A novel model for malware propagation on wireless sensor networks.

The main goal of this work was to propose a novel mathematical model for malware propagation on wireless sensor networks (WSN). Specifically, the proposed model was a compartmental and global one whose temporal dynamics were described by means of a system of ordinary differential equations. This proposal was more realistic than others that have appeared in the scientific literature since. On the one hand, considering the specifications of malicious code propagation, several types of nodes were considered (susceptible, patched susceptible, latent non-infectious, latent infectious, compromised non-infectious, compromised infectious, damaged, ad deactivated), and on the other hand, a new and more realistic term of the incidence was defined and used based on some particular characteristics of transmission protocol on wireless sensor networks.

Smart Buildings IoT Networks Accuracy Evolution Prediction to Improve Their Reliability Using a Lotka-Volterra Ecosystem Model.

Internet of Things (IoT) is the paradigm that has largely contributed to the development of smart buildings in our society. This technology makes it possible to monitor all aspects of the smart building and to improve its operation. One of the main challenges encountered by IoT networks is that the the data they collect may be unreliable since IoT devices can lose accuracy for several reasons (sensor wear, sensor aging, poorly constructed buildings, etc.). The aim of our work is to study the evolution of IoT networks over time in smart buildings. The hypothesis we have tested is that, by amplifying the Lotka-Volterra equations as a community of living organisms (an ecosystem model), the reliability of the system and its components can be predicted. This model comprises a set of differential equations that describe the relationship between an IoT network and multiple IoT devices. Based on the Lotka-Volterra model, in this article, we propose a model in which the predators are the non-precision IoT devices and the prey are the precision IoT devices. Furthermore, a third species is introduced, the maintenance staff, which will impact the interaction between both species, helping the prey to survive within the ecosystem. This is the first Lotka-Volterra model that is applied in the field of IoT. Our work establishes a proof of concept in the field and opens a wide spectrum of applications for biology models to be applied in IoT.

Big data and machine learning in critical care: Opportunities for collaborative research.

The introduction of clinical information systems (CIS) in Intensive Care Units (ICUs) offers the possibility of storing a huge amount of machine-ready clinical data that can be used to improve patient outcomes and the allocation of resources, as well as suggest topics for randomized clinical trials. Clinicians, however, usually lack the necessary training for the analysis of large databases. In addition, there are issues referred to patient privacy and consent, and data quality. Multidisciplinary collaboration among clinicians, data engineers, machine-learning experts, statisticians, epidemiologists and other information scientists may overcome these problems. A multidisciplinary event (Critical Care Datathon) was held in Madrid (Spain) from 1 to 3 December 2017. Under the auspices of the Spanish Critical Care Society (SEMICYUC), the event was organized by the Massachusetts Institute of Technology (MIT) Critical Data Group (Cambridge, MA, USA), the Innovation Unit and Critical Care Department of San Carlos Clinic Hospital, and the Life Supporting Technologies group of Madrid Polytechnic University. After presentations referred to big data in the critical care environment, clinicians, data scientists and other health data science enthusiasts and lawyers worked in collaboration using an anonymized database (MIMIC III). Eight groups were formed to answer different clinical research questions elaborated prior to the meeting. The event produced analyses for the questions posed and outlined several future clinical research opportunities. Foundations were laid to enable future use of ICU databases in Spain, and a timeline was established for future meetings, as an example of how big data analysis tools have tremendous potential in our field.

Simulación de la propagación de un brote por Acinetobacter baumannii en entornos hospitalarios / Simulation of an outbreak of Acinetobacter baumannii in hospitals

Introducción. Las infecciones por Acinetobacter baumannii se han convertido en un hecho habitual y preocupante en los ambientes hospitalarios. Consecuentemente son de especial importancia aquellas aplicaciones que permitan no sólo simular la aparición y propagación de un brote, sino también evaluar las posibles medidas de control. El desarrollo de modelos matemáticos juega un papel decisivo en esta tarea. Material y métodos. Se desarrolló un modelo matemático determinista basado en ecuaciones diferenciales ordinarias, cuyas variables y parámetros fueron identificados a partir del conocimiento de la epidemiología y de las características de A. baumannii. Dicho modelo fue analizado cualitativamente e implementado computacionalmente. Resultados. La implementación computacional del modelo teórico posibilitó obtener múltiples simulaciones a partir de diferentes condiciones iniciales. El análisis cualitativo de las mismas permitió definir de manera explícita las medidas de control más efectivas a la hora de controlar esta infección nosocomial. Conclusiones. La herramienta desarrollada es de gran utilidad en la gestión (predicción del comportamiento y evaluación de contramedidas profilácticas) de brotes por A. baumannii. Se demuestra de manera teórica la eficacia de medidas higiénicas y de cribado (AU)

