0.025, respectively).Conclusion: Hot-water bathing, particularly with a bath-to-bed interval of 61–160 min, was significantly associated with a lower prevalence of nocturia among older adults.

Renal cell carcinoma (RCC) features altered lipid metabolism and accumulated polyunsaturated fatty acids (PUFAs). Elongation of very long–chain fatty acid (ELOVL) family enzymes catalyze fatty acid elongation, and ELOVL5 is indispensable for PUFAs elongation, but its role in RCC progression remains unclear. Here, we show that higher levels of ELOVL5 correlate with poor RCC clinical prognosis. Liquid chromatography/electrospray ionization‐tandem mass spectrometry analysis showed decreases in ELOVL5 end products (arachidonic acid and eicosapentaenoic acid) under CRISPR/Cas9‐mediated knockout of ELOVL5 while supplementation with these fatty acids partially reversed the cellular proliferation and invasion effects of ELOVL5 knockout. Regarding cellular proliferation and invasion, CRISPR/Cas9‐mediated knockout of ELOVL5 suppressed the formation of lipid droplets and induced apoptosis via endoplasmic reticulum stress while suppressing renal cancer cell proliferation and in vivo tumor growth. Furthermore, CRISPR/Cas9‐mediated knockout of ELOVL5 inhibited AKT Ser473 phosphorylation and suppressed renal cancer cell invasion through chemokine (C‐C motif) ligand‐2 downregulation by AKT‐mTOR‐STAT3 signaling. Collectively, these results suggest that ELOVL5‐mediated fatty acid elongation promotes not only cellular proliferation but also invasion in RCC. Elevated ELOVL5 expression is associated with poor renal cancer clinical prognosis. ELOVL5 promotes cellular proliferation by inhibiting apoptosis. ELOVL5 promotes cellular invasion via the AKT‐mTOR‐STAT3‐CCL2 signaling pathway.

A mutual relationship between nocturia and sleep disturbances is assumed; however, evidence for these associations in the general population remains limited, particularly regarding sleep-promoting lifestyle habits. This cross-sectional internet study examined associations between nocturia, sleep issues, and lifestyle habits perceived as promoting sleep in 3,317 participants in July 2019. The prevalence of nocturia increased with age, while overall sleep satisfaction tended to improve with age. However, individuals with more frequent nocturnal voids reported lower sleep satisfaction. Sleep dissatisfaction was significantly correlated with nocturnal urinary frequency in both men ( r  = 0.16) and women ( r  = 0.18, p  < 0.001), emphasizing the impact of nocturia on sleep quality. Furthermore, it revealed that nocturia was associated with various sleep issues. In men, mid-wakefulness (OR = 3.32, p  < 0.001) and difficulty falling asleep (OR = 1.37, p  < 0.050) were key factors, whereas in women, mid-wakefulness (OR = 11.2, p  < 0.001) and shallow sleep (OR = 1.77, p  = 0.010) were significant. Notably, it was found that lifestyle habits, such as drinking tea or alcohol, which can exacerbate nocturia and reduce sleep quality, are undertaken with intention of promoting good sleep. Conversely, good bedding (OR = 0.75, p  = 0.010) was associated with fewer nocturnal voids. These findings highlight the complex interplay between nocturia, sleep issues, and lifestyle behaviors, providing valuable insights for addressing these interconnected issues.

