Associations, causation and model in psychiatry

This paper discusses models, associations and causation in psychiatry. The different types of association (linear, positive, negative, exponential, partial, U shaped relationship, hidden and spurious) between variables involved in mental disorders are presented as well as the use of multiple regression analysis to disentangle interrelatedness amongst multiple variables. A useful model should have internal consistency, external validity and predictive power; be dynamic in order to accommodate new sound knowledge; and should fit facts rather than they other way around. It is argued that whilst models are theoretical constructs they also convey a style of reasoning and can change clinical practice. Cause and effect are complex phenomena in that the same cause can yield different effects. Conversely, the same effect can have a different range of causes. In mental disorders and human behaviour there is always a chain of events initiated by the indirect and remote cause; followed by intermediate causes; and finally the direct and more immediate cause. Causes of mental disorders are grouped as those: (i) which are necessary and sufficient; (ii) which are necessary but not sufficient; and (iii) which are neither necessary nor sufficient, but when present increase the risk for mental disorders.

Propolis: A complex natural product with a plethora of biological activities that can be explored for drug development

The health industry has always used natural products as a rich, promising, and alternative source of drugs that are used in the health system. Propolis, a natural resinous product known for centuries, is a complex product obtained by honey bees from substances collected from parts of different plants, buds, and exudates in different geographic areas. Propolis has been attracting scientific attention since it has many biological and pharmacological properties, which are related to its chemical composition. Several in vitro and in vivo studies have been performed to characterize and understand the diverse bioactivities of propolis and its isolated compounds, as well as to evaluate and validate its potential. Yet, there is a lack of information concerning clinical effectiveness. The goal of this review is to discuss the potential of propolis for the development of new drugs by presenting published data concerning the chemical composition and the biological properties of this natural compound from different geographic origins.

Cognitive processes affect the gait of subjects with Parkinson’s and Alzheimer’s disease in dual tasks

Objective To investigate the relation between gait parameters and cognitive impairments in subjects with Parkinson’s disease (PD) and Alzheimer’s disease (AD) during the performance of dual tasks. Methods This was a cross-sectional study involving 126 subjects divided into three groups: Parkinson group (n = 43), Alzheimer group (n = 38), and control group (n = 45). The subjects were evaluated using the Timed Up and Go test administered with motor and cognitive distracters. Gait analyses consisted of cadence and speed measurements, with cognitive functions being assessed by the Brief Cognitive Screening Battery and the Clock Drawing Test. Statistical procedures included mixed-design analyses of variance to observe the gait patterns between groups and tasks and the linear regression model to investigate the influence of cognitive functions in this process. A 5% significant level was adopted. Results Regarding the subjects’ speed, the data show a significant difference between group vs task interaction (p = 0.009), with worse performance of subjects with PD in motor dual task and of subjects with AD in cognitive dual task. With respect to cadence, no statistical differences was seen between group vs task interaction (p = 0.105), showing low interference of the clinical conditions on such parameter. The linear regression model showed that up to 45.79%, of the variance in gait can be explained by the interference of cognitive processes. Conclusion Dual task activities affect gait pattern in subjects with PD and AD. Differences between groups reflect peculiarities of each disease and show a direct interference of cognitive processes on complex tasks.

Concepts and objects of awareness in Alzheimer’s disease: an updated systematic review

ABSTRACT Objectives To compare and discuss the objects of awareness in Alzheimer’s disease (AD): awareness of cognitive deficits, of functional activities, of social-emotional functioning and behavioral impairment. Methods A search in the PsycINFo, Pilots, PubMed/Medline and ISI electronic databases according to Prisma methodology was performed. We included studies about awareness in people with AD published between 2010 and 2015, with the combination of keywords: “Alzheimer AND awareness of deficits”, “Alzheimer AND anosognosia”, “Alzheimer AND insight”, “dementia AND awareness of deficits”, “dementia AND anosognosia”, “dementia AND insight”. The articles were categorized according to the specific object of awareness. Results Seven hundred and ten records were identified and, after application of the exclusion criteria, 191 studies were retrieved for potential use. After excluding the duplicates, 46 studies were included. Most studies assessed the cognitive domain of awareness, followed by the functional, social-emotional, and behavioral impairment domains. Memory deficits were not sufficient to explain impaired awareness in AD. Longitudinal studies did not find discrepancies between patients and caregivers’ reports, indicating that awareness is not related to cognition. Conflicting findings were observed, including the relation between awareness, mood, severity of disease, and personal characteristics. Conclusions The studies show lack of conceptual consensus and significant methodological differences. The inclusion of samples without differentiation of dementia etiology is associated to symptomatic differences, which affect awareness domains. Awareness in AD is a complex and multidimensional construct. Different objects elicit different levels of awareness.

