The posttraumatic stress disorder project in Brazil: neuropsychological, structural and molecular neuroimaging studies in victims of urban violence

<p>Abstract</p> <p>Background</p> <p>Life trauma is highly prevalent in the general population and posttraumatic stress disorder is among the most prevalent psychiatric consequences of trauma exposure. Brazil has a unique environment to conduct translational research about psychological trauma and posttraumatic stress disorder, since urban violence became a Brazilian phenomenon, being particularly related to the rapid population growth of its cities. This research involves three case-control studies: a neuropsychological, a structural neuroimaging and a molecular neuroimaging study, each focusing on different objectives but providing complementary information. First, it aims to examine cognitive functioning of PTSD subjects and its relationships with symptomatology. The second objective is to evaluate neurostructural integrity of orbitofrontal cortex and hippocampus in PTSD subjects. The third aim is to evaluate if patients with PTSD have decreased dopamine transporter density in the basal ganglia as compared to resilient controls subjects. This paper shows the research rationale and design for these three case-control studies.</p> <p>Methods and design</p> <p>Cases and controls will be identified through an epidemiologic survey conducted in the city of São Paulo. Subjects exposed to traumatic life experiences resulting in posttraumatic stress disorder (cases) will be compared to resilient victims of traumatic life experiences without PTSD (controls) aiming to identify biological variables that might protect or predispose to PTSD. In the neuropsychological case-control study, 100 patients with PTSD, will be compared with 100 victims of trauma without posttraumatic stress disorder, age- and sex-matched controls. Similarly, 50 cases and 50 controls will be enrolled for the structural study and 25 cases and 25 controls in the functional neuroimaging study. All individuals from the three studies will complete psychometrics and a structured clinical interview (the Structured Clinical Interview for DSM-IV and the Clinician-Administered PTSD Scale, Beck Anxiety Inventory, Beck Depression Inventory, Global Assessment of Function, The Social Adjustment Scale, Medical Outcomes Study 36-Item Short-Form Health Survey, Early Trauma Inventory, Clinical global Impressions, and Peritraumatic Dissociative Experiences Questionnaire). A broad neuropsychological battery will be administered for all participants of the neuropsychological study. Magnetic resonance scans will be performed to acquire structural neuroimaging data. Single photon emission computerized tomography with [(99m)Tc]-TRODAT-1 brain scans will be performed to evaluate dopamine transporters.</p> <p>Discussion</p> <p>This study protocol will be informative for researchers and clinicians interested in considering, designing and/or conducting translational research in the field of trauma and posttraumatic stress disorder.</p

Human subcortical brain asymmetries in 15,847 people worldwide reveal effects of age and sex

The two hemispheres of the human brain differ functionally and structurally. Despite over a century of research, the extent to which brain asymmetry is influenced by sex, handedness, age, and genetic factors is still controversial. Here we present the largest ever analysis of subcortical brain asymmetries, in a harmonized multi-site study using meta-analysis methods. Volumetric asymmetry of seven subcortical structures was assessed in 15,847 MRI scans from 52 datasets worldwide. There were sex differences in the asymmetry of the globus pallidus and putamen. Heritability estimates, derived from 1170 subjects belonging to 71 extended pedigrees, revealed that additive genetic factors influenced the asymmetry of these two structures and that of the hippocampus and thalamus. Handedness had no detectable effect on subcortical asymmetries, even in this unprecedented sample size, but the asymmetry of the putamen varied with age. Genetic drivers of asymmetry in the hippocampus, thalamus and basal ganglia may affect variability in human cognition, including susceptibility to psychiatric disorders

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

AI is a viable alternative to high throughput screening: a 318-target study

: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery

Associação do índice tornozelo-braço com inflamação e alterações minerais ósseas em pacientes em hemodiálise Asociación del índice Tobillo-Brazo con la inflamación y trastornos minerales óseos en pacientes en hemodiálisis Association of ankle-arm index with inflammation and mineral bone disorder in hemodialysis patients

