Early and late neurodegeneration and memory disruption after intracerebroventricular streptozotocin

Glucose metabolism and insulin signaling disruptions in the brain have been proposed as a likely etiology of Alzheimer's disease. The aim of the present study was to investigate the time course of cognitive impairments induced by intracerebroventricular injection of streptozotocin (STZ) in rats and correlate them with the ensuing neurodegenerative process. Early and late effects of STZ were evaluated by using the reference and working memory versions of the Morris' water maze task and the evaluation of neurodegenerative markers by immunoblotting and the Fluoro-jade C histochemistry. The results revealed different types of behavioral and neurodegenerative responses, with distinct time courses. We observed an early disruption on the working memory as early as 3 h after STZ injections, which was followed by degenerative processes in the hippocampus at 1 and 15 days after STZ injections. Memory disruption increases over time and culminates with significant changes in amyloid-beta peptide and hyperphosphorylated Tau protein levels in distinct brain structures. These findings add information on the Alzheimer's disease-like STZ animal model and on the mechanisms underlying neurodegenerative processes. (C) 2012 Elsevier Inc. All rights reserved.

Intervenções psicoeducacionais para cuidadores de idosos com demência: uma revisão sistemática

OBJETIVO: Identificar modelos de intervenções psicoeducacionais e os seus efeitos em cuidadores de idosos com demência. MÉTODOS: Levantamento de estudos publicados entre janeiro de 2000 e abril de 2012 nas bases de dados PubMed, Web of Knowledge, Lilacs e SciELO, utilizando as seguintes palavras-chave "psychoeducational and caregiver", "cuidador e demência e psicoeducação" e "cuidador e intervenção". Apenas os artigos que denominavam a intervenção estudada como psicoeducação fazem parte do presente estudo. RESULTADOS: Foram encontrados 27 artigos com relatos acerca do impacto de intervenções psicoeducacionais em cuidadores de idosos com demência. Os resultados mais prevalentes desses estudos são: melhora do bem-estar dos cuidadores (37% dos estudos); aumento do uso de estratégias de enfrentamento (30%); diminuição de pensamentos disfuncionais (30%); aumento do conhecimento sobre os serviços disponíveis (19%); melhora da autoeficácia (15%); e aumento de habilidades para o cuidado (11%). A abordagem psicoeducacional descrita nos estudos é do âmbito informativo, cognitivo-comportamental, com técnicas de gerenciamento de estresse e de emoções; técnicas de resolução de problemas e apoio emocional. CONCLUSÃO: A intervenção psicoeducacional contribui significativamente para a melhora do bem-estar do cuidador, contudo ainda é necessária uma padronização dessa abordagem, em termos de estrutura, duração e conteúdos ministrados, para que haja evidências mais precisas do efeito desse tipo de intervenção.

New perspective on the pathophysiology of panic: merging serotonin and opioids in the periaqueductal gray

Panic disorder patients are vulnerable to recurrent panic attacks. Two neurochemical hypotheses have been proposed to explain this susceptibility. The first assumes that panic patients have deficient serotonergic inhibition of neurons localized in the dorsal periaqueductal gray matter of the midbrain that organize defensive reactions to cope with proximal threats and of sympathomotor control areas of the rostral ventrolateral medulla that generate most of the neurovegetative symptoms of the panic attack. The second suggests that endogenous opioids buffer normal subjects from the behavioral and physiological manifestations of the panic attack, and their deficit brings about heightened suffocation sensitivity and separation anxiety in panic patients, making them more vulnerable to panic attacks. Experimental results obtained in rats performing one-way escape in the elevated T-maze, an animal model of panic, indicate that the inhibitory action of serotonin on defense is connected with activation of endogenous opioids in the periaqueductal gray. This allows reconciliation of the serotonergic and opioidergic hypotheses of panic pathophysiology, the periaqueductal gray being the fulcrum of serotonin-opioid interaction.

