CoordenaÃÃo de AperfeiÃoamento de Pessoal de NÃvel Superior / A pele do bebà quando internado em uma Unidade de Terapia Intensiva Neonatal (UTIN), apresenta predisposiÃÃo a ser lesionada, diante da necessidade de muitos procedimentos especÃficos, acabando por expÃ-lo a manipulaÃÃes necessÃrias, mas um tanto desgastantes para o mesmo. Objetivou-se avaliar as lesÃes de pele que acometem recÃm-nascidos internados em uma UTIN. Estudo prospectivo, quantitativo, exploratÃrio descritivo, realizado no perÃodo de marÃo a maio/2007, numa instituiÃÃo pÃblica em Fortaleza-CE. ConstituÃram o universo e a amostra 137 recÃm-nascidos, que estiveram internados nas UTIN, os quais todos foram autorizados à participaÃÃo nesta pesquisa pelos pais. Destes, 36 apresentaram lesÃes de pele. Na coleta de dados, utilizou-se um instrumento que permitiu o registro das lesÃes atravÃs da observaÃÃo direta dos recÃm-nascidos durante a higiene corporal, trocas: de fralda, de sonda, de venda ocular; retiradas: de membrana semipermeÃvel, bandagem adesiva elÃstica e/ou micropore, eletrodos, hidrocolÃide que estavam fixados diretamente na pele destes, durante as punÃÃes, dentre outros procedimentos. Investigou-se 137 recÃm-nascidos, a maioria prematuro (80%), sexo masculino (63%), nascido de parto abdominal (61%), apgar de 7 a 10 no 1 minuto (40%), diagnosticados com prematuridade moderada (49%), baixo peso ao nascer (39%), adequado para a idade gestacional (74%), medindo entre 41 e 47cm (44%). Destes, 36 recÃm-nascidos (26%) apresentaram lesÃes de pele, totalizando 51 lesÃes. Foram identificadas: hematomas (46%), eritemas (18%), escoriaÃÃes (12%), equimoses (10%), pÃstulas (6%), descamaÃÃes (4%), mielomeningocele (2%) e gastrosquise (2%). Quando ocorreram as lesÃes, os recÃm-nascidos estavam em uso de hidrataÃÃo venosa (84%), antibiÃtico (78%), ventilaÃÃo mecÃnica (53%), fototerapia (33%), nutriÃÃo parenteral (27%), hemotransfusÃo (8%), oxihood (8%), cpap nasal (6%) e O2 circulante (4%); acomodados em incubadora aquecida (86%), incubadora de transporte (10%) e em berÃo de calor radiante (4%). Predominaram lesÃes nos membros (52%), no tronco (24%), na cabeÃa (16%) e em outros (8%). As associaÃÃes realizadas foram: punÃÃo arterial (32%), extravasamento (14%), assadura (14%), punÃÃo venosa (8%), impetigo (4%), indeterminada (4%), mà formaÃÃo congÃnita (4%), retirada da membrana transparente (4%), retirada da bandagem adesiva (4%), ressecamento da pele (4%), infecÃÃo (2%), retirada da fita hipoalergÃnica (2%) e tocotraumatismo (2%). Quanto a Ãrea da lesÃo (40%) eram < 1cm2, no tamanho 68% eram lesÃes entre 1 e 2cm. A maioria tinha a forma geogrÃfica (38%) e distribuiÃÃo localizada (92%). Os recÃm-nascidos que desenvolveram lesÃes tinham diagnÃsticos de âprematuridadeâ (92%), âsÃndrome do desconforto respiratÃrioâ (43%), âasfixiaâ (24%), ârecÃm-nascido a termoâ (8%); ârisco de infecÃÃoâ (6%), ârisco de hipoglicemiaâ (6%), âgastrosquiseâ (2%) e âmielomeningoceleâ (2%). A maioria nasceu com peso entre 550 - 999g, (47%), sendo o peso destes no dia em que ocorreu a lesÃo entre 455 - 999g, (47%). A maioria eram neonatos (84%) e as lesÃes (47%) surgidas antes do 7 dia de vida. Ao associar: tipos de lesÃes, diagnÃsticos, PN e IG dos RNâs, somente o diagnÃstico âprematuridadeâ apresentou associaÃÃo estatÃstica significante: âp de Fisher-Freeman-Halton = 0,496â. Consagra-se na trajetÃria deste estudo o cuidado de enfermagem ao RN que, indiscutivelmente, deve ser holÃstico e diferenciado, considerando suas peculiaridades. / Infants in the Neonatal Intensive Care Unit (NICU) often get skin lesions on account of the many stressful procedures they are exposed to. This prospective, quantitative and descriptive study was carried out at a public health facility in Fortaleza (Northeastern Brazil) from March to May 2007, in order to investigate skin lesion patterns in infants in the NICU setting. The study population consisted of 137 hospitalized infants. Informed written consent was obtained from the infantsâ caretakers. The data collection instrument registered skin lesions through direct observation during bathing, change of diapers, catheters and eye patches and during removal of semi-permeable membranes, elastic adhesive bandages and/or micropores, electrodes and hydrocolloid dressings applied to the skin during punction, among other procedures. Eighty percent