Internship in arrhythmology

The arrhythmology focuses on the diagnosis and treatment of heart rhythm disorders and their complications, and has undergone a dramatic evolution over the past two decades. The widespread use of catheter ablation, the introduction of implantable cardioverter defibrillators for the prevention of sudden cardiac death and, finally, the development of cardiac resynchronization therapy led to a gradual loss of the impact of antiarrhythmic drugs as a therapeutic approach. This report was performed as a result of an internship performed in Cardiac Physiology with the duration of 400 hours. The main goal of the internship was to strengthen theoretical knowledge and acquire practical experience in the varied fields of arrhythmology, especially in the areas of Cardiac Pacing and Electrophysiology. During the internship were performed 41 electrophysiologic studies, where Atrioventricular Node Reentrant Tachycardia and Atrial Fibrillation were the most observed arrhythmias. New technologies such as three-dimensional mapping for electrophysiology studies are developing quickly and being use on a daily basis, as they prove to have safe and higher success rates. The proof is that in approximately half of the studies, one of the two mapping systems available, Carto or NavX, was used. In addition, were interrogated 283 pacemakers during the pacing clinics, being the dual chamber with DDD pacing mode the most encountered device. A large number of devices with Cardiac Resynchronization Therapy and/or Implantable Cardioverter Defibrillators were also observed. This report is divided into three chapters. Chapter I is constituted by a revision of the literature and includes concepts such as definition and mechanisms of cardiac arrhythmias; a brief description of the varied diagnostic tools and its recommendations; and a presentation of the different therapeutic approaches available and its indications. The second chapter is a descriptive drawing of the activity performed in the modules of Electrophysiology and Pacing. Lastly, the chapter III presents two clinical cases in Electrophysiology considered interesting from a clinical point of view.

Functional Neuroimaging of the Social Regulation of Emotion in Schizophrenia

Negative symptoms in schizophrenia are characterized by deficits in normative experiences and expression of emotion. Social anhedonia (diminished pleasure from social experiences) is one negative symptom that may impact patients’ motivation to engage in meaningful social relationships. Past research has begun to examine the mechanisms that underlie social anhedonia, but it is unclear how this lack of social interest may impact the typically positive effects of social buffering and social baseline theory whereby social support attenuates stress. The present pilot study examines how social affiliation through hand holding is related to subjective and neural threat processing, negative symptoms, and social functioning. Twenty-one participants (14 controls; 7 schizophrenia) developed social affiliation with a member of the research staff who served as the supportive partner during the threat task. Participants displayed greater subjective benefit to holding the hand of their partner during times of stress relative to being alone or with an anonymous experimenter, as indicated by self-reported increased positive valence and decreased arousal ratings. When examining the effects of group, hand holding, and their interaction on the neurological experience of threat during the fMRI task, the results were not significant. However, exploratory analyses identified preliminary data suggesting that controls experienced small relative increases in BOLD signal to threat when alone compared to being with the anonymous experimenter or their partner, whereas the schizophrenia group results indicated subtle relative decreases in BOLD signal to threat when alone compared to either of the hand holding conditions. Additionally, within the schizophrenia group, more positive valence in the partner condition was associated with less severe negative symptoms, better social functioning, and more social affiliation, whereas less arousal was correlated with more social affiliation. Our pilot study offers initial insights about the difficulties of building and using social affiliation and support through hand holding with individuals with schizophrenia during times of stress. Further research is necessary to clarify which types of support may be more or less beneficial to individuals with schizophrenia who may experience social anhedonia or paranoia with others that may challenge the otherwise positive effects of social buffering and maintaining a social baseline.

Transcatheter Closure of Atrial Septal Defects in a Center With Limited Resources: Outcomes and Short Term Follow-Up