The tumor microenvironment (TME) modulates therapeutic response and prognosis in patients with bladder cancer (BC). The roles of two phospholipase D (PLD) isoforms, PLD1 and PLD2 (hydrolysis of phosphatidylcholine to phosphatidic acid), in cancer cells have been well‐studied in numerous cancer types, but their roles in the TME remain unclear. We used a mouse BC Pld2‐KO carcinogenesis model and global transcriptomic analysis to reveal that PLD2 was significantly involved in BC progression through immunosuppressive pathways in the TME. We therefore focused on PLD2 and tumor‐associated macrophages (TAMs), which were increased in Pld2‐KO mice and further associated with poor prognoses in BC patients. In vitro, we found that Pld2‐KO mouse TAMs had significantly enhanced proliferation, correlating closely with increased interleukin‐1β (IL‐1β) production. These results indicate that PLD2 suppresses BC progression by regulation of IL‐1β secretion from TAMs in the TME, suggesting that PLD2 could serve as a potential therapeutic target for modifying the TME in BC. We reveal that phospholipase D2 (PLD2) knockout promotes bladder cancer progression through immunosuppressive modulation involving tumor‐associated macrophages (TAMs) in the tumor microenvironment. Notably, knockout of Pld2 increased TAMs and interleukin‐1β (IL‐1β) production, suggesting that PLD2 suppresses bladder cancer progression by regulating IL‐1β secretion from TAMs.

Squalene, a natural triterpene with antioxidant, anti-inflammatory, and immunostimulatory properties, holds promise for cancer therapy. Here, we examined a previously developed, diethylene glycol derivative of squalene (SQ-diEG) and investigated its in vivo anti-carcinogenic effects in bladder cancer. C57BL/6 mice were treated with 0.025% N-butyl-N-(4-hydroxybutyl) nitrosamine (BBN) to induce bladder cancer, with SQ-diEG or PBS (control) administered orally from Week 0. SQ-diEG significantly reduced bladder cancer incidence to 3.7% after 8 weeks, compared to 21.4% in controls (p = 0.025). Transcriptomic analysis indicated that SQ-diEG may exert anti-carcinogenic effects by reducing ROS-mediated DNA damage, enhancing the immune microenvironment, and modulating cholesterol biosynthesis via SQLE downregulation. In vitro, SQ-diEG inhibited proliferation and induced apoptosis in bladder cancer cell lines. This study is the first to demonstrate that SQ-diEG significantly reduces bladder cancer in a BBN mouse model, highlighting potential for therapeutic development. Further research is needed to elucidate the mechanisms and long-term efficacy of SQ-diEG.

Background To identify the prognosis of Japanese patients with collecting duct carcinoma (CDC). Methods We used a hospital-based cancer registry data in Japan to extract CDC cases that were diagnosed in 2013, histologically confirmed, and determined the first course of treatment. We further investigated treatment modalities and estimated overall survival (OS) by the Kaplan–Meier method. Results A total of 61 CDC patients were identified. The 5-year OS rate for all CDC patients who were diagnosed in Japan during 2013 was 23.6% (95% CI: 15.0–37.4), with a median OS of 14 months (95% CI: 12–24). The 5-year OS rate for CDC patients at stages I, III, and IV were 53.0% (95% CI: 29.9–94.0), 35.7% (95% CI: 19.8–64.4), and 3.4% (95% CI: 0.5–23.7), respectively. Noteworthy, the 1-year OS for stage IV patients was 27.6% (95% CI: 0.5–23.7) and the median OS was only 5 months (95% CI: 4–12). We further examined the OS for advanced disease according to treatment modalities. The median OS of patients who undertook chemotherapy alone was significantly shorter than patients who undertook surgery alone for advanced disease (4 months [95% CI: 4-NA] vs. 15 months [95% CI: 13–68]; p  < 0.001) and surgery-only patients had a similar median OS as surgery-plus-chemotherapy patients (19 months [95% CI: 13-NA]; p  < 0.001). Moreover, a multivariable analysis for the OS in advanced disease revealed that surgery-plus-chemotherapy patients had significantly more favorable prognoses (HR 0.21, 95% CI: 0.07–0.57). Conclusions Japanese CDC patients face poor prognoses similar to Western countries, especially in advanced cases that receive only chemotherapy. Surgery appears necessary for advanced disease.

