Association between electroencephalogram-based sleep characteristics and physical health in the general adult population.

We examined the associations between electroencephalogram (EEG)-based sleep characteristics and physical health parameters in general adults via a cross-sectional study recruiting 100 volunteers aged 30-59 years. Sleep characteristics were measured at home using a portable multichannel electroencephalography recorder. Using the k-means + + clustering method, according to 10 EEG-based parameters, participants were grouped into better (n = 39), middle (n = 46), and worse (n = 15) sleep groups. Comparing 50 physical health parameters among the groups, we identified four signals of difference (P < 0.05), including systolic (sBP) and diastolic blood pressure (dBP), γ-glutamyl transpeptidase (γ-GTP), and serum creatinine, where sBP reached a Bonferroni-corrected threshold (P < 0.001). The sBP was higher by 7.9 (95% confidence interval 1.9-13.9) and 15.7 (7.3-24.0) mmHg before adjustment and 5.4 (- 0.1-10.9) and 8.7 (1.1-16.3) mmHg after adjustment for age, sex, body mass index, smoking, drinking habits, and 3% oxygen desaturation index in the middle and worse sleep groups, respectively, than in the better group. As another approach, among 500 combinations of EEG-based and physical health parameters, there were 45 signals of correlation, of which 4 (N1% and sBP, dBP, γ-GTP, and triglycerides) reached a Bonferroni-corrected threshold (P < 0.0001). Thus, EEG-based sleep characteristics are associated with several physical health parameters, particularly sBP.

The impact of rotating work schedules, chronotype, and restless legs syndrome/Willis-Ekbom disease on sleep quality among female hospital nurses and midwives: A cross-sectional survey.

BACKGROUND: Decreases in subjective sleep quality are prevalent among nurses and midwives engaged in rotating shift work. OBJECTIVES: The present study aimed to examine the relationship between differences in work schedules and subjective sleep quality among female nursing staff. DESIGN: A cross-sectional survey design was used for descriptive and logistic regression analyses. Data collection was conducted from December 2016 to September 2017. SETTINGS: Participants were recruited from five regional core hospitals in Japan. PARTICIPANTS: A total of 1253 nurses and midwives were included in the final analysis. METHODS: Subjective sleep quality was assessed using the Japanese version of the Pittsburgh Sleep Quality Index. Chronotype and social jet lag were calculated for both work day and work-free day. Symptoms related to restless legs syndrome/Willis-Ekbom disease were assessed using the Japanese version of the Cambridge-Hopkins questionnaire short form 13. Participants with the urge to move their legs, though not fulfilling the restless legs syndrome/Willis-Ekbom disease criteria, were classified as having leg motor restlessness. Logistic regression analyses for poor sleep were adjusted for age, body mass index, smoking, drinking, menstruation status, the presence of premenstrual syndrome, and the presence of a spouse. RESULTS: Rates of poor sleep (Pittsburgh Sleep Quality Index score ≥6) among those working, day shifts, rotating 12.5 hour night shifts, rotating 16 hour night shifts, and three-shift rotations were 41.2%, 51.1%, 44.5%, and 60.4%, respectively. Approximately 40% of three-shift rotation workers experienced difficulty initiating sleep. Shift workers tended to exhibit evening chronotype, delayed sleep phase, and high social jet lag. The prevalence of restless legs syndrome/Willis-Ekbom disease was 2.5%. Leg motor restlessness was observed in. 15.5% of participants. The adjusted odds ratios (95% confidence interval) of three-shift work (vs. day shift), evening chronotype (vs. morning chronotype), and the presence of leg motor restlessness (vs. no leg motor restlessness) for those with poor sleep were 2.20 (1.47-3.30), 1.95 (1.29-2.94), and 1.66 (1.15-2.39), respectively. CONCLUSIONS: Regardless of the working schedules, rates of poor sleep were high among female hospital nurses and midwives. Our findings suggest that poor sleep quality is influenced by three-shift rotation, the evening chronotype, and leg motor restlessness.