Percutaneous handling of coronary lesions >20mm through stents. Is there a first choice strategy?

OBJECTIVE - This study compared the early and late results of the use of one single stent with those of the use of multiple stents in patients with lesions longer than 20mm. METHODS - Prospective assessment of patients electively treated with stents, with optimal stent deployment and followed-up for more than 3 months. From February '94 to January '98, 215 patients with lesions >20mm were treated. These patients were divided into 2 groups as follows: Group A - 105 patients (49%) with one stent implanted; Group B - 110 patients (51%) with multiple stents implanted. RESULTS - The mean length of the lesions was 26mm in group A (21-48mm) versus 29mm in group B (21-52mm) (p=0.01). Major complications occurred in one patient (0.9%) in group A (subacute thrombosis, myocardial infarctionand death) and in 2 patients (1.8%) in group B (one emergency surgery and one myocardial infarction) (p=NS). The results of the late follow-up period (>6 months) were similar for both groups (group A = 82% vs group B = 76%; p=NS), and we observed an event-free survical in 89% of the patients in group A and in 91% of the patients in group B (p=NS). Angina (group A = 11% vs group B = 7%) and lesion revascularization (group A = 5% vs group B = 6%; p=NS) also occurred in a similar percentage. No infarction or death was observed in the late follow-up period; restenosis was identified in 33% and 29% of the patients in groups A and B, respectively (p=NS). CONCLUSION - The results obtained using one stent and using multiple stents were similar; the greater cost-effectiveness of one stent implantation, however, seems to make this strategy the first choice.

Heart transplantation in neonates and children. Intermediate-term results

OBJECTIVE: To assess intermediate-term outcome in children who have undergone orthotopic heart transplantation. METHODS: We carried out a longitudinal and prospective study between October '92 and June '99 comprising 20 patients with ages ranging from 12 days to 7 years (mean of 2.8 years). We employed a double immunosuppression protocol with cyclosporine and azathioprine and induction therapy with polyclonal antithymocyte serum. Survival and complications resulting from the immunosuppression protocol were analyzed. RESULTS:The double immunosuppression protocol and the induction therapy with polyclonal antithymocyte serum resulted in an actuarial survival curve of 90% and 78.2% at 1 and 6 years, respectively, with a mean follow-up period of 3.6 years. One patient died due to acute rejection 40 days after transplantation; another patient died 2 years after transplantation due to lymphoproliferative disorder; a third patient died because of primary failure of the graft; and a fourth patient died due to bronchopneumonia. The major complications were as follows: acute rejection, infection, nephrotoxicity, and systemic hypertension. The means of rejection and infection episodes per patient were 2.9 and 3.4, respectively. After one year of transplantation, a slight reduction in the creatinine clearance and systemic hypertension were observed in 7 (38.9%) patients. CONCLUSION: Heart transplantation made life possible for those patients with complex congenital heart diseases and cardiomyopathies in refractory congestive heart failure constituting a therapeutical option for this group of patients in the terminal phase.

In-line rheo-optical microstructural characterization of complex polymer systems

Tese de Doutoramento em Ciência e Engenharia de Polímeros e Compósitos.

