Evidence-based clinical decision-making : Conceptual and empirical foundations for an integrative psychological and neurobiological transtheoretical metamodel

The dialogue between psychotherapy and neuroscience is ongoing. Previous meta-analytic research suggests that 35% of psychotherapy outcome variance is not fully explained, whereas 30% is attributed to patient variables, 15% to therapeutic relationship, 10% to specific therapeutic techniques, 7% to therapist variables and 3% to other factors (Norcross & Wampold, 2019). Several authors emphasize the need for integrative, metatheoretical or transtheoretical approaches to enhance conceptual understanding of clinical phenomena, augmenting psychotherapy responsiveness to patients’ significant variables, such as maladaptive patterns, states of mind, relational styles, emotional difficulties, neurocognitive deficits, and psychological needs. The present doctoral proposal aims to respond to these claims through the establishment of preliminary conceptual and empirical foundations for an Integrative Psychological and Neurobiological Transtheoretical Metamodel. First, an extensive literature review of the relationships between psychotherapy and neuroscience was performed to establish theoretical and conceptual integration of different components of the presently proposed model. Second, several methodological aspects were described to systematize the complex data acquisition process. Third, seven studies were conducted, and implications of the results were discussed. Fourth, an integrative discussion was elaborated, emphasizing the major and general implications of the results for clinical practice and future research. The first empirical study aimed to develop and/or adapt self-report assessment measures to evaluate several psychological variables (e.g., metacognition, states of mind), which resulted in five scientific articles. Thus, the Metacognitive Self-assessment Scale (Pedone et al., 2017) and the Inventory of Interpersonal Problems – 32 (IIP-32, Barkham et al., 1998) were validated and adapted to European Portuguese. The State of Mind Questionnaire (SMQ, Faustino et al., 2021b, Emotional Processing Difficulties Scale – R (EPDS-R, Faustino et al., in press) and the Clinical Decision-Making Inventory (Faustino & Vasco, in press) were developed. All instruments showed satisfactory psychometric properties. Nevertheless, the SMQ showed low reliability in the composite scales in smaller subsamples. For the second empirical study, the main aims were to explore the complex relationships between early disorder determinants, maladaptive schemas and states of mind, defensive maneuvers and critical consequences, mental skills and processes, and adaptive self-domains. This was performed with Structural Equation Modeling (SEM). Results showed significant sequential and mediational models between maladaptive schemas, defensive maneuvers and dysfunctional consequences, mental abilities and processes, and adaptive self-domains with psychological needs. Maladaptive schemas and states of mind were both predictors and mediators in several models. However, the relationship between maladaptive schematic functioning and symptomatology had less significant mediations with the same variables. For the third study, the main aims were to explore the relationships of early disorder determinants, maladaptive schematic functioning and states of mind, defensive maneuvers and dysfunctional consequences, mental abilities and processes, and adaptive self-domains, with several neurocognitive variables. Executive functions were negatively correlated with maladaptive schematic functioning and with defensive maneuvers and dysfunctional consequences. Memory only correlated with psychological needs, self-confidence and with dysfunctional interpersonal cycles. These results emphasize previous assumptions that there is a difference between self-report questionnaires and neuropsychological assessment measures which may difficult the integrated study of psychological and neurocognitive processes. The fourth study aimed to explore the associations of affective subliminal processing with dispositional states and contextual states, defined in the present work as early disorder determinants, schematic functioning, and defensive maneuvers and dysfunctional consequences, mental abilities and processes, and adaptive self-domains. Results showed strong correlations between maladaptive schematic functioning, coping responses, emotional processing difficulties, and expressive suppression with behavioral responses. Dispositional traits and contextual states seem to be associated with affective processing, especially when it comes to the neutral valence of the subliminal stimuli. ERPs waveforms showed an amplitude modulation with a temporal progression: in the first 100 msec the waveform amplitude was highest to the negative condition; Later on, in the time windows after 350 msec, the neutral condition was the one that elicited the ERPs’ heist amplitude. These indexes a cascade of reactions, first a priority to nonconscious negative stimulation; and after that, a later processing phase of affective-cognitive interpretation (350msc) in which neutral stimuli acquire a meaning according to schemas. The fifth study explored the diagnostic and or transdiagnostic potential of early disorder determinants, maladaptive schematic functioning and states of mind, defensive maneuvers and dysfunctional consequences, mental abilities and processes, and adaptive self-domains. Results showed that only early complex trauma and expressive suppression were not statistically different in two subsamples. Individuals in the low-symptoms sub-sample reported lower levels of maladaptive schematic functioning, defensive maneuvers, and psychological inflexibility than individuals in the higher-symptoms subsample. The sixth study was focused on the exploration of the temporal stability of maladaptive schematic functioning and states of mind, defensive maneuvers and dysfunctional consequences, mental abilities, and adaptive self-domains. Results showed significant differences between moment one and two, with a descending pattern in the mean scores of dysfunctional variables. An inverse pattern was found regarding the adaptive variables. However, mean scores of some variables, such as early maladaptive schemas, emotional schemas, psychological needs, and cognitive reappraisal were not statistically significant. The seventh study aimed to explore associations of early disorder determinants, maladaptive schemas and states of mind, defensive maneuvers and critical consequences, mental skills and processes and adaptive self-domains, with an empirical based clinical profile (e.g., psychotherapy and motivational stage, coping styles). Results showed significant negative correlations between maladaptive schematic functioning and stage process, motivational stage, therapeutic relationship, attachment style, reactance, and coping style. An inverse pattern was found regarding the adaptive variables. These preliminary results seem to support a theoretically- and empirically-based integrative and transtheoretical metamodel focused on unifying psychotherapy and neuroscience into a coherent framework. Further research is required to augment and enhance the presently proposed model