Association between chronic kidney disease and carotid intima-media thickness in relation to circulating CD34-positive cell count among community-dwelling elderly Japanese men.

BACKGROUND AND AIMS: Endothelial injury is well-known as a process that can lead to chronic kidney disease (CKD) and atherosclerosis. Hematopoietic activity is known to be associated inversely with CKD and positively with atherosclerosis. Since bone-derived progenitor cells (CD34-positive cells) contribute to endothelial repair (including the progression of atherosclerosis), understanding the association between CKD and carotid intima-media thickness (CIMT), in relation to circulating CD34-positive cell count, may be an efficient means of clarifying the mechanisms underlying endothelial activity. METHODS: We conducted a cross-sectional study of 570 elderly Japanese men aged 60-69 years, who underwent a general health check-up. Participants were stratified as per a median circulating CD34-positive cell count (1.01 cells/µL). RESULTS: Independent of the known cardiovascular risk factors, CIMT was found to be positively associated with CKD in the participants with high circulating CD34-positive cell counts but not in participants with low counts. Odds ratios were 1.40 (1.04, 1.89) for participants with high and 1.01 (0.72, 1.43) for participants with low circulating CD34-positive cell counts after adjustment for known cardiovascular risk factors at 95% confidence intervals for CKD with one standard deviation increment of CIMT. CONCLUSIONS: A positive association between CIMT and CKD was observed among participants with high circulating CD34-positive cell counts but not among participants with low counts. Endothelial repair activity might determine the association between CKD and CIMT.

Human T-Cell Leukemia Virus-1 Infection Is Associated With Atherosclerosis as Measured by Carotid Intima-Media Thickness in Japanese Community-Dwelling Older People.

The association between human T-cell leukemia virus-1 (HTLV-1) and atherosclerosis remains to be determined. This case-control study aimed to investigate this association as measured by carotid intima-media thickness (CIMT). HTLV-1 infection was positively associated with CIMT, independent of atherosclerotic risks.

Inhibition of G0/G1 Switch 2 Ameliorates Renal Inflammation in Chronic Kidney Disease.

Chronic kidney disease (CKD) is a global health problem, and novel therapies to treat CKD are urgently needed. Here, we show that inhibition of G0/G1 switch 2 (G0s2) ameliorates renal inflammation in a mouse model of CKD. Renal expression of chemokine (C-C motif) ligand 2 (Ccl2) was increased in response to p65 activation in the kidneys of wild-type 5/6 nephrectomy (5/6Nx) mice. Moreover, 5/6Nx Clk/Clk mice, which carry homozygous mutations in the gene encoding circadian locomotor output cycles kaput (CLOCK), did not exhibit aggravation of apoptosis or induction of F4/80-positive cells. The renal expression of G0s2 in wild-type 5/6Nx mice was important for the transactivation of Ccl2 by p65. These pathologies were ameliorated by G0s2 knockdown. Furthermore, a novel small-molecule inhibitor of G0s2 expression was identified by high-throughput chemical screening, and the inhibitor suppressed renal inflammation in 5/6Nx mice. These findings indicated that G0s2 inhibitors may have applications in the treatment of CKD.

A case of pyometra treated with endoscopic ultrasound-guided drainage.

A 90-year-old woman was admitted to our hospital because of a high-grade fever and appetite loss. On computed tomography scan, a huge cystic lesion about 10 cm in diameter was observed in the pelvic cavity, attached to the vagina and the neck of uterus. Pyometra was strongly suspected; however, a probe could not be inserted into the opening of the uterus because of atrophic changes. Therefore, we decided to perform endoscopic ultrasound (EUS)-guided drainage of the pyometra using the transrectal route. Foul-smelling yellow-brown pus was aspirated. A guide-wire was inserted and a 7 Fr catheter was inserted into the pyometra through an external fistula. We thus completed the treatment of pyometra without surgical resection.

