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Patient response to antipsychotic drugs varies and may be related to clinical and genetic heterogeneity. This study aimed to determine the performance of clinical, genetic, and hybrid models to predict the response of first episode of psychosis (FEP). patients to the antipsychotic risperidone. We evaluated 141 antipsychotic-naïve FEP patients before and after 10 weeks of risperidone treatment. Patients who had a response rate equal to or higher than 50% on the Positive and Negative Syndrome Scale were considered responders (n = 72; 51%). Analyses were performed using a support vector machine (SVM), k-nearest neighbors (kNN), and random forests (RF). Clinical and genetic (with single-nucleotide variants [SNVs]) models were created separately. Hybrid models (clinical+genetic factors) with and without feature selection were created. Clinical models presented greater balanced accuracy 63.3% (confidence interval [CI] 0.46-0.69) with the SVM algorithm than the genetic models (balanced accuracy: 58.5% [CI 0.41-0.76] - kNN algorithm). The hybrid model, which included duration of untreated psychosis, Clinical Global Impression-Severity scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84] - RF algorithm). A hybrid model, including clinical and genetic predictors, can provide enhanced predictions of response to antipsychotic treatment.

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INTRODUCTION: Schizophrenia is a debilitating disorder that affects a significant proportion of the population and leads to impaired functionality and long-term challenges. The first episode of psychosis (FEP) is a critical intervention stage for improving long-term outcomes. The GAPi program was established in São Paulo, Brazil to provide early intervention services and evaluate biomarkers in individuals with FEP. This article delineates the objectives of the GAPi program, detailing its innovative research protocol, examining the clinical outcomes achieved, and discussing the operational challenges encountered during its initial decade of operation. METHODS: The study comprised a prospective cohort of antipsychotic-naïve individuals with first-episode psychosis aged between 16 and 35 years. Participants were recruited from a public psychiatric facility in São Paulo. Emphasizing the initiative's commitment to early intervention, clinical assessments were systematically conducted at baseline and at two months, one year, two years, and five years of treatment to capture both short- and medium-term outcomes. Various assessment tools were utilized, including structured interviews, symptom scales, the Addiction Severity Index, and functional assessments. RESULTS: A total of 232 patients were enrolled in the cohort. Among them, 65.95 % completed the 2-month follow-up. Most patients presented with schizophrenia spectrum disorders, followed by bipolar disorder and major depressive disorder with psychotic features. Treatment response rates and remission rates were evaluated at different time points, with promising outcomes observed. The program also assessed socio-demographic factors, substance use, family history, and genetic and biomarker profiles, providing valuable data for research. DISCUSSION: The GAPi program has emerged as the largest ongoing cohort of antipsychotic-naïve first-episode psychosis in Latin America, contributing to the understanding of early psychosis in low- and middle-income countries. Despite operational challenges, the program has demonstrated efficacy in reducing the duration of untreated psychosis and in improving clinical outcomes. A multidisciplinary approach, including pharmacological treatment, psychosocial interventions, and family involvement, has been instrumental in enhancing treatment adherence and long-term prognosis. CONCLUSION: The GAPi program represents a valuable model for early intervention in first-episode psychosis and provides insights into the pathophysiology, treatment, and long-term outcomes of individuals with schizophrenia and related disorders. Continued research and resource allocation are essential for addressing operational challenges and expanding early intervention services in low- and middle-income countries.

