A case of aortic root replacement for annuloaortic ectasia due to Takayasu's arteritis in active inflammatory phase.

A 39-year-old man was admitted with acute heart failure due to severe aortic regurgitation induced by annuloaortic ectasia associated with Takayasu's arteritis. Because of the active inflammatory phase associated with Takayasu's arteritis, surgery is typically performed following immune suppression by steroid therapy. Herein, we report a favorable recovery in the active inflammatory phase. Steroid therapy was initiated shortly following surgery. The decision to perform aortic root replacement without prior steroid therapy was made because the patient's risk of subsequent heart failures was deemed high and was complicated by other comorbidities.

Edge-preserving smoothing filter using fast M-estimation method with an automatic determination algorithm for basic width.

Digital filtering is essential for digital imaging, image recognition, and super-resolution technology. For example, the presence of noise in images captured by digital cameras causes deterioration of the image quality and image recognition rate. In order to improve the image recognition rate, noise reduction and edge preservation must be performed during preprocessing. Noise is generally reduced using low-pass filters, such as the Gaussian filter. Although they reduce noise, such filters also have the properties of blurring edge. A strong edge blur reduces the accuracy of the feature detection in image recognition. Therefore, in our previous study, a fast M-estimation Gaussian filter for images (FMGFI) was proposed as an image filter that simultaneously achieves denoising and edge preservation. In the FMGFI, the setting of the optimal basic width of the 2nd order B-spline basis functions is important for achieving simultaneous denoising and edge preservation. In this method, the optimal basic width of the FMGFI was determined not only by manually setting the basic width but also by human judgment of the filtered images. Consequently, the inability to automatically determine the optimal basic width hindered efficient denoising during image processing Therefore, in this research, we develop and propose a method that can automatically determine the optimal basic width of the FMGFI. The previously proposed method calculates using the same basic width for all the pixels over the entire image; in contrast, the proposed method calculates using the basic width automatically determined for each pixel. The experiments confirmed that the method proposed in this study achieves higher denoising and edge preservation performance than the ones used in previous research. The results also showed that it has the highest denoising performance against salt-and-pepper noise as compared to other filters: non-local mean filter, Gaussian filter, median filter, bilateral filter, adaptive bilateral filter, and FMGFI. The experimental results for the Gaussian noise sowed that the proposed method has the same denoising and edge preservation performance as the other filters in visual evaluation. From the above, the proposed method is expected to contribute to efficient denoising and improvement of image quality by using it as a preprocessing.

Head Injury Assessment in the Elite Level Rugby Union in Japan: Review of 3 Seasons.

Head Injury Assessment (HIA) is the screening tool for head injury during a rugby game. The purpose of this study was to investigate the epidemiology of HIA in the Japan Rugby Top League (JRTL). The incidences of HIA, defined concussion (per 1,000 player-hours) and repeated concussions were evaluated in three seasons (2016-17, 2017-18, 2018-19; total 360 games). The HIA incidence rates were 12.7 (95% confidence interval 9.5-15.9), 20.8 (16.8-24.9), and 25.0 (20.5-29.5) in each season. HIA-1 criteria 2, which is applied for suspected concussion cases, was performed for 46 cases in the 2016-17 season, 81 cases in the 2017-18 season, and 88 cases in the 2018-19 season. The concussion incidence rates were significantly greater in the 2017-18 season (9.6/1000 player-hours, 95% confidence interval 6.8-12.4) and the 2018-19 season (14.4, 11-17.8) compared to the 2016-17 season (4.8, 2.8-6.8). The number of repeated concussion cases in the same season was 1 in the 2016-17 season and 4 in both the 2017-18 and 2018-19 seasons. This study confirmed significantly higher HIA and concussion incidence rates over time. Although the HIA system might have been established in the three seasons in JRTL, comprehensive management needs to be improved to prevent repeated concussions.

Diagnostic performance of nutritional indicators in patients with heart failure.

