Background/Aims: Several studies have assessed the effect of cool temperature on colonic peristalsis. Transient receptor potential melastatin 8 (TRPM8) is a temperature-sensitive ion channel activated by mild cooling expressed in the colon. We examined the antispasmodic effect of cool temperature on colonic peristalsis in a prospective, randomized, single-blind trial and based on the video imaging and intraluminal pressure of the proximal colon in rats and TRPM8-deficient mice. Methods: In the clinical trial, we randomly assigned a total of 94 patients scheduled to undergo colonoscopy to 2 groups: the mildly cool water (n = 47) and control (n = 47) groups. We used 20 mL of 15°C water for the mildly cool water. The primary outcome was the proportion of subjects with improved peristalsis after treatment. In the rodent proximal colon, we evaluated the intraluminal pressure and performed video imaging of the rodent proximal colon with cool water administration into the colonic lumen. Clinical trial registry website (Trial No. UMIN-CTR; UMIN000030725). Results: In the randomized controlled trial, after treatment, the proportion of subjects with no peristalsis with cool water was significantly higher than that in the placebo group (44.7% vs 23.4%; P < 0.05). In the rodent colon model, cool temperature water was associated with a significant decrease in colonic peristalsis through its suppression of the ratio of peak frequency (P < 0.05). Cool temperaturetreated TRPM8-deficient mice did not show a reduction in colonic peristalsis compared with wild-type mice. Conclusion For the first time, this study demonstrates that cool temperature-dependent suppression of colonic peristalsis may be associated with TRPM8 activation.

Background: Currently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP).We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously. Materials and Methods: Healthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gramstained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared. Results: Measuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood. Conclusion Calculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate.

Background: Currently, supplementary serological testing for β-D glucan (BDG) is often selected to diagnose deep mycosis in care covered by the health insurance in Japan. The Wako method used by our center has low sensitivity, and different studies have used different cut-off values due to factors that cause false positives and false negatives. One possible cause of false negatives is the use of platelet-rich plasma (PRP) as the sample material. Because phagocytic white blood cells (WBC) are precipitated by centrifugation and only plasma is measured, it seems unlikely that the actual amount of BDG is being measured when using PRP. Further, a frequent cause of false positives is contamination from blood products and gauze containing BDG. To resolve these issues, the blood cell separator, hydroxyethyl starch, is used to precipitate only the red blood cells to obtain leukocyte-rich plasma (LRP).We hypothesized that it might be possible to improve the diagnostic rate of deep mycosis by measuring the BDG content of plasma containing WBC and fungal components and by comparing the BDG content of PRP and LRP measured simultaneously. Materials and Methods: Healthy human blood, albumin-added blood, wrung-out gauze fluid-added blood, and fungal solution-added blood were prepared, and PRP and LRP were prepared using hydroxyethyl starch. The BDG content of each sample was measured using the Wako method and compared. In addition, PRP and LRP of fungal-added blood were Gramstained and examined under a microscope, and the number of WBCs and phagocytosed fungi was counted visually and compared. Results: Measuring the BDG content of LRP confirmed that there were no false positives with LRP, and in vitro experiments comparing albumin-added false-positive blood to fungal-added blood showed significant differences between PRP and LRP only in the fungal-added blood. Conclusion Calculating the BDG-ratio (LRP/PRP) by measuring both LRP and PRP may eliminate false positives and false negatives of true deep mycosis and improve the diagnostic rate.

The agenesis of the gonads and adrenal gland in revealed by knockout mouse studies strongly suggested a crucial role for Nr5a1 (SF-1 or Ad4BP) in organ development. In relation to these striking phenotypes, NR5A1/Nr5a1 has the potential to reprogram cells to steroidogenic cells, endow pluripotency, and regulate cell proliferation. However, due to limited knowledge regarding NR5A1 target genes, the mechanism by which NR5A1/Nr5a1 regulates these fundamental processes has remained unknown. Recently, newlyestablished technologies have enabled the identification of NR5A1 target genes related to multiple metabolic processes, as well as the aforementioned biological processes. Considering that active cellular processes are expected to be accompanied by active metabolism, NR5A1 may act as a key factor for processes such as cell differentiation, proliferation, and survival by coordinating these processes with cellular metabolism. A complete and definite picture of the cellular processes coordinated by NR5A1/Nr5a1 could be depicted by accumulating evidence of the potential target genes through whole genome studies.