of the infants were premature, 63% were male, 61% were caesarean births, 40% presented first-minute apgar scores of 7-10, 49% were diagnosed with moderate prematurity, 74% were full-term, 39% had low birth weight and 44% measured 41â47cm. Thirty-six infants had skin lesions (total 51 lesions) in the form of bruises (46%), erythema (18%), excoriation (12%), ecchymosis (10), pustulas (6%), scaling (4%), myelomeningocele (2%) or gastroschisis (2%). The lesions were inflicted while the infants were being treated with intravenous hydration (84%), antibiotics (78%), mechanical ventilation (53%), phototherapy (33%), parenteral nutrition (27%), blood transfusion (8%), oxygen hood (8%), nasal cpap (6%) or circulating oxygen (4%), or were in a heated incubator (86%), transport incubator (10%) or heated crib (4%). Lesions were observed most often on limbs (52%), torso (24%), head (16%) and other sites (8%). The causes identified were arterial puncture (32%), leaking (14%), contact dermatitis (14%), vein puncture (8%), impetigo (4%), undetermined (4%), congenital malformation (4%), removal of the caul (4%), removal of adhesive bandage (4%), skin dryness (4%), infection (2%), removal of hypoallergenic tape (2%) and birth traumatism (2%). Forty percent of lesions measured < 1cm2 and 68% measured 1-2cm. Most were well defined (38%) and/or localized (92%). Infants with lesions presented prematurity (92%), syndrome of respiratory distress (43%), asphyxia (24%), full-term delivery (8%); risk of infection (6%), risk of hypoglycemia (6%), gastroschisis (2%) or myelomeningocele (2%). Most (47%) weighed 550-999g at birth, with lesions occurring at 455-999g in 47%. Most were newborn (84%) and lesions appeared before the seventh day of life in 47% of cases. Among the parameters lesion type, diagnosis, PN, IG and prematurity, only the latter presented a statistically significant association (p=0.496, by the Fisher-Freeman-Halton test). The study shows the importance of providing the newborn with good-quality holistic nursing care with a view to the special needs of this patient population.

A encefalopatia hipóxico-isquêmica neonatal, ou simplesmente hipóxia-isquemia (HI) neonatal, é uma das principais causas de morbidade e mortalidade em neonatos humanos. De 20% a 50% dos recém-nascidos com HI severa morrem no período perinatal. Quando sobrevivem, 25% apresentam deficiências neuropsicológicas, como dificuldade de aprendizado, epilepsia e paralisia cerebral. Devido a isso, a eficácia de possíveis agentes neuroprotetores tem sido testada em modelos animais. Há razão para se pensar que a progesterona tem um forte potencial para o tratamento da HI neonatal, já que a sua utilização tem se mostrado benéfica em pesquisas relacionadas com lesão cerebral traumática, lesão cerebral isquêmica e outros modelos de lesão do sistema nervoso central (SNC) em adultos. Inúmeros estudos têm mostrado que o modelo animal de HI de Rice e Vannucci (1981) em animais neonatos, utilizado no presente trabalho, pode produzir lesões no sistema nervoso central relativamente previsíveis, e que estas lesões encefálicas parecem semelhantes às observadas clinicamente em humanos (SALMASO et al., 2014). Para a realização do modelo de HI foram utilizados ratos Wistar com idade de 7 dias (P7). Após a oclusão da carótida esquerda, os animais foram colocados em câmaras para exposição à atmosfera hipóxica com 8% O2/92% N2 por 90 minutos. Os animais foram divididos em cinco grupos experimentais: SHAM, HI, HI+PROG-PRÉ (PRÉ), HI+PROG-PÓS (PÓS), HI+PROG-PRÉ/PÓS (PP). Os termos PRÉ e PÓS referem-se à administração de progesterona (na dose de 5 mg/kg) antes ou após o procedimento de HI neonatal . Dependendo do grupo experimental, os animais foram tratados com progesterona imediatamente antes da isquemia e/ou 6 e 24 horas após o início da hipóxia. Foram analisados o peso corporal dos animais (imediatamente antes da isquemia e 6, 24 e 48 horas após o início da hipóxia), o volume de lesão cerebral, além da expressão das proteínas p-Akt e caspase-3 pela técnica de Western blotting. / Neonatal hypoxic-ischemic encephalopathy or simply neonatal hypoxia-ischemia (HI) is a main cause of morbidity and mortality in human neonates. Moreover, 25% of survivors show neuropsychological dysfunctions such as learning difficulties, epilepsy and cerebral palsy. Because of this, the