Tricuspid and mitral remodelling in atrial fibrillation: a three-dimensional echocardiographic study.

AIMS: Atrial fibrillation (AF) is associated with atrial enlargement, mitral annulus (MA) and tricuspid annulus (TA) dilation, and atrial functional regurgitation (AFR). However, less is known about the impact of AF on both atrioventricular valves in those with normal and abnormal ventricular function. We aimed to compare the remodelling of the TA and MA in patients with non-valvular AF without significant AFR. METHODS AND RESULTS: Ninety-two patients referred for transoesophageal echocardiography were included and categorized into three groups: (i) AF with normal left ventricular (LV) function (Normal LV-AF), n = 36; (ii) AF with LV systolic dysfunction (LVSD-AF), n = 29; and (iii) Controls in sinus rhythm, n = 27. Three-dimensional MA and TA geometry were analysed using automated software. In patients with AF regardless of LV function, the MA and TA areas were larger compared with controls (LVSD-AF vs. Normal LV-AF vs. Controls, end-systolic MA: 5.2 ± 1.1 vs. 4.5 ± 0.7 vs. 3.9 ± 0.7 cm2/m2; end-systolic TA: 5.6 ± 1.3 vs. 5.3 ± 1.3 vs. 4.1 ± 0.7 cm2/m2; P < 0.05 for each comparison with Controls). TA and MA areas were not statistically different between the two AF groups. The TA increase over controls was greater than that of the MA in the Normal LV-AF group (27.7% vs. 15.6%, P = 0.041). Conversely, in the LVSD-AF group, MA and TA increased similarly (35.9% vs. 32.4%, P = 0.660). CONCLUSION: Patients with AF showed dilation of both TA and MA compared with patients in sinus rhythm. In patients with normal LV function, AF was associated with greater TA dilation than MA dilation whereas in patients with LVSD the TA and MA were equally dilated.

Understanding tricuspid valve remodelling in atrial fibrillation using three-dimensional echocardiography.

AIMS: Atrial fibrillation (AF) has been associated with tricuspid annulus (TA) dilation in patients with severe functional tricuspid regurgitation (TR); however, the impact of AF is less clear in patients without severe TR. Our aim was to characterize TA remodelling in patients with AF in the absence of severe TR using 3D transoesophageal echocardiography (TOE). METHODS AND RESULTS: Ninety patients underwent clinically indicated transthoracic and TOE: non-structural (NS)-AF (n = 30); AF with left heart disease (LHD) (n = 30), and controls in sinus rhythm (n = 30). Three-dimensional TOE datasets were analysed to measure TA dimensions using novel dedicated tricuspid valve software. The NS-AF group showed biatrial dilatation and normal right ventricular (RV) size with decreased longitudinal function compared to controls, whereas the LHD-AF group showed biatrial dilatation, RV enlargement, decreased biventricular function, and higher systolic pulmonary artery pressure compared with the other groups. Indexed TA area, minimum diameter, maximum diameter, and total perimeter were significantly larger in the NS-AF group than in controls (measurements in end-diastole: 6.4 ± 1.1 vs. 5.0 ± 0.6 cm2/m2, 1.8 ± 0.3 vs. 1.6 ± 0.2 cm/m2, 2.1 ± 0.3 vs. 1.9 ± 0.2 cm/m2, and 6.6 ± 0.9 vs. 5.9 ± 0.7 cm/m2, respectively, all P < 0.05). There was no significant difference in any indexed TA parameter between AF groups. TA circularity index (ratio between minimum and maximal diameters) and TA fractional area change between end-diastole and end-systole were no different among the three groups. CONCLUSION: AF is associated with right atrial and tricuspid annular remodelling independent of the presence of LHD in patients with intrinsically normal tricuspid leaflets without severe TR.

Understanding Non-P2 Mitral Regurgitation Using Real-Time Three-Dimensional Transesophageal Echocardiography: Characterization and Factors Leading to Underestimation.

BACKGROUND: P2 prolapse is a common cause of degenerative mitral regurgitation (MR); echocardiographic characteristics of non-P2 prolapse are less known. Because of the eccentric nature of degenerative MR jets, the evaluation of MR severity is challenging. The aim of this study was to test the hypotheses that (1) the percentage of severe MR determined by transthoracic echocardiography (TTE) would be lower compared with that determined by transesophageal echocardiography (TEE) in patients with non-P2 prolapse and also in a subgroup with "horizontal MR" (a horizontal jet seen on TTE that hugs the leaflets without reaching the atrial wall, particularly found in non-P2 prolapse) and (2) the directions of MR jets between TTE and real-time (RT) three-dimensional (3D) TEE would be discordant. METHODS: One hundred eighteen patients with moderate to severe and severe degenerative MR defined by TEE were studied. The percentage of severe MR between TTE and TEE was compared in P2 and non-P2 prolapse groups and in horizontal and nonhorizontal MR groups. Additionally, differences in the directions of the MR jets between TTE and RT 3D TEE were assessed. RESULTS: Eighty-six percent of patients had severe MR according to TEE. TTE underestimated severe MR in the non-P2 group (severe MR on TTE, 57%; severe MR on TEE, 85%; P < .001) but not in the P2 group (severe MR on TTE, 79%; severe MR on TEE, 91%; P = .157). Most "horizontal" MR jets were found in the non-P2 group (85%), and this subgroup showed even more underestimation of severe MR on TTE (TTE, 22%; TEE, 89%; P < .001). There was discordance in MR jet direction between two-dimensional TTE and RT 3D TEE in 41% of patients. CONCLUSIONS: Non-P2 and "horizontal" MR are significantly underestimated on TTE compared with TEE. There is substantial discordance in the direction of the MR jet between RT 3D TEE and TTE. Therefore, TEE should be considered when these subgroups of MR are observed on TTE.

