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Late-onset hypogonadism, a male age-related syndrome characterized by a decline in testosterone production in the testes, is commonly treated with testosterone replacement therapy, which has adverse side effects. Therefore, an alternative treatment is highly sought. Supplementation of a high dosage of biotin, a water-soluble vitamin that functions as a coenzyme for carboxylases involved in carbohydrate, lipid, and amino acid metabolism, has been shown to influence testis functions. However, the involvement of biotin in testis steroidogenesis has not been well clarified. In this study, we examined the effect of biotin on testosterone levels in mice and testis-derived cells. In mice, intraperitoneal treatment with biotin (1.5 mg/kg body weight) enhanced testosterone levels in the serum and testes, without elevating serum levels of pituitary luteinizing hormone. To investigate the mechanism in which biotin increased the testosterone level, mice testis-derived I-10 cells were used. The cells treated with biotin increased testosterone production in a dose- and time-dependent manner. Biotin treatment elevated intracellular cyclic adenosine monophosphate levels via adenylate cyclase activation, followed by the activation of protein kinase A and testosterone production. These results suggest that biotin may have the potential to improve age-related male syndromes associated with declining testosterone production.

This study investigated the safety and efficacy of orthokeratology in myopic children in Japan. Prospective clinical trial. This study enrolled myopic children aged 6–16 years with a spherical equivalent of −1.00 D to −4.00 D and astigmatism of −1.5 D or lower, whose parents could manage contact lens use and could provide written informed consent. The children were treated with orthokeratology lenses (BREATH-O CORRECT R, Universal View Co., Ltd.) for 3 years. Slit-lamp findings, visual acuity, intraocular pressure, subjective refraction, corneal topography, corneal endothelial cell density, corneal thickness, and axial length were regularly assessed. This study included 96 eyes of 48 patients (average age, 10.7 ± 2.08 years). The average baseline spherical equivalent was −2.46 ± 0.97 D. The average baseline uncorrected visual acuity was 0.74 ± 0.32 logMAR, with significant improvement to −0.08 ± 0.18 logMAR at 4 weeks and 0.02 ± 0.21 logMAR at 3 years (both p

AIM To investigate intrapartum fetal heart rate (FHR) patterns in women with chorioamnionitis at or beyond 34 weeks of gestation in relation to neonatal outcome and to compare clinical and subclinical chorioamnionitis. METHODS A retrospective questionnaire survey on deliveries during 2015 was conducted by the Perinatology Committee of the Japan Society of Obstetrics and Gynecology from 2016 to 2018. A total of 498 singleton births complicated by chorioamnionitis delivered at ≥34 weeks of gestation without major congenital malformations were included. The subjects were divided into clinical and subclinical chorioamnionitis groups based on Lencki's criteria. Poor perinatal outcome was defined as death or brain damage. We analyzed clinical features, FHR patterns in the last 2 h before delivery, gestational age, birthweight, Apgar score, umbilical arterial blood gas analysis, and infant's outcome. RESULTS Incidence of chorioamnionitis at ≥34 weeks of gestation was 0.59% (522/87827). Clinical and subclinical chorioamnionitis comprised 240 and 258 cases, respectively. Abnormal FHR patterns (late deceleration or decreased baseline variability) were significantly associated with poor perinatal outcome. Combined late deceleration and decreased variability showed low positive predictive value (12.8%) and high negative predictive value (99.5%), and was significantly associated with long-term poor outcome in clinical chorioamnionitis only (odds ratio: 29.4, p

An ovarian malignant melanoma sometimes occurs from ovarian teratoma. Ovarian metastatic malignant melanoma is extremely rare. We describe a patient in whom vulvar melanoma (previously resected) metastasized to the ovary, making ovarian metastatic malignant melanoma. A 43-year-old Japanese woman was referred to us because of left ovarian tumor. She had undergone resection for malignant melanoma on the right labia minora with inguinal lymph node metastasis (pT1bN1aM0, stage IIIA, FIGO 2008). Eighteen months after this surgery, CT scans revealed left ovarian tumor and swelled pelvic lymph nodes, with a pelvic examination disclosing a left adnexal solid mass, with normal serum CA125 level (21.7 U/mL). Laparotomy revealed a left solid ovarian tumor measuring 4 cm, which was covered with a smooth grayish capsule. The right ovary, uterus, and pelvic cavity appeared normal. Upon sectioning during the surgery, the cross-sectional surface of the left ovary revealed a dark brown solid tumor. Following an intra-operative frozen-section diagnosis as metastatic melanoma, total hysterectomy with bilateral salpingo-oophorectomy and pelvic lymph dissection was performed. Histological examination confirmed the diagnosis as malignant melanoma metastasis to the left ovary and the obturator lymph node: the same laterality (left) as the primary site. The tumor was entirely composed of malignant melanoma cells with no evidence of teratoma. Combined chemotherapy with dabrafenib mesylate and trametinib was planned based on the positive BRAF mutations. This case highlights the importance that physicians should have high index of suspicion for the occurrence of ovarian melanoma metastasis after melanoma surgery. We also made extensive literature review on this issue, of which description may contribute to better understanding of this condition.

Neurologic complications are seen often after the surgery of the thoracic aorta that uses selective antegrade cerebral perfusion. The objective of this study was to evaluate the impact of atherosclerotic risk factors on neurologic complications in patients who underwent surgery to the thoracic aorta using SCP. Data were collected retrospectively on 94 patients who underwent elective ascending aorta/aortic arch replacement. Concomitant procedures were performed as needed. All patients had magnetic resonance imaging (MRI), angiography (MRA) and carotid ultrasound before surgery. Individual cognitive status was measured using four neuropsychological tests before surgery and 7 days after extubation. We compared perioperative factors for risk factors associated with postoperative stroke and postoperative cognitive decline (POCD). 11 patients had strokes after surgery. Operation and extracorporeal circulation times were significantly longer in patients with stroke than those without stroke. Coronary artery disease and SCP time > 150 min were independently associated with postoperative stroke. Of the 83 patients without postoperative stroke, 20 suffered POCD. POCD patients had a significantly higher rate of heterogeneous carotid plaque, and operation time was significant longer in patients with POCD than those without POCD. Independent predictors of POCD were concomitant CABG, heterogeneous carotid plaque, history of cerebrovascular disease and operation time > 450 min. We found that prolonged SCP time and coronary artery disease increased the risk of postoperative stroke. Heterogeneous carotid plaque, history of cerebrovascular disease, concomitant CABG and prolonged operation time were further significant predictors of POCD.