Behavioral meaningful opioidergic stimulation activates kappa receptor gene expression

The periaqueductal gray (PAG) has been reported to be a location for opioid regulation of pain and a potential site for behavioral selection in females. Opioid-mediated behavioral and physiological responses differ according to the activity of opioid receptor subtypes. The present study investigated the effects of the peripheral injection of the kappa-opioid receptor agonist U69593 into the dorsal subcutaneous region of animals on maternal behavior and on Oprk1 gene activity in the PAG of female rats. Female Wistar rats weighing 200-250 g at the beginning of the study were randomly divided into 2 groups for maternal behavior and gene expression experiments. On day 5, pups were removed at 7:00 am and placed in another home cage that was distant from their mother. Thirty minutes after removing the pups, the dams were treated with U69593 (0.15 mg/kg, sc) or 0.9% saline (up to 1 mL/kg) and after 30 min were evaluated in the maternal behavior test. Latencies in seconds for pup retrieval, grouping, crouching, and full maternal behavior were scored. The results showed that U69593 administration inhibited maternal behavior (P < 0.05) because a lower percentage of kappa group dams showed retrieval of first pup, retrieving all pups, grouping, crouching and displaying full maternal behavior compared to the saline group. Opioid gene expression was evaluated using real-time reverse-transcription polymerase chain reaction (RT-PCR). A single injection of U69593 increased Oprk1 PAG expression in both virgin (P < 0.05) and lactating female rats (P < 0.01), with no significant effect on Oprm1 or Oprd1 gene activity. Thus, the expression of kappa-opioid receptors in the PAG may be modulated by single opioid receptor stimulation and behavioral meaningful opioidergic transmission in the adult female might occur simultaneously to specific changes in gene expression of kappa-opioid receptor subtype. This is yet another alert for the complex role of the opioid system in female reproduction

Comparison of child self-reports and parent proxy-reports on quality of life of children with attention deficit hyperactivity disorder

Abstract Background Attention deficit hyperactivity disorder (ADHD) is a neurobiological condition that affects 3%–7% of the pediatric population and significantly compromises the quality of life (QoL) of these individuals. The aim of the current study was to compare child self-reports and parent proxy reports on the QoL of children with ADHD. Methods Forty-five children with ADHD, combined type, aged 8–12 years without comorbidities, were compared with 43 typically developing children. PedsQL™ 4.0 (Pediatric QoL Inventory™) Generic Core Scales (physical, emotional, social, and school functioning) were completed by families and children self-reporting their health-related QoL. Results Children with ADHD reported themselves significantly lowered their PedsQL™ scores on all dimensions in comparison to typically developing children. Statistically significant differences were observed in social functioning (p = 0.010), school functioning (p <0.001), psychosocial health (p <0.001), and total score (p = 0.002). The physical functioning and emotional functioning dimensions did not differ significantly between groups, with p = 0.841 and p = 0.070, respectively. Parents of children with ADHD also reported lower PedsQL™ scores, with statistically significant differences in all dimensions. The relationship between child self-reports and parent proxy reports indicated that there is greater agreement among children with ADHD, except for the school functioning. Conclusions This suggests that children with the disorder and their parents have a perception of the functional limitations the disorder brings. It is therefore important to undertake studies to verify the QoL in children with ADHD that aim to provide and measure the scope of the well-being of these children.