AIMS: The aim of this study was to compare the diagnostic performance of the nutritional indicators, the mini nutritional assessment-short form (MNA-SF), the geriatric nutritional risk index (GNRI), and the controlling nutritional status (CONUT), in heart failure (HF) patients. METHODS AND RESULTS: Nutritional status was prospectively assessed by the aforementioned three nutritional indicators in 150 outpatients with HF who were then followed for 1 year. The prevalence of patients with the nutritional risk as assessed by the MNA-SF, GNRI, and CONUT scores was 50.0%, 13.3%, and 54.0%, respectively. There was slight agreement of nutritional risk assessment between the MNA-SF and GNRI scores (κ coefficient = 0.16), as well as the GNRI and CONUT scores (κ = 0.11), but poor agreement between the MNA-SF and CONUT scores (κ = -0.09). The CONUT score had the lowest area under the curve (AUC) for the identification of low body weight, low muscle mass, and low physical function among the three indicators (all P < 0.05). Compared with the MNA-SF score, both the GNRI and CONUT scores had lower AUCs for the identification of reduced dietary intake and weight loss (all P < 0.05). There was no significant difference in predicting all-cause mortality or HF rehospitalization among the three indicators. The prescription of statins reduced the diagnostic performance of the CONUT score, as the CONUT score includes cholesterol level assessment. CONCLUSIONS: Of the three indicators, the diagnostic ability of the MNA-SF score was the highest, and that of the CONUT score was the lowest, for the assessment of HF patient nutritional status. The CONUT score may misrepresent nutritional status, particularly in patients receiving statins.

Impact of citrus fruit intake on the mental health of patients with chronic heart failure.

BACKGROUND: The full impact of the intake of citrus fruits on the risk of depression in individuals with chronic heart failure (HF) is unknown. Here, we examined the associations between the estimated habitual intakes of citrus fruits and depressive symptoms in patients with chronic HF. METHODS: We enrolled 150 stable outpatients with chronic HF who had a history of worsening HF. To assess the patients' daily dietary patterns, we used a brief self-administered diet-history questionnaire to calculate the daily consumption of foods and nutrients. To assess the patients' mental state, we used a nine-item Patient Health Questionnaire (PHQ-9). RESULTS: Twelve patients (8%) were identified as having moderate-to-severe depression (PHQ-9 score ≥10). The patients with PHQ-9 ≥10 had lower daily intakes of citrus fruits compared to those with no or mild depressive symptoms (PHQ-9 <10). The daily intakes of various antioxidants, including vitamin C, ß-carotene, and ß-cryptoxanthin, all of which are abundant in citrus fruits, were reduced in the patients with PHQ-9 ≥10, accompanied by higher serum levels of 8-isoprostane (an oxidative stress marker). A multivariate logistic regression analysis using forward selection showed that a lowered daily intake of citrus fruits was an independent predictor of the comorbidity of moderate-to-severe depression in patients with chronic HF, after adjustment for age, gender, and the hemoglobin value. CONCLUSIONS: A lower daily consumption of citrus fruits was associated with higher prevalence of depression in patients with chronic HF. Our findings support the hypothesis that a daily consumption of citrus fruits has a beneficial effect on the prevention and treatment of depression in chronic HF patients.

Impact of Inadequate Calorie Intake on Mortality and Hospitalization in Stable Patients with Chronic Heart Failure.

Malnutrition is highly prevalent in patients with heart failure (HF), but the precise impact of dietary energy deficiency on HF patients' clinical outcomes is not known. We investigated the associations between inadequate calorie intake and adverse clinical events in 145 stable outpatients with chronic HF who had a history of hospitalization due to worsening HF. To assess the patients' dietary pattern, we used a brief self-administered diet-history questionnaire (BDHQ). Inadequate calorie intake was defined as <60% of the estimated energy requirement. In the total chronic HF cohort, the median calorie intake was 1628 kcal/day. Forty-four patients (30%) were identified as having an inadequate calorie intake. A Kaplan-Meier analysis revealed that the patients with inadequate calorie intake had significantly worse clinical outcomes including all-cause death and HF-related hospitalization during the 1-year follow-up period versus those with adequate calorie intake (20% vs. 5%, p < 0.01). A multivariate logistic regression analysis showed that inadequate calorie intake was an independent predictor of adverse clinical events after adjustment for various factors that may influence patients' calorie intake. Among patients with chronic HF, inadequate calorie intake was associated with an increased risk of all-cause mortality and rehospitalization due to worsening HF. However, our results are preliminary and larger studies with direct measurements of dietary calorie intake and total energy expenditure are needed to clarify the intrinsic nature of this relationship.