Purpose: To study the changes of the visual function and ocular and systemic symptoms following blepharoptosis surgery.Methods: Seventy-eight involutional blepharoptosis patients (72.1 ± 6.4 years) underwent levator advancement procedure. Before and at 2 months after the surgery, OPD-Scan III (Nidek) was used to measure corneal astigmatism, total higher order aberrations (HOAs), and area ratio (AR), an index of the objective contrast sensitivity. FVA-100 (Nidek) was used to determine the functional visual acuity (FVA) and visual maintenance ratio (VMR). The ocular and systemic symptoms were also determined by a questionnaire using visual analogue scale (VAS) scores.Results: Before surgery, the corneal astigmatism, HOAs, AR, FVA, and VMR were 1.56 ± 0.52 diopters (D), 0.23 ± 0.24 µm, 14.8 ± 4.2%, 0.68 ± 0.32 logMAR units and 0.76 ± 0.06, respectively. After surgery, these values were 1.29 ± 0.41 D, 0.19 ± 0.21 µm, 18.6 ± 3.4%, 0.31 ± 0.18 logMAR units and 0.88 ± 0.03, respectively. Corneal astigmatism and HOAs were significantly reduced after surgery (P=0.007 and P=0.023, paired t test, respectively), and AR, FVA and VMR were significantly improved after surgery (P=0.033, P=0.012 and P=0.016, respectively). The VAS scores significantly improved after surgery, and this improvement was positively and significantly correlated with the increase of the AR (r=0.421, P=0.003) and the VMR (r=0.497, P =0.005).Conclusions: Blepharoptosis surgery is visual functionally beneficial and can help to reduce the ocular and systemic symptoms.

At Numanohama Marsh on the rocky Sanriku coast in northeast Japan, we identified 17 sand layers with sedimentary structures characteristic of event deposits (i.e., a sharp erosional contact with the underlying unit, a normal and/or inverse grading structure, parallel/cross lamination, mud clasts, and/or a thin mud layer). Abundant marine nannofossils, coccoliths, and the small catchment area in the narrow valley suggest that these event layers were likely formed by inundations during tsunamis or storms. Among the 17 sand layers, nine contained gravels derived from the beach, riverbed, or slope areas. Six event layers contained all three of these gravels, suggesting a strong inflow current that transported round pebbles from the beach, erosion of wall rock in the valley during the inflow and outflow phases, and a backwash current that caused sub-angular riverbed gravel to accumulate in lowland areas. These six layers were traced up to 490 m inland from the coastline (present elevation: 7 m above mean sea level) and were several cm thick at almost every survey point. We concluded that these six event layers are tsunami deposits, and dating results revealed that they correlate with the 2011 Tohoku-oki earthquake; the 1933 and 1896 Sanriku-oki earthquakes; any of the 1763 Aomori-oki, 1793 Miyagi-oki, and 1856 Aomori-oki earthquakes; the 1611 Tohoku-oki earthquake; and the 869 Tohoku-oki (Jogan) earthquake. In addition, changes in the sedimentary environment inferred from diatom assemblages were well correlated with the deposition of three of the event layers. Two historical earthquakes — the 1454 and 1611 Tohoku-oki earthquakes — have been previously suggested as being the immediate predecessors of the 2011 Tohoku-oki earthquake, and our dating results favor the 1611 earthquake. Although the source region of the 869 Tohoku-oki (Jogan) earthquake has been estimated to have been off the Fukushima and Miyagi prefectures, our results suggest that the source region extended further north along the Japan Trench.

AIM Diabetes mellitus (DM) is a major complication in pregnancy. Placental lesions with DM remain unclear and controversial. Recently, the terms of placental pathological findings, such as maternal and fetal vascular malperfusions (MVM and FVM, respectively) were introduced by the Amsterdam Placental Workshop Group Consensus Statement (APWGCS). FVM cases were classified as the partial obstruction type (global FVM) and the complete obstruction type (segmental FVM). The aim of this study was to clarify the pathological characteristics of the placenta with pregestational DM/gestational DM; GDM according to APWGCS. METHODS We studied the placentas of 182 DM women (27 pregestational DM and 155 GDM) and control placentas of 460 women without DM during 2011-2018. We excluded cases of intrauterine fetal death or multiple pregnancies. We reviewed microscopical findings including, MVM, FVM, chorioamnionitis with the slides according to the APWGCS. RESULTS Microscopically, the incidence of FVM was significantly higher in GDM patients than control (17% vs. 10%, p = 0.0138), but not significant in pregestational DM (11%, p = 0.7410). Segmental FVM (complete obstruction) was significantly more observed in GDM than control group (5% vs. 0.4%, p = 0.0013). Segmental FVM in GDM showed high incidence of light-for-dates infant (three of seven cases, 43%, p = 0.0288). In addition, several segmental FVM findings (villous stromal-vascular karyorrhexis and stem vessel occlusion) were frequently noted in 2 or 3 points positive of 75 g oral glucose tolerance test than 1 point positive GDM. CONCLUSION Our placental findings suggest disorder of carbohydrate metabolism might affect the fetal vascular damage, especially complete fetal vascular obstruction.

The pregnane X receptor (PXR) is the key regulator of our defense mechanism against foreign substances such as drugs, dietary nutrients, or environmental pollutants. Because of increased health consciousness, the use of dietary supplements has gradually increased, and most of them can activate PXR. Therefore, an analysis of the interaction between drugs and nutrients is important because altered levels of drug-metabolizing enzymes or transporters can remarkably affect the efficiency of a co-administered drug. In the present study, we analyzed the effect of vitamin K-mediated PXR activation on drug metabolism-related gene expression in intestine-derived LS180 cells via gene expression studies and western blotting analyses. We demonstrated that menaquinone 4 (MK-4), along with other vitamin Ks, including vitamin K1, has the potential to induce MDR1 and CYP3A4 gene expression. We showed that PXR knockdown reversed MK-4-mediated stimulation of these genes, indicating the involvement of PXR in this effect. In addition, we showed that the expression of MDR1 and CYP3A4 genes increased synergistically after 24 h of rifampicin and MK-4 co-treatment. Our study thus elucidates the importance of drug–nutrient interaction mediated via PXR.

