Yunguirius gen. nov., a new genus of Coelotinae (Araneae, Agelenidae) spiders from southwest China.

A new genus of the subfamily Coelotinae F. O. Pickard-Cambridge, 1893, Yunguiriusgen. nov. is described, comprising two new species and three species previously described in Draconarius Ovtchinnikov, 1999, all from southwest China: Y.duogesp. nov. (♀), Y.xiangdingsp. nov. (♀), Y.ornatus (Wang, Yin, Peng & Xie, 1990) comb. nov. (♂♀) (the type species of Yunguiriusgen. nov.), Y.subterebratus (Zhang, Zhu & Wang, 2017) comb. nov. (♀), and Y.terebratus (Peng & Wang, 1997) comb. nov. (♂♀). Molecular analyses support Yunguiriusgen. nov. as a monophyletic group, with the Sinodraconarius clade as its sister group: Yunguiriusgen. nov. + (Hengconarius + (Nuconarius + Sinodraconarius)).

Puzzling (IRIDA-Like and Hemolytic) Anemia in a Child With Idiopathic Pulmonary Hemosiderosis.

Before the diagnosis of idiopathic pulmonary hemosiderosis (IPH), unexplained or puzzling anemia may precede and delay in the diagnosis of pediatric IPH is common. A 5.8 years old female child initiated with iron-refractory iron deficiency anemia-like iron deficiency and hemolytic anemia and at 6.8 years of age IPH was materialized, when the patient showed the triad signs of IPH with hemosiderin-laden alveolar macrophages in gastric aspirate. Although time to the diagnosis was previously reported to be ranged from 16 to 30 months, in our case it took 12 months from the initial anemia to IPH diagnosis.

Students' perception of a hybrid interprofessional education course in a clinical diabetes setting: a qualitative study.

OBJECTIVES: To explore what the student participants learned and how they felt about the use of three educational settings, namely, face-to-face workshop setting, asynchronous and synchronous online learning environments and interactions with outpatients in a real-world clinical setting in a hybrid interprofessional education course. METHODS: This qualitative study used semi-structured in-depth interviews with healthcare undergraduate student participants in a course comprising workshops in three educational settings. A total of 15 healthcare undergraduate students, which included four medical, three pharmacy, five nursing and three nutrition students, completed this IPE course. All students agreed to participate in the study. We conducted four focus groups selected using convenient sampling. Focus group transcripts were analysed using the 'Steps for Coding and Theorization' qualitative data analysis method. We investigated the students' perception through the experience of three educational settings in the hybrid interprofessional education course. RESULTS: The students recognised that this course had three types of educational spaces, namely, real, semi-real and unreal. Then, the positive changes in the awareness of students are trained in recognition of the patient perspective, the recognition of the roles discharged by the other professions and the recognition of the functions of their own profession after experiencing the educational spaces designated for this course. CONCLUSIONS: The repeated experience of participants to real, semi-real and unreal educational spaces promoted changes over time in the students' awareness of interprofessional competencies with respect to patient-centred care and ameliorated their readiness to undertake interprofessional tasks.

Heart Rate Reduction Improves Right Ventricular Function and Fibrosis in Pulmonary Hypertension.