In vivo profiling of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced estrogenic/anti-estrogenic effects in female estrogen-responsive reporter transgenic mice.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD), commonly referred to simply as "dioxin", is a persistent environmental pollutant. Because of its high environmental persistence and biological accumulation, humans and animals are often exposed to TCDD. Therefore, the harmful effects on humans and animals is a major concern. Although studies have elucidated the adverse estrogenic and anti-estrogenic effects of TCDD, it is unclear in which tissues TCDD exerts these effects in vivo. To investigate the estrogen-related effects of TCDD in various tissues, we generated an improved estrogen-responsive reporter transgenic mouse in which the luciferase gene luc2 is expressed in response to estrogenic signals. Using these mice, we clarified that TCDD inhibits estrogenic signaling in liver and kidney but enhances estrogenic signaling in the pituitary gland in the same individual. Expression of aryl hydrocarbon receptor, aryl hydrocarbon receptor nuclear translocator, and estrogen receptor alpha mRNA was detected in liver, kidney, and pituitary gland, suggesting that the effects of TCDD on estrogenic signaling in these organs is independent of the expression pattern of these receptors. Thus, our results indicate that TCDD exerts both estrogenic and anti-estrogenic tissue-specific effects within the same individual.

Progressive Mobilization Program for Patients With Acute Heart Failure Reduces Hospital Stay and Improves Clinical Outcome.

Background: Early ambulation has been shown to be associated with shorter hospital stay and better clinical outcomes in patients with acute heart failure (HF). Early mobilization program in combination with structured exercise training is recommended, but has yet to be developed and implemented in HF. Methods and Results: We developed a progressive mobilization program for HF patients that classifies the mobilization process into 7 stages based on disease condition and physical function. We retrospectively analyzed 136 patients with acute HF (80±11 years), who were assigned either to the mobilization program (intervention group, n=75) or to usual care (control group, n=61). The program was safely implemented without any adverse events. Hospital stay was significantly reduced in the intervention group compared with the control group (33±25 vs. 51±36 days, P<0.01). The intervention group had higher activities of daily living (ADL) score at discharge evaluated using the Barthel index (64±38 vs. 49±36, P<0.05). The intervention group also had a higher percentage of discharge to home (71% vs. 52%, P<0.05) and a lower rate of HF-related readmission (16% vs. 36%, P<0.05) compared with the control group. Conclusions: The progressive mobilization program for acute HF was feasible and was associated with better ADL and reduced hospital stay, leading to improvement of clinical outcome.

Citrus peel polymethoxyflavones, sudachitin and nobiletin, induce distinct cellular responses in human keratinocyte HaCaT cells.

A variety of polyphenols have been isolated from plants, and their biological activities have been examined. Sudachitin (5,7,4'-trihydroxy-6,8,3'-trimethoxyflavone) is a polymethoxyflavone that is isolated from the peel of Citrus sudachi. Although we previously reported that sudachitin possesses an anti-inflammatory activity, its other biological activities are not yet understood. In this study, we report a novel biological activity of sudachitin, which selectively induced apoptosis in human keratinocyte HaCaT cells. Another polymethoxyflavone, nobiletin (5,6,7,8,3',4'-hexamethoxyflavone), promoted autophagy but not apoptosis in HaCaT cells. On the other hand, 3'-demethoxysudachitin (5,7,4'-trihydroxy-6,8-dimethoxyflavone) failed to induce apoptosis and autophagy. These results show that three polymethoxyflavones have different effects on apoptosis and autophagy in HaCaT cells. Understanding the structure and biological activity of polymethoxyflavones may lead to the discovery of potential candidates for cancer drug development without significant toxic side effects. Abbreviations: ROS: reactive oxygen species; DMSO: dimethyl sulfoxide; MTT: 3-(4, 5-dimethylthiazol-2yl)-2, 5-diphenyltetrazolium bromide; GAPDH: glyceraldehyde-3-phosphate dehydrogenase; PARP: poly(ADP-ribose) polymerase; PI: propidium iodide; MAPK: mitogen-activated protein kinase.

Alisol B, a triterpene from Alismatis rhizoma (dried rhizome of Alisma orientale), inhibits melanin production in murine B16 melanoma cells.

To develop new whitening agents from natural products, we screened 80 compounds derived from crude drugs in Kampo medicine in a melanin synthesis inhibition assay using murine B16 melanoma cells. The screen revealed that treatment with alisol B, a triterpene from Alismatis rhizoma, significantly decreased both melanin content and cellular tyrosinase activity in B16 cells. However, alisol B did not directly inhibit mushroom tyrosinase activity in vitro. Therefore, we investigated the mechanism underlying the inhibitory effect of alisol B on melanogenesis. Alisol B suppressed mRNA induction of tyrosinase and its transcription factor, microphthalmia-associated transcription factor (MITF). Furthermore, alisol B reduced the phosphorylation of CREB and maintained the activation of ERK1/2. These results suggest that the reduction in melanin production by alisol B is due to the downregulation of MITF through the suppression of CREB and activation of ERK and that alisol B may be useful as a new whitening agent.