effectiveness of potential neuroprotective agents has been tested in animal models. There is a reason to suppose that progesterone has a strong potential for the treatment of neonatal HI since its use has been shown to be beneficial in researches related to traumatic brain injury, ischemic brain injury and other central nervous system injury models (CNS) in adults. Several studies have shown that the newborn animal model of HI developed by Rice and Vannucci (1981), and used in the present study, can produce lesions in the central nervous system which are predictable and similar to those observed clinically in humans. In order to perform the HI model we used 7 days old (P7) Wistar rats. After occlusion of the left carotid, the animals were placed in hypoxic chambers and exposed to the hypoxic atmosphere (8% O2/92% N2 for 90 minutes). The animals were divided into five groups: SHAM, HI, HI+PROG-PRÉ (PRÉ), HI+PROG-PÓS (PÓS), HI+PROG-PRÉ/PÓS (PP).The PRÉ and PÓS terms refer to the administration of progesterone (5 mg/kg) before and/or after the HI procedure. Progesterone was administered immediately before ischemia, 6 and 24 hours after the beginning of hypoxia, depending on the experimental group. Body weight was evaluated immediately before ischemia and/or 6 and 24 hours after the start of hypoxia. The volume of brain damage, in addition to the expression of p-Akt and caspase-3 were also evaluated.

Déficits na regulação serotoninérgica dos circuitos catecolaminérgicos tem sido propostos como um mecanismo relacionado à etiologia dos transtornos de humor. Projeções do núcleo mediano da rafe (MnR) modulam a atividade dopaminérgica no prosencéfalo e são também parte de um sistema de inibição/desinibição comportamental que se assemelha às variações nos níveis de atividade apresentados durante os polos do transtorno bipolar. O objetivo do presente estudo foi avaliar se as alterações comportamentais induzidas pela inativação do MnR podem ser um modelo animal para estudo da mania humana. No Capítulo I, o procedimento de lesão eletrolítica do MnR foi realizado em ratos Wistar machos, tendo como controles os grupos lesão fictícia e intacto. Os resultados confirmaram a capacidade desta manipulação experimental em reproduzir hiperatividade e estereotipia crônicas, aumento na frequência de respostas positivamente reforçadas por solução de sacarose e padrão comportamental de dominância social. Ainda, foi demonstrada a potencialidade do tratamento crônico com lítio em reduzir a hiperatividade. No Capítulo II foram realizadas lesões eletrolíticas do MnR em camundongos C57BL/6J machos, tendo novamente como controles os grupos lesão fictícia e intacto. Os resultados demonstraram desenvolvimento de hiperatividade, estereotipia e maior frequência de exposição a situações aversivas/de risco nos testes do labirinto em cruz elevado e do claro/escuro. O tratamento crônico com lítio atenuou ou reverteu parte destas alterações comportamentais. Análises do tecido encefálico demonstraram níveis terapêuticos equivalentes de LiCl em todos os grupos submetidos ao tratamento e a histologia confirmou o sítio de lesão. O conjunto dos dados obtidos sugere a adequação do modelo proposto pelo atendimento aos critérios de validade de face e preditiva apresentando como vantagens a mimetização de diversos sintomas do transtorno e a cronicidade destes. Ainda, a reprodutibilidade dos efeitos da lesão em diferentes espécies sugere a existência de homologia evolutiva, acrescentando fundamentos à validade de constructo hipotetizada. Por fim, destaca-se que este modelo de mania parece ser heurístico pela possibilidade de contribuir para a investigação dos mecanismos de ação do lítio e para a compreensão das relações de oposição entre os sistemas neurotransmissores excitatórios e inibitórios como parte da neurobiologia dos transtornos de humor / Deficits in serotoninergic regulation of catecholaminergic circuits have been proposed as a mechanism related to the etiology of mood disorders. Projections from the median raphe nucleus (MnR) modulate the dopaminergic activity in the forebrain and are also part of a behavioral disinhibition/inhibition system that resembles the variations in activity levels shown during the poles of bipolar disorder. The aim of the present study was to evaluate if the behavioral effects induced by the inactivation of the MnR can be