Background: Falls in hospitalized patients are a significant healthcare concern. This study examined whether circadian lighting, which helps to regulate circadian rhythms, reduces fall risk. Methods: A retrospective study was conducted in a 49-bed subacute and rehabilitation ward after the renovation and the installation of circadian lighting. Patients admitted during the five months with circadian lighting (intervention group) were compared to those admitted in the previous five months under fluorescent lighting (control group). Circadian lighting was defined as at least 275 equivalent melanopic lux between 7 a.m. and 12 p.m. Results: Significantly fewer patients in the intervention group experienced falls (7.4% vs. 15.0%, p = 0.0182). Logistic regression analysis identified circadian lighting as a protective factor (adjusted odds ratio [aOR] = 0.558, 95% confidence interval [CI]: 0.351–0.887, p = 0.0137), while age ≥ 80 (aOR = 2.48, 95% CI: 1.18–5.21, p = 0.0167) and anticonvulsant use (aOR = 3.68, 95% CI: 1.39–9.72, p = 0.0087) were significant risk factors. Conclusion: Circadian lighting was associated with a reduction in the number of patients who experienced falls, while advanced age and anticonvulsant use were significant risk factors.

Background Genitourinary sarcomas are rare in adults and few large-scale studies on adult genitourinary sarcoma are reported. We aimed to elucidate the clinical characteristics, survival outcomes, and prognostic factors for overall survival of adult genitourinary sarcoma in Japan. Methods A hospital-based cancer registry data in Japan was used to identify and enroll patients diagnosed with genitourinary sarcoma in 2013. The datasets were registered from 121 institutions. Results A total of 116 men and 39 women were included, with a median age of 66 years. The most common primary site was the kidney in 47 patients, followed by the paratestis in 36 patients. The most common histological type was liposarcoma in 54 patients, followed by leiomyosarcoma in 25 patients. The 5-year overall survival rates were 57.6%. On univariate analysis, male gender, paratestis as primary organ, and histological subtype of liposarcoma were predictive of favorable survival while primary kidney, bladder, or prostate gland location were predictive of unfavorable survival. On multivariate analysis, primary paratestis was an independent predictor of favorable survival while primary kidney, bladder, or prostate gland were independent predictors of unfavorable survival. Conclusions This is the first report showing the clinical characteristics and survival outcomes of adult genitourinary sarcoma in Japan using a real-world large cohort database.

Background Older men often experience nocturnal urination difficulties, reflected by diurnal differences in maximum urine flow (Qmax). Since lower urinary tract symptoms and pathological comorbidities are frequent in older men, it remains unclear whether this diurnal variation is a physiological or pathological phenomenon. Our aim was to quantify the diurnal variability of Qmax in healthy young participants under varying daylight conditions in a stable environment to discern potential underlying causes of nocturnal urination difficulties. Methods Twenty-one healthy young men were recruited in a 4-day study utilizing daytime (08:00–18:00) exposure with two light conditions in randomized order: dim (< 50 lx) or bright (~2500 lx). Day 1 was for acclimation, and urine flow was assessed from day 2. The participants urinated ad libitum during day 2 and then at fixed 3–4-h intervals thereafter (days 3–4). Regular urination Qmax at late night (04:00) on day 4 was compared with the nearest voided volume during daytime of day 3 (mDay). Results Morning Qmax scores (after bed—11:00) on day 2 were significantly lower than evening (17:00—before pre-sleep) in bright conditions and those of daytime (11:00–17:00), evening (17:00—before pre-sleep), and pre-sleep in dim conditions. Pre-sleep Qmax during the ad libitum period was significantly higher in dim than bright conditions. Late-night Qmax values (04:00) on day 4 were significantly lower than Qmax scores of mDay on day 3 in both light conditions. Conclusions Healthy young men had a clear diurnal Qmax difference that decreased during late night and morning. In addition, the pre-sleep Qmax values in dim daylight were significantly higher than in bright daylight. Taken together, we conclude that late-night and morning decreases in Qmax are an instinctive physiological phenomenon in humans, and the diurnal difference of Qmax can be influenced by daylight conditions.