PERK Is a Haploinsufficient Tumor Suppressor: Gene Dose Determines Tumor-Suppressive Versus Tumor Promoting Properties of PERK in Melanoma.

The unfolded protein response (UPR) regulates cell fate following exposure of cells to endoplasmic reticulum stresses. PERK, a UPR protein kinase, regulates protein synthesis and while linked with cell survival, exhibits activities associated with both tumor progression and tumor suppression. For example, while cells lacking PERK are sensitive to UPR-dependent cell death, acute activation of PERK triggers both apoptosis and cell cycle arrest, which would be expected to contribute tumor suppressive activity. We have evaluated these activities in the BRAF-dependent melanoma and provide evidence revealing a complex role for PERK in melanoma where a 50% reduction is permissive for BrafV600E-dependent transformation, while complete inhibition is tumor suppressive. Consistently, PERK mutants identified in human melanoma are hypomorphic with dominant inhibitory function. Strikingly, we demonstrate that small molecule PERK inhibitors exhibit single agent efficacy against BrafV600E-dependent tumors highlighting the clinical value of targeting PERK.

Síntomas de ansiedad y depresión en adolescentes escolarizados de 10 a 17 años en Chía, Colombia / Symptoms of anxiety and depression in adolescents between 10 to 17 year-old attending schools in Chía, Colombia

Objetivo Estimar la prevalencia de síntomas ansiosos y depresivos en adolescentes escolarizados entre los 10-17 años, de la comunidad de Chía Cundinamarca, utilizando las escalas CDI y SCARED, durante los años 2008 a 2010. Metodología Estudio de corte transversal, realizado en 538 estudiantes. Se identificaron las variables socio demográficas: edad, sexo, seguridad social y centro educativo de procedencia (público, privado, oficial o urbano). Se aplicaron las escalas CDI y SCARED. Resultados Se detectaron síntomas ansiosos o depresivos en el 40,5 % de la población estudiada (538); de los cuales el 28,3 % presentó síntomas sugestivos de ansiedad exclusivamente, con síntomas depresivos exclusivamente en 3,3 % y síntomas tanto de ansiedad, como de depresión en 8,9 %. Los síntomas ansiosos fueron más frecuentes en las mujeres y los síntomas depresivos y mixtos se presentaron con más frecuencia en hombres. Se encontró mayor prevalencia de síntomas depresivos 6,9 % en hombres vs 5,4 % en mujeres, dato que no fue estadísticamente significativo. Conclusión Los síntomas ansiosos y depresivos son frecuentes en adolescentes, se hace indispensable sospecharlos y diagnosticarlos tempranamente, con el fin de poder brindar una atención oportuna. Se deben implementar estrategias que permitan detectar factores protectores y de riesgo para evitar que se desarrollen trastornos mayores, diseñando programas de educación encaminados hacia una buena salud mental de niños y adolescente.

Objective This study was aimed at estimating the prevalence of symptoms of depression and anxiety amongst 10 to 17 year-old adolescents still attending school using the CDI and SCARED questionnaires for early screening in Chía, a town near Bogota, from 2008 to 2010. Method This was a cross-sectional study of prevalence. Results 37 % of the 538 adolescents interviewed had anxiety symptoms, 12.3 % had depression symptoms and 9% presented anxiety and depression symptoms, males having greater prevalence for depression symptoms (6.9 % cf 5.4 % for females) but lacking statistical significance. There was a greater tendency for anxiety symptoms to be found in adolescents attending public schools. Concerning co morbidity, more anxiety symptoms were found in adolescents having depression symptoms. Conclusions It was concluded that anxiety and depression symptoms are real at this age, this being reason enough why it is necessary to suspect and detect them on time so that adolescents can receive suitable attention. Protective factors must be strengthened for this to happen and there must be real awareness by everybody to create educational and health programmes directed towards ensuring good mental health.

[Symptoms of anxiety and depression in adolescents between 10 to 17 year-old attending schools in Chía, Colombia]. / Síntomas de ansiedad y depresión en adolescentes escolarizados de 10 a 17 años en Chía, Colombia.

OBJECTIVE: This study was aimed at estimating the prevalence of symptoms of depression and anxiety amongst 10 to 17 year-old adolescents still attending school using the CDI and SCARED questionnaires for early screening in Chía, a town near Bogota, from 2008 to 2010. METHOD: This was a cross-sectional study of prevalence. RESULTS: 37% of the 538 adolescents interviewed had anxiety symptoms, 12.3% had depression symptoms and 9% presented anxiety and depression symptoms, males having greater prevalence for depression symptoms (6.9% cf 5.4% for females) but lacking statistical significance. There was a greater tendency for anxiety symptoms to be found in adolescents attending public schools. Concerning co morbidity, more anxiety symptoms were found in adolescents having depression symptoms. CONCLUSIONS: It was concluded that anxiety and depression symptoms are real at this age, this being reason enough why it is necessary to suspect and detect them on time so that adolescents can receive suitable attention. Protective factors must be strengthened for this to happen and there must be real awareness by everybody to create educational and health programmes directed towards ensuring good mental health.