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The inheritance patterns of asymmetry in mouth opening in zebrafish were investigated using crossing experiments. Zebrafish exhibit asymmetric laterality in mouth opening, with each individual having either a leftward (righty) or rightward (lefty) bias. All righty incrosses produced only righty F(1), whereas all lefty incrosses resulted in an F(1) L:R ratio of 2:1. All test crosses between lefty and righty individuals resulted in an F(1) L:R=1:1. These results were consistent with the hereditary pattern for Japanese medaka, three Tanganyikan cichlids, and a Japanese riverine goby. The pattern suggests a one-locus two-allele Mendelian model of inheritance, with the lefty allele being dominant over righty and the dominant homozygote being lethal. To determine the reason for the absence of lefty homozygotes, the survival rates of the offspring were examined according to developmental stage. Survival did not differ among combinations of parent laterality. Thus the mechanism underlying the lethality of the dominant homozygote remains unclear. This study showed that the mouth-opening laterality of zebrafish is genetically determined and that the direction follows a Mendelian inheritance pattern that is shared among cypriniform zebrafish, beloniform medaka, perciform cichlids, and a goby, suggesting a common genetic background in mouth-opening laterality among these species.

Tuna-farming is expanding worldwide, necessitating the monitoring/managing of its effects on the natural environment. In Japan, tuna-farming is conducted on coral reefs that have been damaged by mass-bleaching events and crown-of-thorns starfish (COTS) outbreaks. This study focused on the coral community on an artificial substrate of tuna-farm to reveal the possible effects of tuna-farming on the natural environment. Corals flourished on ropes suspended in the farm in the Amami Islands, southern Japan. These were moored 3 m below the sea-surface in 50-m-deep water. The coral community on the rope was analyzed and compared with those on natural substrata on two adjacent COTS-damaged reefs and with that in a protected reef. Corals were monitored throughout a year. Sixty coral species grew on the ropes, that corresponds to 27.3% of the 220 species known from Amami. The coral community was unique, dominated by massive faviid corals. On the ropes, the water temperature rarely exceeded 30.0 °C and no corals on the rope were severely bleached or covered by sedimentation during the observations. The tuna-farm infrastructure provided corals with a suitable habitat, and species-rich coral communities were established. These coral communities are an important node connecting tuna-farms and the natural environment.

The asymmetry of mouth morphology, in which the mouth opens either leftward or rightward, is a unique example of antisymmetry that is widely found in fishes, such as Tanganyikan scale-eating cichlids, herbivorous cichlids, and the Japanese freshwater goby. This dimorphism is thought to be heritable in a Mendelian manner similar to that of the dominance of the lefty allele over righty, with homozygotes of lefty alleles being absent. This study aims to reveal whether this trait is inherited in the same Mendelian manner in fishes other than those examined to date, and whether the absence of the dominant homozygote is due to a lethal effect. We conducted F(1) and F(2) breeding experiments using the Tanganyikan cichlid Julidochromis transcriptus and Japanese medaka Oryzias latipes. For both J. transcriptus and O. latipes, the F(1) generations produced by incrossing lefty parents showed a lefty:righty ratio of 2:1, whereas incrosses of righties produced only righty offspring. Test crosses between lefty and righty produced a 1:1 ratio of lefty and righty offspring. These results are consistent with the inheritance model in which righty is homozygous for a recessive righty allele and lefty is heterozygous for dominant lefty and recessive righty alleles, in agreement with previous observations. The F(2) test cross also confirmed this pattern. Furthermore, no lethal effects on hatchability of O. latipes were detected, refuting the suggestion that the dominant homozygote is embryonic lethal. We conclude that mouth laterality is inherited in the same Mendelian manner in these two species, similar to that other fish species studied previously. However, the reason for absence of the dominant homozygote remains unclear.

