Mitochondrial dysfunction in fatty acid β-oxidation disorders

Mitochondria are central organelles for cell survival with particular relevance in energy production and signalling, being mitochondrial fatty acid β–oxidation (FAO) one of the metabolic pathways harboured in this organelle. FAO disorders (FAOD) are among the most well studied inborn errors of metabolism, mainly due to their impact in health. Nevertheless, some questions remain unsolved, as their prevalence in certain European regions and how pathophysiological determinants combine towards the phenotype. Analysis of data from newborn screening programs from Portugal and Spain allowed the estimation of the birth prevalence of FAOD revealing that this group of disorders presents in Iberia (and particularly in Portugal) one of the highest European birth prevalence, mainly due to the high birth prevalence of medium chain acyl-CoA dehydrogenase deficiency. These results highlight the impact of this group of genetic disorders in this European region. The characterization of mitochondrial proteome, from patients fibroblasts with FAOD, namely multiple acyl-CoA dehydrogenase deficiency (MADD) and long chain acyl-CoA dehydrogenase deficiency (LCHADD), provided a global perspective of the mitochondrial proteome plasticity in these disorders and highlights the main molecular pathways involved in their pathogenesis. Severe MADD forms show an overexpression of chaperones, antioxidant enzymes (MnSOD), and apoptotic proteins. An overexpression of glycolytic enzymes, which reflects cellular adaptation to energy deficiency due to FAO blockage, was also observed. When LCHADD fibroblasts were analysed a metabolic switching to glycolysis was also observed with overexpression of apoptotic proteins and modulation of the antioxidant defence system. Severe LCHADD present increased ROS alongside with up regulation of MnSOD while moderate forms have lower ROS and down-regulation of MnSOD. This probably reflects the role of MnSOD in buffering cellular ROS, maintain them at levels that allow cells to avoid damage and start a cellular response towards survival. When ROS levels are very high cells have to overexpress MnSOD for detoxifying proposes. When severe forms of MADD were compared to moderate forms no major differences were noticed, most probably because ROS levels in moderate MADD are high enough to trigger a response similar to that observed in severe forms. Our data highlights, for the first time, the differences in the modulation of antioxidant defence among FAOD spectrum. Overall, the data reveals the main pathways modulated in FAOD and the importance of ROS levels and antioxidant defence system modulation for disease severity. These results highlight the complex interaction between phenotypic determinants in FAOD that include genetic, epigenetic and environmental factors. The development of future better treatment approaches is dependent on the knowledge on how all these determinants interact towards phenotype.!

Strength of visual percept generated by famous faces perceived without awareness: effects of affective valence, response latency, and visual field

Participants who were unable to detect familiarity from masked 17 ms faces ([Stone and Valentine, 2004] and [Stone and Valentine, in press-b]) did report a vague, partial visual percept. Two experiments investigated the relative strength of the visual percept generated by famous and unfamiliar faces, using masked 17 ms exposure. Each trial presented simultaneously a famous and an unfamiliar face, one face in LVF and the other in RVF. In one task, participants responded according to which of the faces generated the stronger visual percept, and in the other task, they attempted an explicit familiarity decision. The relative strength of the visual percept of the famous face compared to the unfamiliar face was moderated by response latency and participants’ attitude towards the famous person. There was also an interaction of visual field with response latency, suggesting that the right hemisphere can generate a visual percept differentiating famous from unfamiliar faces more rapidly than the left hemisphere. Participants were at chance in the explicit familiarity decision, confirming the absence of awareness of facial familiarity.