Catheter ablation of atriofascicular Mahaim fibers guided by the activation potential

OBJECTIVE: To determine whether recording of the activation potential may be used as an isolated criterion to guide catheter ablation of atriofascicular Mahaim fibers. METHODS: We studied 6 patients (5 females, mean age of 26±7.3 years) with paroxysmal tachycardias with a wide QRS complex, whose electrophysiological study diagnosed atriofascicular Mahaim fibers. Mapping and catheter ablation were performed in sinus rhythm, guided only by the recording of the activation potential of the fiber. RESULTS: Efficacy in ablation was achieved in all patients. The fibers were located in the right lateral region of the tricuspid ring in 3 patients, right posterolateral region in 2, and right anterolateral region in 1. A mean of 5.3±3 radiofrequency applications was performed. The mean fluoroscopy time was 46.6±25 minutes, and the mean duration of the procedure was 178.6±108 minutes. No complication occurred. In a mean 20-month follow-up, all patients were asymptomatic and receiving no antiarrhythmic drugs. CONCLUSION: Catheter ablation of Mahaim fibers may be performed with good safety and efficacy by mapping the activation potential of the tricuspid ring in sinus rhythm.

Right ventricular diastolic dysfunction in the postoperative period of tetralogy of Fallot

OBJECTIVE: To assess right ventricular diastolic function in the intermediate postoperative period of repair of tetralogy of Fallot. METHODS: We carried out a case-control study with 60 patients divided into 2 groups as follows: 1) group I - 30 patients who had undergone repair of tetralogy of Fallot and 2) group II - 30 healthy children. The 2 groups were paired for age, sex, and body surface. The flows in the pulmonary and tricuspid valves were analyzed with Doppler echocardiography. The presence of anterograde flow at the end of diastole in the pulmonary artery defined restrictive right ventricular physiology. Surgical, radiological, electrocardiographic, and echocardiographic variables were analized in the group I. RESULTS: The velocity of the A wave and the E/A ratio for the tricuspid valve showed significant differences between the groups. Cases with E/A < 1.30 predominated in inspiration (group I - 19/30, and group II - 5/30). The duration of the QRS complex on the electrocardiogram was significantly increased in patients with E/A <1.30. Nineteen (63.3%) patients had restrictive right ventricular physiology, which had a longer postoperative period, longer duration of the QRS complex, and a lower E/A ratio in inspiration. The surgical and radiological variables showed no statistical difference. CONCLUSION: Restrictive right ventricular physiology was detected on the intermediate follow-up of most patients undergoing repair of tetralogy of Fallot. The postoperative period and QRS duration were increased in patients with impairment in diastolic function.

Técnicas Experimentales para Caracterizar Flujos Complejos. Experimental techniques for complex flows characterization.