Dripping water from a faucet is a typical example exhibiting rich nonlinear phenomena. For such a system, the time stamps at which water drops separate from the faucet can be directly observed in real experiments, and the time series of intervals \tau_n between drop separations becomes a subject of analysis. Even if the mass m_n of a drop at the onset of the n-th separation, which cannot be observed directly, exhibits perfectly deterministic dynamics, it sometimes fails to obtain important information from time series of \tau_n. This is because the return plot \tau_n-1 vs. \tau_n may become a multi-valued function, i.e., not a deterministic dynamical system. In this paper, we propose a method to construct a nonlinear coordinate which provides a "surrogate" of the internal state m_n from the time series of \tau_n. Here, a key of the proposed approach is to use ISOMAP, which is a well-known method of manifold learning. We first apply it to the time series of $\tau_n$ generated from the numerical simulation of a phenomenological mass-spring model for the dripping faucet system. It is shown that a clear one-dimensional map is obtained by the proposed approach, whose characteristic quantities such as the Lyapunov exponent, the topological entropy, and the time correlation function coincide with the original dripping faucet system. Furthermore, we also analyze data obtained from real dripping faucet experiments which also provides promising results., Comment: 9 pages, 10 figures

S-1, an oral fluoropyrimidine, is one of the standard chemotherapeutic agents for the treatment of metastatic gastric cancer(MGC). However, the most effective second-line regimen after failure of treatment with first-line agents such as S-1 is yet to be determined. The aim of this study was to investigate the various second-line chemotherapy regimens in MGC patients.We retrospectively studied patients with MGC who received second-line treatment after failure of the first-line S-1 or S-1/cisplatin treatment. The overall survival times with each second-line regimen were determined using the Kaplan-Meier method, and the effect on overall survival was analyzed using Cox regression analysis.The median survival time for all patients was 14. 2 months(95% confidence interval(CI): 12. 88-15. 43 months)with a 1-year survival rate of 60. 4%. Kaplan-Meier analysis revealed that the second-line regimens containing irinotecan significantly improved the median survival time as compared to regimens without irinotecan(median survival time: 16. 5 and 13. 8 months, respectively). Cox regression analysis showed that irinotecan-containing regimens were associated with improved overall survival(hazard ratio: 0. 165; 95% CI: 0. 041-0. 665).The use of irinotecan-containing regimens as second-line chemotherapy after failure of first-line S-1 therapy may be beneficial for MGC patients.

BACKGROUND: Asymmetry in animal bodies and behavior has evolved several times, but our knowledge of their linkage is limited. Tanganyikan scale-eating cichlids have well-known antisymmetry in their bodies and behavior; individuals open their mouths leftward (righty) or rightward (lefty), and righties always attack the right flank of the prey, whereas lefties attack the left. This study analyzed the morphological asymmetry in a scale-eating characiform, Exodon paradoxus, and its behavioral handedness. METHODOLOGY/PRINCIPAL FINDINGS: Each eight E. paradoxus was observed for 1-h with a prey goldfish in an aquarium to detect the behavioral handedness. Following the experiment, the lateral differences in the mandibles and head-inclination of these eight and ten additional specimens were analyzed. Both measurements on the morphology showed a bimodal distribution, and the laterality identified by these two methods was always consistent within a given individual, indicating that the characin has morphological antisymmetry. Furthermore, this laterality significantly corresponded to behavioral handedness; that is, lefties more often rasped scales from the right flank of the prey and vice versa. However, the correlation between laterality and handedness is the opposite of that in the cichlids. This is due to differences in the feeding apparatus and technique. The characin has cuspids pointing forward on the external side of the premaxilla, and it thrusts its dominant body side outward from its body axis on the flank of the prey to tear off scales. By contrast, the cichlids draw their dominant body side inward toward the axis or rotate it to scrape or wrench off scales with the teeth lined in the opened mouth. CONCLUSIONS/SIGNIFICANCE: This study demonstrated that the antisymmetry in external morphology and the corresponding behavioral handedness have evolved in two lineages of scale-eating fishes independently, and these fishes adopt different utilization of their body asymmetry to tear off scales.

