Threat directionality modulates defensive reactions in humans: cardiac and electrodermal responses.

Features of threatening cues and the associated context influence the perceived imminence of threat and the defensive responses evoked. To provide additional knowledge about how the directionality of a threat (i.e. directed-towards or away from the viewer) might impact defensive responses in humans, participants were shown pictures of a man carrying a gun (threat) or nonlethal object (neutral) directed-away from or towards the participant. Cardiac and electrodermal responses were collected. Compared to neutral images, threatening images depicting a gun directed-towards the participant induced sustained bradycardia and an increased electrodermal response, interpreted as immobility under attack. This defensive immobility reaction is evoked by high perceived threat and inescapable situations and indicates intense action preparation. Pictures of guns directed-away from the participant induced shorter bradycardia and no significant modulation of the electrodermal response compared to neutral pictures, which might be consistent with the perception of a less threatening situation. The results show that the directionality of threat stimuli is a key factor that prompts different patterns of defensive responses.

Decoding negative affect personality trait from patterns of brain activation to threat stimuli.

INTRODUCTION: Pattern recognition analysis (PRA) applied to functional magnetic resonance imaging (fMRI) has been used to decode cognitive processes and identify possible biomarkers for mental illness. In the present study, we investigated whether the positive affect (PA) or negative affect (NA) personality traits could be decoded from patterns of brain activation in response to a human threat using a healthy sample. METHODS: fMRI data from 34 volunteers (15 women) were acquired during a simple motor task while the volunteers viewed a set of threat stimuli that were directed either toward them or away from them and matched neutral pictures. For each participant, contrast images from a General Linear Model (GLM) between the threat versus neutral stimuli defined the spatial patterns used as input to the regression model. We applied a multiple kernel learning (MKL) regression combining information from different brain regions hierarchically in a whole brain model to decode the NA and PA from patterns of brain activation in response to threat stimuli. RESULTS: The MKL model was able to decode NA but not PA from the contrast images between threat stimuli directed away versus neutral with a significance above chance. The correlation and the mean squared error (MSE) between predicted and actual NA were 0.52 (p-value=0.01) and 24.43 (p-value=0.01), respectively. The MKL pattern regression model identified a network with 37 regions that contributed to the predictions. Some of the regions were related to perception (e.g., occipital and temporal regions) while others were related to emotional evaluation (e.g., caudate and prefrontal regions). CONCLUSION: These results suggest that there was an interaction between the individuals' NA and the brain response to the threat stimuli directed away, which enabled the MKL model to decode NA from the brain patterns. To our knowledge, this is the first evidence that PRA can be used to decode a personality trait from patterns of brain activation during emotional contexts.

Asymmetric parasitic twins - Heteropagus.

BACKGROUND: Asymmetric or heteropagus conjoined twins is a rare occurrence, with an incidence of one case in 1-2 million. Conjoined twins are classified according to their symmetry, place of fusion, and grade of duplication. METHODS: We report here an extremely rare presentation of parasitic twins not described before. We describe macro and micro anatomic alterations and discuss the aspects of this peculiar presentation and the importance of prenatal diagnosis. RESULTS: The case of a twenty-three-year-old patient, with monochorionic, monoamniotic asymmetrically-conjoined twin pregnancy, discovered at 29 weeks of gestational age. We believe that this report calls attention to this presentation and the importance of prenatal care and management. The twins were delivered vaginally without life. The twins' combined weight was 1.300 gr. They were bonded in the left cervical region. CONCLUSION: This report may help to find strategies for clinical decisions in future cases. Antepartum diagnosis is important to the management, preoperative planning, and outcomes. Prenatal imaging exams like echocardiography, CT, MRI, and ultrasonography are feasible and can provide relevant information about malformation severity and prognosis.

How do you perceive threat? It's all in your pattern of brain activity.

Whether subtle differences in the emotional context during threat perception can be detected by multi-voxel pattern analysis (MVPA) remains a topic of debate. To investigate this question, we compared the ability of pattern recognition analysis to discriminate between patterns of brain activity to a threatening versus a physically paired neutral stimulus in two different emotional contexts (the stimulus being directed towards or away from the viewer). The directionality of the stimuli is known to be an important factor in activating different defensive responses. Using multiple kernel learning (MKL) classification models, we accurately discriminated patterns of brain activation to threat versus neutral stimuli in the directed towards context but not during the directed away context. Furthermore, we investigated whether it was possible to decode an individual's subjective threat perception from patterns of whole-brain activity to threatening stimuli in the different emotional contexts using MKL regression models. Interestingly, we were able to accurately predict the subjective threat perception index from the pattern of brain activation to threat only during the directed away context. These results show that subtle differences in the emotional context during threat perception can be detected by MVPA. In the directed towards context, the threat perception was more intense, potentially producing more homogeneous patterns of brain activation across individuals. In the directed away context, the threat perception was relatively less intense and more variable across individuals, enabling the regression model to successfully capture the individual differences and predict the subjective threat perception.