Variants of Hepcidin Gene Promoter Modulate Iron Status in H63d Individuals

Background: HFE is a major histocompatibility complex class I-like protein that is mutated in Hereditary Hemochromatosis (HH). Despite C282Y being the most common HH-associated HFE mutation, there are other reported mutations, such as H63D, with an uncertain role in the pathogenesis of the disease. Hepcidin is a crucial regulator of systemic iron homeostasis, controlling the absorption of iron by enterocytes and its release by macrophages. Mutations in this gene (HAMP) result in the development of a juvenile type of HH. Also, it has been shown that a polymorphism in HAMP promoter (c.-582A>G) is associated with an increase of serum ferritin levels in beta-thalassemia major patients but not in normal individuals. Objectives/Methods: We screened for the presence of polymorphisms in the HAMP promoter in 266 individuals with ferritin levels higher than 400ng/mL, being: i) 191 individuals homozygous or heterozygous for the H63D mutation (group 1) and ii) 75 individuals carrying one or more C282Y alleles (HH/CY, HH/YY or HD/CY), (group 2). To assess whether HAMP promoter polymorphisms are changing the hepcidin expression in response to an external stimulus we performed luminescence assays in Huh-7 cell line. Results: Our data show that, in our sample, the c.-582A>G polymorphism is in linkage with another one, the c.-1010C>T. These polymorphisms were found in a significant higher frequency in group 1 (31.2% of allele G and T, respectively) than in the general population (16.4%; p<0.001). On the contrary, they were found at a slight higher, but not significant, frequency at group 2 (21.3%), comparing with general population (p=0.186). Functional in vitro studies, using stimulus as holo-transferrin, ferric citrate, IL-6 or GDF15, revealed no differences in the activity of the HAMP promoter in the presence or absence of the polymorphisms. However, further analysis with some other stimuli, such as hypoxia or BMPs must be performed. Conclusions: c.-582A>G/c.-1010C>T polymorphisms seem to be modulators of iron overload development in individuals carrying the H63D mutation. However, the mechanism subjacent to this observation remains elusive.Parcialmente financiado por FCT: Programa de Financiamento Plurianual do CIGMH e Bolsa de Doutoramento SFRH/BD/60718/2009

Differential HFE Gene Expression is Regulated by Alternative Splicing in Human Tissues