En ambientes fluviales, la interacción del flujo con la geometría del cauce y con los sedimentos del lecho define una dinámica turbulenta compleja en permanente evolución. El nivel de complejidad del flujo aumenta ante la presencia de estructuras hidráulicas (pilas de puentes, protecciones contra erosión, etc.). La mayoría de los ríos, o canales naturales, presentan confluencias y bifurcaciones, en donde se genera una convergencia (o divergencia) del flujo con el resultado de un ambiente hidrodinámico complejo en la cercanía de las uniones (Kenworthy y Rhoads 1995). Bajo estas condiciones no es posible extrapolar las soluciones tradicionales básicas de las ecuaciones de gobierno desarrolladas para canales rectos y uniformes. Algunas investigaciones experimentales realizadas en estos sistemas son las de Best (1988), Rhoads y Sukhodolov (2001), Richardson et al. (1996); Richardson y Thorne (1998, 2001); Parsons et al. (2004); Szupiany et al. (2005).Por otro lado, la zona costera en ambientes marítimos se caracteriza por la existencia de diversos procesos dinámicos, entre los que se destacan la acción de olas, corrientes, interacción olas-corrientes, transporte de sedimentos y cambios batimétricos. Estos se manifiestan en una alteración morfodinámica de la playa generando superficies potenciales de erosión. Así, el diseño de las protecciones costeras (ya sean continuas, como escolleras o muros verticales; o discontinuas como espigones o diques externos) sometidas al clima marítimo bajo distintas condiciones de olas y mareas, alteran los patrones de circulación y de transporte afectando la morfodinámica en su zona de influencia y plantean, por ejemplo, la necesidad de ajustes de los coeficientes de estabilidad y pesos de los bloques de roca de las escolleras. Los problemas generados, son especialmente complejos ya que deben considerarse para su estudio, los niveles de turbulencia, la transmisión del oleaje sobre o a través de la estructura, difracción alrededor de la misma, refracción y shoaling sobre un fondo dinámico, reflexión en la estructura, etc. (Alsina et al., 2007) Revisiones bibliográficas previas muestran que, en ambos ambientes (fluvial y marítimo), es necesario optimizar las técnicas experimentales existentes para que ellas permitan caracterizar con precisión los flujos turbulentos complejos presentes. El objetivo general propuesto en esta investigación es contribuir a mejorar el conocimiento de los procesos hidrodinámicos de flujos turbulentos naturales con y sin la presencia de estructuras hidráulicas que den lugar a formaciones complejas (3D). Para alcanzar este objetivo se propone realizar una recopilación de antecedentes y un análisis crítico detallado de los equipos de ultima generación para mediciones de flujo con alta frecuencia y resolución disponibles en el Laboratorio de Hidráulica (LH) de la Universidad Nacional de Córdoba (UNC): ADV 3D (Acoustic Doppler Velocimeter de Sontek) y laser PIV 2D (Particle Image Velocimeter de Dantec). A estos equipamientos se le agrega un moderno equipo de generación bidimensional de oleaje con absorción dinámica (adquiridos a HR Ltd. en 2007 por el CAI 085 del FONTAR). Finalmente se prevé utilizar este equipamiento durante el desarrollo de experimentos y mediciones los cuales se realizarán sobre modelos físicos fluviales y costeros diseñados y construidos con y sin estructuras que interactúen con flujo turbulentos complejos. Los resultados obtenidos en este proyecto permitirá alcanzar una mejor comprensión de los procesos hidrodinámicos de los flujos turbulentos complejos, lo cual es necesario y de gran utilidad para realizar un manejo apropiado de los ambientes fluviales y marítimos, teniendo como campo directo de aplicación el correcto diseño de estructuras hidráulicas, asistiendo a la toma de medidas correctivas en sistemas naturales sometidos a procesos erosivos o de sedimentación, y contribuyendo de esta forma al manejo ambientalmente sustentable de los recursos.

Dinámica Cuántica de Sistemas Complejos: Fundamentos y Aplicaciones. Quantum Dynamics in Complex Systems: Fundamentals and Aplications.

El procedimiento de revertir la dinámica colectiva (diablillo de Loschmidt apresurado) mediante un pulso de radio frecuencia, permite generar un Eco de Loschmidt, es decir la refocalización de una excitación localizada. Alternativamente, en acústica es posible implementar un Espejo de Reversión Temporal, que consiste en la progresiva inyección de una débil excitación ultrasónica en la periferia de un sistema, para construir una excitación que se propaga "hacia atrás". Así, podemos afirmar que es posible revertir y controlar la dinámica. Sin embargo, aún no se posee una comprensión detallada de los mecanismos que gobiernan estos procedimientos. Este proyecto busca responder las preguntas que posibilitan esta comprensión.

Procesos oxidativos en matrices alimentarias complejas. Oxidative processes in complex food matrices.