The potential benefit of heart rate reduction (HRR), independent of ß-blockade, on right ventricular (RV) function in pulmonary hypertension (PH) remains undecided. We studied HRR effects on RV fibrosis and function in PH and RV pressure-loading models. Adult rats were randomized to 1) sham controls, 2) monocrotaline (MCT)-induced PH, 3) SU5416 + hypoxia (SUHX)-induced PH, or 4) pulmonary artery banding (PAB). Ivabradine (IVA) (10 mg/kg/d) was administered from 2 weeks after PH induction or PAB. Exercise tolerance, echocardiography, and pressure-volume hemodynamics were obtained at a terminal experiment 3 weeks later. RV myocardial samples were analyzed for putative mechanisms of HRR effects through fibrosis, profibrotic molecular signaling, and Ca++ handling. The effects of IVA versus carvedilol on human induced pluripotent stem cell-derived cardiomyocytes beat rate and relaxation properties were evaluated in vitro. Despite unabated severely elevated RV systolic pressures, IVA improved RV systolic and diastolic function, profibrotic signaling, and RV fibrosis in PH/PAB rats. RV systolic-elastance (control, 121 ± 116; MCT, 49 ± 36 vs. MCT+IVA, 120 ± 54; PAB, 70 ± 20 vs. PAB+IVA, 168 ± 76; SUHX, 86 ± 56 vs. SUHX +IVA, 218 ± 111; all P < 0.05), the time constant of RV relaxation, echo indices of RV function, and fibrosis (fibrosis: control, 4.6 ± 1%; MCT, 13.4 ± 6.5 vs. MCT+IVA, 6.7 ± 2.6%; PAB, 11.4 ± 4.5 vs. PAB+IVA, 6.4 ± 5.1%; SUHX, 10 ± 4.6 vs. SUHX+IVA, 3.9 ± 2.2%; all P < 0.001) were improved by IVA versus controls. IVA had a dose-response effect on induced pluripotent stem cell-derived cardiomyocytes beat rate by delaying Ca++ loss from the cytoplasm. In experimental PH or RV pressure loading, HRR improves RV fibrosis, function, and exercise endurance independent of ß-blockade. The balance between adverse tachycardia and bradycardia requires further study, but judicious HRR may provide a promising strategy to improve RV function in clinical PH.

Pulmonary artery banding is a relevant model to study the right ventricular remodeling and dysfunction that occurs in pulmonary arterial hypertension.

Right ventricular (RV) dysfunction determines mortality in patients with pulmonary arterial hypertension (PAH) and RV pressure loading. Experimental models commonly use Sugen hypoxia (SuHx)-induced PAH, monocrotaline (MCT)-induced PAH, or pulmonary artery banding (PAB). Because PAH models cannot interrogate RV effects or therapies independent of pulmonary vascular effects, we aimed to compare RV function and fibrosis in experimental PAB vs. PAH. Thirty rats were randomized to either sham controls, PAB, SuHx-, or MCT-induced PAH. RV pressures and function were assessed by high-fidelity pressure-tipped catheters and by echocardiography. RV myocyte hypertrophy, fibrosis, and capillary density were quantified from hematoxylin-eosin, picrosirius red-stained, and CD31-immunostained RV sections, respectively. RV pressures and the RV-to-left ventricular pressure ratio were significantly increased in all three groups to a similar degree (PAB 65 ± 17 mmHg, SuHx 72 ± 16 mmHg, and MCT 70 ± 12 mmHg) vs. controls (23 ± 2 mmHg, all P < 0.01). RV dilatation, hypertrophy, and fibrosis were similarly increased, and capillary density decreased, in the three models (RV fibrosis; PAB 13.3 ± 3.6%, SuHx 9.8 ± 3.0% and MCT 10.9 ± 2.4% vs control 5.5 ± 1.1%, all P < 0.05). RV function was similarly decreased in all models vs. controls. We observed comparable RV dilatation, hypertrophy, systolic and diastolic dysfunction, fibrosis, and capillary rarefaction in rat models of PAB, SuHx-, and MCT-induced PAH. These results suggest that PAB, when sufficiently severe, induces features of maladaptive RV remodeling and can be used to investigate RV pathophysiology and therapy effects independent of pulmonary vascular resistance.NEW & NOTEWORTHY Although animal models of pulmonary arterial hypertension and pressure loading are important to study right ventricular (RV) pathophysiology, pulmonary arterial hypertension models cannot interrogate RV responses independent of pulmonary vascular effects. Comparing three commonly used rat models under similar elevated RV pressure, we found that all models resulted in comparable maladaptive RV remodeling and dysfunction. Thus, these findings suggest that the pulmonary artery banding model can be used to investigate mechanisms of RV dysfunction in RV pressure overload and the effect of potential therapies.