The purpose of this study was to evaluate the direct effects of restrictive mitral annuloplasty on mitral valve geometry.We studied 23 patients (mean age: 63 ± 5 years) with functional mitral regurgitation (moderate to severe) and advanced cardiomyopathy (ejection fraction: 25 ± 8%) with ischemic (n = 15) or nonischemic (n = 8) conditions, who underwent restrictive annuloplasty. We determined annular septal-lateral diameter, tenting height, tenting area, vertical length of coaptation of the mitral leaflets (coaptation length), and ratio of coaptation length to septal-lateral diameter (coaptation length index) at end-systole, before and after surgery, using transthoracic echocardiography.Annular septal-lateral diameter, tenting height, and tenting area were significantly decreased (34 ± 7 to 20 ± 5 mm, P0.05; 9 ± 4 to 5 ± 2 mm, P0.05; 210 ± 120 to 80 ± 50 mm(2) , P0.05, respectively), whereas coaptation length and coaptation length index were significantly increased (3.4 ± 1.3 to 6.5 ± 2.9 mm, P0.05; 0.11 ± 0.06 to 0.33 ± 0.15, P0.05, respectively). Spearman's rank correlation analysis revealed that these five variables had a statistically significant correlation with the degree of mitral regurgitation. Furthermore, stepwise regression analysis showed that coaptation length index, in contrast to coaptation length, was the most important correlate with the degree of mitral regurgitation.Our simplified parameters were useful for quantitative and geometrical descriptions of mitral valve geometry, and may also provide important information for developing a surgical strategy for functional mitral regurgitation.

Three new flavonoid glycosides (cissosides I, II, and III) and a new benzofuran-type stilbene (cissusin) were isolated from the methanolic extract of the aerial parts of Cissus sicyoides cultivated in Brazil. Their structures were elucidated on the basis of chemical and physicochemical evidence. The inhibitory effects of the isolated constituents on the release of beta-hexosaminidase as a marker of degranulation in rat basophilic leukemia (RBL-2H3) cells were examined. Cissusin, flavonols (kaempferol, quercetin), flavones (7,3',4'-trihydroxyflavone, lanceolatin B), pterocarpanes (homopterocarpin), chalcones (isoliquiritigenin, E-7-O-methylpongamol), and tryptanthrin markedly inhibited the release of beta-hexosaminidase.

The synthronized states for two kinds of asymmetric N-map coupled system (N=2, 3, 4) are investigated with a linear stability theory. In each case, the boundary of the stability region in the coupling-parameter space is expressed by a linear or a quadratic equation. Global bifurcation structures for these systems are also studied

Graft replacement of an inflammatory abdominal aortic aneurysm is rather troublesome due to the marked adhesion to surrounding organs and thickened wall, which is mostly too hard and inflexible to allow the artery to be fitted to a prosthetic graft. For one such case, we developed a novel and unique technique for a distal anastomosis using a tapered elephant trunk. This technique was designed on the assumption of further aneurysmal changes and enabled us to create a secure anastomosis at the enlarged inflammatory part of the common iliac artery. The distal flow to both the external and internal iliac arteries was well maintained without any complications.

Two chaotic attractors with rotation numbers Pm = Fm-r/Fm, Fm being the moth Fibonacci number, and pm+! just before their attractor-merging crisis converge to the critical golden torus as m -H)(). A critical scaling is shown to hold for those chaotic attractors for large m; leading to a universal spectrum of the local expansion rates of nearby orbits. The two-frequency dynamical systems exhibit a great variety of bifurcations in the two-dimensional space of parameters which control the ratio of the two frequen­ cies and the strength of the nonlinearity, resulting in fascinating chaotic attractors.l) A typical example of the two-frequency systems is the sine-circle map,l),2) which is the map on a circle [0,1] onto itself and expressed as

Diffusion of chaotic orbits is one of the most important transport processes in various physical systems.1H) In particular, mixing and diffusion in hamiltonian (i.e., conservative) systems have been realized to be the most fundamental feature of chaos since the discovery of Lagrangian turbulence) and dynamical localization in quantum chaos.) A chaotic orbit in hamiltonian systems sticks to the critical tori in the chaos border repeatedly with an inverse-power distribution:jOf sticking times, producing a long-time correlation of chaotic orbits.) This long-time correlation causes anomalous phenomena for various coarse-grained dynamic quantities. In this paper, we shall discuss diffusion in the conservative standard maps in terms of a new statisticalmechanical approach recently developed.) The conservative standard maps are given byl),7)