Introduction. Acinetobacter baumannii infections have increased over time becoming a significant issue. Consequently, those applications that allow to predict the evolution of an outbreak and the relevance of the different control methods, are very important. The design of mathematical models plays a central role in this topic. Material and methods. Development of a deterministic mathematical model based on ordinary differential equations whose variables and parameters are defined upon the basis of knowledge of the epidemiology and characteristics of A. baumannii. This model is analyzed from a qualitative point of view and, also, its computational implementation is derived. Results. Several simulations were obtained developed from different initial conditions. The qualitative analysis of these simulations provides formal evidence of most effective control measures. Conclusions. The implementation of the computational model is an extremely useful tool in terms of managing A. baumannii outbreaks. There is mathematical proof of the fact that the observance of efficient hygiene and screening rules reduces the number of infected patients (AU)

[Noma/Cancrum oris: a neglected disease]. / La enfermedad de Noma/cancrum oris: una enfermedad olvidada.

Noma is an aggressive orofacial gangrenous pathology that damages hard and soft tissues of the mouth and the face. Throughout the centuries it has been present around the globe, but nowadays it has practically disappeared from developed countries and mainly affects children from the most disadvantaged places, especially in Africa. Noma disease is a multifactorial process; malnutrition, debilitating diseases (bacterial or viral systemic diseases, HIV-associated immunosuppression, etc.) and intraoral infections are some of the factors implied. The characteristic tissue necrosis is produced by a polymicrobial infection. Fusobacterium necrophorum, Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum, Bacteroides fragilis, Bacillus cereus, Trueperella pyogenes, spyrochetes, etc, are some of the species that have been isolated from the affected areas. Without treatment, noma is lethal in a short period of time, and the patients that survive show severe sequelae that hinder their life and interpersonal relationships. The aim of this paper is to unify the existing information and to promote wider knowledge and awareness among the population.

La enfermedad de Noma/cancrum oris: una enfermedad olvidada / Noma/Cancrum oris: a neglected disease

La enfermedad de Noma es una patología gangrenosa agresiva orofacial que daña a tejidos duros y blandos de la boca y de la cara. A lo largo de los siglos ha estado presente en todo el planeta, aunque en la actualidad ha desaparecido prácticamente de los países desarrollados, afectando casi siempre a niños de los lugares más desfavorecidos, especialmente en el continente africano. Es un proceso multifactorial en el que intervienen factores como la malnutrición, las enfermedades debilitantes (infecciones sistémicas bacterianas o víricas, inmunodepresión asociada al VIH, etc.) y las infecciones intraorales. La necrosis tisular característica la origina una infección polimicrobiana. Algunas de las especies que se han aislado de las zonas afectadas son: Fusobacterium necrophorum, Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum, Bacteroides fragilis, Bacillus cereus, Trueperella pyogenes, espiroquetas, etc. Sin tratamiento es letal en poco tiempo, y los pacientes que sobreviven presentan graves secuelas que dificultan su vida y sus relaciones interpersonales. El objetivo de esta revisión es unificar la información existente y promover un mayor conocimiento y concienciación de la población (AU)

Noma is an aggressive orofacial gangrenous pathology that damages hard and soft tissues of the mouth and the face. Throughout the centuries it has been present around the globe, but nowadays it has practically disappeared from developed countries and mainly affects children from the most disadvantaged places, especially in Africa. Noma disease is a multifactorial process; malnutrition, debilitating diseases (bacterial or viral systemic diseases, HIV-associated immunosuppression, etc.) and intraoral infections are some of the factors implied. The characteristic tissue necrosis is produced by a polymicrobial infection. Fusobacterium necrophorum, Prevotella intermedia, Prevotella melaninogenica, Fusobacterium nucleatum, Bacteroides fragilis, Bacillus cereus, Trueperella pyogenes, spyrochetes, etc, are some of the species that have been isolated from the affected areas. Without treatment, noma is lethal in a short period of time, and the patients that survive show severe sequelae that hinder their life and interpersonal relationships. The aim of this paper is to unify the existing information and to promote wider knowledge and awareness among the population (AU)

[Prevention of an outbreak of Acinetobacter baumannii in intensive care units: study of the efficacy of different mathematical methods]. / Prevención de un brote de Acinetobacter baumannii en una unidad de cuidados intensivos: eficacia de diversos métodos matemáticos.