Various Joyful Encounters with the Dystopias of Affective Capitalism

This article contends that what appear to be the dystopic conditions of affective capitalism are just as likely to be felt in various joyful encounters as they are in atmospheres of fear associated with post 9/11 securitization. Moreover, rather than grasping these joyful encounters with capitalism as an ideological trick working directly on cognitive systems of belief, they are approached here by way of a repressive affective relation a population establishes between politicized sensory environments and what Deleuze and Guattari (1994) call a brain-becoming-subject. This is a radical relationality (Protevi, 2010) understood in this context as a mostly nonconscious brain-somatic process of subjectification occurring in contagious sensory environments populations become politically situated in. The joyful encounter is not therefore merely an ideological manipulation of belief, but following Gabriel Tarde (as developed in Sampson, 2012), belief is always the object of desire. The discussion starts by comparing recent efforts by Facebook to manipulate mass emotional contagion to a Huxleyesque control through appeals to joy. Attention is then turned toward further manifestations of affective capitalism; beginning with the so-called emotional turn in the neurosciences, which has greatly influenced marketing strategies intended to unconsciously influence consumer mood (and choice), and ending with a further comparison between encounters with Nazi joy in the 1930s (Protevi, 2010) and the recent spreading of right wing populism similarly loaded with political affect. Indeed, the dystopian presence of a repressive political affect in all of these examples prompts an initial question concerning what can be done to a brain so that it involuntarily conforms to the joyful encounter. That is to say, what can affect theory say about an apparent brain-somatic vulnerability to affective suggestibility and a tendency toward mass repression? However, the paper goes on to frame a second (and perhaps more significant) question concerning what can a brain do. Through the work of John Protevi (in Hauptmann and Neidich (eds.), 2010: 168-183), Catherine Malabou (2009) and Christian Borch (2005), the article discusses how affect theory can conceive of a brain-somatic relation to sensory environments that might be freed from its coincidence with capitalism. This second question not only leads to a different kind of illusion to that understood as a product of an ideological trick, but also abnegates a model of the brain which limits subjectivity in the making to a phenomenological inner self or Being in the world.

Somatic pedagogies: Critiquing and resisting the affective discourse of the neoliberal state from an embodied anarchist perspective.

This paper takes as its context widespread feelings of anxiety within neoliberal society caused by a combination of material and discursive factors including precarious access to work and resources. It is argued that the state uses ‘discourses of affect’ to produce compliant subjects able to deal with (and unable to desire beyond) neoliberal precarity and anxiety. Critical education theorists have argued that discourses of ‘well-being’, emotional support and self-help have gained increasing purchase in mainstream education and in popular culture. These discourses are dangerous because they are individualized and depoliticized, and undermine collective political struggle. At the same time there has been a ‘turn to affect’ in critical academia, producing critical pedagogies that resist state affective discourse. I argue that these practices are essential for problematizing neoliberal discourse, yet existing literature tends to elide the role of the body in effective resistance, emphasising intellectual aspects of critique. The paper sketches an alternative, drawing on psychoanalytic and practiced pedagogies that aim to transgress the mind-body dualism and hierarchy, in particular Roberto Freire’s work on Somatherapy.

Incongruence between clinicians’ assessment and self-reported functioning is related with psychopathology among patients diagnosed with gastrointestinal disorders

In a previous exploratory study we observed no relevant differences in psychopathology, personality, and functioning between inpatients diagnosed with gastrointestinal motor disorders (GMDs) or functional gastrointestinal disorders (FGDs) [1]. However, we observed higher levels of incongruence between clinician-assessed performance status and patients’ self-reported levels of functioning among patients diagnosed with FGDs. Likewise, research in other medical conditions has shown incongruences between self-reported and clinician-reported or objective measures [2]. Furthermore, in a study on chronic depression, the authors found that discrepancies between patients’ and physicians’ assessments of medical comorbidities were related to higher levels of depressive symptomatology [3]. In this line, the aim of this study was to explore whether the inconsistencies between clinician-assessed and patient self-reported levels of functioning could be related to psychopathology among patients admitted for evaluation of gastrointestinal motility.

A Multinational Health Professional Perspective of the Prevalence of Mood Disorders in Patients with Acute and Chronic Wounds.

Recent research has started to identify mood disorders and problems associated with acute and chronic wounds, which have been shown to contribute to delayed healing, poor patient well-being and a reduced quality of life. Furthermore, mood disorders have been shown to have a negative impact on financial costs for service providers and the wider society in terms of treatment and sickness absence. This study aimed to survey a multinational sample of health professionals to explore their perspective and awareness of mood disorders amongst acute and chronic wound patients. Responses were received from n = 908 health professionals working in Asia, Africa, Australia, Europe, North America and South America. A strong awareness of the prevalence of mood disorders appeared to be widespread among the health professionals across the world, in addition to a view on the potential factors contributing to these problems with mood. Despite this, it was thought that few patients were actually receiving treatment for their mood disorders. Implications for clinical practice include the need for health professionals to actively engage with their patients to enable them to learn from their experiences. Studies that explore the benefits of treatments and techniques appropriate for minimising mood disorders in patients with wounds would provide empirical evidence for health professionals to make recommendations for patients with acute and chronic wounds.

