Psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A)

Objective: Sleep disturbances play a fundamental role in the pathophysiology posttraumatic stress disorder (PTSD), and are not only a secondary feature. The aim of this study was to validate and assess the psychometric properties of the Brazilian version of the Pittsburgh Sleep Quality Index Addendum for PTSD (PSQI-A-BR), a self-report instrument designed to assess the frequency of seven disruptive nocturnal behaviors, in a sample of participants with and without PTSD. Methods: PSQI-A was translated into Brazilian Portuguese and applied to a convenience sample of 190 volunteers, with and without PTSD, who had sought treatment for the consequences of a traumatic event. Results: The PSQI-A-BR displayed satisfactory internal consistency (Cronbach's coefficient of 0.83 between all items) and convergent validity with the Clinician Administered PTSD Scale (CAPS), even when excluding sleep-related items (r = 0.52). Test-retest yielded high agreement in the global PSQI-A-BR, with good stability over time (r = 0.88). A global PSQI-A-BR cutoff score of 7 yielded a sensitivity of 79%, specificity of 64%, and a global score of 7 yielded a positive predictive value of 93% for discriminating participants with PTSD from those without PTSD. Conclusion: The PSQI-A-BR is a valid instrument for PTSD assessment, applicable to both clinical and research settings.Universidade Federal de São Paulo (UNIFESP) Department of PsychiatryUniversity of Pittsburgh School of Medicine Department of PsychiatryUniversidade Federal de São Paulo (UNIFESP) Department of PsychobiologyUNIFESP, Department of PsychiatryUNIFESP, Department of PsychobiologySciEL

Schizophrenia and work: aspects related to job acquisition in a follow-up study

Objective: Work is considered one of the main forms of social organizationhowever, few individuals with schizophrenia find work opportunities. The purpose of this study was to evaluate the relationship between schizophrenia symptoms and job acquisition. Method: Fifty-three individuals diagnosed with schizophrenia from an outpatient treatment facility were included in an 18-month follow-up study. After enrollment, they participated in a prevocational training group. At the end of training (baseline) and 18 months later, sociodemographic, clinical data and occupational history were collected. Positive and negative symptoms (Positive and Negative Syndrome Scale - PANSS), depression (Calgary Depression Scale), disease severity (Clinical Global Impression - CGI), functionality (Global Assessment of Functioning - GAF), personal and social performance (Personal and Social Performance - PSP) and cognitive functions (Measurement and Treatment Research to Improve Cognition in Schizophrenia - MATRICS battery) were applied at baseline and at the end of the study. Results: Those with some previous work experience (n = 19) presented lower scores on the PANSS, Calgary, GAF, CGI and PSP scales (p < 0.05) than those who did not work. Among those who worked, there was a slight worsening in positive symptoms (positive PANSS). Conclusions: Individuals with less severe symptoms were more able to find employment. Positive symptom changes do not seem to affect participation at workhowever, this calls for discussion about the importance of employment support.Programa de Esquizofrenia (PROESQ)Centro de Atencao Integrada a Saude Mental (CAISM)Fundacao de Amparo a Pesquisa do Estado de Sao Paulo (FAPESP) [2011/50740-5]Coordenacao de Aperfeicoamento de Pessoal de Nivel Superior (CAPES)FAPESPConselho Nacional de Desenvolvimento Cientifico e Tecnologico (CNPq)CAPESUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Carlos UFSCar, Dept Med, Sao Carlos, SP, BrazilUniv Fed Sao Carlos, Dept Terapia Ocupac, Sao Carlos, SP, BrazilFac Ciencias Med Santa Casa Sao Paulo, Dept Psiquiatria, Sao Paulo, SP, BrazilUniv Fed Sao Paulo UNIFESP, Dept Psiquiatria, Sao Paulo, SP, BrazilFAPESP [2011/50740-5]Web of Scienc

Current and future chemotherapy for Chagas disease

Luís Gaspar is thankful to FCT for funding (scholarship reference: SFRH/BD/81604/2011). The research leading to these results has received funding from the European Community’s Seventh Framework Programme under grant agreement No.602773 (Project KINDRED) and No. 603240 (Project NMTrypI).American trypanosomiasis, commonly called Chagas disease, is one of the most neglected illnesses in the world and remains one of the most prevalent chronic infectious diseases of Latin America with thousands of new cases every year. The only treatments available have been introduced five decades ago. They have serious, undesirable side effects and disputed benefits in the chronic stage of the disease – a characteristic and debilitating cardiomyopathy and/or megavisceras. Several laboratories have therefore focused their efforts in finding better drugs. Although recent years have brought new clinical trials, these are few and lack diversity in terms of drug mechanism of action, thus resulting in a weak drug discovery pipeline. This fragility has been recently exposed by the failure of two candidates, posaconazole and E1224, to sterilely cure patients in phase 2 clinical trials. Such setbacks highlight the need for continuous, novel and high quality drug discovery and development efforts to discover better and safer treatments. In this article we will review past and current findings on drug discovery for Trypanosoma cruzi made by academic research groups, industry and other research organizations over the last half century. We will also analyze the current research landscape that is now better placed than ever to deliver alternative treatments for Chagas disease in the near futurePostprintPeer reviewe