It is shown that the singularity spectrum I(a) of the natural invariant measure in the driven damped pendulum exhibits three types of linear slopes at bifurcation points of chaos, which agree with theoretical estimates of the linear slopes . . Chaotic attractors of dissipative differential systems have fascinating multi­ fractal structures. I) Recently it has been shown that the structures could be char­ acterized by the generalized dimensions D(q), (-=

Objectives: The effects of restrictive annuloplasty on mitral leaflet coaptation in a clinical setting have not been fully elucidated. We developed a novel simplified method for assessing the actual degree of coaptation and investigated changes caused by its use. Based on our findings, we evaluated the direct effects of restrictive annuloplasty on mitral leaflet coaptation and the mechanism regulating mitral regurgitation. Methods and Results: We studied 23 patients (mean 60 years old) with functional mitral regurgitation (grade 3 to 4+) with congestive heart failure (LV ejection fraction 32±10%) due to idiopathic (n=8) or ischemic (n=15) who underwent mitral valve repair with restrictive annuloplasty and 20 normal control subjects. We measured the septal-lateral diameter, tenting height, tenting area, and coaptation length of the mitral valve in 4-chamber, 2-chamber, and long-axis views at mid-systole before and after surgery using transthoracic and transesophageal echocardiography procedures. Coaptation length was calculated with the following formula: Ad-Ac, where Ad equals the whole length of the anterior leaflet during the diastolic phase and Ac equals the length of the non-coaptation free portion of the anterior leaflet at mid-systole. Coaptation length index was defined as the ratio of coaptation length to septal-lateral diameter. Results: Tenting height and tenting area were significantly decreased, while coaptation length and coaptation length index were significantly increased (Table ). In multivariate analysis, coaptation length index showed a statistically significant negative correlation with degree of residual MR (r=0.77, p Conclusion: Our novel simplified method provided quantitative and morphological descriptions of mitral leaflet coaptation, and can also provide important information for developing a surgical strategy for regulation of MR. Table

Introduction: Periodic leg movements during sleep (PLM), regularly recurring movements of the legs during sleep, cause frequent arousal and intermittent eleva- tions of blood pressure and heart rate. One study showed that PLM disorder (PLMD) was associated with increased mortality in patients with chronic heart fail- ure. However, clinical significance of PLMD in hospitalized patients following acute decompensated heart failure (ADHF) remains unknown. Methods: After the initial improvement of acute signs and symptoms of ADHF, we performed polysomnogra- phy on consecutive patients who were left ventricular ejection fraction (LVEF) ! 50%, and were hospitalized due to ADHF between 2012 and 2014. PLMD was defined as PLM index S 25 that we thought was moderate-to-severe PLM. The risks for composite of all-cause mortality and re-hospitalization, were assessed by stepwise multivariable Cox proportional model including variables showing P!0.15 in univar- iate analyses. Results: Overall, 94 patients were enrolled. PLMD was found in 24 patients (26%). At a median follow-up of 5.2 months, 30 patients had an episode of rehospitalization and/or death (32%). In the multivariable analysis, presence of PLMD was significantly associated with increased risk of rehospitalization and/or mortality (hazard ratio, 2.34; P50.024) independent from hemoglobin level and severity of sleep disordered breathing. Conclusion: Presence of PLMD was indepen- dently associated with increased risk of rehospitalization and/or mortality even in hospitalized patient following ADHF.

We present herein a simple and uniform repair technique for combined aortic arch and root aneurysms. Our method is performed under an open distal procedure and includes selective antegrade cerebral perfusion, adequate myocardial preservation, a four-branched composite valve graft, and a long elephant trunk anastomosis proximal to the innominate artery. The technique was designed to reduce morbidity and mortality associated with aortic arch and root replacements, as well as allow for easier performance of subsequent downstream operations.