Fluoxetine exposure during pregnancy and lactation: effects on acute stress response and behavior in the novelty-suppressed feeding are age and gender-dependent in rats

Fluoxetine (FLX) is commonly used to treat anxiety and depressive disorders in pregnant women. Since FLX crosses the placenta and is excreted in milk, maternal treatment with this antidepressant may expose the fetus and neonate to increased levels of serotonin (5-HT). Long-term behavioral abnormalities have been reported in rodents exposed to higher levels of 5-HT during neurodevelopment. In this study we evaluated if maternal exposure to FLX during pregnancy and lactation would result in behavioral and/or stress response disruption in adolescent and adult rats. Our results indicate that exposure to FLX influenced restraint stress-induced Fos expression in the amygdala in a gender and age-specific manner. In male animals, a decreased expression was observed in the basolateral amygdala at adolescence and adulthood; whereas at adulthood, a decrease was also observed in the medial amygdala. A lack of FLX exposure effect was observed in females and also in the paraventricular nucleus of both genders. Regarding the behavioral evaluation, FLX exposure did not induce anhedonia in the sucrose preference test but decreased the latency to feed of both male and female adolescent rats evaluated in the novelty-suppressed feeding test. In conclusion, FLX exposure during pregnancy and lactation decreases acute amygdalar stress response to a psychological stressor in males (adolescents and adults) as well as influences the behavior of adolescents (males and females) in a model that evaluates anxiety and/or depressive-like behavior. Even though FLX seems to be a developmental neurotoxicant, the translation of these findings to human safe assessment remains to be determined since it is recognized that not treating a pregnant or lactating woman may also impact negatively the development of the descendants.

Language and Embodiment: sensory-motor and linguistic-social experience. Evidence on sentence comprehension

In this work I address the study of language comprehension in an “embodied” framework. Firstly I show behavioral evidence supporting the idea that language modulates the motor system in a specific way, both at a proximal level (sensibility to the effectors) and at the distal level (sensibility to the goal of the action in which the single motor acts are inserted). I will present two studies in which the method is basically the same: we manipulated the linguistic stimuli (the kind of sentence: hand action vs. foot action vs. mouth action) and the effector by which participants had to respond (hand vs. foot vs. mouth; dominant hand vs. non-dominant hand). Response times analyses showed a specific modulation depending on the kind of sentence: participants were facilitated in the task execution (sentence sensibility judgment) when the effector they had to use to respond was the same to which the sentences referred. Namely, during language comprehension a pre-activation of the motor system seems to take place. This activation is analogous (even if less intense) to the one detectable when we practically execute the action described by the sentence. Beyond this effector specific modulation, we also found an effect of the goal suggested by the sentence. That is, the hand effector was pre-activated not only by hand-action-related sentences, but also by sentences describing mouth actions, consistently with the fact that to execute an action on an object with the mouth we firstly have to bring it to the mouth with the hand. After reviewing the evidence on simulation specificity directly referring to the body (for instance, the kind of the effector activated by the language), I focus on the specific properties of the object to which the words refer, particularly on the weight. In this case the hypothesis to test was if both lifting movement perception and lifting movement execution are modulated by language comprehension. We used behavioral and kinematics methods, and we manipulated the linguistic stimuli (the kind of sentence: the lifting of heavy objects vs. the lifting of light objects). To study the movement perception we measured the correlations between the weight of the objects lifted by an actor (heavy objects vs. light objects) and the esteems provided by the participants. To study the movement execution we measured kinematics parameters variance (velocity, acceleration, time to the first peak of velocity) during the actual lifting of objects (heavy objects vs. light objects). Both kinds of measures revealed that language had a specific effect on the motor system, both at a perceptive and at a motoric level. Finally, I address the issue of the abstract words. Different studies in the “embodied” framework tried to explain the meaning of abstract words The limit of these works is that they account only for subsets of phenomena, so results are difficult to generalize. We tried to circumvent this problem by contrasting transitive verbs (abstract and concrete) and nouns (abstract and concrete) in different combinations. The behavioral study was conducted both with German and Italian participants, as the two languages are syntactically different. We found that response times were faster for both the compatible pairs (concrete verb + concrete noun; abstract verb + abstract noun) than for the mixed ones. Interestingly, for the mixed combinations analyses showed a modulation due to the specific language (German vs. Italian): when the concrete word precedes the abstract one responses were faster, regardless of the word grammatical class. Results are discussed in the framework of current views on abstract words. They highlight the important role of developmental and social aspects of language use, and confirm theories assigning a crucial role to both sensorimotor and linguistic experience for abstract words.