Interpersonal Relationships in the Primary Classroom: an Analysis of Social and Affective Outcomes

Recent research regarding the quality of relationships in primary classrooms has focused largely on the enhancement and development of cognitive skills. The study reported here focused on a range of social and affective outcomes with the intention of broadening our understanding of the classroom as an interactive system, from the child's perspective. This paper provides empirical evidence on children's perceptions at Key Stage 2 (pupil age 7-11 years) of their relationships with teachers, other adults and children. Data were collected via an attitudinal questionnaire survey in nine primary schools in England. Results indicate that, in addition to the development of social skills, children also valued academic confidence, learning and the involvement of their parents in homework, and that these were associated with the interactions and routines established within the primary classroom settings. Some variations in terms of pupil age, teacher career phase, and the socio-economic context of the school were identified; however, the importance of the relationship between pupil and teacher remained consistent across schools.

Case-series Evaluating a Transdiagnostic Cognitive-behavioral Treatment For Co-occurring Anxiety Disorders.

Background. Patients with anxiety disorder diagnoses commonly have more than one anxiety diagnosis. While cognitive-behavioral interventions have proven efficacy in treating single anxiety disorder diagnoses, there has been little investigation of their efficacy in treating cooccurring anxiety disorders. Aims. To evaluate the efficacy of a transdiagnostic cognitive-behavioral intervention for treating co-occurring anxiety disorders. Methods. An A-B single case study design (N = 6) was used to evaluate the efficacy of a 12 to 13 session modular transdiagnostic cognitive-behavioral intervention for treating co-occurring anxiety disorders across patients with at least two of the following diagnoses: GAD, Social Phobia, Panic Disorder and/or OCD. Results. Five of the six participants completed treatment. At post-treatment assessment the five treatment completers achieved diagnostic and symptomatic change with three participants being diagnosis free. All participants who completed treatment no longer met criteria for any DSM-IV-TR Axis-I diagnosis at the three-month follow-up assessment, and demonstrated reliable and clinically-significant improvements in symptoms. Across the participants, statistically significant improvements from pre- to post-intervention were found on measures of anxiety, depression and general well-being, and all improvements were maintained at three-month follow-up. Conclusions. Results suggest that transdiagnostic cognitive behavioral interventions can be of benefit to patients with co-occurring anxiety disorders.

Relationship between happiness, stress and musculoskeletal disorders in portuguese dentists

Tese de doutoramento, Medicina Dentária (Dentisteria Conservadora), Universidade de Lisboa, Faculdade de Medicina Dentária, 2016

Affective Computing to Enhance E-Learning in Segregated Societies

According to UN Women, to build stronger economies, it is essential to empower women to participate fully in economic life across all sectors. Increasing women and girls’ education enhances their chances to participate in the labor market. In certain cultures, like in Saudi Arabia, women contribution to the public economy growth is very limited. According to the World Bank, less than 20 percent of the female population participate in the labor force. This low participation rate has many reasons. One of them, is the educational level and educational quality for females. Although Saudi Arabia has about thirty three universities, opportunities are still limited for women because of the restrictions of access put upon them. A mixture of local norms, traditions, social beliefs, and principles preventing women from receiving full benefits from the educational system. Gender segregation is one of the challenges that limits the women access for education. It causes a problem due to the shortage of female faculty throughout the country. To overcome this problem, male faculty are allowed to teach female students under certain regulations and following a certain method of education delivery and interaction. However, most of these methods lack face-to-face communication between the teacher and students, which lowers the interactivity level and, accordingly, the students’ engagement, and increases the need for other alternatives. The e-learning model is one of high benefit for female students in such societies. Recognizing the students’ engagement is not straightforward in the e-learning model. To measure the level of engagement, the learner’s mood or emotions should be taken into consideration to help understanding and judging the level of engagement. This paper is to investigate the relationship between emotions and engagement in the e-learning environment, and how recognizing the learner’s emotions and change the content delivery accordingly can affect the efficiency of the e-learning process. The proposed experiment alluded to herein should help to find ways to increase the engagement of the learners, hence, enhance the efficiency of the learning process and the quality of learning, which will increase the chances and opportunities for women in such societies to participate more effectively in the labor market.