We previously reported an orexigenic action of oral zinc administration in male Sprague-Dawley (SD) rats during an early stage of feeding with a zinc-deficient diet, without decreased zinc concentrations in tissues. The overall conclusion was that orally but not intraperitoneally administered zinc stimulates food intake in short-term zinc-deficient-diet fed rats. We here investigate the mechanism of the orexigenic action of zinc using GC-MS/MS-targeted metabolomic analysis in the rat hypothalamus. Four-week-old, male SD/Slc rats were used, and after 2 days of feeding with a zinc-deficient diet, 3 mg of ZnSO4 in 5 mL saline solution were administered to each rat either orally or intraperitoneally. Three hours after administration, the rats were sacrificed and the hypothalamus were excised and analyzed. We found that the oral administration group showed increased concentrations of 3-aminopropanoic acid (β-alanine), hypotaurine, dopamine, and biotin. In light of metabolomic analysis of these results, we indicate directions for further research.

The grain size distribution of a tsunami deposit may have a correlation with the tsunami inundation process, and further with the tsunami source characteristics. We test this hypothesis using thickness and grain size distribution data of the 2011 Tohoku tsunami deposit in Numanohama coast, Iwate Prefecture, Japan. Here, we build and validate a tsunami sediment transport model that can simulate deposit thickness and grain size distribution. Our numerical model has three layers: parent (bed), deposit (bed), and suspended load layers. The two bed-layers contain information about the grain size distribution. This numerical model can handle a wide range of grain sizes from 0.063 (4ϕ) to 5.657 mm (−2.5ϕ). The grain size distributions at 12 sample points along a 900 m transect from the beach, through a marsh, and up to the inundation limit, are used to validate the tsunami sediment transport model. We adopt a reference tsunami source model that can well reproduce the observed tsunami run-up heights ranging from 16 to 35 m along the steep valley during the 2011 tsunami. The simulated sand thickness distribution along the transect is consistent with the observed thickness ranging from 3 to 23 cm. The computed net erosion and deposition suggest that most of the sand deposit was originated from the near shore. The shapes of the simulated grain size distributions represented by their sorting, skewness, kurtosis, and mean at most of the sample sites are similar to the observations. The differences between the observed and simulated peak of grain size distributions are less than 1ϕ. To evaluate the sensitivity to the tsunami source model, we test five tsunami scenarios which are modified from the reference source model. While the tsunami scenario with 120% of the reference amplitude can also reproduce the thickness and grain size distribution, the scenarios with amplitudes smaller than 80% of the reference or with wave periods shorter than 50% of the reference source model underestimate the thickness and cannot reproduce the grain size distributions. Our simulation results suggest that it is possible to estimate tsunami wave amplitude and wave period from sediment deposit thickness and grain size distribution data.

We found seven event deposits during the past 3800 years in a total of 16 geological core samples from a coastal lowland in Fukushima Prefecture, about 12 km north of the Fukushima Daiichi Nuclear Power Station. The event deposits consisted of well-sorted and rounded fine to coarse sand with single normal grading structures, parallel laminae, mud drapes, rip-up clasts, and erosional basal contacts. They were distributed about 2 km inland from the current shoreline and commonly became thinner landward. The third and fifth sand layers were characterized by many climbing ripples and parallel and trough-cross bedding that were probably caused by storm surges or some other events during the period of absent beach ridges. The other deposits were characterized by sedimentological features common to tsunami deposits. The top layer appeared to have been deposited by the 2011 Tohoku tsunami, and the second layer might have been resulted from the AD 869 Jogan Tohoku tsunami. The other three tsunami deposits corresponded to tsunami events between the second and fourth centuries AD, the sixth and fourth centuries BC, and the twelfth and ninth centuries BC. The average recurrence interval of the paleo-tsunamis was estimated to be 560–950 years. These dates are mostly consistent with previous studies of the Sendai plain, suggesting that paleo-tsunamis that reached the Sendai plain also reached the coast of Fukushima Prefecture. However, no trace was found from an earthquake around the 15th century, which had been considered as a predecessor of the 2011 Tohoku earthquake (Mw 9.0) in the tsunami deposit surveys in Sendai plain.

A geological survey was conducted in a small valley along the Sanriku coast, and the grain compositions of both autochthonous gravels and the 2011 tsunami deposit from the Tohoku-oki earthquake were investigated to reveal the depositional form of the tsunami deposits on the ria-type coast. The features of autochthonous gravels in the beach, riverbed, and slope areas are characterized by a combination of their rock type and roundness. The roundness values of the beach and slope gravels are large (0.8–0.9) and small (0.1–0.2), respectively, regardless of rock type, and the riverbed gravels are typically granite rocks with an intermediate roundness (0.4–0.5). The 2011 tsunami deposits along the survey transect include the above autochthonous gravels and show several characteristic features, such as a sharp erosional contact with the underlying peaty soil, normal and/or inverse grading structures, mud sheets, and richness in gravels in the lower unit, while the thickness shows no systematic changes with the distance from the coast. The presence of slope gravels suggests high tsunami inundation and flux, which eroded bare rock and talus and transported them to the valley plain by backwash current. The mixture of beach and riverbed deposits implies the formation of both an upstream current from the beach, which transported beach pebbles inland, and a backwash current along the channel, which accumulated sub-angular riverbed gravels around the river mouth. The characteristics of the 2011 tsunami deposit on the Sanriku coast, where narrow valleys are surrounded by high cliffs with steep slopes, are significantly different from those of sandy tsunami deposits in Sendai Plain, where a flat plain develops within several kilometers of the coastline. The differences among sedimentary facies are affected by the topography and autochthonous deposits.

This study examined factors related to sexual assault among early adolescents in Japan. During a 6-month period, an anonymous questionnaire survey was distributed to 1,246 students ages 13– 15 years at eight junior high schools. Consent to participation in this study was obtained from a total of 1,125 (90.3%) students. It was found that the prevalence of sexual assault was higher among both female and male students who had sent a message/photo to or met a person they initially contacted via the Internet, while the prevalence was lower among students with a conservative attitude toward sexual activity. In addition, female students who recognized the signs of dating violence had less experience of sexual assault. These findings indicate the need for increased education about the Internet and dating violence for effective prevention of sexual assault.