Hide and Seek with Massive Fields in Modulus Mediation.

We study the modulus mediation of supersymmetry breaking motivated by superstring theory. We show that the renormalization group running of the soft supersymmetry breaking parameters due to the interactions of massive fields is canceled by the threshold corrections at one-loop order, if their mass is given by nonperturbative dynamics controlled by the same modulus that mediates supersymmetry breaking and a sum rule of the modular weights holds for the Yukawa couplings. As an example, we discuss order reduction of lepton flavor violation in the supersymmetric seesaw mechanism, which revives the parameter space already excluded.

Tissue Motion Annular Displacement of the Mitral Valve Can Be a Useful Index for the Evaluation of Left Ventricular Systolic Function by Echocardiography in Normal Children.

As the important role of longitudinal shortening in ventricular function has been well recognized over the past decade, evaluation of longitudinal systolic function of the left ventricle has become a subject of growing interest. Tissue motion annular displacement of the mitral valve (TMAD) is a new parameter of longitudinal systolic function. Although some studies have reported that this new parameter correlates with left ventricular ejection fraction (LVEF) in adults, little is known about TMAD in normal children. In this work, we investigated 94 children with no history of cardiovascular disease. TMAD was measured in the apical four-chamber view using the two-dimensional speckle tracking technique. Three points for tracking were selected in a diastolic frame: the lateral mitral valve annulus, medial mitral valve annulus, and left ventricular apex. The value was expressed as the percentage of displacement of the midpoint of the mitral valve annulus, using software to correct for left ventricular length at end-diastole. Pearson's coefficient was used to estimate the correlation between TMAD and left ventricular systolic function parameters including the biplane modified Simpson method-derived ejection fraction and global longitudinal strain (GLS). We also analyzed the correlation between TMAD and heart rate (HR), height, age, and body surface area (BSA). TMAD was found to correlate significantly with LVEF (r = 0.71, p < 0.01) and GLS (r = -0.77, p < 0.01). However, no correlation was revealed for HR (r = -0.14, p = 0.19), height (r = -0.17, p = 0.10), age (r = -0.19, p = 0.09), or BSA (r = -0.19, p = 0.08). These results indicate that TMAD is useful for assessing LVEF and longitudinal systolic function in normal children, and is not influenced by changes in HR, height, age, or BSA.

Experimental Right Ventricular Hypertension Induces Regional ß1-Integrin-Mediated Transduction of Hypertrophic and Profibrotic Right and Left Ventricular Signaling.

BACKGROUND: Development of right ventricular (RV) hypertension eventually contributes to RV and left ventricular (LV) myocardial fibrosis and dysfunction. The molecular mechanisms are not fully elucidated. METHODS AND RESULTS: Pulmonary artery banding was used to induce RV hypertension in rats in vivo. Then, we evaluated cardiac function and regional remodeling 6 weeks after pulmonary artery banding. To further elucidate mechanisms responsible for regional cardiac remodeling, we also mimicked RV hypertensive stress by cyclic mechanical stretching applied to confluent cultures of cardiac fibroblasts, isolated from the RV free wall, septal hinge points, and LV free wall. Echocardiography and catheter evaluation demonstrated that rats in the pulmonary artery banding group developed RV hypertension with leftward septal displacement, LV compression, and increased LV end-diastolic pressures. Picrosirius red staining indicated that pulmonary artery banding induced marked RV fibrosis and dysfunction, with prominent fibrosis and elastin deposition at the septal hinge points but less LV fibrosis. These changes were associated with proportionally increased expressions of integrin-ß1 and profibrotic signaling proteins, including phosphorylated Smad2/3 and transforming growth factor-ß1. Moreover, mechanically stretched fibroblasts also expressed significantly increased levels of α-smooth muscle actin, integrin-ß1, transforming growth factor-ß1, collagen I deposition, and wrinkle formation on gel assays, consistent with myofibroblast transformation. These changes were not observed in parallel cultures of mechanically stretched fibroblasts, preincubated with the integrin inhibitor (BTT-3033). CONCLUSIONS: Experimentally induced RV hypertension triggers regional RV, hinge-point, and LV integrin ß1-dependent mechanotransduction signaling pathways that eventually trigger myocardial fibrosis via transforming growth factor-ß1 signaling. Reduced LV fibrosis and preserved global function, despite geometrical and pressure aberrations, suggest a possible elastin-mediated protective mechanism at the septal hinge points.