Background: Transcatheter closure of atrial septal defects (ASD) has been accepted world-wide as an alternative to surgical closure with excellent results. This interventional, non-surgical technique plays an important role in the treatment of ASD mostly in the developing world where resources are limited. Objectives: To report the outcomes and short term follow-up of transcatheter closure of ASD over a 12-year period at our institution with limited resources. Patients and Methods: This retrospective study included all patients with the diagnosis of secundum ASD and significant shunting (Qp/Qs > 1.5:1) as well as dilated right atrium and right ventricle who had transcatheter closure at Integrated Cardiovascular Center (PJT), Dr. Cipto Mangunkusumo Hospital between October 2002 and October 2014. One hundred fifty-two patients enrolled in this study were candidates for device closure. Right and left heart cardiac catheterization was performed before the procedure. All patients underwent physical examination, ECG, chest X-ray and transthoracal echocardiography (TTE) prior to device implantation. Results: A total of 152 patients with significant ASD underwent device implantation. Subjects’ age ranged from 0.63 to 69.6 years, with median 9.36 years and mean 16.30 years. They consisted of 33 (21.7%) males and 119 (78.3%) females, with mean body weight of 29.9 kg (range 8 to 75; SD 18.2). The device was successfully implanted in 150 patients where the majority of cases received the Amplatzer septal occluder (147/150; 98%) and the others received the Heart Lifetech ASD occluder (3/150, 2%), whereas two other cases were not suitable for device closure and we decided for surgical closure. The mean ASD size was 19.75 (range 14 - 25) mm. During the procedure, 5 (4.9%) patients had bradycardia and 3 (2.9%) patients had supraventricular tachycardia (SVT), all of which resolved. Conclusions: In our center with limited facilities and manpower, transcatheter closure of atrial septal defect was effective and safe as an alternative treatment to surgery. The outcome and short-term follow-up revealed excellent results, but long-term follow-up is needed.

Supressão do ruído de rolamento superficial utilizando a transformada Curvelet

Among the many types of noise observed in seismic land acquisition there is one produced by surface waves called Ground Roll that is a particular type of Rayleigh wave which characteristics are high amplitude, low frequency and low velocity (generating a cone with high dip). Ground roll contaminates the relevant signals and can mask the relevant information, carried by waves scattered in deeper regions of the geological layers. In this thesis, we will present a method that attenuates the ground roll. The technique consists in to decompose the seismogram in a basis of curvelet functions that are localized in time, in frequency, and also, incorporate an angular orientation. These characteristics allow to construct a curvelet filter that takes in consideration the localization of denoise in scales, times and angles in the seismogram. The method was tested with real data and the results were very good

Efectos hemodinámicos en bloqueo caudal con bupivacaína en niños/as sometidos a cirugía de hemicuerpo inferior. Hospital José Carrasco Arteaga, Cuenca. Enero 2014 – julio 2015

Antecedentes: el bloqueo caudal con bupivacaína, es una técnica anestésica ampliamente utilizada en niños, debido a su fácil uso, que se realiza bajo anestesia general en plano superficial; sin embargo, puede haber fenómenos de cardiotoxicidad como taquicardia, además de neurotoxicidad como convulsiones, dependiendo de la dosis usada y comorbilidades asociadas. Objetivo: determinar los efectos hemodinámicos en bloqueo caudal con bupivacaína en niños/as sometidos a cirugía de hemicuerpo inferior. Hospital José Carrasco Arteaga de Cuenca, de enero del 2014 a julio del 2015. Antecedentes: el bloqueo caudal con bupivacaína, es una técnica anestésica ampliamente utilizada en niños, debido a su fácil uso, que se realiza bajo anestesia general en plano superficial; sin embargo, puede haber fenómenos de cardiotoxicidad como taquicardia, además de neurotoxicidad como convulsiones, dependiendo de la dosis usada y comorbilidades asociadas. Objetivo: determinar los efectos hemodinámicos en bloqueo caudal con bupivacaína en niños/as sometidos a cirugía de hemicuerpo inferior. Hospital José Carrasco Arteaga de Cuenca, de enero del 2014 a julio del 2015. Metodología: estudio descriptivo, retrospectivo, de corte transversal. Los datos fueron recolectados de los registros intraoperatorios del HJCA, ingresados en formularios y tabulados en el programa SPSS V.15, mediante frecuencia, media, y porcentajes. Se presentaron resultados por medio de tablas y gráficos, y cumpliendo con los objetivos planteados. Resultados: la edad frecuente estuvo entre 2 a 3 años, y media de 4,59 ± 3,1 años; peso frecuente entre 10 - 19 kilogramos, media de 18.3 ± 8,6 kg, sexo predominante fue masculino con 78%. La cirugía más frecuente: la circuncisión con 31,3 %. La modificación de la frecuencia cardiaca fue la disminución de hasta 10% en la mayoría de variables. Y la modificación de la presión arterial sistólica y diastólica fue la disminución entre 11 y 20%. Conclusiones: las variables hemodinámicas tuvieron similares comportamientos en relación con las características personales. La cirugía con mayor variación hemodinámica fue la orquidopexia; la cirugía más frecuente con bloqueo caudal fue la circuncisión, la dosis de bupivacaina más usado fue 2mg/kg

Régulation de la prolifération des cellules musculaires lisses vasculaires par l’activation in vivo du récepteur natriurétique de type C.