A laser endoscopy system was developed in 2012. The system allows blue laser imaging (BLI), BLI-bright, and linked color imaging (LCI) to be performed as modes of narrow-band light observation; these modes have been reported to be useful for tumor detection and characterization. Furthermore, an innovative endoscopy system using four-light emitting diode (LED) multilight technology was released in 2016 to 2017 in some areas in which laser endoscopes have not been approved for use, including the United States and Europe. This system enables blue light imaging (this is also known as BLI) and LCI with an LED light source instead of a laser light source. Several reports have shown that these modes have improved tumor detection. In this paper, we review the efficacy of BLI and LCI with laser and LED endoscopes in tumor detection and characterization.
Colorectal Neoplasms ; Endoscopes ; Endoscopy ; Europe ; United States

BACKGROUND: To develop human space exploration, it is necessary to study the effects of an isolated and confined environment, as well as a microgravity environment, on cerebral circulation. However, no studies on cerebral circulation in an isolated and confined environment have been reported. Therefore, we investigated the effects of a 14-day period of confinement in an isolated environment on dynamic cerebral autoregulation. METHODS: We participated in an isolation and confinement experiment conducted by the Japan Aerospace Exploration Agency in 2016. Eight healthy males were isolated and confined in a facility for 14 days. Data were collected on the days immediately before and after confinement. Arterial blood pressure waveforms were obtained using a finger blood pressure monitor, and cerebral blood flow velocity waveforms in the middle cerebral artery were obtained using transcranial Doppler ultrasonography for 6 min during quiet rest in a supine position. Dynamic cerebral autoregulation was evaluated by transfer function analysis between spontaneous variability of beat-to-beat mean arterial blood pressure and mean cerebral blood flow velocity. RESULTS: Transfer function gain in the low- and high-frequency ranges increased significantly (0.54 ± 0.07 to 0.69 ± 0.09 cm/s/mmHg and 0.80 ± 0.05 to 0.92 ± 0.09 cm/s/mmHg, respectively) after the confinement. CONCLUSION: The increases observed in transfer function gain may be interpreted as indicating less suppressive capability against transmission from arterial blood pressure oscillation to cerebral blood flow velocity fluctuation. These results suggest that confinement in an isolated environment for 14 days may impair dynamic cerebral autoregulation. TRIAL REGISTRATION UMIN000020703 , Registered 2016/01/22.
Adult ; Cerebrovascular Circulation ; physiology ; Confined Spaces ; Homeostasis ; physiology ; Humans ; Male ; Middle Aged ; Space Flight ; Young Adult

OBJECTIVE: Carcinosarcoma of the uterine corpus has a poor prognosis. Although pathological necrosis is a prognostic factor of endometrial cancer, the clinicopathological influences of an unenhanced region observed on magnetic resonance imaging (MRI) are inconclusive. The aim of our study was to determine the clinicobiological impact of the presence of an unenhanced region on MRI, which can represent necrosis, in uterine carcinosarcoma. METHODS: The clinicopathological factors of 29 patients diagnosed with uterine carcinosarcoma were assessed retrospectively. The percentage of the tumor that was unenhanced on MRI was determined. The clinicopathological factors related to the unenhanced regions were evaluated. The prognostic significance was assessed using the Kaplan-Meier method and Cox regression model. RESULTS: Although the presence of pathological necrosis was not a poor prognostic factor (p=0.704), unenhanced regions on MRI correlated with poor prognosis when the unenhanced regions in the tumor accounted for more than 10% of the total tumor (p=0.019). The percentage of unenhanced regions was positively correlated with stage (p=0.028; r=0.4691) and related to tumor size (p=0.086; r=0.3749). The Cox regression analysis indicated that the presence of lymph node (LN) metastasis and more than 10% of the tumor being unenhanced on MRI were prognostic factors of overall survival in the univariate analyses (p=0.018 and p=0.047, respectively). CONCLUSION: The unenhanced region on MRI, which represents pathological necrosis, reflects tumor progression, and semi-quantification of the region is useful to predict the prognosis in patients with uterine carcinosarcoma.
Carcinosarcoma* ; Endometrial Neoplasms ; Female ; Humans ; Lymph Nodes ; Magnetic Resonance Imaging* ; Methods ; Necrosis ; Neoplasm Metastasis ; Prognosis ; Retrospective Studies ; Uterine Neoplasms