Background - The pathophysiology of HFE-derived Hereditary Hemochromatosis and the function of HFE protein in iron homeostasis remain uncertain. Also, the role of alternative splicing in HFE gene expression regulation and the possible function of the corresponding protein isoforms are still unknown. The aim of this study was to gain insights into the physiological significance of these alternative HFE variants. Methodology/Principal Findings - Alternatively spliced HFE transcripts in diverse human tissues were identified by RT-PCR, cloning and sequencing. Total HFE transcripts, as well as two alternative splicing transcripts were quantified using a real-time PCR methodology. Intracellular localization, trafficking and protein association of GFP-tagged HFE protein variants were analysed in transiently transfected HepG2 cells by immunoprecipitation and immunofluorescence assays. Alternatively spliced HFE transcripts present both level- and tissue-specificity. Concerning the exon 2 skipping and intron 4 inclusion transcripts, the liver presents the lowest relative level, while duodenum presents one of the highest amounts. The protein resulting from exon 2 skipping transcript is unable to associate with β2M and TfR1 and reveals an ER retention. Conversely, the intron 4 inclusion transcript gives rise to a truncated, soluble protein (sHFE) that is mostly secreted by cells to the medium in association with β2M. Conclusions/Significance - HFE gene post-transcriptional regulation is clearly affected by a tissue-dependent alternative splicing mechanism. Among the corresponding proteins, a sHFE isoform stands out, which upon being secreted into the bloodstream, may act in remote tissues. It could be either an agonist or antagonist of the full length HFE, through hepcidin expression regulation in the liver or by controlling dietary iron absorption in the duodenum.This work was partially supported by Fundação para a Ciência e a Tecnologia (FCT; grant PTDC/SAU/GMG/64494/2006) and Programa de Financiamento Plurianual do CIGMH. RM and BS were supported by FCT fellowships (SFRH/BD/21340/2005 and SFRH/BD/60718/2009)

Implementação eficiente do Shared Nearest Neighbour em dados espaciais

A taxa de colecta de dados espaciais está a aumentar e os algoritmos de agrupamento tornam-se cada vez mais populares, pois não necessitam de informação a priori. Contudo, estes algoritmos requerem um tempo de execução significativo e várias corridas para alcançar os melhores resultados. O Shared Nearest Neighbour (SNN) é um algoritmo de agrupamento cuja complexidade temporal no pior caso é O(n2), comprometendo a sua escalabilidade. Neste artigo, conjuga-se o SNN com estruturas de dados métricas que dão suporte à procura dos K vizinhos mais próximos, permitindo melhorar a sua complexidade temporal no caso esperado para O(n _ log(n)), com conjuntos de dados espaciais. Propomos, ainda, uma estratégia de reaproveitamento entre corridas do cálculo dos K vizinhos mais próximos, atingindo a complexidade de O(n). Através dos resultados experimentais, que avaliam a escalabilidade desta solução e a comparam com uma versão original do SNN, são obtidos ganhos muito significativos

A soluble HFE splice variant seems to regulate the expression of duodenal cytochrome b and hephaestin contributing to iron metabolism regulation

INTRODUCTION: Hereditary Hemochromatosis is an autosomal recessive disorder characterized by excessive intestinal iron absorption and pathological iron deposition in organs such as liver, heart and pancreas. The disease is predominantly caused by homozygosity for the p.C282Y mutation in HFE, which impairs protein association with its chaperone beta-2 microglobulin (B2M), for correct folding and traffic to the cell surface. Several alternative HFE transcripts have been reported but their functional significance remains elusive. Since we have identified an alternative HFE transcript due to intron 4 inclusion, we aimed to investigate its physiological role on iron homeostasis. MATERIALS AND METHODS: We analysed the expression level of the alternative transcript in several human tissues by quantitative Real-Time PCR. In addition, we produced the corresponding GFP-tagged HFE protein variant. HepG2 cells were transfected with this construct and protein cellular location analyzed by immunofluorescence using several antibodies. In parallel, immunoprecipitation was performed. Finally, the variant was over-expressed in a duodenal cell line (Hutu-80) under normal and iron overload conditions and the expression of several iron metabolism related genes (TFR1, DMT1, CYBRD1, SLC40A1 and HEPH) was evaluated by quantitative Real-Time PCR. RESULTS: We have found that the HFE_intron 4 inclusion transcript has an ubiquitous expression, being its relative expression higher in duodenum and lower in the liver. Also, we found that it gives rise to a truncated soluble protein (sHFE) that is secreted by cells maintaining its interaction with B2M. Its overexpression in HuTu-80 cells revealed that the sHFE is able to down-regulate the duodenal cytochrome b (CYBRD1) expression, as it happens with the HFE_full length protein. Also, it seems to play a specific role in the regulation of hephaestin (HEPH) expression. CONCLUSIONS: Through this study we might have unveiled the contribution of the sHFE variant to iron homeostasis. In fact, sHFE may be secreted into the bloodstream and act in remote tissues such as duodenum, down-regulating the expression of some of the iron metabolism related genes, as CYBRD1 and HEPH, and consequently reducing dietary iron absorption, preventing iron overload and contributing to iron metabolism regulation. Partially funded by FCT: PTDC/SAU-GMG/64494/2006; CIGMH; SFRH/BD/21340/2005 and SFRH/BD/60718/2009. The authors declare no competing interests