INTRODUCTION: Although in past decades, Acinetobacter baumanni infections have been sporadically identified in hospitals, nowadays the nosocomial infections due to this pathogen have notably increased. Its importance is due to its multidrug- resistance, morbidity and mortatility in healthcare settings. Consequently, it is important to predict the evolution of these outbreaks in order to stablish the most efficient control measures. There are several experimental studies shown that the compliance with hand and environmental hygiene and the efficient management of the healthcare work help to control the evolution of these outbreaks. The goal of this work is to formally proof these experimental results by means of the analysis of the results provided by the model. METHODS: A stochastic mathematical model based on cellular automata was developed. The variables and parameters involved in it have been identified from the knowledge of the epidemiology and main characteristics of Acinetobacter infections. RESULTS: The model provides several simulations from different initial conditions. The analysis of these results proofs in a formal way that the compliance with hand and environmental hygiene and an efficient plannification of the work of healtcare workers yield a decrease in the colonized patients. Moreover, this is the unique model proposed studying the dynamics of an outbreak of A. baumanni. CONCLUSIONS: The computational implementation of the model provides us an efficient tool in the management of outbreaks due to A. baumanni. The analysis of the simulations obtained allows us to obtain a formal proof of the behaviour of the measures for control and prevention.

Las bacterias anaerobias 150 años después de su descubrimiento por Pasteur / Anaerobic bacteria 150 years after their discovery by Pasteur

El año 2011 marcó el 150 aniversario del descubrimiento de las bacterias anaerobias por Louis Pasteur. Tras este tiempo el interés biomédico por ellas se mantiene, y Clostridium difficile es probablemente la que más interés despierta en la actualidad. En estos últimos años se han producido importantes avances en taxonomía gracias al desarrollo tecnológico e informático, particularmente en el campo de la genética; así, se han caracterizado un número importante de nuevas especies implicadas en infecciones humanas y se han reclasificado algunas ya conocidas. A nivel patogénico, algunos anaerobios de la microflora que no se habían aislado de infecciones humanas se han aislado en algún cuadro clínico, ha habido emergencia o reemergencia de algunas especies y cuadros, ciertos anaerobios se han relacionado con síndromes infecciosos establecidos, ha aumentado la virulencia de algunas cepas y se han formulado hipótesis sobre su participación en ciertas enfermedades. En cuanto al diagnóstico, la generalización del MALDI-TOF ha supuesto una reducción de tiempo y un abaratamiento en la identificación que mejora día a día según se optimizan las bases de datos. La aplicación de la PCR en tiempo real ha sido otro gran avance, y la secuenciación del ARNr 16S y otros genes es ya una realidad para muchos laboratorios. Los anaerobios han ido aumentando su resistencia a los antimicrobianos, y la aparición de la resistencia a carbapenem y metronidazol y la mutirresistencia son ya una realidad. En esta última situación linezolid puede ser una buena alternativa en Bacteroides. Fidaxomicina es el único antianaerobio introducido en los últimos años, en concreto para la diarrea por C. difficile. Por último, se han desarrollado modelos matemáticos para el estudio de esta especie

In 2011 we celebrated the 150 th anniversary of the discovery of anaerobic bacteria by Louis Pasteur. The interest of the biomedical community on such bacteria is still maintained, and is particularly focused on Clostridium difficile. In the past few years important advances in taxonomy have been made due to the genetic, technological and computing developments. Thus, a significant number of new species related to human infections have been characterised, and some already known have been reclassified. At pathogenic level some specimens of anaerobic microflora, that had not been isolated from human infections, have been now isolated in some clinical conditions. There was emergence (or re-emergence) of some species and clinical conditions. Certain anaerobic bacteria have been associated with established infectious syndromes. The virulence of certain strains has increased, and some hypotheses on their participation in certain diseases have been given. In terms of diagnosis, the routine use of MALDI-TOF has led to a shortening of time and a cost reduction in the identification, with an improvement directly related to the improvement of data bases. The application of real-time PCR has been another major progress, and the sequencing of 16s rRNA gene and others is currently a reality for several laboratories. Anaerobes have increased their resistance to antimicrobial agents, and the emergence of resistance to carbapenems and metronidazole, and multi-resistance is a current reality. In this situation, linezolid could be an effective alternative for Bacteroides. Fidaxomicin is the only anti-anaerobic agent introduced in the recent years, specifically for the diarrhoea caused by C. difficile. Moreover, some mathematical models have also been proposed in relation with this species

Prevención de un brote de Acinetobacter baumannii en una unidad de cuidados intensivos: eficacia de diversos métodos matemáticos / Prevention of an outbreak of Acinetobacter baumannii in intensive care units: study of the efficacy of different mathematical methods