Withdrawing from Atmosphere: An Ontology of Air partitioning and Affective Engineering

The main objective of this text is to warn against atmospherics. However comfortable it might appear, an atmosphere is politically suspicious because it numbs a body into an affective embrace of stability and permanence. It becomes doubly suspicious because a body desires to be part of the atmosphere. For this reason, I rethink both affect and atmosphere ontologically rather than phenomenologically. I argue that an atmosphere is engineered by subsuming individual affects to what I call, following Sloterdijk, an atmospheric glasshouse. I suggest that this happens in four steps: a distinction between inside and outside through partitioning; inclusion of the outside inside; illusion of synthesis; and dissimulation. In order to do this, I begin with air as the elemental paradox of ontological continuum and rupture. I carry on with the passage from air to atmosphere while retaining the discourse around continuum and rupture. Finally, I indicate a way of rupturing the atmospheric continuum through the ontological movement of withdrawal from the atmosphere. The ultimate goal of the article is to sketch a problematic of atmospherics that puts together without synthesising an elemental ontology of continuum and rupture.

Withdrawing from atmosphere: An ontology of air partitioning and affective engineering

The main objective of this text is to warn against atmospherics. However comfortable it might appear, an atmosphere is politically suspicious because it numbs a body into an affective embrace of stability and permanence. It becomes doubly suspicious because a body desires to be part of the atmosphere. For this reason, I rethink both affect and atmosphere ontologically rather than phenomenologically. I argue that an atmosphere is engineered by subsuming individual affects to what I call, following Sloterdijk, an atmospheric glasshouse. I suggest that this happens in four steps: a distinction between inside and outside through partitioning; inclusion of the outside inside; illusion of synthesis; and dissimulation. In order to do this, I begin with air as the elemental paradox of ontological continuum and rupture. I carry on with the passage from air to atmosphere while retaining the discourse around continuum and rupture. Finally, I indicate a way of rupturing the atmospheric continuum through the ontological movement of withdrawal from the atmosphere. The ultimate goal of the article is to sketch a problematic of atmospherics that puts together without synthesising an elemental ontology of continuum and rupture.

Behavioral and synaptic circuit analysis in models of neuropsychiatric disorders: Dissecting the in vivo role of the postsynaptic density proteins nArgBP2 and Shank3 using genetic engineered mice

Dissertation presented to obtain the Ph.D degree in Biology

Mutilations Due to Medical Disorders in Children

Soft-tissue and bone necrosis, although rare in childhood, occasionally occur in the course of infectious diseases, either viral or bacterial, and seem to be the result of hypoperfusion on a background of disseminated intravascular coagulation. Treatment consists in correction of septic shock and control of necrosis. Necrosis, once started, shows extraordinarily rapid evolution, leading to soft-tissue and bone destruction and resulting in anatomic, functional, psychological, and social handicaps. Ten mutilated children were treated from January 1986 to January 1999 in Hospital de Dona Estefaˆ nia, Lisbon, Portugal. One was recovering from hemolytic-uremic syndrome with a severe combined immunodeficiency, another malnourished, anemic child had malaria, and three had chicken pox (in one case complicated by meningococcal septicemia). There were three cases of meningococcal and two of pyocyanic septicemia (one in a burned child and one in a patient with infectious mononucleosis). The lower limbs (knee,leg, foot) were involved in five cases, the face (ear, nose, lip) in four, the perineum in three, the pelvis (inguinal region, iliac crest) in two, the axilla in one, and the upper limb (radius, hand) in two. Primary prevention is based on early recognition of risk factors and timely correction. Secondary prevention consists of immediate etiologic and thrombolytic treatment to restrict the area of necrosis. Tertiary prevention relies on adequate rehabilitation with physiotherapy and secondary operations to obtain the best possible functional and esthetic result.