We evaluated the effect of sivelestat sodium (SiV), a novel synthesized polymorphonuclear (PMN) elastase inhibitor, on acute lung injury (ALI) caused by cardiopulmonary bypass (CPB).Fourteen patients who underwent cardiopulmonary surgery using CPB, followed by the development of both systemic inflammatory response syndrome (SIRS) and ALI, were treated with either 0.2 mg/kg per hour SiV (SiV group, n = 7) or saline (control group, n = 7) for 4 days from the time of arrival in the intensive care unit.The SiV group had a significantly lower ratio of serum PMN elastase and interleukin (IL)-8, a significantly lower ratio of the respiratory index, and a significantly higher ratio of PaO(2)/FiO(2) after 24 h of treatment than the control group.Sivelestat sodium suppressed the production of PMN elastase and IL-8, resulting in improved respiratory function in patients with ALI caused by CPB.

A 49-year-old man, who had suffered from acute myocardial infarction due to left main trunk occlusion, developed cardiogenic shock and was successfully treated with an implantation of a left ventricular assist system with left ventricular apical drainage. At present he is awaiting a heart transplant at approximately 485 days since the operation. The timely application of a left ventricular assist system before the development of multiple organ failure is thus considered to be effective for patients demonstrating acute myocardial infarction with cardiogenic shock.

p14 activates p53 by inhibiting MDM2 expression and arrests the cell cycle in G1 and G2/M. Abnormal p14 expression has been reported in various human cancers. This study investigated p14 expression in endometrioid adenocarcinoma of the uterine corpus in an attempt to clarify its correlation with other cell cycle-regulators and clinicopathologic parameters. The specimen studied consisted of 124 endometrioid adenocarcinomas, 20 normal endometria, and 20 endometrial hyperplasias. Immunohistochemical staining of formalin-fixed and paraffin-embedded tissues was performed using a Catalyzed Signal Amplification System. Cells with5% positive staining were classified as positive for p14. A staining score of 1 was adopted when the percentage of positive nuclei was5%, a score of 2 when it was 5 to 50%, and a score of 3 when it was50%. In normal endometrium, the frequency of positive staining in the proliferative phase and secretory phase was 50% (4/8) and 58.3% (7/12), with staining scores of 1.8+/-0.9 and 1.6+/-0.5, respectively. The frequency of staining in simple hyperplasia (SH), complex hyperplasia (CH), and complex atypical hyperplasia (CAH) was 88.9% (8/9), 25% (1/4), and 42.9% (3/7), respectively; the staining scores were 1.9+/-0.3, 1.3+/-0.5, and 1.4+/-0.5, respectively. Among endometrioid adenocarcinomas, the frequency of staining of well-differentiated (G1), moderately differentiated (G2), and poorly differentiated (G3) adenocarcinomas was 69% (49/71), 64% (16/25), and 42.9% (12/28) respectively, with staining scores of 2.1+/-0.8, 2+/-0.9, and 1.8+/-1, respectively. Thus expression levels of p14 were higher in G1 tumors than in normal endometria or endometrial hyperplasias, and the frequency of its staining in endometrioid carcinomas was inversely correlated with histologic grade. The staining score for endometrioid adenocarcinomas also was inversely correlated with the labeling index (LI) of Ki-67, but not with that of cyclin A, cyclin D1, cyclin E, cdk2, p27, p53, or other clinicopathologic parameters. In conclusion, p14 expression correlated with histologic grade and Ki-67, but not other prognostic factors in endometrioid adenocarcinoma. Long-term follow-up studies are needed to analyze the significance of p14 expression in these tumors.