Pulsed ac Stark shifts monitored by Raman Ramsey fringes in sodium vapor.

We have employed Raman Ramsey fringes (RRFs) in sodium vapor to measure ac Stark shifts of the hyperfine levels by an off-resonant shift laser pulse. The ac Stark shifts are directly monitored by the RRF peak shifts and are proportional to the power and the pulse width and antiproportional to the detuning frequency of the shift laser. These findings endorse RRFs to be a strong tool for monitoring small pulsed perturbations.

Enhanced in vivo gene transfer into the placenta using RGD fiber-mutant adenovirus vector.

Among viral vectors, the fiber-mutant adenovirus vector carrying the Arg-Gly-Asp (RGD) peptide sequence (Ad-RGD) seems to have potential for both clinical gene therapy and basic research. As a part of a thorough evaluation of Ad-RGD in preclinical studies, we designed an experiment to investigate in detail the distribution of Ad-RGD compared with conventional adenovirus vector (WT-Ad) in pregnant mice. Surprisingly, Ad-RGD had substantial placental tropism, at 10-100 times that of WT-Ad. Transgene expression was sustained for at least 7 days, and Ad-RGD expressing firefly luciferase or red fluorescent protein has so far caused no placental dysfunction leading to fetal death. Ad-RGD showed high levels of transduction efficiency in in vitro-differentiated trophoblast stem cells, in which higher expression of αvß3 integrin than in undifferentiated cells was observed. Our results suggest that the use of Ad-RGD or another RGD-mediated targeting strategy holds promise for drug delivery to the placenta.

Enhancement of tongue carcinogenesis in Hras128 transgenic rats treated with 4-nitroquinoline 1-oxide.

Transgenic rats carrying human c-Ha-ras proto-oncogene (Hras128 rats) have been shown to be highly susceptible to induction of tumors. We have found an early induction of tongue tumors in Hras128 rats treated with 4-nitroquinoline 1-oxide (4NQO). 4NQO was administered to the Hras128 and wild-type Sprague-Dawley (SD) rats for 4 and 8 weeks, respectively. The experiment was terminated at 14 (Hras128 rats) and 28 (SD rats) weeks. Either during or after treatment with 4NQO, dysplastic hyperplasia, papilloma and squamous cell carcinoma were found on the tongue of both Hras128 and wild-type rats, with a higher incidence and multiplicity in Hras128 rats. Treatment of the Hras128 rats with 4NQO significantly increased cell proliferation in the tumor compared to the control rats. In the tongue tumors of the Hras128 rats, there was a significant increase in the mRNA expression levels of cyclin D1 and COX2. To examine whether this experimental system is useful for screening of the candidate agents for cancer preventive effect, nimesulide, a selective COX2 inhibitor, was tested in the present model. Nimesulide significantly decreased total multiplicity of tongue lesions compared to the control rats. Treatment of Hras128 rats with nimesulide caused a significant decrease in the levels of mRNA expression of cyclin D1 and COX2 in the tumor. Therefore, the current 4NQO-induced Hras128 rat tongue carcinogenesis model provides a simple and rapid system for investigating carcinogenesis process and evaluating the effect of possible cancer preventive agents for human tongue cancer.

Structure-dependent activation of peroxisome proliferator-activated receptor (PPAR) gamma by organotin compounds.

Organotin compounds such as tributyltin (TBT) and triphenyltin (TPT) are frequent environmental contaminants and are suspected of disrupting endocrine function in vertebrates and invertebrates. Previously, we reported that TBT and TPT function as powerful agonists for peroxisome proliferator-activated receptor (PPAR) gamma and stimulate adipocyte differentiation via the PPARgamma signaling pathway. Our current study investigates the structure-dependent binding of butyltin and phenyltin compounds to PPARgamma and their ability to activate the receptor. A Scatchard analysis with purified recombinant PPARgamma demonstrated that [(14)C]TPT binds to PPARgamma with an equilibrium dissociation constant (K(d)) of 66.6+/-5.2 nM, which approximated the 46.2+/-2.5 nM K(d) of a typical PPARgamma agonist, [(3)H]rosiglitazone (Rosi). TBT, TPT, diphenyltin (DPT), and tetrabutyltin (TeBT) blocked the binding of [(3)H]Rosi to PPARgamma in a competitive manner, and all tested organotin compounds except monobutyltin blocked the binding of [(14)C]TPT to PPARgamma in a competitive manner. Unexpectedly, Rosi did not compete at all with [(14)C]TPT for binding to PPARgamma, and contrary to the results of the competition assay, TBT and TeBT, but not dibutyltin, transcriptionally activated a GAL-PPARgamma chimeric receptor. All tested phenyltin compounds transcriptionally activated GAL-PPARgamma with an order of potency of TPT>DPT>monophenyltin. In addition, treatment of human choriocarcinoma cells with TBT, TeBT, and all tested phenyltin compounds stimulated production of human chorionic gonadotropin, which is upregulated by PPARgamma-mediated transcription. Our observations indicate that trialkylated and triphenylated tin compounds are the most potent PPARgamma agonists among the alkylated and phenylated tin compounds, and a phenyl substituent on a tin atom enhances the potency of organotin compounds as a PPARgamma agonist much more than a butyl substituent.