Le remodelage vasculaire dû à l’hyper-prolifération cellulaire des cellules musculaires lisses vasculaires (CMLVs) observé chez les rats spontanément hypertendus (RSH) est associé à l’hypertension artérielle. Nous avons précédemment démontré que le traitement in vivo des RSH par l’agoniste spécifique du récepteur du peptide natriurétique de type C (NPR-C), le C-ANP4-23 atténue l’hyper-prolifération des CMLVs. Nous avons entrepris cette étude afin d’investiguer si l’effet antiprolifératif du C-ANP4-23 agit par l’entremise de l’inhibition de la surexpression des protéines du cycle cellulaire, et afin d’en explorer les mécanismes sous-jacents. Pour cette étude, des RSH et des rats Wistar Kyoto (WKYs) âgés de deux semaines ont été injectés en intra-péritonéale par le C-ANP4-23 de 2 jusqu’à 8 semaines d’âge, deux fois par semaine et sacrifiés à la 9ème semaine. La pression artérielle a été mesurée par méthode Queue-coiffe, la prolifération des CMLVs a été déterminée par incorporation de thymidine et par test MTT, et l’expression des protéines a été quant à elle déterminée par technique d’immunobuvardage de type Western. Les CMLVs des RSH ont démontré une prolifération élevée en comparaison avec celles des WKYs, et le traitement par le C-ANP4-23 a atténué l’hyperprolifération à un niveau de contrôle. De plus, la surexpression des cyclines D1/A/E, des kinases cyclines dépendantes 2 et 4 (cdk2, cdk4), de la forme phosphorylée de la protéine du rétinoblastome et des protéines Gαi des CMLV des RSH a été atténuée à un niveau de contrôle. Par ailleurs, l’hyperphosphorylation d’ERK1/2, AKT, EGF-R, PDGF-R, IGF-R et de c-Src a significativement diminué par le traitement au C-ANP4-23. En outre, le niveau élevé de l’anion superoxyde (O2-), l’activité de la NADP(H) oxydase et de ses sous unités chez les RSH ont été atténués par le C-ANP4-23 .Ces résultats indiquent que l’activation in vivo de NPR-C atténue la surexpression des protéines du cycle cellulaire via l’inhibition de l’activité élevée du stress oxydatif, de c-Src et de l’activation de EGF-R, PDGF- R, IGF-R, de la signalisation de MAPK et la surexpression des protéines Gαi résultant ainsi en l’inhibition de l’hyperprolifération des CMLVs des RSH. Ainsi, il peut être suggéré que le C-ANP4-23 pourrait être utilisé comme agent thérapeutique pour le traitement des complications vasculaires associées à l’hypertension et à l’athérosclérose.

Effects of advanced glycation end-products (AGEs) on retinal pigment epithelial (RPE) cells lysosomal function:implications for age-related macular degeneration (AMD)

Purpose: RPE lysosomal dysfunction is a major contributor to AMD pathogenesis. Controlled activity of a major class of RPE proteinases, the cathepsins, is crucial in maintaining correct lysosomal function. Advanced glycation end-products (AGEs) accumulate in the Bruch’s membrane (BM) with age, impacting critical RPE functions and in turn, contributing to the development of AMD. The aim of this study was to assess the effect of AGEs on lysosomal function by analysing the expression, processing and activity of the cysteine proteinases cathepsins B, L and S, and the aspartic proteinase cathepsin D. Methods: ARPE-19 cells were cultured on AGE-containing BM mimics (matrigel) for 14 days and compared to untreated substrate. Expression levels and intracellular processing of cathepsins B, D, L and S, were assessed by qPCR and immunoblotting of cell lysates. Lysosomal activity was investigated using multiple activity assays specific to each of the analysed cathepsins. Statistical analysis was performed using the Student’s independent T-test. Results: AGE exposure produced a 36% decrease in cathepsin L activity when compared to non-treated controls (p=0.02, n= 3) although no significant changes were observed in protein expression/processing under these conditions. Both the pro and active forms of cathepsin S decreased by 40% (p=0.04) and 74% (p=0.004), respectively (n=3). In contrast, the active form of the cathepsin D increased by 125% (p=0.005, n= 4). However, no changes were observed in the activity levels of both cathepsins S and D. In addition, cathepsin B expression, processing and activity also remained unaltered following AGE exposure. Conclusions: AGEs accumulation in the extracellular matrix, a phenomenon associated with the natural aging process of the BM, attenuates the expression, intracellular processing and activity of specific lysosomal effectors. Altered enzymatic function may impair important lysosomal processes such as endocytosis, autophagy and phagocytosis of photoreceptor outer segments, each of which may influence the age-related dysfunction of the RPE and subsequently, AMD pathogenesis.