Heart rate reduction improves biventricular function and interactions in experimental pulmonary hypertension.

The objective of the present study was to investigate mechanisms of heart rate (HR) reduction on biventricular function and interactions in experimental pulmonary arterial hypertension (PAH). We compared cardiac cycle mechanics and interventricular interactions in 15 sham, 8 monocrotaline-PAH, 9 PAH + carvedilol, and 8 PAH + ivabradine rats. We used echocardiography to assess biventricular function, timing of cardiac cycle events, and septal position in PAH rats and related HR reduction effects on biventricular function measured by echocardiography and conductance catheter. HR was 302 beats/min in PAH + carvedilol rats and 303 beats/min in PAH + ivabradine rats versus 359 beats/min in PAH rats ( P < 0.01). Sham rats showed temporal alignment between right ventricular (RV) and left ventricular (LV) events, whereas PAH rats showed increased biventricular isovolumic contraction times (ICTs), delayed RV peak radial motion, and impaired early relaxation. Temporal malalignment was associated with decreased tricuspid and mitral diastolic annular peak velocities (3.7 vs. 6.4 and 3.4 vs. 5.3 cm/s, respectively, P < 0.001), delayed and shortened biventricular filling, and reduced early diastolic LV filling velocity (0.56 vs. 0.81 cm/s, P < 0.01). LV eccentricity index was increased at systole (2.0 vs. 1.2, P < 0.001), early diastole (2.1 vs. 1.1, P < 0.001), and end diastole (1.6 vs. 1.1, P < 0.001) in PAH versus sham rats. HR reduction with carvedilol and ivabradine shortened biventricular ICTs and the time to biventricular peak radial motion, improved RV relaxation, and increased early diastolic LV filling through reduced interventricular interaction and improved timing. These improvements corresponded with enhanced hemodynamics (increased cardiac output, RV contractility, and diastolic relaxation). In conclusion, HR reduction by carvedilol and ivabradine improves biventricular filling and hemodynamics in experimental PAH through realignment of RV-LV cardiac cycle events and improved interventricular interactions. NEW & NOTEWORTHY Carvedilol improves biventricular function in experimental pulmonary arterial hypertension, but the mechanisms of heart rate reduction versus ß-blocker effect are inadequately defined. Here, we demonstrate that reducing heart rate using either carvedilol or ivabradine (hyperpolarization-activated current inhibitor without ß-blocker effect) improves right ventricular filling and biventricular hemodynamics through the realignment of right ventricular-left ventricular cardiac cycle events and improved interventricular interactions.

Regional septal hinge-point injury contributes to adverse biventricular interactions in pulmonary hypertension.

Death and morbidity in pulmonary arterial hypertension (PAH) are often due to right ventricular (RV) failure and associated left ventricular (LV) dysfunction. We investigated regional myocardial remodeling and function as the basis for adverse ventricular-ventricular interactions in experimental chronic RV pressure overload. Two distinct animal models were studied: A rabbit model of increased RV pressure-load through progressive pulmonary artery banding A rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH). Regional myocardial function was assessed by speckle-tracking strain echocardiography and ventricular pressures measured by catheterization before termination. Regional RV and LV myocardium was analyzed for collagen content, apoptosis and pro-fibrotic signaling gene and protein expression. Although the RV developed more fibrosis than the LV; in both models the LV was substantially affected. In both ventricles, particularly the LV, fibrosis developed predominantly at the septal hinge-point regions in association with decreased regional and global circumferential strain, reduced global RV and LV function and up-regulation of regional transforming growth factor-ß1 (TGFß1) and apoptosis signaling. A group of PAH rats who received the TGFß blocker SB431542 showed improved RV function and reduced regional hinge-point myocardial fibrosis. RV pressure-loading and PAH lead to biventricular TGFß1 signaling, fibrosis and apoptosis, predominantly at the septal hinge-point regions, in association with regional myocardial dysfunction. This suggests that altered geometry and wall stress lead to adverse RV-LV interactions through the septal hinge-points to induce LV fibrosis and dysfunction.