Introducción. Las infecciones nosocomiales por Acinetobacter baumannii han pasado de ser un hecho poco representativo a habitual en muchos servicios de Medicina Intensiva por su frecuencia, mortalidad asociada y resistencia a los antimicrobianos. Cuando se produce un brote es importante poder predecir su evolución y el impacto global e individualizado de los diferentes métodos de control. Se ha demostrado experimentalmente que tomar determinadas medidas (lavado de manos, planificación del trabajo del personal sanitario, etc.) ayuda a controlar y prevenir tanto la aparición como la extensión de dichos brotes. El objetivo es demostrar de manera formal los resultados empíricos comentados anteriormente valiéndonos de un novedoso modelo matemático. Material y Métodos. Se desarrolló un modelo matemático estocástico basado en autómatas celulares. A partir del conocimiento de la epidemiología y de las características de A. baumanii se identificaron las variables y los parámetros del modelo. Resultados. El modelo proporciona múltiples simulaciones usando diferentes condiciones iniciales. Su análisis demuestra formalmente que el cumplimiento con las normas de higiene así como una correcta planificación del trabajo del personal sanitario reduce el número de pacientes colonizados. Asimismo, no existe en la literatura especializada otro modelo matemático que estudie la dinámica de un brote por A. baumannii. Conclusiones. La implementación computacional del modelo proporciona una herramienta de gran utilidad para la comunidad sanitaria en la gestión de brotes por A. baumanii en ambientes hospitalarios. Se prueba matemáticamente como unas eficientes medidas higiénicas y de planificación del trabajo del personal sanitario reducen el número de pacientes colonizados (AU)

Introduction. Although in past decades, Acinetobacter baumanni infections have been sporadically identified in hospitals, nowadays the nosocomial infections due to this pathogen have notably increased. Its importance is due to its multidrug-resistance, morbidity and mortatility in healthcare settings. Consequently, it is important to predict the evolution of these outbreaks in order to stablish the most efficient control measures. There are several experimental studies shown that the compliance with hand and environmental hygiene and the efficient management of the healthcare work help to control the evolution of these outbreaks. The goal of this work is to formally proof these experimental results by means of the analysis of the results provided by the model. Methods. A stochastic mathematical model based on cellular automata was developed. The variables and parameters involved in it have been identified from the knowledge of the epidemiology and main characteristics of Acinetobacter infections. Results. The model provides several simulations from different initial conditions. The analysis of these results proofs in a formal way that the compliance with hand and environmental hygiene and an efficient plannification of the work of healtcare workers yield a decrease in the colonized patients. Moreover, this is the unique model proposed studying the dynamics of an outbreak of A. baumanni. Conclusions. The computational implementation of the model provides us an efficient tool in the management of outbreaks due to A. baumanni. The analysis of the simulations obtained allows us to obtain a formal proof of the behaviour of the measures for control and prevention (AU)

[Anaerobic bacteria 150 years after their discovery by Pasteur]. / Las bacterias anaerobias 150años después de su descubrimiento por Pasteur.

In 2011 we celebrated the 150th anniversary of the discovery of anaerobic bacteria by Louis Pasteur. The interest of the biomedical community on such bacteria is still maintained, and is particularly focused on Clostridium difficile. In the past few years important advances in taxonomy have been made due to the genetic, technological and computing developments. Thus, a significant number of new species related to human infections have been characterised, and some already known have been reclassified. At pathogenic level some specimens of anaerobic microflora, that had not been isolated from human infections, have been now isolated in some clinical conditions. There was emergence (or re-emergence) of some species and clinical conditions. Certain anaerobic bacteria have been associated with established infectious syndromes. The virulence of certain strains has increased, and some hypotheses on their participation in certain diseases have been given. In terms of diagnosis, the routine use of MALDI-TOF has led to a shortening of time and a cost reduction in the identification, with an improvement directly related to the improvement of data bases. The application of real-time PCR has been another major progress, and the sequencing of 16srRNA gene and others is currently a reality for several laboratories. Anaerobes have increased their resistance to antimicrobial agents, and the emergence of resistance to carbapenems and metronidazole, and multi-resistance is a current reality. In this situation, linezolid could be an effective alternative for Bacteroides. Fidaxomicin is the only anti-anaerobic agent introduced in the recent years, specifically for the diarrhoea caused by C.difficile. Moreover, some mathematical models have also been proposed in relation with this species.

[Mathematical modelling of the propagation of infectious diseases: where we came from, and where we are going]. / Modelización matemática de la propagación de enfermedades infecciosas: de dónde venimos y hacia dónde vamos.