Theoretical and implementation aspects in the mechanization of the metatheory of programming languages

Interactive theorem provers are tools designed for the certification of formal proofs developed by means of man-machine collaboration. Formal proofs obtained in this way cover a large variety of logical theories, ranging from the branches of mainstream mathematics, to the field of software verification. The border between these two worlds is marked by results in theoretical computer science and proofs related to the metatheory of programming languages. This last field, which is an obvious application of interactive theorem proving, poses nonetheless a serious challenge to the users of such tools, due both to the particularly structured way in which these proofs are constructed, and to difficulties related to the management of notions typical of programming languages like variable binding. This thesis is composed of two parts, discussing our experience in the development of the Matita interactive theorem prover and its use in the mechanization of the metatheory of programming languages. More specifically, part I covers: - the results of our effort in providing a better framework for the development of tactics for Matita, in order to make their implementation and debugging easier, also resulting in a much clearer code; - a discussion of the implementation of two tactics, providing infrastructure for the unification of constructor forms and the inversion of inductive predicates; we point out interactions between induction and inversion and provide an advancement over the state of the art. In the second part of the thesis, we focus on aspects related to the formalization of programming languages. We describe two works of ours: - a discussion of basic issues we encountered in our formalizations of part 1A of the Poplmark challenge, where we apply the extended inversion principles we implemented for Matita; - a formalization of an algebraic logical framework, posing more complex challenges, including multiple binding and a form of hereditary substitution; this work adopts, for the encoding of binding, an extension of Masahiko Sato's canonical locally named representation we designed during our visit to the Laboratory for Foundations of Computer Science at the University of Edinburgh, under the supervision of Randy Pollack.

Work and Family: a complex interplay. An Italian application of the DISC Model on health care workers

The present thesis investigates the issue of work-family conflict and facilitation in a sanitarian contest, using the DISC Model (De Jonge and Dormann, 2003, 2006). The general aim has been declined in two empirical studies reported in this dissertation chapters. Chapter 1 reporting the psychometric properties of the Demand-Induced Strain Compensation Questionnaire. Although the empirical evidence on the DISC Model has received a fair amount of attention in literature both for the theoretical principles and for the instrument developed to display them (DISQ; De Jonge, Dormann, Van Vegchel, Von Nordheim, Dollard, Cotton and Van den Tooren, 2007) there are no studies based solely on psychometric investigation of the instrument. In addition, no previous studies have ever used the DISC as a model or measurement instrument in an Italian context. Thus the first chapter of the present dissertation was based on psychometric investigation of the DISQ. Chapter 2 reporting a longitudinal study contribution. The purpose was to examine, using the DISC model, the relationship between emotional job characteristics, work-family interface and emotional exhaustion among a health care population. We started testing the Triple Match Principle of the DISC Model using solely the emotional dimension of the strain-stress process (i.e. emotional demands, emotional resources and emotional exhaustion). Then we investigated the mediator role played by w-f conflict and w-f facilitation in relation to emotional job characteristics and emotional exhaustion. Finally we compared the mediator model across workers involved in chronic illness home demands and workers who are not involved. Finally, a general conclusion, integrated and discussed the main findings of the studies reported in this dissertation.