FUNDAMENTO: O índice tornozelo-braço (ITB) reduzido, inflamação e distúrbio mineral ósseo (DMO) estão associados com aumento no risco de morte e complicações cardiovasculares em pacientes em hemodiálise (HD), mas a relação entre esses fatores necessita ser elucidada. OBJETIVO: Avaliar a associação entre ITB anormal e DMO com inflamação em pacientes em HD. MÉTODOS: Esta análise transversal avaliou 478 pacientes em HD por pelo menos 1 ano. O ITB foi avaliado através de um Doppler portátil e manômetro de coluna de mercúrio. Os pacientes foram divididos em três grupos, de acordo com o ITB (baixo: <0,9, normal: 0,9 a 1,3, e alto: >1,3). As medidas de proteína C-reativa foram utilizadas como marcador inflamatório, enquanto a DMO foi avaliada através dos níveis de cálcio, fósforo e hormônio paratireoidiano intacto (iPTH). RESULTADOS: Os participantes tinham 54 (18 a 75) anos, 56% eram do sexo masculino, 17% eram diabéticos e estavam em HM por 5 (1 a 35) anos. A prevalência de ITB baixo, normal e alto AAI foi 26,8%, 64,6% e 8,6%, respectivamente. Usando um modelo de regressão logística condicional com procedimento backward, idade (p<0,001), diabetes (p= 0,001), e níveis de proteína C-reativa >6 mg/L (p= 0,006) estavam associados com a presença de ITB baixo, enquanto o sexo masculino (p<0,001), diabetes (p= 0,001) e produto cálcio x fósforo elevado (p= 0,026) estavam associados com ITB alto. CONCLUSÃO: Em pacientes em HD, a presença de diabetes estava associada com ITB alto e baixo. O risco de ter ITB baixo parece aumentar com a idade e inflamação, enquanto a DMO estava associada com ITB alto.<br>FUNDAMENTO: El índice tobillo-brazo (ITB) reducido, la inflamación y el trastorno mineral óseo (TMO) se asocian con mayor riesgo de muerte y complicaciones cardiovasculares en pacientes sometidos a hemodiálisis (HD), pero la relación entre estos factores debe ser aclarada. Objetivos: Evaluar la asociación entre el ITB anormal la TMO con inflamación en paciente en HD. MÉTODOS: Este análisis transversal evaluó a 478 pacientes en HD durante al menos 1 año. El ITB se midió con un Doppler portátil y manómetro de columna de mercurio. Los pacientes fueron divididos en tres grupos, de acuerdo al ITB (bajo: < 0,9, normal: 0,9 a 1,3, y alto: > 1,3). Las mediciones de proteína C-reactiva se utilizaron como marcador inflamatorio, mientras que la TMO se evaluó a través de los niveles de calcio, fósforo y hormona paratiroidea intacta (iPTH). RESULTADOS: Los participantes tenían 54 (18-75) años, el 56% eran del sexo masculino, el 17% eran diabéticos y estaban se encontraban en HD por 5 (1 a 35) años. La prevalencia de ITB bajo, normal y alto ITB fue de un 26,8%, un 64,6% y un 8,6% respectivamente. Al utilizar un modelo de regresión logística condicional con el procedimiento backward (hacia atrás), diabetes (p < 0,001), y niveles de proteína C-reactiva > 6 mg/l (p = 0,006) estaban asociados con la presencia de ITB bajo, mientras que el sexo masculino (p < 0,001), diabetes (p = 0,001) y producto calcio x fósforo elevado (p = 0,026) estaban asociados con ITB alto. CONCLUSIÓN: En los pacientes en HD, la presencia de la diabetes estaba asociada con ITB alto y bajo. El riesgo de tener ITB bajo parece aumentar con la edad y la inflamación, mientras que la TMO estaba asociada con ITB alta. (Arq Bras Cardiol 2011;96(5):405-410)<br>BACKGROUND: Reduced ankle-arm index (AAI), inflammation and mineral bone disorder (MBD) are all associated with increased risk of death and cardiovascular complications in patients on hemodialysis (HD), but the association between them deserves clarification. OBJECTIVE: To evaluate the association between abnormal AAI with MBD and inflammation in patients on HD. METHODS: This was a cross-sectional analysis of 478 patients on hemodialysis for at least one year. The AAI was evaluated using a portable Doppler and mercury column manometer. Patients were divided into 3 groups, according to AAI (low: <0.9, normal: 0.9 to 1.3, and high: >1.3). C-reactive protein measurement was used as an inflammatory marker, whereas MBD was evaluated by calcium, phosphorus and intact parathyroid hormone levels. RESULTS: Participants were 54 (18 to 75) years old, 56% males, 17% diabetics, and had been on hemodialysis for a mean of 5 (1 to 35) years. The prevalence of low, normal and high AAI was 26.8%, 64.6% and 8.6%, respectively. Using a backward conditional logistic regression model, age (p<0.001), diabetes (p= 0.001), and C-reactive protein levels >6 mg/L (p= 0.006) were associated with the presence of low AAI, whereas male gender (p<0.001), diabetes (p= 0.001) and elevated calcium x phosphorus product (p= 0.026) were associated with high AAI. CONCLUSION: In patients on hemodialysis, the presence of diabetes was associated with both low and high AAI. The risk of having low AAI seems to be increased by aging and inflammation, whereas BMD was associated with high AAI