considered an animal model for studying the human mania. In Chapter I, the MnR electrolytic lesion was performed in male Wistar rats, having as control groups sham operated and intact animals. The results confirmed the capacity of this experimental manipulation to reproduce chronic hyperactivity and stereotypy, increased response frequency positively reinforced by sucrose solution and a social dominant behavioral pattern. Furthermore, it was shown the potentiality of the lithium treatment in reducing the hyperactivity. In Chapter II MnR electrolytic lesions were performed in C57BL/6J mice, having as control groups sham operated and intact animals. The results demonstrated the development of hyperactivity, stereotypy and increased frequency of exposure to aversive situations/\"risk taking\" in the elevated plus maze and light/dark box tests. Chronic treatment with lithium attenuated or reversed some of these behavioral alterations. Encephalic tissue analysis showed equivalent lithium therapeutic levels in all treated groups and the histology confirmed the lesion site. The set of data obtained suggests the suitability of the proposed model for attending criteria for face and predictive validities presenting advantages such as the mimicking of several disorder symptoms and the chronicity of them. Also, the reproducibility of the effects of the lesion in different species suggests the existence of evolutionary homology and adds basis to the construct validity hypothesized. Finally, it is emphasized that this model of mania seems to be heuristic by the possibility to contribute to the investigation of lithium mechanisms of action and for understanding the opposite relations between excitatory and inhibitory neurotransmitter systems as part of the neurobiology of mood disorders

Escherichia coli enteropatogênica (EPEC) é um dos principais agentes de diarréia em crianças nos países em desenvolvimento. Esse patótipo pode ser classificado em dois grupos: EPEC típica (t-EPEC) e EPEC atípica (a-EPEC). O objetivo principal deste estudo foi traçar o perfil plasmidial de 78 amostras de a-EPEC bem como investigar em 72 amostras a presença de genes de virulência descritos em outros patótipos de DEC para procura de um marcador de virulência específico deste grupo de amostras. Foi detectada a presença de alguns genes de virulência como: pet (5,5%), pic (2,7%), astA (18%), efa1/lifA, toxB (2,7%), ldaH (8,3%) e ehly1 (4,2%). Os perfis plasmidiais obtidos permitiram verificar que entre as 78 amostras analisadas, 12 não possuem plasmídio, 33 possuem plasmídios entre 50 a 90 kb e 38 possuem plasmídios entre 90 a 124 kb. A pesquisa dos grupos de incompatibilidade revelou que os grupos IncFIB e IncF são os mais freqüentes entre as amostras de a-EPEC. Os resultados de RFLP do DNA plasmidial das amostras do sorotipo O55:H7 sugeriu que existem seqüências de nucleotídeos comuns entre os plasmídios. Os dados obtidos também permitiram inferir a existência de fragmentos de DNA plasmidial comum entre amostras de EHEC O157:H7 e amostras de a-EPEC O55:H7. A função biológica dos plasmídios de a-EPEC e a relação com o plasmídio pO157 necessitam de estudos complementares. / Escherichia coli (EPEC) is one of the main agents of diarrhea in children in developing countries. This pathotype can be classified in two groups: typical EPEC (t-EPEC) and atypical EPEC (a-EPEC). The aim of this study was to determine the plasmid profile of 78 strains of a-EPEC and investigate 72 strains for the presence of virulence genes described in other DEC. It was detected the presence of some virulence genes: pet (5,5%), pic (2,7%), astA (18%), efa1/lifA, toxB (2,7%), ldaH (8,3%) e ehly1 (4,2%). The plasmid profiles obtained allowed us to verify that among the 78 samples analyzed, 12 did not have plasmids, 33 strains have plasmids ranging between 50 and 90 kb, and 38 have plasmids ranging between 90 to 124 kb. Incompatibility groups analysis revealed that IncFIB and IncF groups are the most frequent among the samples of a-EPEC. RFLP analysis of plasmid DNA of strains of serotype O55:H7 suggested that there are nucleotide sequences common to the plasmids. The data also allowed inferring the existence of fragments of plasmid DNA common to EHEC O157:H7 and a-EPEC O55:H7. The biological function of aEPEC plasmid and the relationship with pO157 requires further studies.