Objective: Prosthetic valve endocarditis remains a challenging complication after heart valve replacement. To identify predictive risk factors, we have reviewed 30 patients who underwent surgery for prosthetic valve endocarditis between March 1986 and May 1999.Methods: There were 15 men and 15 women (mean age 51 years). Prosthetic valve endocarditis was classified as early (≦ 1 year after operation) in 10 cases, and as late in the other 20 cases. The most common indication for surgery was moderate to severe congestive heart failure due to prosthetic valve dysfunction in 21 (70%) patients. The average follow-up period was 6.5 years, with a range of 0.3 to 14.1 years.Results: The most common microorganism was Staphylococcus epidermidis in both patients with early (50%) and late prosthetic valve endocarditis (25%). The in-hospital mortality was 13.3% (4/30). There were six late deaths. The actuarial survival at 5 years was 78% and 66% at 10 years. An early onset of prosthetic valve endocarditis was the only significant determinant of both in-hospital mortality (p=0.005) and overall mortality (p=0.1). Emergency surgery had a statistically significant relationship with in-hospital mortality (p=0.5). No significant influence on mortality after reoperation for prosthetic valve endocarditis was found in age, sex, valve position, antecedent native valve endocarditis, or in the type of pathological findings (ring abscess, valve dehiscence, and vegetation).Conclusion: Early onset of prosthetic valve endocarditis and emergency surgery were important risk factors for mortality due to prosthetic valve endocarditis.

We obtain logarithmic behaviours of a four-point correlation function in the c=-2 conformal field theory by using the Feigin-Fuchs construction. It becomes an indeterminate form by a naive evaluation, but is obtained by introducing an appropriate regularization procedure., Comment: LaTeX, 7 pages

superior cavopulmonary anastomosis was effective and functioned well for 2 years in a patient with huge right ventricular fibroma. As for methodology of superior cavopulmonary anastomosis, bidirectional Glenn anastomosis is preferred to hemi-Fontan procedure because the superior vena cava should be disconnected from the right atrium to guard cavopulmonary anastomosis against tumor extension into the right atrium or right atrial thrombus secondary to right ventricular obstruction. Although surgical excision does not cure the primary disease in metastatic tumors of the heart, palliative resection may be justified for immediate life-threatening danger due to an intracavity space-occupying lesion. Additional bidirectional cavopulmonary anastomosis may provide assurance in long-term pulmonary blood flow in unresectable cardiac metastasis.

Purpose It is well known that aortic insufficiency (AI) is related to poor prognosis during left ventricular assisting device (LVAD) support. Since AHA announced destination therapy as a Class I therapy, weight is attached to AI management. We investigated the pathological change of the aortic valve after long-term LVAD support. Methods and Materials Thirty-three hearts removed at heart transplantation were investigated. Twenty-nine patients were supported by extracorporeal pulsatile device (Nipro-LVAD) and 4 patients by implantable devices (Heartmate II, Jarvik 2000, Novacor, EVAHEART, 1 case each). We compared the histological change of the aortic valve with the results of echocardiogram. Results The mean duration of LVAD support until heart transplantation was 972±324 (ranged from 416 to 1697) days. Although AI was detected in only one patient before LVAD implantation, it was detected in 19 patients before the transplantation. Pathological examination revealed that the aortic valve became thinner in all patients, ranged from 120 to 1400 micrometer. Micro thrombus on cusps and collagen proliferation in the spongiosa layer were also recognized. [ figure 1 ] Partial aortic valve fusion was seen in 4 recipients and curling of cusp tips was detected in 22 patients. Statistically, there was no close correlation between aortic valve thickness and LVAS support duration time, the grade of AI, nor cardiac function. Conclusions Degenerative aortic valve change was recognized after long-term LVAD support. Now that implantable continuous flow LVAD becomes the mainstream, we need to take more notice of AI during LVAD support.

The Role of Cardiologists in the Era of Implantable Left Ventricular Assist Device Therapies in Advanced Heart Failure OSAMU SEGUCHI, YOSHIHIRO MURATA, MASANOBU YANASE, HIROKI HATA, TOMOYUKI FUJITA, TAKESHI NAKATANI Department of Transplantation, National Cerebral and Cardiovascular Center, Osaka, Japan, Department of Cardiothoracic Surgery, National Cerebral and Cardiovascular Center, Osaka, Japan

Reoperative surgical intervention for a new-onset aortic arch dissection following a Bentall procedure or graft replacement for the ascending aorta is often difficult, especially in elderly patients. Herein, we report a re-do arch replacement method using a trifurcate-branched graft and long elephant trunk anastomosis at the composite root graft on the ascending aorta. The present technique is feasible as an alternative for new-onset or residual aortic arch aneurysm, as well as dissection following an operation for the ascending aorta.