Technical acquisition and dosimetric assessment of iodine-125 permanent brachytherapy in localized prostate cancer: our first series of 100 patients.

OBJECTIVES: To assess our initial experience in the treatment of localized prostate cancer using low-dose-rate brachytherapy (LDR-brachytherapy) with iodine-125. METHODS: One-hundred consecutive patients received LDR-brachytherapy between July 2004 and October 2006. Seventy-six patients were treated with seed implantation alone, whereas 24 patients were treated with a combination of brachytherapy and external beam radiotherapy. The minimal percentage of the dose received by 90% of the prostate gland (%D90), the percentage prostate volume receiving 100% of the prescribed minimal peripheral dose (V100), and the operation time were compared among every 10 consecutive patients. RESULTS: The means of %D90 and V100 were 109.6% and 93.4%, respectively. When compared with the first 10 patients, both D90 and V100 showed significant improvement in the following 10 consecutive patients. Similarly, the mean operation time decreased significantly according to the accumulated number of patients. CONCLUSIONS: Our initial experience with the first 100 cases suggests that LDR-brachytherapy needs accumulation of many more patients to obtain high-quality post-implant dosimetric outcomes.

Anti-tumor effects of liposome-encapsulated titanium dioxide in nude mice.

Anatase particles of titanium dioxide (TiO2) absorb ultraviolet (UV) light which is shorter than 415 nm. Photoexcited TiO2, a strong oxidizer, is expected to inhibit malignant cell growth. Liposomes accelerate endophagocytosis to the cytoplasm of encapsulated materials. In this study, we examined anti-tumor effects of TiO2 and liposome-encapsulated TiO2 (LT) with UVA irradiation by an air pouch cancer model using NBT-II bladder cancer cells, which simulates bladder cancer. Injection of TiO2 or LT into the air pouch was followed by UVA irradiation via the opened pouch. Tumors of TiO2 + UVA and LT + UVA groups showed more pronounced necrotic areas, apoptotic indices, nitrotyrosine formation, tumor growth inhibition and increased survival compared with control groups. Especially the LT + UVA group showed more remarkable anti-tumoral effects than the TiO2 + UVA group, which was associated with higher TiO2 incorporation. These findings suggest that LT might be more effective than noncoated TiO2 in the treatment of bladder cancer.

Prostatic volume and volume-adjusted prostate-specific antigen as predictive parameters for T1c prostate cancer.

We examined the usefulness of the volume-adjusted prostate-specific antigen (PSA) parameters for prediction of T1c prostate cancer on 210 patients who had abnormal PSA levels but no abnormal findings in digital transrectal examination (DRE) or transrectal ultrasonography (TRUS). PSA, prostate volume (PV), transition zone volume (TZV), PSAD (PSA/PV) and PSATZD (PSA/TZV) were assessed with the receiver operating characteristic (ROC) curve and the area under the curve (AUC). Simple and stepwise logistic regression models were used to calculate the odds ratios of these parameters. Fifty-three (25.2%) of all 210 patients and 31 (19.9%) of 156 patients with intermediate PSA levels had biopsy-proved prostate cancer. The ROC curves of all patients revealed that PSA, PV, TZV, PSAD and PSATZD had significant predictive values, while AUCs of PV, PSAD and PSATZD had significant predictive values as compared to that of PSA. In the patients with intermediate PSA levels, the ROC curves revealed that PV, TZV, PSAD and PSATZD had significant predictive values, but there were no significant differences in AUCs among these parameters. The stepwise logistic regression analysis showed that PV and PSATZD were significant predictive parameters in all patients and that PSATZD was the only significant predictive parameter in the patients with intermediate PSA levels. In conclusion, not only PSAD and PSATZD but also PV and TZV had significant predictive values in discriminating prostate cancer. However, the multivariate analysis showed that PSATZD had the strongest predictive value in all patients and in those with intermediate PSA levels.

[Initial conservative treatment for grade 3 Ta-1 superficial bladder cancer].

