El arte como terapia en salud mental

Los planes de atención de enfermería actuales recogen nuevas intervenciones, alternativas a los cuidados convencionales y algunas de ellas poco estudiadas, como lo es el uso de distintas formas de arte como terapia complementaria a un tratamiento médico. Uno de los campos donde más fuerza tiene es en el de la salud mental, ya que permite actuar tanto de forma terapéutica como preventiva. La arteterapia engloba intervenciones con cualquier forma de arte como la pintura, la fotografía, la música o el teatro. Su terreno de actuación, además de la parte puramente asistencial, incluye el ámbito social y educativo que en muchas ocasiones son olvidados en los cuidados enfermeros. Una revisión de este tipo es necesaria para guiar las intervenciones enfermeras englobadas en la mejora de la comunicación no verbal en pacientes con los que la psicoterapia tradicional a través del diálogo no es eficaz y como herramienta de estimulación cognitiva y prevención de síntomas depresivos o ansiosos que conllevan muchas patologías médicas. El objetivo de esta revisión es mostrar una visión general de la situación actual de este tipo de terapia, repasando su evolución histórica y valorar su eficacia a partir de la evidencia científica encontrada. Para ello se realizó un análisis de las publicaciones que tratan este tema, incluyendo artículos de investigación que analizan el efecto de distintos tipos de terapias con arte sobre diversos trastornos, teniendo siempre en cuenta el tipo de artículo analizado así como la calidad científica de las publicaciones.

Development of a Cationic Mucic Acid Polymer-Based Nanoparticle siRNA Delivery System

Cancer chemotherapy has advanced from highly toxic drugs to more targeted treatments in the last 70 years. Chapter 1 opens with an introduction to targeted therapy for cancer. The benefits of using a nanoparticle to deliver therapeutics are discussed. We move on to siRNA in particular, and why it would be advantageous as a therapy. Specific to siRNA delivery are some challenges, such as nuclease degradation, quick clearance from circulation, needing to enter cells, and getting to the cytosol. We propose the development of a nanoparticle delivery system to tackle these challenges so that siRNA can be effective.

Chapter 2 of this thesis discusses the synthesis and analysis of a cationic mucic acid polymer (cMAP) which condenses siRNA to form a nanoparticle. Various methods to add polyethylene glycol (PEG) for stabilizing the nanoparticle in physiologic solutions, including using a boronic acid binding to diols on mucic acid, forming a copolymer of cMAP with PEG, and creating a triblock with mPEG on both ends of cMAP. The goal of these various pegylation strategies was to increase the circulation time of the siRNA nanoparticle in the bloodstream to allow more of the nanoparticle to reach tumor tissue by the enhanced permeation and retention effect. We found that the triblock mPEG-cMAP-PEGm polymer condensed siRNA to form very stable 30-40 nm particles that circulated for the longest time – almost 10% of the formulation remained in the bloodstream of mice 1 h after intravenous injection.

Chapter 3 explores the use of an antibody as a targeting agent for nanoparticles. Some antibodies of the IgG1 subtype are able to recruit natural killer cells that effect antibody dependent cellular cytotoxicity (ADCC) to kill the targeted cell to which the antibody is bound. There is evidence that the ADCC effect remains in antibody-drug conjugates, so we wanted to know whether the ADCC effect is preserved when the antibody is bound to a nanoparticle, which is a much larger and complex entity. We utilized antibodies against epidermal growth factor receptor with similar binding and pharmacokinetics, cetuximab and panitumumab, which differ in that cetuximab is an IgG1 and panitumumab is an IgG2 (which does not cause ADCC). Although a natural killer cell culture model showed that gold nanoparticles with a full antibody targeting agent can elicit target cell lysis, we found that this effect was not preserved in vivo. Whether this is due to the antibody not being accessible to immune cells or whether the natural killer cells are inactivated in a tumor xenograft remains unknown. It is possible that using a full antibody still has value if there are immune functions which are altered in a complex in vivo environment that are intact in an in vitro system, so the value of using a full antibody as a targeting agent versus using an antibody fragment or a protein such as transferrin is still open to further exploration.

In chapter 4, nanoparticle targeting and endosomal escape are further discussed with respect to the cMAP nanoparticle system. A diboronic acid entity, which gives an order of magnitude greater binding (than boronic acid) to cMAP due to the vicinal diols in mucic acid, was synthesized, attached to 5kD or 10kD PEG, and conjugated to either transferrin or cetuximab. A histidine was incorporated into the triblock polymer between cMAP and the PEG blocks to allow for siRNA endosomal escape. Nanoparticle size remained 30-40 nm with a slightly negative ca. -3 mV zeta potential with the triblock polymer containing histidine and when targeting agents were added. Greater mRNA knockdown was seen with the endosomal escape mechanism than without. The nanoparticle formulations were able to knock down the targeted mRNA in vitro. Mixed effects suggesting function were seen in vivo.