To test whether SKF 38393 could ontogenetically sensitize dopamine (DA) D$\sb1$ receptors and whether this sensitization would be associated with biochemical changes, intact and neonatal 6-hydroxydopamine (6-OHDA)-lesioned rats (200 $\mu$g i.c.v.) were treated daily from birth with SKF 38393 (3.0 mg/kg i.p. x 28 days) or its vehicle. In DA D$\sb1$ neonatally sensitized 6-OHDA rats, enhanced locomotor responses were observed with the first SKF 38393 challenge dose (3.0 mg/kg i.p.) at 6 weeks. This response increased further with weekly SKF 38393 treatments. Enhanced stereotyped behaviors were seen in both lesioned and sensitized rats at 8 weeks. There was no change in the percentage of high affinity D$\sb1$ sites in these groups of rats. Striatal mRNA levels for D$\sb1$ receptors were reduced in the lesioned rats, but restored to control level after treatments with SKF 38393 in adulthood. Basal, DA-, NaF- and forskolin-stimulated adenylate cyclase activities were similar among treatment groups. Striatal DA content was reduced ($>$99%), whereas serotonin (5-HT) content was elevated ($>$50%) in the 6-OHDA groups. To study possible interaction between DA and 5-HT systems, the effects of a series of 5-HT agents on the induction of oral activity were determined. The 5-HT$\sb{\rm 1C}$ receptor agonist, m-chlorophenylpiperazine (m-CPP), produced a marked increase in oral activity in 6-OHDA-lesioned rats. The respective 5-HT$\sb{\rm 1A}$ and 5-HT$\sb{\rm 1B}$ agonists, 8-OH-DPAT and CGS-12066B did not increase oral activity. The m-CPP-induced oral response in the lesioned rats was attenuated by mianserin, a 5-HT$\sb{\rm 1C}$ antagonist, but not by ketanserin or MDL-72222, 5-HT$\sb2$ and 5-HT$\sb3$ antagonists, respectively. Although the supersensitized oral response of lesioned rats to m-CPP was not attenuated by SCH 23390, the enhanced response of SKF 38393 was attenuated by mianserin. Additionally, mRNA levels for 5-HT$\sb{\rm 1C}$ receptor were not altered in both intact and lesioned rats. These findings demonstrate that ontogenetic treatments of neonatal 6-OHDA-lesioned rats with a D$\sb1$ agonist produce partial sensitization of DA D$\sb1$ receptors in adulthood without altered biochemical markers, and that this neonatal lesion is associated with both supersensitized DA D$\sb1$ and 5-HT$\sb{\rm 1C}$ receptors. Moreover, induction of oral activity by DA agonists is mediated via a serotonergic system.

Purpose: This in vitro study evaluated the effectiveness of using a 37% phosphoric acid liquid etchant along with MI Paste Plus™ powered technology compared to using MI Paste Plus™ alone or to an artificially created saliva solution in decreasing the demineralization and enhancing the remineralization of artificial carious lesions created on extracted human teeth. The teeth were analyzed and compared using polarized light microscopy, quantitative light-induced fluorescence, and digital photography. Materials and Methods: One hundred three recently extracted non-carious human third molar teeth without observable white-spot lesions, decalcification, or dental fluorosis were selected for this twelve day study and randomly divided into four treatment groups as follows: Group 1 (Control) - Artificial saliva solution (27 teeth) Group 2 (MIP) - MI Paste Plus™ application for 30 minutes daily for 12 days (26 teeth) Group 3 (15MIP) - 15 second etch every third day and MI Paste Plus™ application for 30 minutes daily for 12 days (25 teeth) Group 4 (1MIP) - 1 minute etch on day one ONLY and application of MI Paste Plus™ for 30 minutes daily for 12 days (25 teeth). Results: Results of one<–>way ANOVA revealed there was a significant effect for the type of treatment on the lesion depth (p = 0.0027). The post-hoc Tukey-Kramer's test indicated there was a statistically significant difference between the two groups (15MIP and 1MIP) that incorporated an acid etch in combination with MI Paste Plus™ and the group with exposure to MI Paste Plus™ alone (MIP). In addition, results of one<–>way ANOVA showed that there was no statistically significant effect for type of treatment on the change in fluorescence (p = 0.1417) or the change in density (p = 0.1934). Conclusions: The results of the present study revealed there was a significant effect for the type of treatment on the lesion depth (p = 0.0027). However, the only significant difference found was between the two groups (15MIP and 1MIP) that incorporated an acid etch in combination with MI Paste Plus™ and the group with exposure to MI Paste Plus™ alone (MIP). Thus, daily applications of MI Paste Plus™, with or without an acid etch, did not produce a statistically significant difference in mean lesion depth when compared to the control (artificial saliva group). In addition, the results of the present study showed that there was no statistically significant effect for type of treatment on the change in fluorescence (p = 0.1417) or the change in density (p = 0.1934). Further research is needed to evaluate MI Paste Plus™ capability in prevention of demineralization and/or enhancement of remineralization by conducting randomized clinical trials.