This work deals with the study of the use of mathematical models to simulate the spreading of infectious diseases. There is no doubt about the importance of the use of computational tools that allow the health staff to model and predict the spreading of an infectious disease. Using such tools one can establish and simulate disease control strategies. The development of such technologies is a multidisciplinary issue; in this sense, the mathematical algorithms -that must be computationally implemented- play a central role. The main goal of this work is to highlight among health community the increasing importance of the use of mathematical models for epidemic disease spreading. Consequently, the main features of such models are introduced and their classification is stated taking into account the behavior, the basic population unit or the mathematical objects used. An exhaustive search of related papers through the most important databases (Medline and Web of Science) are performed. The main conclusion obtained from this work is the central role that mathematical models can play in the simulation of epidemic spreading; moreover,some ideas about the future research are stated.

Modelización matemática de la propagación de enfermedades infecciosas: de dónde venimos y hacia dónde vamos / Mathematical modelling of the propagation of infectious diseases: where we came from, and where we are going

Es de indudable importancia dotar al gestor sanitario de herramientas que permitan predecir el comportamiento de la propagación de una enfermedad infecciosa, de manera que a partir de las mismas se pueden establecer y simular estrategias de control. El desarrollo de tales herramientas es de carácter pluridisciplinar siendo la base de las mismas, algoritmos o modelos matemáticos que son implementados computacionalmente. En este trabajo se muestra el funcionamiento de estos modelos matemáticos y se detalla su clasificación atendiendo a diferentes factores. Además se lleva a cabo un estudio cuantitativo de los mismos haciendo uso de las principales bases de datos relacionadas con el tema de estudio (Medline y Web of Science). De este trabajo se concluye el importante papel que pueden jugar los modelos matemáticos a la hora de simular los procesos infecciosos y, asimismo, se proponen futuras y eficaces vías de investigación en la modelización matemática de enfermedades infecciosas(AU)

This work deals with the study of the use of mathematical models to simulate the spreading of infectious diseases. There is no doubt about the importance of the use of computational tools that allow the health staff to model and predict the spreading of an infectious disease. Using such tools one can establish and simulate disease control strategies. The development of such technologies is a multidisciplinary issue; in this sense, the mathematical algorithms –that must be computationally implemented- play a central role. The main goal of this work is to highlight among health community the increasing importance of the use of mathematical models for epidemic disease spreading. Consequently, the main features of such models are introduced and their classification is stated taking into account the behavior, the basic population unit or the mathematical objects used. An exhaustive search of related papers through the most important databases (Medline and Web of Science) are performed. The main conclusion obtained from this work is the central role that mathematical models can play in the simulation of epidemic spreading; moreover, some ideas about the future research are stated(AU)

Modelos matemáticos en el estudio de la resistencia a los antimicrobianos. Perspectivas a partir de un metaanálisis / Matematical modeling of antibiotic resistance. Perspectives from a meta-analysys

La resistencia a los antimicrobianos es uno de los principales problemas a los que se enfrenta la comunidad sanitaria internacional. El estudio de la resistencia se debe realizar desde un enfoque pluridisciplinar y en este sentido se analiza el papel que puede jugar la Modelización Matemática en este escenario. Así se realiza un análisis tanto cuantitativo como cualitativo de los trabajos que han aparecido en la literatura científica mediante una búsqueda en las principales bases de datos: MEDLINE, SCOPUS e ISI Web of Science. Tras el análisis realizado en este estudio se observa que son pocos los trabajos relacionados con la temática objeto de estudio pero han sido publicados en revistas de un alto impacto; asimismo podemos afirmar que el desarrollo de modelos matemáticos puede jugar un papel muy importante a la hora de analizar y estudiar tanto los tratamientos para prevenir la aparición de las resistencias como el establecimiento y evaluación de estrategias de control en ambientes hospitalarios y la predicción del comportamiento de las infecciones por cepas resistentes(AU)

The antibiotic resistance is one of the greatest challenges of the international health community. The study of antibiotic resistance must be a multidisciplinary task and, in this sense, the main goal of this work is to analyze the role that Mathematical Modeling can play in this scenario. A qualitative and cuantitative analysis of the works published in the scientific literature is done by means of a search in the most important databases: MEDLINE, SCOPUS and ISI Web of Science. Consequently, there are few papers related to our topic but the existing works have been published in high-quality and impact international journals. Moreover, we can state that mathematical models are a very important and useful tool to analyze and study both the treatments protocols for resistance prevention and the assesment of control strategies in hospital environtment, or the prediction of the evolution of diseases due to resistant strains(AU)

[Antibiotheraphy in the 21st century, antibacterials for the second decade. Posibilities or realities in the future?]. / Antibioterapia para el siglo XXI, antibacterianos para la segunda década. ¿Posibilidades o realidades en un futuro?