MYC amplification is associated with poor survival in small cell lung cancer: a chromogenic in situ hybridization study.

PURPOSE: Small cell lung cancer (SCLC) is a highly aggressive tumor, and few studies have examined the amplification status of the MYC gene in tumor samples using chromogenic in situ hybridization (CISH). Emerging target treatments associated with MYC status in SCLC necessitates the evaluation of MYC using current methodologies, such as CISH. In this study, we evaluated tissue samples from untreated patients to determine the relation between MYC amplification and clinical and pathological factors, including survival. METHODS: Formalin-fixed paraffin-embedded tumor samples were obtained from 77 patients with SCLC who underwent a diagnostic biopsy for SCLC. The samples were analyzed by CISH using a MYC probe (ZytoDot(®) CISH probe). The relationship between cytogenetic analysis, pathologic characteristics and survival time was evaluated using the Chi-square test, Fisher's test and Mann-Whitney method. A regression model was constructed to exclude any confounding factors. RESULTS: Of 77 samples, 64.9 % were from bronchi biopsy and the remainder was from the mediastinal, cervical and supraclavicular lymph nodes. The MYC oncogene was amplified in 20 % of the tumors. After the multivariate regression analysis, patients with MYC amplification had a significantly shorter survival time (4.67 weeks) versus patients without MYC amplification (26.15 weeks) (p = 0.02, CI 1.355-10.261). CONCLUSION: MYC amplification is a frequent event in SCLC and is related to a short survival time. MYC amplification may be an independent prognostic factor for SCLC. Further studies are required to support this finding and clarify the role of MYC in SCLC tumorigenesis.

Exposure to trauma-relevant pictures is associated with tachycardia in victims who had experienced an intense peritraumatic defensive response: the tonic immobility.

Tonic immobility is an involuntary, last-ditch defensive reaction characterized by physical inactivity in a context of inescapable threat that has been described in many species, including humans. The occurrence of this defensive response is a predictor of the severity of psychiatric disorders and may be considered as an index of an intense reaction to a traumatic event. Here, we investigated whether the retrospective reports of peritraumatic tonic immobility reaction in participants exposed to a traumatic event would modify their cardiac responses to pictures related to their trauma. Using a questionnaire of life-threating events, we selected students who experienced violent crime as their most intense trauma and students who had never experienced a violent crime trauma, but experienced other traumatic events. All participants completed a questionnaire that estimated the intensity of tonic immobility during their most intense trauma. Electrocardiographic recordings were collected during exposure to pictures. Participants viewed emotional pictures (human attack with guns) and neutral pictures. These emotional stimuli were selected to be trauma-relevant to the violent crime group and non trauma-relevant to the no violent crime trauma group. Violent crime group showed a positive correlation between heart rate changes after viewing trauma-related pictures and tonic immobility scores. We observed that low tonic immobility scores were associated with bradycardia and high scores with tachycardia in response to trauma-relevant pictures. For the no violent crime group, no significant correlation was detected. These results suggest that the relevance of the stimuli and the magnitude of the defensive response during a previous trauma event were important factors triggering more intense defensive responses.

Peritraumatic tonic immobility is associated with posttraumatic stress symptoms in undergraduate Brazilian students.

OBJECTIVE: Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive value of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. METHODS: One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. RESULTS: We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (ß = 1.99, p = 0.017). CONCLUSIONS: This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.

Peritraumatic tonic immobility is associated with posttraumatic stress symptoms in undergraduate Brazilian students / A imobilidade tônica peritraumática está associada aos sintomas do transtorno de estresse pós-traumático em estudantes brasileiros de graduação

OBJECTIVE: Tonic immobility is a defensive reaction occurring under extreme life threats. Patients with posttraumatic stress disorder (PTSD) reporting peritraumatic tonic immobility show the most severe symptoms and a poorer response to treatment. This study investigated the predictive falue of tonic immobility for posttraumatic stress symptoms in a non-clinical sample. METHODS: One hundred and ninety-eight college students exposed to various life threatening events were selected to participate. The Posttraumatic Stress Disorder Checklist - Civilian Version (PCL-C) and tonic immobility questions were used. Linear regression models were fitted to investigate the association between peritraumatic tonic immobility and PCL-C scores. Peritraumatic dissociation, peritraumatic panic reactions, negative affect, gender, type of trauma, and time since trauma were considered as confounding variables. RESULTS: We found significant association between peritraumatic tonic immobility and PTSD symptoms in a non-clinical sample exposed to various traumas, even after regression controlled for confounding variables (β = 1.99, p = 0.017). CONCLUSIONS: This automatic reaction under extreme life threatening stress, although adaptive for defense, may have pathological consequences as implied by its association with PTSD symptoms.