The aim of the present study was to identify clinicopathological factors in long-term survivors following ovarian cancer recurrence. The patients who achieved longer survival after recurrence (n=18) and those who succumbed to the disease earlier (n=47) were identified and analyzed. There were no significant differences in age, performance status, stage distribution or histology between the two groups. Additionally, no significant difference was observed in progression-free survival after primary therapy. Multivariate analyses revealed that the predictive factors for long-term survival were i) secondary debulking surgery (OR=13.3; 95% CI: 1.39–226.7), ii) favourable response rate of second-line chemotherapy (OR=46.5; 95% CI: 1.84–313-4), and iii) ≥3 regimens after first recurrence (OR=9.01; 95% CI: 1.28–117.7). This study revealed that prolonged post-progression survival was associated with post-recurrence treatment. Therefore, appropriate selection of secondary debulking surgery and better chemotherapeutic response may lead to prolonged post-progression survival in recurrent ovarian cancer patients.

Recently, generic drugs of paclitaxel have been commonly used mainly by economic reasons; however, predictive factors for toxicities are not fully determined. Hypersensitivity reaction (HSR) is one of the most important adverse events in the paclitaxel-based therapy, and sometimes leads to lethal condition. The aim of the study was to identify predictors for HSR in patients treated with paclitaxel-based regimens. All the patients treated with chemotherapy including paclitaxel at our hospital between 1998 and 2013 were retrospectively evaluated. Clinicopathological factors of the patients that developed HSR and those without HSR were compared, and predictive factors for HSR were identified. Among 414 patients enrolled in the study, 26 patients (6.3%) developed HSR. Multivariate analyses showed that younger age (odds ratio 6.31), a history of allergy (odds ratio 3.79), and short-course premedication (odds ratio 14.1) were identified as predictive factors for HSR. There was no significant difference in the incidence of HSR between original paclitaxel and generic drug. The incidence of HSR was higher as the number of these predictors was accumulated. Three factors were identified as predictive factors for HSR: younger age, a history of allergy, and short-course premedication. Accumulation of these factors increased the incidence of HSR; however, the use of generic drug was not associated HSR in gynecologic cancer patients.

International audience; This study focuses on Okinawa and Yoron islands, in order to better understand tectonics in the Ryukyu Arc related to the subduction zone. We used coral microatolls-known for their centimetric accuracy in the record of relative sea-level (RSL) changes-to reconstruct RSL changes over the last century from living microatolls. A fossil microatoll in Yoron was used to discuss possible RSL changes beyond the last century. The signal consists of emergence whose rate varies through time, interrupted by decadal to multidecadal periods of sudden and/or gradual submergence and by interannual sea-level falls. Comparison with other existing RSL records in the arc highlights RSL variability along the arc. This pattern contrasts with the homogeneous and linear absolute regional sea-level rise, implying that this latter signal cannot fully explain our observations and that an additional process is required. We suggest the subduction zone as a possible source for generating centimetric scale RSL changes observed in coral microatolls. We tested how the Ryukyu megathrust could explain our observations with elastic dislocation modeling. The emergence trend could be explained by interseismic loading on the plate interface with a minimum coupling rate of 25%, which is higher than previous estimates based on short instrumental records. As for the submergence events that occurred regularly in the coral record, we show that they could be explained by slow slip events on the shallower part of the megathrust or in the transition zone. Such process could accommodate a significant part of the total convergence.

Geranylgeraniol (GGOH), a natural isoprenoid found in plants, has anti-inflammatory effects via inhibiting the activation of nuclear factor-kappa B (NF&kappa, B). However, its detailed mechanism has not yet been elucidated. Recent studies have revealed that isoprenoids can modulate signaling molecules in innate immune responses. We found that GGOH decreased the expression of lipopolysaccharide (LPS)-induced inflammatory genes in human macrophage-like THP-1 cells. Furthermore, we observed that the suppression of NF&kappa, B signaling proteins, in particular interleukin-1 receptor-associated kinase 1 (IRAK1) and tumor necrosis factor receptor-associated factor 6 (TRAF6), occurred in GGOH-treated cells prior to LPS stimulation, suggesting an immunomodulatory effect. These results indicate that GGOH may modulate and help prevent excessive NF&kappa, B activation that can lead to numerous diseases.

Type-2 bitter-taste receptors (TAS2Rs) are important for the evaluation of food quality and the nutritional control in animals. Mutations in some TAS2Rs including TAS2R38 are known to increase susceptibility to various diseases. However, the involvement of TAS2Rs in cancers has not been well understood. We conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer and gastric cancer. We selected the two TAS2Rs because they carry virtually non-functional alleles in human populations. We found that cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls. On the other hand, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among controls as suggested in a previous study. The AVI/AVI genotype was therefore considered to increases cancer risk. In contrast, we also found that homozygous (PAV/PAV) PTC tasters are less frequent among cancer patients, suggesting that the PAV/PAV is a cancer resistant genotype that decreases cancer risk. Genotype frequencies for heterozygous AVI/PAV genotype were not significantly different between the two groups. It is suggested that the risk and resistance of cancers is antagonistically controlled by the two TAS2R38 alleles, PAV and AVI, rather than by the AVI allele alone.

Recently, the number of dry eye cases has dramatically increased. Thus, it is important that easy screening, exact diagnoses, and suitable treatments be available. We developed 3 original and noninvasive assessments for this disorder. First, a DR-1 dry eye monitor was used to determine the tear meniscus height quantitatively by capturing a tear meniscus digital image that was analyzed by Meniscus Processor software. The DR-1 meniscus height value significantly correlated with the fluorescein meniscus height (r = 0.06, Bland-Altman analysis). At a cutoff value of 0.22 mm, sensitivity of the dry eye diagnosis was 84.1% with 90.9% specificity. Second, the Tear Stability Analysis System was used to quantitatively measure tear film stability using a topographic modeling system corneal shape analysis device. Tear film stability was objectively and quantitatively evaluated every second during sustained eye openings. The Tear Stability Analysis System is currently installed in an RT-7000 autorefractometer and topographer to automate the diagnosis of dry eye. Third, the Ocular Surface Thermographer uses ophthalmic thermography for diagnosis. The decrease in ocular surface temperature in dry eyes was significantly greater than that in normal eyes (P < 0.001) at 10 seconds after eye opening. Decreased corneal temperature correlated significantly with the tear film breakup time (r = 0.572; P < 0.001). When changes in the ocular surface temperature of the cornea were used as indicators for dry eye, sensitivity was 0.83 and specificity was 0.80 after 10 seconds. This article describes the details and potential of these 3 noninvasive dry eye assessment systems.