Childhood Sexual Abuse and Indicators of Immune Activity: A Systematic Review

Background: Childhood sexual abuse (CSA) is a prevalent subtype of early life stress associated with changes in immunological and neuroendocrine systems leading to inflammatory responses of the organism and increasing several inflammatory and immune markers. We aimed to conduct a systematic review concerning the association between CSA and indicators of immune activity.Methods: We conducted a search for articles in PubMed, Scopus, PsycINFO, and Web of Science, using the key words: (“Child sexual abuse” OR “childhood maltreatment” OR “sexual violence” OR “posttraumatic stress disorder” OR “rape”) AND (“cytokines” OR “inflammatory markers” OR “interleukin” OR “tumor necrosis factor” OR “C-reactive protein”). PRISMA guidelines were used in order to improve the quality of this research, and MeSH terms were used in PubMed.Results: A total of 3,583 studies were found and, after application of the exclusion criteria, 17 studies were included in this review. Most studies reported an increase of inflammatory activity associated with the presence of early abuse. IL-6, TNF- α, and C-reactive protein were the most frequently analyzed markers and some studies showed higher levels in individuals that suffered CSA compared with controls, although the results were heterogeneous, as was the assessment of CSA, repeated trauma, and time of occurrence. It was not possible to perform a meta-analysis because the results were diversified.Conclusion: CSA is associated with changes in inflammatory markers levels. Improving the assessment of subtypes of trauma is important to further understand the complex correlations of CSA and its biological consequences such as psychiatric and physical illness in later life

Blocking Zika virus vertical transmission.

The outbreak of the Zika virus (ZIKV) has been associated with increased incidence of congenital malformations. Although recent efforts have focused on vaccine development, treatments for infected individuals are needed urgently. Sofosbuvir (SOF), an FDA-approved nucleotide analog inhibitor of the Hepatitis C (HCV) RNA-dependent RNA polymerase (RdRp) was recently shown to be protective against ZIKV both in vitro and in vivo. Here, we show that SOF protected human neural progenitor cells (NPC) and 3D neurospheres from ZIKV infection-mediated cell death and importantly restored the antiviral immune response in NPCs. In vivo, SOF treatment post-infection (p.i.) decreased viral burden in an immunodeficient mouse model. Finally, we show for the first time that acute SOF treatment of pregnant dams p.i. was well-tolerated and prevented vertical transmission of the virus to the fetus. Taken together, our data confirmed SOF-mediated sparing of human neural cell types from ZIKV-mediated cell death in vitro and reduced viral burden in vivo in animal models of chronic infection and vertical transmission, strengthening the growing body of evidence for SOF anti-ZIKV activity

Análise do teor e da qualidade dos lipídeos presentes em sementes de oleaginosas por rmn de baixo campo

To choose among the variety of oleaginous plants for biodiesel production, the oil content of several matrices was determined through different low-field ¹H nuclear magnetic resonance (NMR) experiments with varied pulse sequences, namely single-pulse, spin-echo, CPMG, and CWFP. The experiments that involved the first three sequences showed high correlation with each other and with the solvent extraction method. The quality of the vegetable oils was also evaluated on the basis of the existing correlation between the T2 values of the oils and their properties, such as viscosity, iodine index, and cetane index. These analyses were performed using HCA and PCA chemometric tools. The results were sufficiently significant to allow separation of the oleaginous matrices according to their quality. Thus, the low-field ¹H NMR technique was confirmed as an important tool to aid in the selection of oleaginous matrices for biodiesel production

Author Correction: Blocking Zika virus vertical transmission.

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Automated Nuclear Analysis of Leishmania major Telomeric Clusters Reveals Changes in Their Organization during the Parasite's Life Cycle

Parasite virulence genes are usually associated with telomeres. The clustering of the telomeres, together with their particular spatial distribution in the nucleus of human parasites such as Plasmodium falciparum and Trypanosoma brucei, has been suggested to play a role in facilitating ectopic recombination and in the emergence of new antigenic variants. Leishmania parasites, as well as other trypanosomes, have unusual gene expression characteristics, such as polycistronic and constitutive transcription of protein-coding genes. Leishmania subtelomeric regions are even more unique because unlike these regions in other trypanosomes they are devoid of virulence genes. Given these peculiarities of Leishmania, we sought to investigate how telomeres are organized in the nucleus of Leishmania major parasites at both the human and insect stages of their life cycle. We developed a new automated and precise method for identifying telomere position in the three-dimensional space of the nucleus, and we found that the telomeres are organized in clusters present in similar numbers in both the human and insect stages. While the number of clusters remained the same, their distribution differed between the two stages. The telomeric clusters were found more concentrated near the center of the nucleus in the human stage than in the insect stage suggesting reorganization during the parasite's differentiation process between the two hosts. These data provide the first 3D analysis of Leishmania telomere organization. The possible biological implications of these findings are discussed

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