Las reacciones bioquímicas que ocurren como consecuencia del tratamiento y almacenamiento de los alimentos, mejoran la seguridad alimentaria, las propiedades sensoriales y la vida útil. Sin embargo, el tratamiento térmico, la exposición a la luz y el oxígeno pueden causar daño oxidativo a los lípidos y proteínas. Los procesos oxidativos de matrices complejas tienen características distintivas que no se manifiestan cuando los componentes son sometidos a oxidación individualmente. La hipótesis de trabajo es que la oxidación de proteínas en matrices alimentarias complejas altera la estructura y las propiedades funcionales de las proteínas y, que las modificaciones que se producen varían según las condiciones de procesamiento y de la composición química del alimento. Nuestros estudios intentan demostrar que el estado oxidativo de las proteínas de un alimento es un parámetro importante para la evaluación de las propiedades funcionales, sensoriales y nutricionales de un producto lácteo. El objetivo general del proyecto es el estudio de los procesos de oxidación de matrices alimentarias complejas (la leche, miel) y su relación con distintos procesos y materiales utilizados en la industria. Es decir, nos proponemos estudiar las consecuencias funcionales y biológicas (calidad nutricional, coagulación) de la oxidación proteica en modelos experimentales “in vitro” y en productos comerciales. 1. Estudiar los fenómenos de peroxidación proteica en leche entera y descremada sometida a los distintos procesos tecnológicos de la producción de leche y queso a escala laboratorio. Se realizarán las mismas experiencias con albúmina sérica y con proteínas aisladas de suero de leche para comparar diferencias entre una matriz compleja y una simple. 2. Determinar la relación entre oxidación y composición proteica de la leche, y los cambios en las fracciones proteicas aisladas (caseínas y beta-lactoglobulina). 3. Analizar el impacto de los procesos tecnológicos a nivel de producción primaria (composición proteica y estado de oxidación) en los indicadores de inflamación (contenido de células somáticas y proteína C Reactiva) y de estado redox (capacidad antioxidante de los productos lácteos y nivel de carbonilos de proteinas). 4. Comparar las características de composición química y el estado de oxidación de leche provenientes de las tres regiones (Buenos Aires, Santa Fe y Córdoba) que conforman la cuenca láctea Argentina. Este objetivo se realizará conjuntamente con los integrantes de nuestro grupo de investigación que trabajan en el Laboratorio de Control de Calidad de la Escuela Superior de Lechería. 5. Determinar los metabolitos secundarios de mieles uniflorales propuestos como responsables de la capacidad antioxidante de estas (polifenoles) y como indicadores de su origen botánico. 6. Valorar la capacidad antioxidante total de mieles uniflorales. 7. Validar los métodos analíticos y semicuantitativos utilizados y a utilizar en el presente proyecto teniendo en cuenta lo efectos de matrices típico de los fluidos biológicos y las mezclas. El estudio de las modificaciones oxidativas de matrices complejas es un tema que es importante tanto desde el punto de vista del conocimiento básico como del aplicado. Nosotros creemos que el presente proyecto aportará conocimiento sobre las características de las vías oxidativas de proteínas en matrices complejas y que podrá ser utilizado para diseñar estrategias productivas tendientes a disminuir el deterioro de la calidad de la leche debido a la exposición a energía radiante. Parte de la experiencia ganada por el grupo ha sido ya volcada a subsanar dificultades y problemas de oxidación y deterioro de la calidad de alimentos. Además, se contribuirá a discernir la paradoja que existe en el área sobre las propiedades oxidantes/antioxidantes de los polifenoles y la relación entre estas y el estado oxidativo de un alimento. The biochemical reactions that occur as a result of food treatment and storage, improve food security, sensory properties and shelf life. Heat treatment, exposure to light and oxygen can cause oxidative damage to lipids and proteins. Oxidative processes in complex matrices display distinctive features that do not appear when the components are individually subjected to oxidation. The hypothesis is that protein oxidation in complex food matrices alters the structure and functional properties of proteins and that the modifications vary according to process conditions and food composition. The main goal is to study oxidation of complex food matrices (milk, honey) with different processes and materials used in the industry. The specific aims are: 1. To study protein oxidation in whole milk and skim subject to various technological processes. The same experiences will be done with serum albumin and isolated whey proteins to compare complex and simple matrices. 2. To determine the relationship between oxidation and milk protein composition, and changes in casein and beta-lactoglobulin. 3. Analyze the impact of technological processes at the level of primary production on markers of inflammation and redox (antioxidant capacity and protein carbonyls). 4. Compare characteristics of chemical composition and oxidation state of milk. 5. Determine secondary metabolites of honey responsible for the antioxidant capacity of these. 6. To evaluate the total antioxidant capacity unifloral honey. This project will provide knowledge about characteristics of oxidative pathways of proteins in complex matrices that can be used to design production strategies aimed at reduce the deterioration of milk quality. Also, it would help to discern the paradox that exists on the oxidants/antioxidants properties of polyphenols and the relationship between these and the oxidative status of a food.