Numerous techniques have been used to reduce epistaxis during nasotracheal intubation. Rhinometry can assess nasal patency in preoperative conditions. However, the possible role of rhinometry in routine nasotracheal intubation has not been studied. One hundred and one patients undergoing dental and maxillofacial surgery that required general anesthesia and nasotracheal intubation were enrolled. We examined whether symmetry or any asymmetry in bilateral airflow patterns by condensation of the expiration, assessed by preoperative rhinometry on seated position, increased the incidence of epistaxis and the need for a nasogastric catheter to guide the endotracheal tube into the oropharynx. We also compared the incidence of changing the site of nasal intubation between the assessment by rhinometry and by cone-beam computed tomography analysis of nasal airspace in the inferior meatus. Patients with any asymmetry in bilateral airflow patterns were 18 % (n = 18), the remaining 82 % (n = 83) had symmetric bilateral nasal cavities. Patients with any asymmetry were more likely to need a guiding nasogastric catheter than patients with symmetry (22 vs. 3.6 %, p = 0.018). The incidence of epistaxis was higher in patients with any asymmetry (39 %) than those with symmetry (16 %), but there was no significant difference between groups (p = 0.055). The site of intubation was changed more frequently based on cone-beam computed tomography analysis than by rhinometry (38 vs. 11 %, p = 0.043). Preoperative rhinometry may be a valuable objective tool to assess nasal patency for nasotracheal intubation in patients who undergo dental and maxillofacial surgery.

Systemic and cellular zinc homeostasis is elaborately controlled by ZIP and ZnT zinc transporters. Therefore, detailed characterization of their expression properties is of importance. Of these transporter proteins, Zip4 functions as the primarily important transporter to control systemic zinc homeostasis because of its indispensable function of zinc absorption in the small intestine. In this study, we closely investigated Zip4 protein accumulation in the rat small intestine in response to zinc status using an anti-Zip4 monoclonal antibody that we generated and contrasted this with the zinc-responsive activity of the membrane-bound alkaline phosphatase (ALP). We found that Zip4 accumulation is more rapid in response to zinc deficiency than previously thought. Accumulation increased in the jejunum as early as 1 day following a zinc-deficient diet. In the small intestine, Zip4 protein expression was higher in the jejunum than in the duodenum and was accompanied by reduction of ALP activity, suggesting that the jejunum can become zinc deficient more easily. Furthermore, by monitoring Zip4 accumulation levels and ALP activity in the duodenum and jejunum, we reasserted that zinc deficiency during lactation may transiently alter plasma glucose levels in the offspring in a sex-specific manner, without affecting homeostatic control of zinc metabolism. This confirms that zinc nutrition during lactation is extremely important for the health of the offspring. These results reveal that rapid Zip4 accumulation provides a significant conceptual advance in understanding the molecular basis of systemic zinc homeostatic control, and that properties of Zip4 protein accumulation are useful to evaluate zinc status closely.

Purpose: To report a new method to analyze sagittal images of the upper eyelid by anterior segment optical coherence tomography (AS-OCT).Methods: Ninety subjects equally divided into young ...

Zinc deficiency causes myriad pathophysiological symptoms, but why distinct phenotypes are generated by zinc deficiency remains unclear. Considering that several ectoenzymes involved in purinergic signaling through extracellular adenine-nucleotide hydrolysis possess zinc ions in their active sites, and disorders in purinergic signaling result in diverse diseases that are frequently similar to those caused by zinc deficiency, herein we examine whether zinc deficiency affects extracellular adenine-nucleotide metabolism. Zinc deficiency severely impairs the activities of major ectoenzymes (ENPP1, ENPP3, NT5E/CD73, and TNAP), and also strongly suppresses adenine-nucleotide hydrolysis in cell-membrane preparations or rat plasma, thereby increasing ATP and ADP levels and decreasing adenosine levels. Thus, zinc deficiency delays both extracellular ATP clearance and adenosine generation, and zinc modulates extracellular adenine-nucleotide metabolism. Since the finely tuned balance between extracellular adenine nucleotides and adenosine is critical for purinergic signaling, these findings provide a novel insight into why zinc deficiency results in diverse symptoms.

We investigated the role of zinc in regulation of food intake using male SD rats during early-stage of zinc deficiency (the 3rd day of the feeding) without decreased zinc concentrations in tissues (hypothalamus and liver). As a result, we found that orally but not intraperitoneal administered zinc stimulates food intake in the short-term zinc-deficient rats. The mRNA expressions of hypothalamic peptides, such as orexin (OX) and neuropeptide Y (NPY), were increased after oral administration of zinc to increase food intake. Pretreatment with an antagonist for the NPY Y1 receptor or the orexin OX1 receptor blocked orexigenic activity by zinc administration. The stimulation of food intake by oral administration of zinc was also abolished by vagotomy. Taken together, our results indicate that zinc stimulates food intake in short-term zinc-deficient rats through the afferent vagus nerve followed by activating the hypothalamic peptide associated with food intake regulation. This study showed the first evidence that gastrointestinal zinc signal is indispensable for the food appetite induction in the experimentally anorexigenic rat. However, since it has not yet been clarified the mechanism involved in zinc sensing by the epithelial membrane of the gastrointestinal tract, further detailed investigations are necessary.

Objective: The aim of the present study was to assess whether hysterectomy with wider resection could improve survival by preventing local recurrence. Methods: Medical charts of the patients with clinical stage I/II endometrial cancers treated at our hospital between 1990 and 2009 were retrospectively analyzed. The primary endpoint was overall survival (OS), and secondary endpoints were progression-free survival (PFS) and adverse effects according to the type of hysterectomy. Results: A total of 247 patients were identified: 46 patients treated with total abdominal hysterectomy (TAH group) and 201 patients with modified radical hysterectomy (mRH group). No significant differences were observed in OS (p = 0.52) and PFS (p = 0.67) between the two groups. Also, there was no significant difference in the distribution of recurrent sites between the two groups. The patients treated with mRH had a longer operation time and more frequently developed severe adverse events, such as blood loss and lymphedema. Conclusion: In our cohorts, there were no significant differences in both PFS and OS according to surgical procedures, and the mRH group more frequently developed severe adverse events. Overall, clinical benefit was not obtained by mRH in patients with clinical stage I/II endometrial carcinomas.