We retrospectively investigated the therapeutic outcomes of our series of 7 Ta and 62 T1 bladder cancers with grade 3 (G3) malignancy in 61 men and 8 women having a mean age of 66.2 years. Following transurethral resection of bladder tumor (TURBT), 35 and 6 patients received intravesical instillations of bacillus Calmette-Guerin (BCG) and anthracycline-derivants, respectively, whereas 15 received no adjuvant therapy. Five and 2 patients received systemic and local chemotherapy with irradiation, respectively, and six underwent radical cystectomy for invasive potential. The 5-year nonrecurrence, progression-free, and overall (cancer-specific) survival rates were 66, 82%, and 76 (88%), respectively, after a median follow-up of 52 months. The 5-year non-recurrence rates were 24% in non-adjuvant, 85% in BCG, 0% in anthracycline-derivants, 65% in systemic and local chemoradiation therapy, and 68% in cystectomy. The 5-year progression-free and overall (cancer-specific) survival rates of the patients treated with BCG instillation were 91% and 94 (100)%. There were no significant differences in the 5-year non-recurrence and progression-free rates between 12 patients with carcinoma in situ (CIS) and 23 patients without CIS. Complete TUR of all visible tumors and a reliable histopathological diagnosis of appropriate specimens bearing the muscle layer are mandatory for assessment of recurrence. G3 Ta-1 bladder cancers and CIS showed a high risk of recurrence, and required aggressive treatment. Since BCG therapy following TURBT significantly reduced the risk of recurrence and progression, adjuvant BCG therapy is considered to be the most promising initial conservative treatment for G3 Ta-1 bladder cancers.

Heme oxygenase-1 accelerates protumoral effects of nitric oxide in cancer cells.

We examined the biological effects of nitric oxide (NO) and its mediator, heme oxygenase-1 (HO-1), in cancer. Urogenital cancer cell lines, SKRC, T24 and DU145, were treated with various concentrations of sodium nitroprusside (SNP), a NO donor. The medium nitrite concentration was exponentially increased according to the concentration of SNP. Cell growth inhibition by NO was observed only at high nitrite concentrations (>20 microM) in DU145 and T24 cells. Nitrite did not inhibit the growth of SKRC cells at any of the concentrations used. Doxorubicin (DXR) inhibited cell growth in the three cell lines, whereas growth inhibition recovered in the presence of <10 microM nitrite. The recovery of DXR-induced growth inhibition was closely associated with an increase in Bcl-2 in the presence of <10 microM nitrite. Vascular endothelial growth factor (VEGF) secretion was also increased in the presence of <10 and <20 microM nitrite, respectively, in DU145 and SKRC or T24 cells. The expression of HO-1 was associated with sensitivity to NO-induced growth inhibition at constitutive levels, and was induced by SNP treatment. HO-1 inhibition by HO-1 antisense S-oligodeoxynucleotide treatment increased NO-induced growth inhibition, and decreased Bcl-2 expression or VEGF secretion in the three cell lines. These findings suggest that the NO/HO-1 system has protumoral effects.

[A case of retroperitoneal bronchogenic cyst].

A 59-year-old hypertensive man was referred to our hospital with a retroperitoneal cystic tumor, measuring 6 cm in diameter that was detected by an ultrasound examination during routine check-up 2 years before coming to our department. During the 2-year follow-up, the cystic tumor gradually increased in size. The patient also became hypertensive with slightly elevated urine levels of noradrenaline and dopamine, while the plasma catecholamines and their metabolites in the urine were within the normal range. Computed tomographic scanning and magnetic resonance imaging revealed a dumbbell-shaped retroperitoneal cyst with dense fluid, measuring 7 x 3.5 x 3 cm in diameter, in the left supra-adrenal and sub-diaphragmatic regions. He underwent extirpation of the cystic tumor with suspicion of adrenal endocrine cystic tumor. The histopathological diagnosis was a bronchogenic cyst, which is an extremely rare developmental anomaly in the retroperitoneal space. We herein report this rare case of retroperitoneal bronchogenic cyst and present a brief review of the previously reported 30 Japanese cases.