Nonverbal emotional regulation in psychotherapy process according to an intersubjective perspective

In recent decades fascinating studies in developmental psychology, especially in infant research (for review see Lavelli, 2007) and recent discoveries in neuroscience (Welsh, et al, 2007; Siegel, 2001; Pally, 2007) have brought great interest to study the mode of sharing subjective experiences (affective states, intentions and attentional focus) in children and adults.It therefore appears today in the clinic is a growing consensus about the fact that the psychological disorder can be read as a deficit in intersubjective processes of affect regulation (see Benecke C. et al 2005; psychodynamic Diagnostic Manual-PDM, 2006) leading many authors to assume the centrality of affect regulation in the construction of the psychotherapeutic process of change (just to name a few Tronick, Greenberg, Stern, Sander, Fonagy, Beebe, Philippot, Rimé etc..). As previously stated, this study has led us to hypothesize that the long process of therapy is to assist with the sessions continue, a growing "emotional attunement" between the communication styles of both patient and therapist. And also to speculate that this synchronization can represent the existence of a significant positive correlation between the increased level of "emotional synchronization" and increased capacity for regulation of emotions by the patient.The research results despite the limitations of small sample showed encouraging results about the verification of the existence of an increasing degree of attunement between therapist and patient long psychotherapy sessions and also showed a good degree of positive correlation between the increase the latter construct and emotional regulation through the implicit mode of expression and nonverbal communication.

Social learning and action understanding in human observers: contributions of sensori-motor constraints and prior information

The aim of this thesis was to investigate the respective contribution of prior information and sensorimotor constraints to action understanding, and to estimate their consequences on the evolution of human social learning. Even though a huge amount of literature is dedicated to the study of action understanding and its role in social learning, these issues are still largely debated. Here, I critically describe two main perspectives. The first perspective interprets faithful social learning as an outcome of a fine-grained representation of others’ actions and intentions that requires sophisticated socio-cognitive skills. In contrast, the second perspective highlights the role of simpler decision heuristics, the recruitment of which is determined by individual and ecological constraints. The present thesis aims to show, through four experimental works, that these two contributions are not mutually exclusive. A first study investigates the role of the inferior frontal cortex (IFC), the anterior intraparietal area (AIP) and the primary somatosensory cortex (S1) in the recognition of other people’s actions, using a transcranial magnetic stimulation adaptation paradigm (TMSA). The second work studies whether, and how, higher-order and lower-order prior information (acquired from the probabilistic sampling of past events vs. derived from an estimation of biomechanical constraints of observed actions) interacts during the prediction of other people’s intentions. Using a single-pulse TMS procedure, the third study investigates whether the interaction between these two classes of priors modulates the motor system activity. The fourth study tests the extent to which behavioral and ecological constraints influence the emergence of faithful social learning strategies at a population level. The collected data contribute to elucidate how higher-order and lower-order prior expectations interact during action prediction, and clarify the neural mechanisms underlying such interaction. Finally, these works provide/open promising perspectives for a better understanding of social learning, with possible extensions to animal models.

Biomedicine and pain

The focus of my research is on contemporary biomedical construction of pain as an object, i.e. the different ways in which pain has been conceptualized and approached as a specific site of investigation in biomedicine. A significant shift in the scientific conception of pain occured in the second half of XXth century. In 1965, Ronald Melzack and Patrick D. Wall propose the Gate Control theory of pain mechanism. This theory denies a fixed and direct relationship between stimulus and pain perception, and emphazises the role played by psychological factors in pain. The IASP utilizes this perspective on the phenomenon, describing pain as “an unpleasant sensory and emotional experience associated to an actual or potential tissue damage or described in the terms of such a damage.” The relationship between pain and damage is pivotal in the definition of pain as a pathological entity. In particular, the biomedical approach to pain appears to be strongly characterized by a dualistic view of its aetiology. Disease conceptions such as “psychogenic pain” and chronic pain are deeply influenced by the ways in which psychological factors have been interpreted as components, or as causes of pain. In the second part of my dissertation, I focus on fibromyalgia, which is emblematic of the problematic acknowledgment of chronic pain as a disease. Even if fibromyalgia is actually treated in Rheumatology, its status as a disease is blurred, mainly because of its complex symptomatology including both physiological manifestations and psychological ones. In the conclusion, I present a scenario of the different ways in which this disease is dealt with in biomedical knowledge, through medical literature, clinical practice, and patients’ accounts. The findings of an ethnographic enquiry in the Rheumatology Division of a local clinic and a visual research on patients’ experiences are analyzed and discussed.