Traumatic injuries lead to articular cartilage lesion formation and result in the development of osteoarthritis. Recent research suggests that the early stage of mechanical injuries involve cell death (apoptosis and necrosis) and inflammation. In this thesis, we focus on building mathematical models to investigate the biological mechanism involving chondrocyte death and inflammatory responses in the process of cartilage degeneration. Chapter 1 describes the structure of articular cartilage, the process of carti- lage degeneration, and reviews of existing mathematical models. Chapter 2 presents a delay-diffusion-reaction model of cartilage lesion formation under cyclic loading. Computational methods were used to simulate the impact of varying loading stresses and erythropoietin levels. The model is parameterized with experimental results, and is therefore clinically relevant. Due to numerical limitations using delay differential equations, a new model is presented using tools for population dynamics. Chapter 3 presents an age and space-structured model of articular cartilage lesion formation un- der a single blunt impact. Age structure is introduced to represent the time delay in cytokine synthesis and cell transition. Numerical simulations produce similar tempo- ral and spatial patterns to our experimental data. In chapter 4, we extend our model under the cyclic loading setting. Chapter 5 builds a spatio-temporal model adapted from the former models, and investigates the distribution of model parameters using experimental data and statistical methods. Chapter 6 concludes.

Philosophical and scientific investigations into the nature of belief and knowledge are ancient, extending back to the beginnings of rational thought. It is not until the last few decades that we have been able to peer into and examine the organ of belief, the brain. Neuroanatomical perspectives have begun to address the long-standing questions of epistemology by identifying specific neural regions that are critical for the storage and evaluations of beliefs. Here, a novel neuroanatomical model of belief and doubt is presented, where post-rolandic association cortices are critical for the storage of beliefs and the prefrontal cortex is necessary for the doubt and evaluation process. It is proposed that the singular function of the prefrontal cortex is "false tagging" (the neuroanatomical essence of doubt) to mental representations in post-rolandic cortices. Individuals that have dysfunction to the prefrontal cortex, such as patients with explicit damage to the prefrontal cortex, from tumor resections or cerebral vascular events, should show a "doubt deficit", accompanied by a general increased belief to information. Evidence is presented indicating that deficiencies in the "false tagging" function may explain a wide assortment of abnormalities in neurological and psychiatric patients. Several experiments in various populations (neurological, developmental, and psychiatric) were conducted to examine the role of specific brain regions in the believing and doubting process. First, two studies gave participants explicitly-labeled false beliefs and measured the ability of the participants to falsify these beliefs. It was predicted that participants with dysfunction to the prefrontal cortex would be poor at falsifying novel beliefs. Results confirmed the predictions. Second, participants were given pairs of statements that represented opposite opinions on some issue and responded by agreeing or disagreeing with each statement. Participants with dysfunction to the prefrontal cortex, who, theoretically, have a "doubt deficit," should show compartmentalized minds, where cognitions are easily believed but rarely doubted against other extant mental information. Results suggested that participants with prefrontal cortex dysfunction were more likely to agree to opposing statements. Third, individuals with dysfunction to the prefrontal cortex should lack a dissonant state that can change attitudes, when two cognitions are in conflict. Using a free-choice paradigm, it was found that participants with prefrontal dysfunction showed either extreme attitude change after choice or no attitude change after choice, which is consistent with a "no dissonance" state. Finally, individuals with compartmentalized minds tend evince an authoritarian personality. A psychometric scale and a behavioral measure of authoritarianism were examined in the participants. Results indicated that participants with prefrontal cortex dysfunction showed increased authoritarianism on the psychometric scale, but decreased authoritarian behavior, reflecting a dissociation between knowledge and behavior. In conclusion, the results support the theoretical assertions that the prefrontal cortex is critical for "false tagging" or doubting cognitive representations. Data from neurological, developmental, and psychiatric populations are broadly consistent with the theory and offer strong external validity.