A review of some antibacterial products is done motivated by the serious situation arisen by the antimicrobial resistance in bacteria. The attention is focus on those drugs with suitable antimicrobial properties that have prospects to be commercialized in the next years because of they are undergoing a clinical development phase (I, II, III). The search for these antibacterial products has been done by an exhaustive study of conference proceedings and web pages of international congresses on chemotherapy, infectious diseases and new antimicrobial drugs. Some of the new antibacterial products acts on known targets, and they belong to already used families. Furthermore, the great majority acts against the gram-positive bacterium. There is also some limited-spectrum antimicrobial drug whose use would minimize the adverse biological effects.

Antibioterapia para el siglo XXI, antibacterianos para la segunda década. ¿Posibilidades o realidades en un futuro? / Antibiotheraphy in the 21st century, antibacterials for the second decade. Posibilities or realities in the future?

Ante la grave situación planteada por la resistencia de las bacterias a los antibióticos se revisan antibacterianos que por sus propiedades antimicrobianas y por encontrarse en registro o en fase de desarrollo clínico (I, II, III) tienen posibilidades de ser comercializados en años venideros. Su búsqueda se ha realizado investigando en los resúmenes de los libros de actas y páginas web de congresos internacionales de quimioterapia, enfermedades infecciosas y nuevos fármacos. Muchos de los nuevos antibacterianos actúan sobre dianas conocidas y pertenecen a familias ya utilizadas en clínica. La mayor parte actúa sobre grampositivos. Hay alguna sustancia con espectro muy reducido cuya posible utilización minimizaría los efectos biológicos adversos(AU)

A review of some antibacterial products is done motivated by the serious situation arisen by the antimicrobial resistance in bacteria. The attention is focus on those drugs with suitable antimicrobial properties that have prospects to be commercialized in the next years because of they are undergoing a clinical development phase (I, II, III). The search for these antibacterial products has been done by an exhaustive study of conference proceedings and web pages of international congresses on chemotherapy, infectious diseases and new antimicrobial drugs. Some of the new antibacterial products acts on known targets, and they belong to already used families. Furthermore, the great majority acts against the gram-positive bacterium. There is also some limited-spectrum antimicrobial drug whose use would minimize the adverse biological effects(AU)

Resonancia magnética funcional en el diagnóstico clínico del déficit de atención y de la agresión impulsiva infantil: Una propuesta exploratoria / Functional magnetic resonance imaging in the clinical diagnostic of the attention deficit disorder and the impulsive aggression in children: An exploratory proposal