Régulation de la prolifération des cellules musculaires lisses vasculaires par l’activation in vivo du récepteur natriurétique de type C

Le remodelage vasculaire dû à l’hyper-prolifération cellulaire des cellules musculaires lisses vasculaires (CMLVs) observé chez les rats spontanément hypertendus (RSH) est associé à l’hypertension artérielle. Nous avons précédemment démontré que le traitement in vivo des RSH par l’agoniste spécifique du récepteur du peptide natriurétique de type C (NPR-C), le C-ANP4-23 atténue l’hyper-prolifération des CMLVs. Nous avons entrepris cette étude afin d’investiguer si l’effet antiprolifératif du C-ANP4-23 agit par l’entremise de l’inhibition de la surexpression des protéines du cycle cellulaire, et afin d’en explorer les mécanismes sous-jacents. Pour cette étude, des RSH et des rats Wistar Kyoto (WKYs) âgés de deux semaines ont été injectés en intra-péritonéale par le C-ANP4-23 de 2 jusqu’à 8 semaines d’âge, deux fois par semaine et sacrifiés à la 9ème semaine. La pression artérielle a été mesurée par méthode Queue-coiffe, la prolifération des CMLVs a été déterminée par incorporation de thymidine et par test MTT, et l’expression des protéines a été quant à elle déterminée par technique d’immunobuvardage de type Western. Les CMLVs des RSH ont démontré une prolifération élevée en comparaison avec celles des WKYs, et le traitement par le C-ANP4-23 a atténué l’hyperprolifération à un niveau de contrôle. De plus, la surexpression des cyclines D1/A/E, des kinases cyclines dépendantes 2 et 4 (cdk2, cdk4), de la forme phosphorylée de la protéine du rétinoblastome et des protéines Gαi des CMLV des RSH a été atténuée à un niveau de contrôle. Par ailleurs, l’hyperphosphorylation d’ERK1/2, AKT, EGF-R, PDGF-R, IGF-R et de c-Src a significativement diminué par le traitement au C-ANP4-23. En outre, le niveau élevé de l’anion superoxyde (O2-), l’activité de la NADP(H) oxydase et de ses sous unités chez les RSH ont été atténués par le C-ANP4-23 .Ces résultats indiquent que l’activation in vivo de NPR-C atténue la surexpression des protéines du cycle cellulaire via l’inhibition de l’activité élevée du stress oxydatif, de c-Src et de l’activation de EGF-R, PDGF- R, IGF-R, de la signalisation de MAPK et la surexpression des protéines Gαi résultant ainsi en l’inhibition de l’hyperprolifération des CMLVs des RSH. Ainsi, il peut être suggéré que le C-ANP4-23 pourrait être utilisé comme agent thérapeutique pour le traitement des complications vasculaires associées à l’hypertension et à l’athérosclérose.

Skin microbiome before development of atopic dermatitis: Early colonization with commensal staphylococci at 2 months is associated with a lower risk of atopic dermatitis at 1 year

Background: Disease flares of established atopic dermatitis (AD) are generally associated with a low-diversity skin microbiota and Staphylococcus aureus dominance. The temporal transition of the skin microbiome between early infancy and the dysbiosis of established AD is unknown. Methods: We randomly selected 50 children from the Cork Babies After SCOPE: Evaluating the Longitudinal Impact Using Neurological and Nutritional Endpoints (BASELINE) longitudinal birth cohort for microbiome sampling at 3 points in the first 6 months of life at 4 skin sites relevant to AD: the antecubital and popliteal fossae, nasal tip, and cheek. We identified 10 infants with AD and compared them with 10 randomly selected control infants with no AD. We performed bacterial 16S ribosomal RNA sequencing and analysis directly from clinical samples. Results: Bacterial community structures and diversity shifted over time, suggesting that age strongly affects the skin microbiome in infants. Unlike established AD, these patients with infantile AD did not have noticeably dysbiotic communities before or with disease and were not colonized by S aureus. In comparing patients and control subjects, infants who had affected skin at month 12 had statistically significant differences in bacterial communities on the antecubital fossa at month 2 compared with infants who were unaffected at month 12. In particular, commensal staphylococci were significantly less abundant in infants affected at month 12, suggesting that this genus might protect against the later development of AD. Conclusions: This study suggests that 12-month-old infants with AD were not colonized with S aureus before having AD. Additional studies are needed to confirm whether colonization with commensal staphylococci modulates skin immunity and attenuates development of AD.