Chapter 5 summarizes the project and provides an outlook on siRNA delivery as well as targeted combination therapies for the future of personalized medicine in cancer treatment.

Kires: a data-centric telerehabilitation system based on kinect

185 p.

Low Molecular Weight Chitosan (LMWC)-based Polyplexes for pDNA Delivery: From Bench to Bedside

Non-viral gene delivery vectors are emerging as a safer alternative to viral vectors. Among natural polymers, chitosan (Ch) is the most studied one, and low molecular weight Ch, specifically, presents a wide range of advantages for non-viral pDNA delivery. It is crucial to determine the best process for the formation of Low Molecular Weight Chitosan (LMWC)-pDNA complexes and to characterize their physicochemical properties to better understand their behavior once the polyplexes are administered. The transfection efficiency of Ch based polyplexes is relatively low. Therefore, it is essential to understand all the transfection process, including the cellular uptake, endosomal escape and nuclear import, together with the parameters involved in the process to improve the design and development of the non-viral vectors. The aim of this review is to describe the formation and characterization of LMWC based polyplexes, the in vitro transfection process and finally, the in vivo applications of LMWC based polyplexes for gene therapy purposes.

Tratamento da Neofobia Alimentar em pacientes com obesidade associada ou não à compulsão alimentar

Tendo como base a visão evolucionista e a abordagem terapêutica cognitivo-comportamental, o objetivo deste trabalho foi propor um protocolomodificado de tratamento para pessoas obesas com compulsão alimentar periódica.A idéia norteadora é que estratégias que foram úteis para a sobrevivência daespécie poderiam estar influenciando no ganho de peso. Entre estas estratégias,destacam-se: a tendência a consumir uma grande quantidade de alimentos, facilitando o consumo de alimentos hipercalóricos; e a neofobia alimentar, dificultando o consumo de frutas, legumes e verduras. Obedecendo à lógicaancestral herdada pela espécie, a primeira proporciona reservas para momentos deescassez de alimentos e a segunda implica em uma recusa em consumir alimentosdesconhecidos evitando que substâncias tóxicas sejam ingeridas. Ambos os fatores poderiam contribuir para a obesidade. Os tratamentos convencionais buscam controlar a ingestão calórica. O que aqui se propõe, além desse controle, é tentardiminuir o nível de neofobia alimentar. Com essa hipótese de trabalho espera-se aumentar o consumo de alimentos, principalmente os mais saudáveis e hipocalóricos, contribuindo para reduzir a ingestão de alimentos hipercalóricos. Otratamento incluiu técnicas de exposição, modelação e imitação adicionadas a umtratamento já utilizado para obesos com compulsão alimentar periódica. Foram criados dois grupos, o primeiro com 4 participantes funcionando como grupo decontrole, que recebeu um tratamento convencional de TCC; o outro, com 6 participantes aqui denominado grupo de intervenção, que recebeu o tratamento deTCC modificado. A pesquisa foi qualificada como quase-experimental. O resultadoobtido foi uma redução do índice de neofobia alimentar, do Índice de massa corporal, um aumento no consumo de alimentos saudáveis e a redução de gordurase açúcares no chamado grupo de intervenção. Embora tenha alcançado estes resultados, o tratamento ainda precisa ser reformulado e ampliado.

Structural Integrity of the Contralesional Hemisphere Predicts Cognitive Impairment in Ischemic Stroke at Three Months

After stroke, white matter integrity can be affected both locally and distally to the primary lesion location. It has been shown that tract disruption in mirror's regions of the contralateral hemisphere is associated with degree of functional impairment. Fourteen patients suffering right hemispheric focal stroke (S) and eighteen healthy controls (HC) underwent Diffusion Weighted Imaging (DWI) and neuropsychological assessment. The stroke patient group was divided into poor (SP; n = 8) and good (SG; n = 6) cognitive recovery groups according to their cognitive improvement from the acute phase (72 hours after stroke) to the subacute phase (3 months post-stroke). Whole-brain DWI data analysis was performed by computing Diffusion Tensor Imaging (DTI) followed by Tract Based Spatial Statistics (TBSS). Assessment of effects was obtained computing the correlation of the projections on TBSS skeleton of Fractional Anisotropy (FA) and Radial Diffusivity (RD) with cognitive test results. Significant decrease of FA was found only in right brain anatomical areas for the S group when compared to the HC group. Analyzed separately, stroke patients with poor cognitive recovery showed additional significant FA decrease in several left hemisphere regions; whereas SG patients showed significant decrease only in the left genu of corpus callosum when compared to the HC. For the SG group, whole brain analysis revealed significant correlation between the performance in the Semantic Fluency test and the FA in the right hemisphere as well as between the performance in the Grooved Pegboard Test (GPT) and theTrail Making Test-part A and the FA in the left hemisphere. For the SP group, correlation analysis revealed significant correlation between the performance in the GPT and the FA in the right hemisphere.