The impact of radical prostatectomy on patient well-being: a prospective urodynamic study focused on detrusor function.

Prostate cancer is common in aged men and radical prostatectomy is established as a therapeutic measure. However, to date there is little information about its impact on voiding function. We conducted a prospective clinical study to elucidate the impact of radical prostatectomy on voiding function in 17 patients with prostate cancer, by urological evaluation including filling and voiding cystometry (pressure flow study). The patients who were estimated as having weak detrusor function including very weak detrusor function at 3 months postoperatively had significantly more frequent urinary incontinence compared with the others (p < 0.05). Of 8 patients who showed urinary incontinence for more than 3 months, 7 (88%) patients developed weak detrusor function at 3 months after operation, but 4 of them were estimated as having normal detrusor function preoperatively. These patients revealed reduced maximum flow rate and significantly increased quality of life score compared with the other patients (p < 0.05). An initially reduced bladder compliance disclosed a tendency to a rapid return to normal with time after surgery. Detrusor overactivity itself and neoadjuvant antiandrogen therapy were not related to prolonged postoperative urinary incontinence. The present study indicates that caution is required when administering medication that could potentially affect detrusor function, regardless of the type of preoperative detrusor function, in patients with persistent urinary incontinence or a reduced urinary stream. Particular emphasis is laid on the importance of urodynamic assessment of post-prostatectomy detrusor function and appropriate management modalities based on the results.

Amphoterin induction in prostatic stromal cells by androgen deprivation is associated with metastatic prostate cancer.

Amphoterin, the major product of the high mobility group-1 gene, is a ligand associated with cancer invasion and metastasis through activation of the receptor for advanced glycation end products (RAGE). Expression of amphoterin and RAGE was examined in prostatectomy specimens from 40 patients with pT3 prostate cancer (18 non-metastatic and 22 metastatic) preoperatively treated with lutenizing hormone-releasing hormone (LH-RH) agonist. Amphoterin expression was detected in tumor cells of 6 (27%) metastatic and 0 non-metastatic cases (p<0.0001). Amphoterin was also detected in prostatic stromal cells of 14 (63%) metastatic cases and 2 (11%) non-metastatic cases (p=0.0010). RAGE production was detected in cancer cells of 16 (73%) metastatic and 6 (33%) non-metastatic cases (p=0.0244). A total of 2 (22%) non-metastatic and 16 (73%) metastatic cases showed co-expression of amphoterin and RAGE in tumor cells or in tumor cells and stromal cells (p=0.0001). The in vitro invasive capacity of PC-3, a prostatic cancer cell line that co-expressed amphoterin and RAGE, was suppressed by treatment with amphoterin antisense S-oligodeoxynucleotide (ODN). Primary cultured human prostatic stromal cells secreted no amphoterin; however, amphoterin secretion was induced by androgen deprivation. The conditioned medium of human prostatic stromal cells deprived of androgen recovered the in vitro invasive capacity of PC-3 cells suppressed by amphoterin antisense S-ODN. These results suggest that androgen deprivation provides a paracrine interaction between cancer and stromal cells through the RAGE-amphoterin system in advanced prostate cancer.

[Primary epididymal leiomyoma: a case report].

A 53-year-old man came to our hospital complaining of painful induration in the left scrotum. It was difficult to determine by manual palpation whether the induration was derived from the testis or paratesticular tissues including epididymis. Computerized tomographic scanning and ultrasonography revealed a left paratesticular mass, 3 cm in diameter, with unclear margin of the atrophic testis, which was suspected as originating from the epididymis. Although tumor extirpation was intended, he underwent inguinal orchiectomy due to strong adhesion of the mass to the ipsilateral atrophic testis. The tumor was opalescent, gum elastic, and solid, measuring 5 x 3 x 2 cm in size. Histopathological examination revealed a primary leiomyoma of the epididymis. The details of this rare case of primary epididymal leiomyoma that originated from the epididymal tail are reported herein.