Attention deficit disorder (ADD) refers to a neurobehavioral condition commonly initiated in childhood. Its clinical diagnosis involves poor attention, distractibility, difficulties to inhibit motor behaviors and cognitive impulsivity. It is suggested that ADD is classified in two general types correlated with different neurocognitive qualities. One is manifested in executive frontal dysfunctions (ADD). In the other type dominates hyperactivity/ impulsivity (ADHD) and it is associated with deficiencies in working memory and alterations in the dorsolateral prefrontal cortex. Results obtained by using electroencephalography, event-related potential paradigms and voxel brain morphometry suggest anomalies in the brain structure and function correlated with ADD, particularly in the frontal, parietal and temporal cortices, in addition to regions involved in the fronto-estriatal connections. On the other hand, functional magnetic resonance imaging (fMRI) constitutes a technique to obtain brain images which can be interpreted as regions and networks of neural activity elicited during the performance of a cognitive process. Based on the information that the ADD patients are susceptible to cognitive interferences, some researches have applied the classical and the counting versions of the Stroop task paradigms in fMRI. In comparison with control subjects, adult patients show alack of neural activation in the anterior cingulated cortex. Nevertheless, results in children are more controversial and attribute neurobiological and social factors in the ADD etiology. The anterior cingulated cortex and prefrontal region of the human brain conform the execution system of attention and their function is essential for emotional processes. The neurocognitive relation between attention and emotion involves the influence of the affective system in the alert and execution systems of attention through reciprocal connections between limbic and frontal regions, which permit a mnemonic and affective valuation of the attended environment. Understanding the relations between attention and emotion is essential in basic and clinical approaches, due to the co-morbidity of ADD with some emotional disorders, such as the oppositional defiant disorder, anxiety and impulsive aggression, the last one elicited by uncontrolled experiences of anger. In this sense, some studies describe that the metabolic brain activity correlated with the experience of anger is manifested in the frontal, anterior cingulated and insular cortices and the temporal pole. Clinical situations require individualized decisions on the immediate and emergent treatment of one case. Furthermore, when the clinical case refers to a behavioral disorder probably related with neurobiological dysfunctions, a comparison of test with control subjects is necessary. In this sense, the present work constitutes an fMRI study designed to evaluate neurological functional alterations in a child patient diagnosed with ADHD, with persistent severe impulsive aggression behaviors that required a swift evaluation to enhance the diagnosis and treatment proposed by other clinical techniques. Besides the patient, three infant participants were evaluated. One of them was diagnosed with ADD but did not manifest aggressive or impulsive behaviors and was not under any pharmacological treatment. The other two healthy children had no neurological and psychiatric disorders history. All the participants presented similar intellectual coefficient and performed the same cognitive and emotional tests. In the case of the patient, test were applied in two conditions: under the proposed pharmacological treatment and without medication. The attention test consisted in a version of the counting Stroop task in Spanish language, presented in a block design through the E-Prime software. Subjects practiced the task in a personal computer before the functional image acquisition and were trained to answer by using a bottom response system that will be used in the scanner. For the emotional-anger paradigm, children were interviewed about scenes and situations of their personal experience which elicited anger and calm. Situations were ordered and planned in a block design to be executed in the magnetic resonance instrument. During the functional images acquisition children listened to the situations conducted by imaginery techniques. Functional images were acquired in a 1.5 T G.E. instrument in the Magnetic Resonance Unit of the Hospital Ángeles Metropolitano in Mexico City. Data were analyzed by using the SPM 5 software applying a contrast using FWE with p < 0.05. Brain coordinates obtained in SPM 5 were converted to the Talairach Deamond system in order to obtain the Brodmann areas related to those coordinates. During the performance of the counting Stroop task, the patient with ADHD under medication manifested activation in frontal areas, but not during the medication suspension trial. Frontal activity identified in this patient in the treatment trial was similar to that identified in the unaggressive ADD patient. In both cases, ADHD without medication and ADD, a lack of activity was identified in the anterior cingulate cortex (ACC). Nevertheless, activation in ACC, in parietal and temporal regions was present in the aggressive patient under treatment but not in the suspension condition. These results may suggest that an inadequate attention process distort the environment stimuli, which is necessary for the subject's correct affective evaluation of the situation. During the experience of anger, the patient under treatment manifested activity in the parahippocampal region, as well as in the anterior and posterior cingulate cortices. Results discussed in this work agree with those previously reported and offer cues to complement the diagnosis and treatment of ADD/ADHD and their relations with emotional disorders. Particularly, the design used here could be used for the analysis and evaluation of some pharmacological and behavioral treatments clinically applied in ADD. In addition, it helps to understand the participation of multipotential brain regions and neural networks involved in several cognitive processes, such as attention, working memory and emotion. Finally, we proposed some ideas to interpret these results using fMRI and ADD: 1. It is necessary a consensual and standard integration of neuropsychological tests which identify different cognitive qualities of ADD. 2. The selection of children samples to study the neurobiology of ADD must include several variables associated with its etiology, such as parental relations, social and scholar environments. 3. Experimental paradigms could be designed to be performed using different neuroimaging techniques, such as fMRI or event-related potential. Thus, the results of the same test can be used to complement different approaches. 4. Results obtained by fMRI must not be understood in a phrenologycal and deterministic approach, but as brain region activations indicating dynamic neural networks.