The relationship between eating behavior and psychological distress among overweight and obese people: is there a role for mindfulness?

This research based on 3 indipendent studies, sought to explore the nature of the relationship between overweight/obesity, eating behaviors and psychological distress; the construct of Mindful eating trough the validation of the Italian adaptation of the Mindful Eating Questionnaire (MEQ); the role of mindfulnessand mindful eating as respectively potential mediator and moderator between overeating behavior (binge eating and emotional overeating) and negative outcomes (psychological distress, body dissatisfaction). All the samples were divided in normal weight, overweight and obese according to BMI categories. STUDY1: In a sample of 691 subjects (69.6% female, mean aged 39.26 years) was found that BMI was not associated with psychological distress, whereas binge eating increases the psychopathological level. BMI and male gender represent negative predictors of psychological distress, but certain types of overeating (i.e., NES/grazing, overeating during or out of meals, and guilt/restraint) result as positive predictors.. STUDY 2 : A sample of 1067 subjects (61.4% female, mean aged 34 years) was analized. The Italian MEQ resulted in a 26-item 4-factor model measuring Disinhibition, Awareness, Distraction, and Emotional response. Internal consistency and test-retest reliability were acceptable MEQ correlated positively with mindfulness (FMI) and it was associated with sociodemographic variables, BMI, meditation. type of exercise and diet. STUDY 3, based on a sample of 502 subjects (68.8% female, mean aged 39.42 years) showed that MEQ and FMI negatively correlated with BES, EOQ, SCL-90-R, and BIAQ. Obese people showed lower level of mindful eating and higher levels of binge eating, emotional overeating, and body dissatisfaction, compared to the other groups Mindfulness resulted to partially mediates the relationship between a) binge eating and psychological distress, b) emotional overeating and psychological distress, c) binge eating and mental well-being, d) emotional overeating and menal well-being. Mindful eating was a moderator only in the relationship between emotional overeating and body dissatisfaction.

Family satisfaction with critical care: measurements and messages

PURPOSE OF REVIEW: Family satisfaction in the ICU reflects the extent to which perceived needs and expectations of family members of critically ill patients are met by healthcare professionals. Here, we present recently developed tools to assess family satisfaction, with a special focus on their psychometric properties. Assessing family satisfaction, however, is not of much use if it is not followed by interpretation of the results and, if needed, consecutive measures to improve care of the patients and their families, or improvement in communication and decision-making. Accordingly, this review will outline recent findings in this field. Finally, possible areas of future research are addressed. RECENT FINDINGS: To assess family satisfaction in the ICU, several domains deserve attention. They include, among others, care of the patient, counseling and emotional support of family members, information and decision-making. Overall, communication between physicians or nurses and members of the family remains a key topic, and there are many opportunities to improve. They include not only communication style, timing and appropriate wording but also, for example, assessments to see if information was adequately received and also understood. Whether unfulfilled needs of individual members of the family or of the family as a social system result in negative long-term sequels remains an open question. SUMMARY: Assessing and analyzing family satisfaction in the ICU ultimately will support healthcare professionals in their continuing effort to improve care of critically ill patients and their families.

Attention-deficit hyperactivity disorder (ADHD) and glial integrity: an exploration of associations of cytokines and kynurenine metabolites with symptoms and attention

In contrast to studies of depression and psychosis, the first part of this study showed no major differences in serum levels of cytokines and tryptophan metabolites between healthy children and those with attention-deficit/hyperactivity disorder of the combined type (ADHD). Yet, small decreases of potentially toxic kynurenine metabolites and increases of cytokines were evident in subgroups. Therefore we examined predictions of biochemical associations with the major symptom clusters, measures of attention and response variability.