Carvedilol improves biventricular fibrosis and function in experimental pulmonary hypertension.

UNLABELLED: Left ventricular (LV) function influences outcomes in right ventricular (RV) failure. Carvedilol reduces mortality in LV failure and improves RV function in experimental pulmonary arterial hypertension (PAH). However, its impact on ventricular-ventricular interactions and LV function in RV afterload is unknown. We investigated effects of carvedilol on biventricular fibrosis and function in a rat model of persistent PAH. Rats were randomized into three groups: Sham controls, PAH, and PAH + carvedilol. Severe PAH was induced by 60 mg/kg subcutaneous monocrotaline. In the treatment group, oral carvedilol (15 mg/kg/day) was started 2 weeks after monocrotaline injection and continued for 3 weeks until the terminal experiment. Echocardiography and exercise performance were performed at baseline and repeated at the terminal experiment with hemodynamic measurements. LV and RV myocardium were analyzed for hypertrophy, fibrosis, and molecular signaling by protein and mRNA analysis. PAH and PAH + carvedilol rats experienced severely elevated pulmonary arterial pressures and RV hypertrophy. Despite similar RV systolic pressures, carvedilol reduced biventricular collagen content (RV fibrosis area; 13.4 ± 6.5 vs. 5.5 ± 2.7 %, p < 0.001) and expression of transforming growth factor-ß1 (TGFß1) (RV TGFß1/glyceraldehyde 3-phosphate dehydrogenase (GAPDH) ratio; 1.16 ± 0.39 vs. 0.57 ± 0.22, p < 0.01) and connective tissue growth factor (CTGF) (RV CTGF/GAPDH ratio; 0.49 ± 0.06 vs. 0.35 ± 0.17, p < 0.05). RV pro-apoptotic caspase-8 was increased in PAH compared to controls and was significantly reduced in both ventricles compared to PAH animals by carvedilol. Tissue effects were accompanied by improved biventricular systolic and diastolic performance and exercise treadmill distance (36 ± 30 vs. 80 ± 33 m, p < 0.05). In RV pressure-load, carvedilol improves biventricular fibrosis and function through abrogation of TGFß1-CTGF signaling. KEY MESSAGE: • RV afterload caused biventricular injury and dysfunction through TGFß1-CTGF signaling. • Carvedilol reduced biventricular TGFß1-CTGF signaling, fibrosis, and apoptosis. • Carvedilol improved cardiac output and biventricular function. • Improved fibrosis and hemodynamics occurred despite persistent RV afterload.

Longitudinal assessment of right ventricular myocardial strain in relation to transplant-free survival in children with idiopathic pulmonary hypertension.