El trastorno por déficit de atención (TDA) es un padecimiento neuroconductual iniciado en la infancia, cuyos criterios diagnósticos incluyen dificultades en la inhibición motora e impulsividad conductual. Tomando en cuenta la evidencia de que los pacientes con TDA son susceptibles a la interferencia cognitiva, la técnica de resonancia magnética funcional ha permitido la obtención de imágenes cerebrales que pueden interpretarse como redes de actividad neuronal, las cuales fueron desencadenadas durante la realización de la tarea Stroop o de interferencia. Algunos hallazgos en individuos sanos sugieren actividad predominante en la corteza anterior del cíngulo durante el proceso de atención selectiva requerido en la ejecución de esta tarea, en tanto que pacientes diagnosticados con TDA muestran ausencia de tal actividad. Diversos autores han señalado la relación neurocognitiva entre la atención y la emoción, a partir de la interacción entre estructuras límbicas y regiones frontales del cerebro. En el caso del TDA, esta relación es relevante debido a su comorbilidad con trastornos de tipo emocional, en particular en el caso de la agresión impulsiva. Ésta es desencadenada por estados incontrolables de ira, cuya experiencia inducida se ha correlacionado con la actividad cerebral de la región frontal, del polo temporal, de la corteza anterior del cíngulo y de la ínsula. Ahora bien, en el ámbito clínico es recurrente la necesidad de una evaluación individualizada y la decisión del tratamiento inmediato y urgente de un caso. El presente trabajo muestra un diseño utilizado en la valoración de alteraciones neurológicas funcionales en un paciente infantil diagnosticado con TDA, cuyos repetidos episodios de comportamientos agresivos requerían una evaluación pronta que complementara el diagnóstico y tratamiento provenientes de otras herramientas clínicas. Con un equipo de resonancia magnética de 1.5 T se registró la actividad cerebral del paciente durante la ejecución de una versión en español de la tarea Stroop por conteo y de un paradigma emocional que consistió en la evocación dirigida de escenas que desencadenaran ira en el sujeto. La obtención de imágenes funcionales se real izó tanto bajo el efecto del tratamiento farmacológico que seguía el paciente, como bajo la suspensión del mismo. Después, se comparó la actividad cerebral del paciente con otro caso infantil diagnosticado con TDA, pero sin presencia de comportamientos agresivos. La actividad cerebral de ambos casos de TDA se comparó con la registrada en dos niños con edad y coeficiente intelectual homogéneos, carentes de historial neurológico y psiquiátrico. Ninguno de los participantes manifestó alteraciones estructurales cerebrales. Los resultados funcionales durante la ejecución Stroop identificaron menor actividad en la corteza anterior del cíngulo en los dos casos diagnosticados con TDA. Durante la experiencia del estado de ira y en comparación con los otros participantes, el paciente bajo efecto del tratamiento manifestó actividad en la región parahipocampal, así como en las cortezas anterior y posterior del cíngulo. Los resultados coinciden con hallazgos reportados sobre la neurobiología del TDA y de la experiencia de ira. Además, otorgan herramientas para el diagnóstico y tratamiento de trastornos de la atención y su relación con trastornos emocionales. Este tipo de diseños contribuye al análisis y observación del efecto de algunos tratamientos, tanto farmacológicos como conductuales, aplicados en la clínica del TDA. En este caso, el tratamiento aplicado al paciente parece actuar a nivel del proceso de atención, pero no en el ámbito del control de la ira. También, proporciona pautas para comprender la participación de regiones cerebrales multipotenciales y las redes neuronales que involucran diferentes procesos cognitivos, como la emoción y la atención.

A neonatal form of Steinert's myotonic dystrophy in twins after in vitro fertilization.

OBJECTIVE: To report a case of nonidentical twins affected with a congenital form of Steinert's myotonic dystrophy (DM1), conceived by IVF owing to parental sterility, in which the mother presented a paucisymptomatic form of DM1 which was diagnosed as a result of the condition inherited by the twins. DESIGN: Case report. SETTING: Neonatal intensive care unit of a tertiary hospital. PATIENT(S): Newborn twins affected with the congenital form of DM1 and a 35-year-old nulliparous mother. INTERVENTION(S): In vitro fertilization. MAIN OUTCOME MEASURE(S): Molecular study of the CTG triplet expansion related with DM1. RESULT(S): Molecular study evidenced a pathologic expansion in both twins as well as in their mother. CONCLUSION(S): This case should serve as a reminder to practitioners that assisted reproductive techniques have opened the possibility that asymptomatic or paucisymptomatic carriers of a genetic syndrome can inadvertently conceive fetuses affected with more serious forms of the illness.

Characterisation of phosphorous forms in wastewater treatment plants.

The removal of different forms of phosphorous (namely total phosphorous, soluble phosphorous, particulate phosphorous and total phosphate) has been studied in two municipal wastewater treatment plants (WWTP) with different characteristics, but without any specific implemented strategy for phosphorous removal. The results obtained for the different forms of phosphorus can be summarised as follows: (1) complete removal of particulate phosphorous is achieved in either primary or secondary clarifiers; (2) total phosphorous concentration in the effluent is mostly soluble phosphorous and this is mainly phosphate; (3) a small amount of soluble phosphorous is removed by biomass growth and/or biosorption; (4) both WWTPs presented a high-buffered behaviour in response to high inlet loading of phosphorous, showing a constant pattern at the outlet of the WWTP; (5) removal of total phosphorous was approximately 60-70% for both WWTPs; and (6) recirculation streams such as supernatant from centrifuge sludge dehydration operation can have a significant contribution to the inlet amount of phosphorous. The results presented in this paper provide a basis to develop prospects for phosphorous removal, which may be adapted to the particular configurations of the WWTP studied.