Placental steroidogenesis in rats is independent of signaling pathways induced by retinoic acids.

We investigated the effects of retinoic acids (RAs) on steroid hormone production and mRNA expression of steroidogenic enzymes in rat placenta in vitro and in vivo. In the rat trophoblast giant cell line Rcho-1, the natural retinoid X receptor (RXR) agonist 9-cis retinoic acid (9cRA) and synthetic RXR agonist LG100268 slightly promoted production of progesterone and androgen, whereas the natural retinoic acid receptor (RAR) agonist all-trans retinoic acid (atRA) and synthetic RAR agonist TTNPB did not. Furthermore, although administration of atRA and 9cRA into the rat uterus at 13.5days postcoitum robustly induced mRNA expression of cellular retinol binding protein II, the gene for which is targeted by RAR and/or RXR, in the placenta, neither RA affected the expression of placental steroidogenic enzymes, and both had little effect on progesterone and androgen levels in the placenta and embryo, suggesting that placental steroidogenesis is not regulated by RAs in rats.

Different SPECT findings before and after Capgras' syndrome in interictal psychosis.

We herein report a case of Capgras' syndrome observed in interictal psychosis in which the single-photon emission computed tomography (SPECT) findings before and after the appearance of the psychotic symptoms differed. SPECT with 99mTc-hexamethyl propyleneamine oxine (HMPAO) revealed worsening of hypoperfusion in the entire right hemisphere after onset of the psychotic symptoms. The enhanced hypoperfusion demonstrated by SPECT in the present case seems to indicate a right interhemispheric disconnection resulting in the occurrence of Capgras' syndrome.

Angiotensin converting enzyme inhibitors attenuated the expression of G-protein coupled receptor kinases in heart failure patients.

BACKGROUND: There are few biological markers, which strictly show the severity of congestive heart failure (CHF). METHODS AND RESULTS: Lymphocyte G-protein coupled receptor kinase (GRK) mRNA expression was measured by quantitative reverse transcription-polymerase chain reaction in 15 CHF patients: 5 patients classified as New York Heart Association class-II treated with angiotensin converting enzyme inhibitor (ACEI) (IIA), 5 patients in class-II without ACEI (IIC), and 5 patients in class-III treated with ACEI (IIIA). GRK mRNA level in IIIA was significantly higher than those in IIA (p<0.05). GRK mRNA level in IIA were significantly lower than those in IIC (p<0.05). CONCLUSIONS: The expression level of lymphocyte GRK might show the severity of CHF, and ACEI treatment could reduce the level of GRK in CHF patients.

Depletion of intracellular Ca2+ store itself may be a major factor in thapsigargin-induced ER stress and apoptosis in PC12 cells.

The mechanisms of intracellular calcium store depletion and store-related Ca(2+) dysregulation in relation to apoptotic cell death in PC12 cells were investigated at physiological temperatures with a leak-resistant fluorescent indicator dye Fura-PE3/AM by a cooled CCD imaging analysis system. Electron microscopic observations have shown thapsigargin (TG; 100 nM)-induced apoptosis in PC12 cells. Thorough starvation of stored Ca(2+) by BAPTA/AM (50 microM), or La(3+) (100 microM) enhanced while dantrolene (100 microM) attenuated the TG-induced apoptosis by preventing a calcium release from internal stores. An immunoblotting analysis revealed an enhanced expression of GRP78, the hallmark of endoplasmic reticulum (ER) stress when cells were treated by TG along with BAPTA/AM. These results indicate that the depletion of the intracellular Ca(2+) stores itself induces the ER stress and apoptosis in PC12 cells without any involvement of the capacitative calcium entry (CCE) or a sustained elevation of intracellular Ca(2+) concentrations ([Ca(2+)](i)).