BACKGROUND: Right ventricular (RV) function is an important determinant of mortality in patients with idiopathic pulmonary arterial hypertension (iPAH). The aim of this study was to serially evaluate global and regional RV two-dimensional strain and their relation to transplantation-free survival in children with iPAH. METHODS: RV regional and global longitudinal strain was retrospectively assessed in children with iPAH. Serial echocardiograms at 3 to 6 months from presentation and then at yearly intervals were analyzed. Results were compared with those from controls and between iPAH survivors (group 1) and those who died or needed transplantation (group 2). Survival stratified by RV global longitudinal strain at presentation was analyzed. RESULTS: Seventeen patients with iPAH (mean age, 8.4 ± 4.8 years; seven male patients), of whom 11 were alive (group 1) and six had died or undergone transplantation (group 2), and 17 age-matched controls were studied. The median follow-up period was 1.5 years (range, 0.04-7.8 years). RV global longitudinal strain was significantly reduced in patients with iPAH compared with controls (-13.5 ± 5.9% vs -24.4 ± 3.9%, P < .001) and in group 2 compared with group 1 at presentation (-9 ± 2.8% vs -16 ± 5.7%, P < .05) and throughout follow-up. During follow-up, RV global and regional longitudinal strain worsened in group 2, especially in RV apical segments (-6.3 ± 5% vs -1.9 ± 1.6% at presentation compared with the last echocardiographic assessment in group 2, P < .05), but was unchanged in group 1. RV global longitudinal strain > -14% predicted transplantation-free survival with 100% sensitivity and 54.5% specificity. CONCLUSIONS: RV strain imaging may be useful for serial follow-up and prognostication in children with iPAH.

Right ventricular diastolic performance in children with pulmonary arterial hypertension associated with congenital heart disease: correlation of echocardiographic parameters with invasive reference standards by high-fidelity micromanometer catheter.

BACKGROUND: Right ventricular diastolic dysfunction influences outcomes in pulmonary arterial hypertension (PAH), but echocardiographic parameters have not been investigated in relation to invasive reference standards in pediatric PAH. We investigated echocardiographic parameters of right ventricular diastolic function in children with PAH in relation to simultaneously measured invasive reference measures. METHODS AND RESULTS: We prospectively recruited children undergoing a clinically indicated cardiac catheterization for evaluation of PAH and pulmonary vasoreactivity testing. Echocardiography was performed simultaneously with invasive reference measurements by high-fidelity micromanometer catheter. For analysis, patients were divided into shunt and nonshunt groups. Sixteen children were studied. In the group as a whole, significant correlations were found among τ and tricuspid deceleration time, E', E/E', TimeE-E', A wave velocity, and global early and late diastolic strain rate. dp/dt minimum correlated significantly with late diastolic tricuspid annular velocity (A'), tissue Doppler imaging-derived systolic:diastolic duration ratio, and global late diastolic strain rate. End-diastolic pressure correlated significantly with tissue Doppler imaging-derived systolic:diastolic duration ratio. On multivariate analysis, tricuspid deceleration time, TimeE-E', and global early diastolic strain rate were independent predictors of τ, whereas tissue Doppler imaging-derived systolic:diastolic duration ratio was an independent predictor of dp/dt minimum. In general, correlations between echocardiographic and invasive parameters were better in the shunt group than in the nonshunt group. CONCLUSIONS: Echocardiography correlates with invasive reference measures of right ventricular diastolic function in children with PAH, although it does not differentiate between early versus late diastolic abnormalities. Newer echocardiographic techniques may have added value to assess right ventricular diastolic dysfunction in this population.

Clinico-radiological spectrum of reversible splenial lesions in children.

Recently, many cases of children presenting reversible splenial lesions during febrile illness (RESLEF) have been reported; however, their overall clinico-radiological features are unclear. To describe the clinico-radiological features, we retrospectively reviewed the etiology (pathogen), clinical course, laboratory data, magnetic resonance imaging and electroencephalography (EEG) findings, therapy, and prognosis of 23 episodes in 22 children (1 child recurred) who presented neurological symptoms, with RESLEF. The etiologies (pathogens) varied. Seizure occurred in 7 episodes, disturbance of consciousness (DC) in 13, and delirious behavior in 18. Serum sodium levels <136 mEq/L were observed in 18 episodes. Lesions outside the splenium were found in 4 cases. Slow waves were observed on EEG in 10 episodes. Methylprednisolone pulse therapy was given in 7 cases. No case resulted in neurological sequelae. Among 23 episodes, clinically mild encephalitis/encephalopathy with a reversible splenial lesion (MERS) was diagnosed in 6 episodes, whereas non-MERS was observed in 17 episodes. No difference was observed in almost all the clinico-radiological features' data between the 2 groups. The largest differences were observed in the rate of purposeless movement, DC, extension of the abnormal lesions outside the splenium, and marked slowing of background activity on EEG. RESLEF exhibit a spectrum of clinico-radiological features. These results suggest that non-MERS and MERS both are a part of a larger pathological condition, which we have termed as RESLEF spectrum syndrome. Given the view that such a syndrome exists, the clinical characteristics and position of non-MERS and MERS become clear.