Addressing the cognitive and social influence inhibitors during the ideation stages of technology roadmapping workshops

Technology roadmapping workshops are essentially a social mechanism for exploring, creating, shaping and implementing ideas. The front-end of a roadmapping session is based on brainstorming in order to tap into the group's diverse knowledge. The aim of this idea stimulation activity is to capture and share as many perspectives as possible across the full scope of the area of interest. The premise to such group brainstorming is that the sharing and exchange of ideas leads to cognitive stimulation resulting in a greater overall group idea generation performance in terms of the number, variety and originality of ideas. However, it must be recognized that the ideation stage in a roadmapping workshop is a complex psychosocial phenomenon with underlying cognitive and social processes. Thus, there are downsides to group interactions and these must be addressed in order to fully benefit from the power of a roadmapping workshop. This paper will highlight and discuss the key cognitive and social inhibitors involved. These include: production blocking, evaluation apprehension, free riding/social loafing, low norm setting/matching. Facilitation actions and process adjustments to counter such negative factors will be identified so as to provide a psychosocial basis for improving the running of roadmapping workshops. © 2009 PICMET.

Analogical reasoning in case-based design

A computer can assist the process of design by analogy by recording past designs. The experience these represent could be much wider than that of designers using the system, who therefore need to identify potential cases of interest. If the computer assists with this lookup, the designers can concentrate on the more interesting aspect of extracting and using the ideas which are found. However, as the knowledge base grows it becomes ever harder to find relevant cases using a keyword indexing scheme without knowing precisely what to look for. Therefore a more flexible searching system is needed.

If a similarity measure can be defined for the features of the designs, then it is possible to match and cluster them. Using a simple measure like co-occurrence of features within a particular case would allow this to happen without human intervention, which is tedious and time- consuming. Any knowledge that is acquired about how features are related to each other will be very shallow: it is not intended as a cognitive model for how humans understand, learn, or retrieve information, but more an attempt to make effective, efficient use of the information available. The question remains of whether such shallow knowledge is sufficient for the task.

A system to retrieve information from a large database is described. It uses co-occurrences to relate keywords to each other, and then extends search queries with similar words. This seems to make relevant material more accessible, providing hope that this retrieval technique can be applied to a broader knowledge base.

Improving effects of huperzine A on spatial working memory in aged monkeys and young adult monkeys with experimental cognitive impairment

Our previous studies demonstrated that huperzine A, a reversible and selective acetylcholinesterase inhibitor, exerts beneficial effects on memory deficits in various rodent models of amnesia. To extend the antiamnesic action of huperzine A to nonhuman primates, huperzine A was evaluated for its ability to reverse the deficits in spatial memory produced by scopolamine in young adult monkeys or those that are naturally occurring in aged monkeys using a delayed-response task. Scopolamine, a muscarinic receptor antagonist, dose dependently impaired performance with the highest dose (0.03 mg/kg, i.m.) producing a significant reduction in choice accuracy in young adult monkeys. The delayed performance changed from an average of 26.8/30 trials correct on saline control to an average of 20.2/30 trials correct after scopolamine administration. Huperzine A (0.01-0.1 mg/kg, i.m.) significantly reversed deficits induced by scopolamine in young adult monkeys on a delayed-response task; performance after an optimal dose (0.1 mg/kg) averaged 25.0/30 correct. In four aged monkeys, huperzine A (0.001-0.01 mg/kg, i.m.) significantly increased choice accuracy from 20.5/30 on saline control to 25.2/30 at the optimal dose (0.001 mg/kg for two monkeys and 0.01 mg/kg for the other two monkeys). The beneficial effects of huperzine A on delayed-response performance were long lasting; monkeys remained improved for about 24 h after a single injection of huperzine A. This study extended the findings that huperzine A improves the mnemonic performance requiring working memory in monkeys, and suggests that huperzine A may be a promising agent for clinical therapy of cognitive impairments in patients with Alzheimer's disease.