OBJETIVO: A imobilidade tônica é uma resposta defensiva que ocorre sob ameaça extrema à vida. Pacientes com transtorno de estresse pós-traumático (TEPT) que relatam imobilidade tônica peritraumática são os que apresentam os sintomas mais graves e a pior resposta ao tratamento. Este estudo investigou o valor preditivo da imobilidade tônica para os sintomas de TEPT em uma amostra não clínica. MÉTODOS: Os participantes da pesquisa foram 198 estudantes universitários expostos a traumas diversos. A versão brasileira do Post-Traumatic Stress Disorder Checklist Civilian Version (PCL-C) e questões referentes à imobilidade tônica foram empregadas. Modelos de regressão linear foram utilizados para investigar a associação dos sintomas de estresse pós-traumático com a imobilidade tônica peritraumática. Foram consideradas como variáveis de confusão a dissociação peritraumática, as reações físicas de pânico peritraumática, o traço de afeto negativo, o gênero, o tipo de trauma e o tempo de trauma. RESULTADOS: Encontrou-se uma associação significativa entre a imobilidade tônica peritraumática e os sintomas de TEPT em uma amostra não clínica exposta a traumas diversos mesmo quando controlada por variáveis de confusão (β = 1,99; p = 0,017). CONCLUSÕES: Esta reação defensiva que ocorre sob intensa ameaça, apesar de adaptativa para a defesa, pode ter consequências patológicas como sugere sua associação aos sintomas de TEPT.

Análise de pacientes com leucemia mieloide crônica com resistência primária ou secundária ao mesilato de imatinibe / Analysis of chronic myelogenous leukemia patients with primary or secondary resistance to imatinib mesylate

O mesilato de imatinibe, como terapia alvo, se revelou altamente eficiente na leucemia mielóide crônica. Um desafio é a resistência primária ou secundária, principalmente nas fases avançadas da doença. Na secundária, as mutações pontuais no domínio quinase ABL são o mecanismo mais frequente. Estudou-se no período de outubro de 2000 a dezembro de 2005, 112 pacientes no Serviço de Hematologia e Hemoterapia da Santa Casa de São Paulo. O objetivo foi caracterizar o perfil dos resistentes e pesquisar a presença de mutação. Encontrou-se maior porcentagem de resistentes nas fases mais avançadas. Foram fatores de risco para resistência na fase crônica o número de plaquetas superior a 450.000/mm³ pré-imatinibe ou plaquetas inferior a 50.000/mm³ durante o tratamento. A taxa de resposta hematológica completa e o tempo para obtenção foram semelhantes entre os resistentes e não resistentes. Observou-se menor sobrevida global nos resistentes. Destacaram-se dez pacientes resistentes com resposta citogenética completa pós 12 meses, "responsivos tardios", cuja freqüência de resposta hematológica e citogenética foi semelhante aos não resistentes (100 por cento). A sobrevida livre de progressão foi similar até aos 40 meses e a sobrevida global até aos 70 meses. A sobrevida global e as respostas foram superiores aos demais resistentes. Referente à pesquisa de mutação, analisou-se 22 resistentes, dos quais oito apresentaram mutação (36,4 por cento). Caracterizou-se maior risco para a condição de mutação, a presença de blastos no sangue periférico ao diagnóstico nos pacientes em fase crônica.

Imatinib mesylate, as target therapy, is highly efficient in chronic myelogenous leukemia. A challenge is primary and secondary resistance, particularly in the advanced phases of the disease. In secondary resistance, point mutations in the ABL dominion are the most common mechanism. From October 2000 to December 2005, 112 patients were investigated in the Hematology and Hemotherapy Service of Santa Casa of Sao Paulo. The aim was to characterize the profile of resistance and study the presence of the mutation. The majority of resistant patients were in the most advanced phases of the disease. Risk factors for resistance in the chronic phase were a platelet count higher than 450,000/mm3 before imatinib treatment or less than 50,000/mm3 during treatment. The total hematological response rate and the time to achieve this were similar between resistant and non-resistant patients. Lower overall survival was observed with resistance. It was notable that ten resistant patients had complete cytogenetic responses after 12 months (late responses) with both hematological and cytogenetic response rates similar to non-resistant patients (100 percent). Survival free from progression was similar up to 40 months and the overall survival rate was comparable up to 70 months. The overall survival and response to treatment were better than for the other resistant patients. In respect to the investigation of mutations, 22 resistant patients were investigated with eight presenting with the mutation (36.4 percent) The presence of blast cells in the peripheral blood at diagnosis of patients in the chronic phase was characterized as a higher risk factor for this mutation.