[A case of fulminant myocarditis successfully treated by percutaneous cardiopulmonary support after 50 minuite-cardiopulmonary resuscitation].

We report a case of an 8-year-old girl with fulminant myocarditis successfully treated with percutaneous cardiopulmonary support (PCPS). She was first taken to our hospital for treatment of suspected infective enterocolitis since her main symptoms were fever, vomiting and diarrhea. On day 2 after admission, her ECG showed wide QRS and echocardiography demonstrated severe hypokinesis. She was transferred to the ICU with suspected acute myocarditis. On admission to the ICU, circulatory collapse was not detected. ECG showed severe bradycardia and ventricular fibrillation after intubation. Cardiopulmonary resuscitation was performed immediately for 50 minutes prior to initiation of PCPS. She was treated intensively with catecholamines, plasma exchange, continuous hemodiafiltration, high-dose gamma-globulin, and high dose methylprednisolone. Hypothermia therapy was also performed. She was weaned from PCPS on day 6 after initiation of PCPS. The patient was finally discharged from the hospital without any neurological complications on day 68 after weaning from PCPS. The proportion of patients in whom cardiopulmonary resuscitation was performed or having ventricular tachycardia or fibrillation were higher in non-survivors than in survivors.

GNOM/FEWER ROOTS is required for the establishment of an auxin response maximum for arabidopsis lateral root initiation.

Lateral root (LR) formation in vascular plants is regulated by auxin. The mechanisms of LR formation are not fully understood. Here, we have identified a novel recessive mutation in Arabidopsis thaliana, named fewer roots (fwr), that drastically reduces the number of LRs. Expression analyses of DR5::GUS, an auxin response reporter, and pLBD16::GUS, an LR initiation marker, suggested that FWR is necessary for the establishment of an auxin response maximum in LR initiation sites. We further identified that the fwr phenotypes are caused by a missense mutation in the GNOM gene, encoding an Arf-GEF (ADP ribosylation factor-GDP/GTP exchange factor), which regulates the recycling of PINs, the auxin efflux carriers. The fwr roots showed enhanced sensitivity to brefeldin A in a root growth inhibition assay, indicating that the fwr mutation reduces the Arf-GEF activity of GNOM. However, the other developmental processes except for LR formation appeared to be unaffected in the fwr mutant, indicating that fwr is a weaker allele of gnom compared with the other gnom alleles with pleiotropic phenotypes. The localization of PIN1-green fluorescent protein (GFP) appeared to be unaffected in the fwr roots but the levels of endogenous IAA were actually higher in the fwr roots than in the wild type. These results indicate that LR initiation is one of the most sensitive processes among GNOM-dependent developmental processes, strongly suggesting that GNOM is required for the establishment of the auxin response maximum for LR initiation, probably through the regulation of local and global auxin distribution in the root.

[Arterial switch operation for transposition of the great arteries with situs inversus and mirror image dextrocardia].

We report a successful arterial switch operation for complete transposition of great arteries with atrial and visceral situs inversus totalis and mirror image dextrocardia in a 12-day-old infant girl. The aorta was located left side-by-side to the pulmonary trunk with a single coronary artery (mirror image of 1RLCx). After French maneuver, the posterior circumference of the neo-aorta was reconstructed. Then the coronary button was transplanted into the neo-aorta with a trap door technique carefully avoiding any twist and over-stretch. The neo-pulmonary trunk was reconstructed with an autologous pericardial patch and sutured to the longitudinal incision made into the left central pulmonary artery. The baby was discharged from hospital and has been doing well without any morbidity relating myocardial ischemia.