Baroreflex Sensitivity and its Association with Arrhythmic Events in Chagas Disease

Background:Sudden death is the leading cause of death in Chagas disease (CD), even in patients with preserved ejection fraction (EF), suggesting that destabilizing factors of the arrhythmogenic substrate (autonomic modulation) contribute to its occurrence.Objective:To determine baroreflex sensitivity (BRS) in patients with undetermined CD (GI), arrhythmogenic CD with nonsustained ventricular tachycardia (NSVT) (GII) and CD with spontaneous sustained ventricular tachycardia (STV) (GIII), to evaluate its association with the occurrence and complexity of arrhythmias.Method:Forty-two patients with CD underwent ECG and continuous and noninvasive BP monitoring (TASK force monitor). The following were determined: BRS (phenylephrine method); heart rate variability (HRV) on 24-h Holter; and EF (echocardiogram).Results:GIII had lower BRS (6.09 ms/mm Hg) as compared to GII (11.84) and GI (15.23). The difference was significant between GI and GIII (p = 0.01). Correlating BRS with the density of ventricular extrasystoles (VE), low VE density (<10/h) was associated with preserved BRS. Only 59% of the patients with high VE density (> 10/h) had preserved BRS (p = 0.003). Patients with depressed BRS had higher VE density (p = 0.01), regardless of the EF. The BRS was the only variable related to the occurrence of SVT (p = 0.028).Conclusion:The BRS is preserved in undetermined CD. The BRS impairment increases as disease progresses, being more severe in patients with more complex ventricular arrhythmias. The degree of autonomic dysfunction did not correlate with EF, but with the density and complexity of ventricular arrhythmias.

Convex and toric geometry to analyze complex dynamics in chemical reaction systems

Convex cone, toric variety, graph theory, electrochemical catalysis, oxidation of formic acid, feedback-loopsbifurcations, enzymatic catalysis, Peroxidase reaction, Shil'nikov chaos

Value of the Qrs-T Angle in Predicting the Induction of Ventricular Tachyarrhythmias in Patients with Chagas Disease

Background:The QRS-T angle correlates with prognosis in patients with heart failure and coronary artery disease, reflected by an increase in mortality proportional to an increase in the difference between the axes of the QRS complex and T wave in the frontal plane. The value of this correlation in patients with Chagas heart disease is currently unknown.Objective:Determine the correlation of the QRS-T angle and the risk of induction of ventricular tachycardia / ventricular fibrillation (VT / VF) during electrophysiological study (EPS) in patients with Chagas disease.Methods:Case-control study at a tertiary center. Patients without induction of VT / VF on EPS were used as controls. The QRS-T angle was categorized as normal (0-105º), borderline (105-135º) or abnormal (135-180º). Differences between groups for continuous variables were analyzed with the t test or Mann-Whitney test, and for categorical variables with Fisher's exact test. P values < 0.05 were considered significant.Results:Of 116 patients undergoing EPS, 37.9% were excluded due to incomplete information / inactive records or due to the impossibility to correctly calculate the QRS-T angle (presence of left bundle branch block and atrial fibrillation). Of 72 patients included in the study, 31 induced VT / VF on EPS. Of these, the QRS-T angle was normal in 41.9%, borderline in 12.9% and abnormal in 45.2%. Among patients without induction of VT / VF on EPS, the QRS-T angle was normal in 63.4%, borderline in 14.6% and abnormal in 17.1% (p = 0.04). When compared with patients with normal QRS-T angle, those with abnormal angle had a fourfold higher risk of inducing ventricular tachycardia / ventricular fibrillation on EPS [odds ratio (OR) 4; confidence interval (CI) 1.298-12.325; p = 0.028]. After adjustment for other variables such as age, ejection fraction (EF) and QRS size, there was a trend for the abnormal QRS-T angle to identify patients with increased risk of inducing VT / VF during EPS (OR 3.95; CI 0.99-15.82; p = 0.052). The EF also emerged as a predictor of induction of VT / VF: for each point increase in EF, there was a 4% reduction in the rate of sustained ventricular arrhythmia on EPS.Conclusions:Changes in the QRS-T angle and decreases in EF were associated with an increased risk of induction of VT / VF on EPS.