Associação do índice tornozelo-braço com inflamação e alterações minerais ósseas em pacientes em hemodiálise

FUNDAMENTO: O índice tornozelo-braço (ITB) reduzido, inflamação e distúrbio mineral ósseo (DMO) estão associados com aumento no risco de morte e complicações cardiovasculares em pacientes em hemodiálise (HD), mas a relação entre esses fatores necessita ser elucidada. OBJETIVO: Avaliar a associação entre ITB anormal e DMO com inflamação em pacientes em HD. MÉTODOS: Esta análise transversal avaliou 478 pacientes em HD por pelo menos 1 ano. O ITB foi avaliado através de um Doppler portátil e manômetro de coluna de mercúrio. Os pacientes foram divididos em três grupos, de acordo com o ITB (baixo: <0,9, normal: 0,9 a 1,3, e alto: &gt;1,3). As medidas de proteína C-reativa foram utilizadas como marcador inflamatório, enquanto a DMO foi avaliada através dos níveis de cálcio, fósforo e hormônio paratireoidiano intacto (iPTH). RESULTADOS: Os participantes tinham 54 (18 a 75) anos, 56% eram do sexo masculino, 17% eram diabéticos e estavam em HM por 5 (1 a 35) anos. A prevalência de ITB baixo, normal e alto AAI foi 26,8%, 64,6% e 8,6%, respectivamente. Usando um modelo de regressão logística condicional com procedimento backward, idade (p<0,001), diabetes (p= 0,001), e níveis de proteína C-reativa &gt;6 mg/L (p= 0,006) estavam associados com a presença de ITB baixo, enquanto o sexo masculino (p<0,001), diabetes (p= 0,001) e produto cálcio x fósforo elevado (p= 0,026) estavam associados com ITB alto. CONCLUSÃO: Em pacientes em HD, a presença de diabetes estava associada com ITB alto e baixo. O risco de ter ITB baixo parece aumentar com a idade e inflamação, enquanto a DMO estava associada com ITB alto

Preparação e caracterização de carvão ativado quimicamente a partir da casca de arroz

This work consists in a study about the chemical activation of charred rice hulls using NaOH as the activation agent. The influence of the naturally-occurring silica was particularly evidenced. X-ray diffraction patterns showed the formation of sodium carbonate and silicates in the activated samples, whereas thermogravimetric curves revealed a strong reduction in the ash content of these samples after washing with water. Nitrogen adsorption data indicated a microporosity development only in the washed samples, with BET surface area values of 450 and 1380 m²/g achieved for the samples activated at 800 &deg;C starting from the precursor with or without silica, respectively

Structural validity and reliability of the Positive and Negative Affect Schedule (PANAS): Evidence from a large Brazilian community sample

Objective: Positive and negative affect are the two psychobiological-dispositional dimensions reflecting proneness to positive and negative activation that influence the extent to which individuals experience life events as joyful or as distressful. The Positive and Negative Affect Schedule (PANAS) is a structured questionnaire that provides independent indexes of positive and negative affect. This study aimed to validate a Brazilian interview-version of the PANAS by means of factor and internal consistency analysis. Methods: A representative community sample of 3,728 individuals residing in the cities of São Paulo and Rio de Janeiro, Brazil, voluntarily completed the PANAS. Exploratory structural equation model analysis was based on maximum likelihood estimation and reliability was calculated via Cronbach's alpha coefficient. Results: Our results provide support for the hypothesis that the PANAS reliably measures two distinct dimensions of positive and negative affect. Conclusion: The structure and reliability of the Brazilian version of the PANAS are consistent with those of its original version. Taken together, these results attest the validity of the Brazilian adaptation of the instrument