Cognitive Tomography Reveals Complex, Task-Independent Mental Representations

Humans develop rich mental representations that guide their behavior in a variety of everyday tasks. However, it is unknown whether these representations, often formalized as priors in Bayesian inference, are specific for each task or subserve multiple tasks. Current approaches cannot distinguish between these two possibilities because they cannot extract comparable representations across different tasks [1-10]. Here, we develop a novel method, termed cognitive tomography, that can extract complex, multidimensional priors across tasks. We apply this method to human judgments in two qualitatively different tasks, "familiarity" and "odd one out," involving an ecologically relevant set of stimuli, human faces. We show that priors over faces are structurally complex and vary dramatically across subjects, but are invariant across the tasks within each subject. The priors we extract from each task allow us to predict with high precision the behavior of subjects for novel stimuli both in the same task as well as in the other task. Our results provide the first evidence for a single high-dimensional structured representation of a naturalistic stimulus set that guides behavior in multiple tasks. Moreover, the representations estimated by cognitive tomography can provide independent, behavior-based regressors for elucidating the neural correlates of complex naturalistic priors. © 2013 The Authors.

Excision of Sleeping Beauty transposons: parameters and applications to gene therapy

A major problem in gene therapy is the determination of the rates at which gene transfer has occurred. Our work has focused on applications of the Sleeping Beauty (SB) transposon system as a non-viral vector for gene therapy. Excision of a transposon from a donor molecule and its integration into a cellular chromosome are catalyzed by SB transposase. In this study, we used a plasmid-based excision assay to study the excision step of transposition. We used the excision assay to evaluate the importance of various sequences that border the sites of excision inside and outside the transposon in order to determine the most active sequences for transposition from a donor plasmid. These findings together with our previous results in transposase binding to the terminal repeats suggest that the sequences in the transposon-junction of SB are involved in steps subsequent to DNA binding but before excision, and that they may have a role in transposase-transposon interaction. We found that SB transposons leave characteristically different footprints at excision sites in different cell types, suggesting that alternative repair machineries operate in concert with transposition. Most importantly, we found that the rates of excision correlate with the rates of transposition. We used this finding to assess transposition in livers of mice that were injected with the SB transposon and transposase. The excision assay appears to be a relatively quick and easy method to optimize protocols for delivery of genes in SB transposons to mammalian chromosomes in living animals. Copyright (C) 2004 John Wiley Sons, Ltd.

Cognitive models in biomimetic pattern cognition

We describe a new model which is based on the concept of cognizing theory. The method identifies subsets of the data which are embedded in arbitrary oriented lower dimensional space. We definite k-mean covering, and study its property. Covering subsets of points are repeatedly sampled to construct trial geometry space of various dimensions. The sampling corresponding to the feature space having the best cognition ability between a mode near zero and the rest is selected and the data points are partitioned on the basis of the best cognition ability. The repeated sampling then continues recursively on each block of the data. We propose this algorithm based on cognition models. The experimental results for face recognition demonstrate that the correct rejection rate of the test samples excluded in the classes of training samples is very high and effective.

Object-recognition with oblique observation directions based on biomimetic pattern recognition

In this paper, we propose a new scheme for omnidirectional object-recognition in free space. The proposed scheme divides above problem into several onmidirectional object-recognition with different depression angles. An onmidirectional object-recognition system with oblique observation directions based on a new recognition theory-Biomimetic Pattern Recognition (BPR) is discussed in detail. Based on it, we can get the size of training samples in the onmidirectional object-recognition system in free space. Omnidirection ally cognitive tests were done on various kinds of animal models of rather similar shapes. For the total 8400 tests, the correct recognition rate is 99.89%. The rejection rate is 0.11% and on the condition of zero error rates. Experimental results are presented to show that the proposed approach outperforms three types of SVMs with either a three degree polynomial kernel or a radial basis function kernel.

scenario-based interactive intention understanding in pen-based user interfaces

Interactive intention understanding is important for Pen-based User Interface (PUI). Many works on this topic are reported, and focus on handwriting or sketching recognition algorithms at the lexical layer. But these algorithms cannot totally solve the problem of intention understanding and can not provide the pen-based software with high usability. Hence, a scenario-based interactive intention understanding framework is presented in this paper, and is used to simulate human cognitive mechanisms and cognitive habits. By providing the understanding environment supporting the framework, we can apply the framework to the practical PUI system. The evaluation of the Scientific Training Management System for the Chinese National Diving Team shows that the framework is effective in improving the usability and enhancing the intention understanding capacity of this system.

Design of slow extraction system for therapy synchrotron

Based on the optimized design of the lattice for therapy synchrotron and considering the requirement of radiation therapy, the third order resonant extraction is adopted. Using the momentum-amplitude selection method, the extraction system is designed and optimized. An extraction efficiency of more than 97% and a momentum spread less than 0.11% are obtained.