Análisis de las capacidades de gestión pública del gobierno de Huaquechula, periodo 2019-2020

"El progreso del municipio en México es fundamental para el bienestar del país, la Constitución reconoce al municipio como la base de la división territorial, organización política y administrativa de los estados de la república, le otorga competencias, facultades y obligaciones. Sin embargo, es una realidad que los gobiernos municipales presentan limitaciones financieras, de autonomía, de profesionalización y organización administrativa para cumplir con éstas, no obstante, tiene una gran relevancia en el desarrollo y unidad nacional al colocarse como el nivel de gobierno más cercano a los ciudadanos. La solución a las limitaciones no está en la implantación de un modelo de gestión ajeno a las condiciones y características del gobierno municipal, sino en la consolidación de las capacidades que ya existen, afianzar el modelo existente y de manera gradual combinarlo con modelos como la Nueva Gestión Pública y Gobernanza, es decir, introducir cambios coherentes con la administración pública municipal, que le permitan operar de mejor manera y satisfacer las demandas de los ciudadanos.

Academic performance evaluation depending of the oriented exercise volume and body coordination quocient on 1st cycle children

Este estudo tem como objetivo analisar se o nível de coordenação motora tem efeitos positivos sobre o rendimento académico nas crianças, nomeadamente na disciplina de português e de matemática, bem como no rendimento académico. A amostra foi composta por 156 crianças entre os 6 e os 9 anos de idade, dos quais 53.8% são do género masculino (n=84) e 46.2% do feminino (n=72). Todos os alunos envolvidos no estudo participam nas aulas de Educação Física, portanto têm pelo menos 60 minutos de prática semanal orientada, mas 15.4% praticam ainda mais uma modalidade na escola, mais concretamente Ballet e/ou Judo sendo o tempo de prática máximo na escola de 150±29.49 minutos semanais. Como instrumento de recolha de dados utilizou-se a bateria de testes de Körperkoordination Test für Kinder (KTK) de Kiphard e Schilling (1974) e um questionário sociodemográfico. Os resultados evidenciam que quanto maior o tempo de exercício físico orientado, mais elevada é a Classificação de Coordenação Corporal KTK, que promove um aumento positivo na avaliação de Português e Matemática, assim como no rendimento académico.This study aims for the analyze of ''movement'' has positive effects on school performance in children, particularly in the evaluation of Portuguese and Math, and the average of both (academic performance). The sample is composed by 156 children between 6 and 9 years old, of which 53.8% (n=84) are boys and 46.2% (n=72) are girls. All students involved in this study participate on Physical Education classes, so they have at least 60 minutes of weekly oriented practice, but more specifically Ballet and/or Judo being the maximum time of practice at school of 150±29.49 minutes a week. As data collection instrument was used the battery test of Körperkoordination Test für Kinder (KTK) de Kiphard e Schilling (1974) and the sociodemographic questionnaire. The results show that the longer the oriented physical activity, higher is the Coordination Body classification of KTK, which promote the positive increase of the evaluation of Portuguese and Math, and so of the academic performance.Este estudio tiene como objetivo analizar el nivel de coordinación tiene efectos positivos sobre el rendimiento académico en los niños, especialmente en la disciplina de portugués y matemáticas, así como el logro académico. La muestra consistió en 156 niños de entre 6 y 9 años de edad, de los cuales el 53,8% son hombres (n = 84) y el 46,2% de las mujeres (n = 72). Todos los estudiantes participaban en las clases de educación física, teniendo al menos 60 minutos de práctica semanal guiada; un 15,4% prácticaba otro deporte en edad escolar, específicamente Ballet y / o el judo es el momento más práctico en la escuela 150 ± 29,49 minutos por semana. Como instrumento de recolección de datos utilizado para probar la batería de pruebas Körperkoordination für Kinder (KTK) y Kiphard de Schilling (1974) y un cuestionario sociodemográfico. Los resultados muestran que la mayor-orientado, mayor tiempo de ejercicio es el Órgano de Coordinación de Clasificación KTK, que promueve un incremento positivo en la evaluación de portugués y matemáticas, así como el rendimiento académico.info:eu-repo/semantics/publishedVersio