Nine event deposits in a small alluvial valley along the Sanriku coast, Japan, were correlated with historical tsunamis and storms that have been recorded in this region since the 15th century. We identified nine sandy layers in 15 geo-slices collected at distances ranging from 140 to 260 m from the coast in a lowland back marsh protected from the sea by a high sandy ridge. Based on their sedimentary characteristics, grain-size distribution, and marine microfossil assemblages, namely Coccoliths, these event layers, which were well preserved in their order of deposition, were probably either tsunami or storm deposits. Diatom analysis revealed four stages of paleo-environmental change from tidal marsh to wetland. The uppermost event layer covering the ground surface is probably the deposit from the 2011 Tohoku-Oki tsunami. Ages for other event deposits were radiometrically dated using 14C, 137Cs and 210Pb with Bayesian estimation. The second event layers can be correlated with the 1960 Chilean or 1968 Aomori-Oki earthquake tsunamis. The candidates for the third event layer are the 1947 Catherine and 1948 Ione typhoons as well as the candidates for the second event layer. The fourth and fifth event layers are likely associated with the 1933 and 1896 Sanriku-Oki earthquake tsunamis. Four lower event layers can be correlated with historical tsunamis and storms that occurred during the 15th to 18th centuries, such as the 1611 Sanriku-Oki earthquake tsunami.

Background: High-temperature-required protein A2 (HtrA2), a protein relating with apoptosis in a caspases-dependent and non-dependent manner, has been reported to be associated with chemosensitivity in several human cancers. Methods: Tissue microarrays made from 142 patients with high-grade serous ovarian adenocarcinoma were evaluated to assess whether HtrA2 expression was related with several clinical parameters. Results: Negative HtrA2 expression was observed in 36 cases (25%) of the patients, and related with significantly lower response rates of primary chemotherapy than those with positive HtrA2 expression (56% vs 83%, P

The activation of JAK2/STAT3 pathway has been reported to have critical roles in several solid tumors. The present study aimed to evaluate the correlation between JAK2/STAT3 activation and clinicopathological parameters in ovarian cancer types. Tissue microarrays made from the patients treated at the National Defense Medical College Hospital between 1984 and 2008 were evaluated using immunohistochemical (IHC) stainings. Medical charts of these patients including IHC results were retrospectively analyzed, and prognostic factors for progression-free survival and overall survival were evaluated. Among 341 enrolled patients, positive expression of p-STAT3 was observed in 95 cases (28%). Positive p-STAT3 was an independent worse prognostic factor for overall survival in all the cases. Additionally, p-STAT3 expression was related with overall survival in patients with clear-cell histology, but not in serous histology. The effect of an inhibitor of STAT3, niclosamide, was evaluated in ovarian clear-cell cancer cells, and niclosamide treatment decreased expression of p-STAT3, leading to increased apoptosis in a dose-dependent manner in vitro. The activation of JAK2/STAT3 pathway had significant impact on survival of ovarian cancers, especially for the cases with clear-cell histology. Although further analyses are needed, suppression of this pathway could be a candidate for the treatment of ovarian cancers.

Type-2 bitter-taste receptors (TAS2Rs) are important for the evaluation of food quality and the nutritional control in animals. Mutations in some TAS2Rs including TAS2R38 are known to increase susceptibility to various diseases. However, the involvement of TAS2Rs in cancers has not been well understood. We conducted a pilot study by genotyping two TAS2R genes, TAS2R38 and TAS2R46, in Japanese cancer patients diagnosed with the following types of cancer: biliary tract cancer, hepatocellular carcinoma, pancreatic cancer, colorectal cancer and gastric cancer. We selected the two TAS2Rs because they carry virtually non-functional alleles in human populations. We found that cancer risk is not associated with any TAS2R46 genotypes since there were no significant differences in genotype frequencies between cancer patients and controls. On the other hand, we confirmed that phenylthiocarbamide (PTC) non-tasters homozygous (AVI/AVI) for TAS2R38 were more frequent among Japanese cancer patients than those among controls as suggested in a previous study. The AVI/AVI genotype was therefore considered to increases cancer risk. In contrast, we also found that homozygous (PAV/PAV) PTC tasters are less frequent among cancer patients, suggesting that the PAV/PAV is a cancer resistant genotype that decreases cancer risk. Genotype frequencies for heterozygous AVI/PAV genotype were not significantly different between the two groups. It is suggested that the risk and resistance of cancers is antagonistically controlled by the two TAS2R38 alleles, PAV and AVI, rather than by the AVI allele alone.

This study aimed to carry out a case-control research study to assess occurrence of clicking of the temporomandibular joint (TMJ) in order to establish the relationship between TMJ clicking and the genotype of “ANKH inorganic pyrophosphate transport regulator” (ANKH) polymorphisms. A sample of 41 first-year dental residents was selected. Each was examined using standard clinical procedures and genotyping techniques. The participation rate was 91.8 %. The prevalence of TMJ clicking was 51.2 % (95 % CI: 35.7–66.7 %). Occurrence of TMJ clicking was not related to age, gender and genotypes of ANKH-OR as well as ANKH-TR polymorphisms (p ≥ 0.165). A similar distribution of ANKH genotypes in TMJ clicking and asymptomatic individuals has been demonstrated by this study. A high percentage of TMJ clicking has been confirmed. Future investigations are indicated.