Background: Calcification of atherosclerotic plaques is associated with vulnerability to rupture and increased risk of myocardial infarction. The mechanism of plaque calcification is unclear, but has been shown to be a cell-mediated process involving complex signaling pathways affecting the osteogenic transcription factor Runt-related transcription factor 2 (Runx2). The type-2 cannabinoid receptor (CB2) modulates processes involved in bone remodeling and our prior studies determined that CB2 alters the composition of early lesions in hyperlipidemic Ldlr-/- mice; however, the function of CB2 in plaque calcification is unknown. Therefore, we tested the hypothesis that CB2 modulates plaque calcification by evaluating the effects of systemic CB2 gene deletion on lesion calcification and aortic expression of Runx2 in Ldlr-/- mice. Results: Groups (n≥8) of 8-week old CB2+/+Ldlr-/- (WT) and CB2-/- Ldlr-/- (CB2-/-) mice were fed a high fat diet (HFD) for up to 24 weeks. Standard blood plasma analysis showed no difference in HFD-induced hyperlipidemia between WT and CB2-/- mice. Aortic levels of endocannabinoids, anandamide and 2-archidonylglycerol, were significantly elevated after 12 weeks of HFD feeding as determined by LC-MS/MS. En face analysis revealed the extent of atherosclerosis in the aortic arch and thoracic aorta did not differ between WT and CB2-/- mice, but was ~1.9-fold greater in the abdominal aortas of CB2-/- mice (17.0±1.3% vs 9.0±1.3%, p=0.002). Calcification of aortic root lesions was ~2.3 fold greater in CB2-/- mice compared to WT mice (12.9±1.1% vs 5.6±1.2%, p=0.002) as revealed by von Kossa staining. Western blot analysis showed significantly increased expression of Runx2 in aortas of WT mice compared to CB2-/- after 20 weeks of HFD (2.55±0.25 fold, p Conclusion: Systemic CB2 deficiency enhances lesion calcification and is associated with altered aortic expression of Runx2. These results provide novel mechanistic insights into the function of CB2 signaling in the pathogenesis of atherosclerosis and vascular calcification that may lead to the development of therapies aimed at stabilizing calcified plaque.

The degree of academic achievement following early onset brain injury is poorly understood. Furthermore, it is unclear if academic success can be predicted by age of onset or other lesion variables (e.g., size, laterality). The purpose of the current study was to describe patterns of academic achievement in individuals with childhood-onset focal brain lesions and to determine the role of variables in the plasticity or vulnerability of the developing brain with regard to achievement. Academic achievement data were collected from 58 individuals with childhood-onset focal brain lesions. The participants' reading, spelling, and arithmetic scores, as measured by the Wide Range Achievement Test, were analyzed in relation to several neuroanatomical variables, including lesion laterality, lesion site, and lesion size. The relationship between achievement and gender, age of onset, etiology, age at testing, and time since lesion onset was also identified. As a group, achievement scores did not differ from normative data, and the majority of the sample demonstrated adequate skills in each domain. However, the frequency of deficits was larger than expected when compared to base rates, suggesting vulnerability to early insult. Achievement scores were correlated with intelligence scores, but did not differ based on lesion laterality, lesion site, age of onset, or etiology. Size of lesion was significantly correlated with reading and spelling but not with arithmetic outcomes. Gender differences were identified, with males performing significantly better on the arithmetic measure than females. The age of onset, age at testing, and time since lesion onset were not correlated with achievement scores in any domain. No interactions were found between lesion laterality and gender or lesion site and lesion laterality. An interaction between gender and lesion site was found, but the significance of the finding is unclear. The current findings provide mixed evidence for the plasticity-vulnerability debate, as many individuals were able to achieve adequate academic skills whereas others demonstrated significant impairments. Further research is needed to elucidate factors that may predict achievement outcomes in individuals with childhood-onset focal brain injury.