[A case of inflammatory myofibroblastic tumor of the retroperitoneum].

Here we report a rare case of inflammatory myofibroblastic tumor of the retroperitoneal space. A 46-year-old woman had had microscopic hematuria for 5 years. Ultrasonographic examination for screening revealed two solid tumors adjacent to the right kidney. These tumors were suspected to be malignant fibrous histiocytoma or liposarcoma by computed tomography and magnetic resonance imaging. She underwent resection of these retroperitoneal tumors and additional right nephrectomy because these tumors were adhered to the kidney and liposarcoma was highly suspected on frozen sections. Histopathologic examination finally revealed that the tumors were inflammatory myofibroblastic tumor arising within Gerota's fasia. She has been followed up for 9 months without any evidence of local recurrence.

Differential effects between amphoterin and advanced glycation end products on colon cancer cells.

Amphoterin is 1 ligand of the receptor for advanced glycation end products (RAGE). We studied expression of amphoterin and RAGE mRNA and proteins in colorectal carcinoma cells and investigated their associations with the invasive activities of cells exposed to advanced glycation end products (AGE). Expression of RAGE and amphoterin was examined in 4 colorectal carcinoma cell lines. All cell lines expressed both RAGE and amphoterin. The effects of RAGE and amphoterin on cell growth (MTT assay), migration (wound healing assay) and invasion (in vitro invasion assay) were tested by treatment of cells with RAGE and amphoterin antisense S-oligodeoxynucleotides (ODNs). Cell growth, migration and invasion were inhibited significantly in Colo320 and WiDr carcinoma cells treated with RAGE and amphoterin antisense S-ODNs compared with sense-treated cells. Differences in ligand activity between amphoterin and AGE were examined with AGE-bovine serum albumin (BSA). AGE-BSA decreased cell growth, migration and invasion of amphoterin antisense S-ODN-treated Colo320 and WiDr cells compared with those of cells treated with Colo320 conditioned medium. Phosphorylation of extracellular signal-regulated kinase-1/2, Rac1 and AKT and production of matrix metalloproteinase 9 were increased to a greater degree by amphoterin than by AGE-BSA. In contrast, production of inducible nitric oxide synthase and nuclear factor-kappaBp65 were increased to a greater degree by AGE-BSA than by amphoterin.

A role of histone H4 hypoacetylation in vascular endothelial growth factor expression in colon mucosa adjacent to implanted cancer in athymic mice cecum.

Expression of angiogenic factors is upregulated in hyperplastic mucosa adjacent to colon cancer, and this upregulation is closely associated with cancer growth and metastasis. We investigated the role of histone acetylation in vascular endothelial growth factor (VEGF) expression in hyperplastic mucosa adjacent to orthotopic colon cancer in mice. In the hyperplastic mucosa adjacent to KM12SM tumor in the cecum of athymic mice, VEGF upregulation was associated with hypoxia-inducible factor (HIF)-1alpha induction. The hyperplastic mucosa also showed hypoacetylation of histone H4 and reduction of both p53 and von Hippel-Lindau (VHL) proteins. To examine the effects of growth factors and cytokines on histone acetylation and levels of p53, VHL and HIF-1alpha, the rat intestinal epithelial cell line IEC6 was treated with epidermal growth factor (EGF) and interleukin (IL)-15 for 35 days. Acetylated histone H4, p53 protein and ubiquitinated protein levels were reduced, whereas HIF-1alpha production was upregulated in EGF- and IL-15-treated IEC6 cells. These findings suggest that EGF- or IL-15-induced histone H4 hypoacetylation is associated with repression of p53 and VHL genes in intestinal epithelial cells. The subsequent suppression of protein ubiquitination leads to upregulation of VEGF production by HIF-1alpha retention.