Background: X-chromosome-linked inhibitor of apoptosis (XIAP) is one of the anti-apoptotic proteins leading to chemoresistance in several cancers. The aim of this study is to evaluate the impact of XIAP expression upon ovarian clear cell carcinoma (CCC) that has a platinum-resistant phenotype. Methods: Tissue microarrays made from 90 CCC patients were analysed for immunohistochemical expression levels of XIAP, c-Met, p-Akt and Bcl-XL. In addition, CCC cell lines were evaluated whether XIAP silencing could modulate sensitivity to platinum agent in vitro. Results: High XIAP expression was observed in 30 (33%) of 90 CCC cases, and was associated with c-Met (

The airway scope (AWS) improves views of the larynx during orotracheal intubation. However, the role of the AWS in routine nasotracheal intubation has not been studied adequately.One hundred and three patients undergoing dental and maxillofacial surgery that required general anesthesia and nasotracheal intubation were enrolled. The study was approved by our Institution Review Board, and written informed consent was obtained from all patients. We evaluated the success rate of AWS intubation and the incidence of difficult nasotracheal intubation using a modified intubation difficulty scale (IDS) to examine preoperative characteristics and intubation profiles. Categories were difficult intubation (IDS ≥5), mildly difficult (IDS = 1-4), and intubation without difficulty (IDS = 0). We also assessed the incidence of the use of Magill forceps or cuff inflation (the cuff of endotracheal tube is inflated with 10-15 ml air) to guide the endotracheal tube into the glottis.AWS nasotracheal intubation was 100% successful. The cuff inflation technique was used in 37 patients. Neither Magill forceps nor other devices were needed for any patient during AWS use. The incidence of difficult nasotracheal intubation was 10% (n = 10). Of the patients, 61% (n = 63) had mildly difficult intubation and 29% (n = 30) had no difficulty. Patients with difficult intubation were more likely to be male and to have a larger tongue and a higher Cormack grade than in the other two groups. Complications, involving minor soft tissue injury, were observed in only 1 patient (1%).The AWS achieves a high success rate for nasotracheal intubation with cuff inflation in patients undergoing dental and maxillofacial surgery.

Purpose To describe a new method of measuring early phase tear clearance by anterior segment optical coherence tomography (AS-OCT). Methods Sixty normal subjects were divided into a young group (30 subjects; 29.6 ± 7.2 years) and an elder group (30 subjects; 71.4 ± 10.8 years). AS-OCT (CASIA SS-1000, Tomey, Japan) with customized software was used to record the tear meniscus at the centre of the lower eyelid. Five microlitres of lukewarm saline solution was dropped into the lower conjunctival sac, and an image of the tear meniscus was obtained immediately and again 30 seconds after natural blinking. The tear meniscus height (TMH) and tear meniscus area (TMA) were measured in the AS-OCT images, and the percentage decrease in the TMH and TMA was used as a measure of the tear clearance. Correlations between tear clearance and clinical features including degree of conjunctivochalasis, degree of protrusion of inferior lacrimal punctum, distance of lacrimal punctum from the Marx line and fluorescein clearance rates were also determined in another healthy population consisting of 30 subjects. Results The OCT tear clearance rate was 35.2 ± 11% for TMH and 28.1 ± 12.4% for TMA in the young group, and 12.4 ± 7.3% and 6.2 ± 9.1%, respectively in the elder group. The differences were significant for both the TMH (p = 0.017) and the TMA (p = 0.024). The OCT-determined tear clearance was positively correlated with the fluorescein clearance rate, and negatively correlated with the distance between the lacrimal punctum and Marx line, degree of conjunctivochalasis and degree of lacrimal punctum protrusion. Conclusion AS-OCT can be used as a rapid, non-invasive and quantitative method of determining the early phase tear clearance rate in a normal healthy population.

OBJECTIVES: Delirium is a common and critical clinical syndrome in older patients. We examined whether abnormalities in the brain that could be assessed by magnetic resonance imaging predisposed patients to develop delirium after coronary artery bypass graft surgery. We also analysed the association between delirium and cognitive dysfunction after coronary artery bypass graft surgery. METHODS: Data were collected prospectively on 153 patients aged 60 years or older who consecutively underwent elective isolated coronary artery bypass graft surgery. All patients were assessed for prior cerebral infarctions and craniocervical artery stenosis by magnetic resonance imaging (MRI) and angiography of their brains. Atherosclerosis of the ascending aorta was examined by epiaortic ultrasound at the time of surgery. Individual cognitive status was measured using four tests in all the patients before surgery and on the seventh postoperative day. A single psychiatrist diagnosed delirium using the Diagnostic and Statistical Manual of Mental Disorders 4th edition IV criteria. RESULTS: Postoperative delirium occurred in 16 patients (10.5%). Compared with patients who did not develop postoperative delirium, delirious patients had significantly higher rates of peripheral artery disease, preoperative decline in global cognitive function and pre-existing multiple cerebral infarctions on MRI. In addition, 9 (56%) of the delirious patients suffered postoperative cognitive dysfunction. Stepwise logistic regression analysis found significant independent predictors of postoperative delirium to be preoperative cerebral infarcts on MRI (odds ratio [OR], 2.26; 95% confidence interval [CI] 1.10–4.78), preoperative decline in global cognitive function (OR 4.54; 95% CI 1.21–16.51) and atherosclerosis of the ascending aorta (OR 2.44; 95% CI 1.03–5.62). CONCLUSIONS :O urfindings suggested that postoperative delirium was associated with pre-existing multiple cerebral infarctions on MRI, preoperative decline in global cognitive function and ascending aortic atherosclerosis in elderly patients undergoing coronary artery bypass graft surgery and increased risk of postoperative cognitive dysfunction.

Background Previous study shown that enzyme treated-rice bran effectively improved hypertension and glucose intolerance in stroke-prone spontaneously hypertensive rat (SHRSP). However, dual fermentation of rice bran’s efficacy against metabolic syndrome in SHRSP is still unknown. Methods Fermented rice bran (FRB) was prepared by dual fermentation of rice bran using fungi and lactic acid bacteria. The effect of FRB on metabolic syndrome in stroke-prone spontaneously hypertensive rats (SHRSP) was investigated by single and chronic supplementation. Results Dual fermentation of rice bran enriches the functional value of rice bran. Single-dose oral administration of FRB (2 g/kg body weight) reduced systolic blood pressure; however, chronic supplementation with 5 % FRB (4 weeks) significantly reduced both systolic and diastolic blood pressure. FRB supplementation improved leptin impairment and increased serum adiponectin levels and angiotensin-converting enzyme inhibitory activity. Furthermore, FRB supplementation improved glucose tolerance and insulin sensitivity as well as serum insulin levels. Lipid profiles were also improved by the regulation of 5′ adenosine monophosphate-activated protein kinase activation. Moreover, supplementation with FRB reduced the expressions of hepatic transcription factors such as liver X receptor alpha, sterol regulatory element-binding protein 1c, and carbohydrate-responsive element-binding protein alpha, as well as their target genes. In conclusion, dietary supplementation with FRB may lower hypertension and alleviate metabolic syndrome. Conclusion Metabolic syndrome was better alleviated with FRB supplementation. We therefore suggest FRB as an alternative medicine to reduce the risks of lifestyle-related diseases.