Objectives: First steps to promote the proper use of medicines in remote islands and rural areas are as follows: (1) recognition of the profession of “pharmacist” from secondary-remote-island residents who do not have a pharmacy or drugstore or the opportunity for pharmacist contact and (2) an understanding by remote-island residents of the advantages of having a “family pharmacist.”
Methods: Repeated “medicine information and consultation sessions” for secondary-remote-island residents of Japan’s Nagasaki Prefecture were held.  Residents were then surveyed for changes in awareness of or demand for pharmacists and the nature of such changes.
Results: Before the information sessions, 29.7% of residents did not recognize the profession of pharmacy, but the extent of their recognition increased after information sessions were concluded.  They were asked “Who explains medicines in a way that is easy to understand ?”; more than half responded “doctors” before the information session, but after information sessions were concluded, those who said “pharmacists” increased.
Conclusion: Conducting “medicine information and consultation sessions” for residents of secondary-remote islands and rural areas enabled them to understand the profession of pharmacy.  The initiatives in the present study are first steps toward promoting proper use of medicines by residents of remote islands and rural areas who use “family pharmacies/pharmacists.”

BACKGROUND/AIMS: There have been few studies on the efficacy of proton pump inhibitors and the doses required to treat dyspeptic symptoms observed in clinical practice. The aim of this study was to compare the efficacy of different doses of omeprazole and different administration methods in Helicobacter pylori-negative, dyspeptic patients. METHODS: Patients with chronic upper abdominal symptoms within the previous 3 months were randomly divided into three groups: a daily, omeprazole 20 mg treatment group (OPZ20, n=61); a daily, omeprazole 10 mg treatment group (OPZ10, n=72); and an on-demand omeprazole 20 mg treatment group (on-demand, n=62). After 4 weeks of administration of the drug, symptom improvement rates were evaluated based on the Overall Global Severity score. RESULTS: The rates of symptom improvement after 4 weeks of treatment were 65.6% (40/61) in the OPZ20 group, 47.2% (34/72) in the OPZ10 group, and 50.0% (31/62) in the on-demand group. The OPZ20 group exhibited a significantly higher improvement rate (p=0.034) than the OPZ10 group. The OPZ20 group had significant improvements in regurgitation, postprandial fullness, vomiting, and bloating compared with the OPZ10 group. CONCLUSIONS: Daily treatment with 20 mg of omeprazole was efficient in treating upper abdominal symptoms. Trial registration: ClinicalTrials.gov, number UMIN000002621.
Dyspepsia ; Helicobacter ; Humans ; Japan ; Omeprazole ; Primary Health Care ; Proton Pump Inhibitors ; Proton Pumps ; Protons ; Vomiting

BACKGROUNDIn an earlier study, we identified a locus for Moyamoya disease (MMD) on 17q25.3.

METHODSLinkage analysis and fine mapping were conducted for two new families in additional to the previously studied 15 families. Three genes, CARD14, Raptor, and AATK, were selected based on key words, namely, "inflammation", "apoptosis", "proliferation", and "vascular system", for further sequencing. A segregation analysis of 34 pedigrees was performed, followed by a case-control study in Japanese (90 cases vs. 384 controls), Korean (41 cases vs. 223 controls), Chinese (23 cases and 100 controls), and Caucasian (25 cases and 164 controls) populations.

RESULTSLinkage analysis increased the LOD score from 8.07 to 9.67 on 17q25.3. Fine mapping narrowed the linkage signal to a 2.1-Mb region. Sequencing revealed that only one newly identified polymorphism, ss161110142, which was located at position -1480 from the transcription site of the Raptor gene, was common to all four unrelated sequenced familial affected individuals. ss161110142 was then shown to segregate in the 34 pedigrees studied, resulting in a two-point LOD score of 14.2 (P = 3.89 × 10(-8)). Its penetrance was estimated to be 74.0%. Among the Asian populations tested (Japanese, Korean, and Chinese), the rare allele was much more frequent in cases (26, 33, and 4%, respectively) than in controls (1, 1, and 0%, respectively) and was associated with an increased odds ratio of 52.2 (95% confidence interval 27.2-100.2) (P = 2.5 × 10(-49)). This allele was, however, not detected in the Caucasian samples. Its population attributable risk was estimated to be 49% in the Japanese population, 66% in the Korean population, and 9% in the Chinese population.

CONCLUSIONss161110142 may confer susceptibility to MMD among East Asian populations.

ELECTRONIC SUPPLEMENTARY MATERIALThe online version of this article (doi:10.1007/s12199-009-0116-7) contains supplementary material, which is available to authorized users.