Repair of persistent truncus arteriosus without a conduit: sleeve resection of the pulmonary trunk from the aorta and direct right ventricle-pulmonary artery anastomosis.

OBJECTIVE: Establishing a new continuity between the right ventricle and the pulmonary artery is the mainstay of repair for persistent truncus arteriosus. We used the Tran Viet-Neveux technique without a Lecomte maneuver to construct the connection without a conduit. Here, we retrospectively review the mid-term surgical results to examine the effectiveness of this approach. METHODS: A cylindrical segment incorporating both pulmonary artery branches was sleeve-resected from the truncal artery. The cylindrical segment was cut in the middle and two truncal arterial flaps were combined to form the posterior floor of the new pulmonary arterial trunk. The edge of the floor was attached directly to the superior margin of an oblique incision made in the left-anterior wall of the right ventricle. A polytetrafluoroethylene monocusp was attached to the lower half margin of the right ventricular incision. A large glutaraldehyde-treated pericardial patch was used to form the anterior hood of the new right ventricular outflow tract. Both great arteries were located in a normal spiral configuration. RESULTS: Ten babies (range: 3 days to 9 months of age) underwent this procedure. The Collett-Edwards classification of persistent truncus arteriosus was type I in five cases and type II in five others. There was one hospital death due to severe respiratory distress. During follow-up (36-60 months, median 54 months), only one re-operation was required to enlarge a left branch pulmonary artery stenosis. Follow-up echocardiography showed pulmonary regurgitation (mild two, moderate seven, and severe one) and mild flow acceleration in the left pulmonary artery branch and right ventricle-pulmonary artery connection in one case. CONCLUSION: This simple modification for surgical correction of persistent truncus arteriosus may be an effective alternative that overcomes conduit-related problems.

Oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in children.

OBJECTIVE: Sildenafil is a strong pulmonary vasodilator that increases the intracellular cyclic guanosine monophosphate concentration through inhibition of phosphodiesterase-5. We assessed the benefit of oral sildenafil for persistent pulmonary hypertension early after congenital cardiac surgery in paediatric patients. METHODS: Sildenafil was administered at a starting dose of 0.5 mg kg(-1) following admission to the intensive care unit. With careful monitoring of haemodynamics, the dose was increased stepwise by 0.5 mg kg(-1) every 4-6 h up to a maximum of 2 mg kg(-1). After successful weaning from a ventilator and from other vasodilators, sildenafil was gradually discontinued over the next 5-7 days. RESULTS: A retrospective review of medical records showed an age distribution of <1 month (n=26), > or = 1-<6 months (n=36), > or = 6-<12 months (n=19), 1-3 years (n=8), 4-9 years (n=9) and >10 years (n=2) at the time of surgery. The surgeries were performed for ventricular septal defect closure (n=17), arterial switch (n=30), truncus arteriosus repair (n=10), complete atrioventricular septal defect repair (n=12), total anomalous venous drainage repair (n=9), and other open-heart surgery (n=22). The aforementioned concomitant inhaled nitrous oxide treatment was performed in 66 patients. Pulmonary arterial pressure decreased in 28, was unchanged in five and elevated in one patient out of the total of 34 cases for which data from continuous pressure monitoring were available. Bosentan was added in three cases with persistent symptoms due to pulmonary hypertension despite sildenafil treatment. After sildenafil administration, modest oxygen desaturation occurred in seven cases, but no 'rebound' pulmonary hypertension occurred. There were no significant adverse events during sildenafil treatment. CONCLUSIONS: Our results suggest that oral sildenafil is a safe and effective alternate for persistent pulmonary hypertension following congenital heart surgery in children.