We previously reported 2 new methods, anterior segment optical coherence tomography (AS-OCT) and polymethylmethacrylate particles suspended in fluorescein solution (PPF), for the evaluation of tear clearance and rapid tear flow after blinking (tear Krehbiel flow). Here, we investigated age-related OCT tear clearance and tear film thickness (TFT) and the potential correlation of OCT tear clearance and PPF velocity indicative of tear Krehbiel flow. Normal subjects separated into young and older groups received 5 μL of saline solution into the lower conjunctival sac, and an image of the central lower eyelid tear meniscus was captured by AS-OCT immediately and 30 seconds after natural blinking. Tear meniscus height (TMH) and tear meniscus area (TMA) were measured, and their percentage decrease was defined as OCT clearance rate. A Spectralis OCT Anterior Segment Module captured the central corneal tear film layer for TFT measurements. OCT clearance rates were significantly higher in young versus older subjects (P = 0.0002). When all subjects were analyzed, age was significantly and negatively correlated with TMH clearance rate (r = -0.4928, P = 0.0003) and TMA clearance rate (r = -0.4596, P = 0.0008). TFT values were significantly and negatively correlated with age (r = -0.6662, P < 0.0001). A second experiment examined tear Krehbiel flow by measuring PPF velocity in frontal and medial gaze positions. The medial gaze position showed significantly increased PPF velocity compared with the frontal gaze position (P = 0.006). Significant and positive correlations were found between OCT clearance rates and PPF velocity (TMH rate: r = 0.2926, P = 0.0392; TMA rate: r = 0.3274, P = 0.0205). AS-OCT and PPF might be novel techniques for quantitative evaluation of tear clearance and Krehbiel flow.

Background: To compare the margin reflex distance of the upper (MRD-1) and lower (MRD-2) eyelids and the eyebrow height (EBH) in patients with involutional and hard contact lens wear--induced blepharoptosis before and after ptosis surgery. Methods: Sixty patients with acquired blepharoptosis were studied. Group 1 consisted of 30 patients with involutional ptosis (age, 75.8 ± 6.4 years), and group 2 consisted of 30 patients with hard contact lens wear–induced ptosis (age, 50.2 ± 7.1 years). All patients underwent bilateral, CO2 laser–assisted levator aponeurosis advancement surgery. A digital image was taken in the primary position before and 2 months after the surgery. The image was analyzed by the ImageJ (NIH, Bethesda, Md.) software. Parameters included MRD-1, MRD-2, EBH, and ocular surface area (OSA). Results: After surgery, all patients had a significant increase in the MRD-1 and OSA and a decrease in the EBH (all P < 0.001). The increase in MRD-1 was significantly larger in group 1 than in group 2 (P = 0.028). The decrease of EBH was significantly greater in group 1 than in group 2 (P = 0.007). Group 1 had a slight decrease in the MRD-2, but group 2 had a significant increase after surgery (P = 0.026). The change in the OSA was not significantly different between the 2 groups. Conclusions: Digital image analyses can be used for precise measurements of the eyelid features. The disparity in the changes of eyelid and eyebrow features between the 2 groups may suggest different responses of the external eyelid muscles to surgery between cases of different etiology.

Frequent mutation of the ARID1A gene has been recently identified in ovarian clear-cell adenocarcinoma (CCA); however, the clinical significance of BAF250a expression encoded by the ARID1A gene remains to be determined. The aim of the present study was to assess whether BAF250a expression had an impact on the clinical features of CCA. A total of 97 cases of CCA treated at a single institution were enrolled in the present study. The tissue samples were evaluated by immunohistochemical staining. BAF250a-deficient expression was observed in 30% (29/97) of all CCA cases. Of this, 19% of non-atypical endometriosis, 26% of atypical endometriosis, 39% of endometriosis-related CCA, 5% of benign clear-cell adenofibroma (CCAF), 5% of borderline CCAF and 10% of CCAF-related CCA. BAF250a-deficient expression was significantly more frequent in endometriosis-related CCA compared with that in CCAF-related CCA (P=0.02). No significant difference was observed in the response rate of primary chemotherapy according to BAF250a expression status (P=0.48). Additionally, BAF250a expression status was not significantly correlated with progression-free and overall survival in patients with CCA. Although loss of BAF250a expression was associated with early tumorigenesis in endometriosis-related CCA, this alteration was not significantly correlated with chemosensitivity and prognoses of CCA. Further biomarker analyses, including BAF250a expression, are required to improve the prognoses of CCA.

Transgenic Drosophila expressing human T2R4 and T2R38 bitter-taste receptors or PKD2L1 sour-taste receptor in the fly gustatory receptor neurons and other tissues were prepared using conventional Gal4/UAS binary system. Molecular analysis showed that the transgene mRNAs are expressed according to the tissue specificity of the Gal4 drivers. Transformants expressing the transgene taste receptors in the fly taste neurons were then studied by a behavioral assay to analyze whether transgene chemoreceptors are functional and coupled to the cell response. Since wild-type flies show strong aversion against the T2R ligands as in mammals, the authors analyzed the transformants where the transgenes are expressed in the fly sugar receptor neurons so that they promote feeding ligand-dependently if they are functional and activate the neurons. Although the feeding preference varied considerably among different strains and individuals, statistical analysis using large numbers of transformants indicated that transformants expressing T2R4 showed a small but significant increase in the preference for denatonium and quinine, the T2R4 ligands, as compared to the control flies, whereas transformants expressing T2R38 did not. Similarly, transformants expressing T2R38 and PKD2L1 also showed a similar preference increase for T2R38-specific ligand phenylthiocarbamide (PTC) and a sour-taste ligand, citric acid, respectively. Taken together, the transformants expressing mammalian taste receptors showed a small but significant increase in the feeding preference that is taste receptor and also ligand dependent. Although future improvements are required to attain performance comparable to the endogenous robust response, Drosophila taste neurons may serve as a potential in vivo heterologous expression system for analyzing chemoreceptor function.