Anatomical basis for the cardiac interventional electrophysiologist

The establishment of radiofrequency catheter ablation techniques as the mainstay in the treatment of tachycardia has renewed new interest in cardiac anatomy. The interventional arrhythmologist has drawn attention not only to the gross anatomic details of the heart but also to architectural and histological characteristics of various cardiac regions that are relevant to the development or recurrence of tachyarrhythmias and procedural related complications of catheter ablation. In this review, therefore, we discuss some anatomic landmarks commonly used in catheter ablations including the terminal crest, sinus node region, Koch’s triangle, cavotricuspid isthmus, Eustachian ridge and valve, pulmonary venous orifices, venoatrial junctions, and ventricular outflow tracts. We also discuss the anatomical features of important structures in the vicinity of the atria and pulmonary veins, such as the esophagus and phrenic nerves. This paper provides basic anatomic information to improve understanding of the mapping and ablative procedures for cardiac interventional electrophysiologists.

Aproximaciones a mindfulness en la psicología contemporánea

Este trabajo es una revisión de literatura que abarca una selección de artículos disponibles en bases de datos especializadas y publicados en el periodo comprendido entre los años 2006 a 2016 para artículos científicos y entre los años 2000 a 2016 para libros. En total se revisaron: 1 tesis doctoral, 1 tesis magistral, 111 artículos y 9 libros o capítulos de libros. Se presentan diversas definiciones de mindfulness y formas de conceptualizarla, sus mecanismos de acción, sus enfoques psicoterapéuticos predominantes, los efectos de su práctica estable, sus principales campos de acción y la importancia de la formación de los docentes que imparten la práctica. Finalmente se presentan algunas conclusiones acerca del diálogo entre la literatura psicológica sobre mindfulness y algunas de las concepciones de la tradición budista en torno a la meditación.

TAZ role in lung cancer: resistance to BET inhibitors and functional interaction with lncRNA

Despite extensive research and introduction of innovative therapy, lung cancer prognosis remains poor, with a five years survival of only 17%. The success of pharmacological treatment is often impaired by drug resistance. Thus, the characterization of response mechanisms to anti-cancer compounds and of the molecular mechanisms supporting lung cancer aggressiveness are crucial for patient’s management. In the first part of this thesis, we characterized the molecular mechanism behind resistance of lung cancer cells to the Inhibitors of the Bromodomain and Extraterminal domain containing Proteins (BETi). Through a CRISPR/Cas9 screening we identified three Hippo Pathway members, LATS2, TAOK1 and NF2 as genes implicated in susceptibility to BETi. These genes confer sensitivity to BETi inhibiting TAZ activity. Conversely, TAZ overexpression increases resistance to BETi. We also displayed that BETi downregulate both YAP, TAZ and TEADs expression in several cancer cell lines, implying a novel BETi-dependent cytotoxic mechanism. In the second part of this work, we attempted to characterize the crosstalk between the TAZ gene and its cognate antisense long-non coding RNA (lncRNA) TAZ-AS202 in lung tumorigenesis. As for TAZ downregulation, TAZ-AS202 silencing impairs NSCLC cells proliferation, migration and invasion, suggesting a pro-tumorigenic function for this lncRNA during lung tumorigenesis. TAZ-AS202 regulates TAZ target genes without altering TAZ expression or localization. This finding implies an uncovered functional cooperation between TAZ and TAZ-AS202. Moreover, we found that the EPH-ephrin signaling receptor EPHB2 is a downstream effector affected by both TAZ and TAZ-AS202 silencing. EPHB2 downregulation significantly attenuates cells proliferation, migration and invasion, suggesting that, at least in part, TAZ-AS202 and TAZ pro-oncogenic activity depends on EPH-ephrin signaling final deregulation. Finally, we started to dissect the mechanism underlying the TAZ-AS202 regulatory activity on EPHB2 in lung cancer, which may involve the existence of an intermediate transcription factor and is the object of our ongoing research.