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BACKGROUND: There is a growing interest in environmental and social determinants of mental health. However, how distance to healthcare and public transportation affect illness is neglected in schizophrenia research. Here, we are interested in how the availability of mental healthcare and the ways to reach it may be associated with psychosis. AIMS: We aim to investigate the association between distances to healthcare units and subway stations and duration of untreated psychosis (DUP) and greater initial severity in an antipsychotic-naïve first episode of psychosis (FEP) sample. METHOD: Using 212 untreated FEP patients' data, we calculated the distances from their residences to the places of interest. Diagnoses comprehended schizophrenia spectrum disorders, depressive and bipolar affective disorders, and substance-induced disorders. Linear regressions were performed with distances as independent variables, DUP and Positive and Negative Syndrome Scale (PANSS) scores as dependent variables. RESULTS: Longer distance to emergency mental healthcare was related to longer DUP (95% CI: p = .034, B = 0.152) and higher total PANSS (95% CI: p = .007, B = 0.0189); longer distance to community mental healthcare units was related to longer DUP (95% CI: p = .004, B = 0.0204) and higher total PANSS (95% CI: p = .030, B = 0.152). Moreover, a longer distance to the closest subway station predicted longer DUP (95% CI: p = .019, B = 0.170). CONCLUSION: Our results indicate that poor healthcare access is related to longer DUP and higher initial PANSS scores. Future research should investigate how investments in mental health access and actions to improve public transport access could impact DUP and treatment outcomes in psychosis patients.

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Zika virus congenital syndrome (ZVCS) is a congenital viral infection resulting from the transmission of the Zika virus (ZV) to the fetus during pregnancy. This report describes a clinical case involving a 20-month-old female child with ZVCS, who presented with systemic changes related to the syndrome, such as microcephaly, arthrogryposis, ocular and auditory changes, and oral changes such as delayed dental eruption, ogival (high-arched) palate, short lip frenum, and altered morphology of a superior primary incisor. For esthetic and functional rehabilitation of the oral health of this child, an indirect composite resin restoration was performed using intraoral digital scanning technology. This case presents an accurate, rapid, and comfortable restorative treatment option that might result in excellent outcomes in children with ZVCS or similar syndromes with neurological impairment.

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BACKGROUND: Psychosis presentation can be affected by genetic and environmental factors. Differentiating between affective and non-affective psychosis (A-FEP and NA-FEP, respectively) may influence treatment decisions and clinical outcomes. The objective of this paper is to examine differences between patients with A-FEP or NA-FEP in a Latin American sample. METHODS: Patients from two cohorts of patients with a FEP recruited from Brazil and Chile. Subjects included were aged between 15 and 30 years, with an A-FEP or NA-FEP (schizophrenia-spectrum disorders) according to DSM-IV-TR. Sociodemographic data, duration of untreated psychosis and psychotic/mood symptoms were assessed. Generalized estimating equation models were used to assess clinical changes between baseline-follow-up according to diagnosis status. RESULTS: A total of 265 subjects were included. Most of the subjects were male (70.9 %), mean age was 21.36 years. A-FEP and NA-FEP groups were similar in almost all sociodemographic variables, but A-FEP patients had a higher probability of being female. At baseline, the A-FEP group had more manic symptoms and a steeper reduction in manic symptoms scores during the follow- up. The NA-FEP group had more negative symptoms at baseline and a higher improvement during follow-up. All domains of The Positive and Negative Syndrome Scale improved for both groups. No difference for DUP and depression z-scores at baseline and follow-up. LIMITATIONS: The sample was recruited at tertiary hospitals, which may bias the sample towards more severe cases. CONCLUSIONS: This is the largest cohort comparing A-FEP and NA-FEP in Latin America. We found that features in FEP patients could be used to improve diagnosis and support treatment decisions.

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Due to the increase in the number of people affected by chronic renal failure, the demand for hemodialysis treatment has increased considerably over the years. In this sense, theoretical and experimental studies to improve the equipment (hemodialyzer) are extremely important, due to their potential impact on the patient's life quality undergoing treatment. To contribute to this research line, this work aims to study the fluid behavior inside a hollow fiber dialyzer using computational fluid dynamics. In that new approach, the blood is considered as multiphase fluid and the membrane as an extra flow resistance in the porous region (momentum sink). The numerical study of the hemodialysis process was based on the development of a mathematical model that allowed analyzing the performance of the system using Ansys® Fluent software. The predicted results were compared with results reported in the literature and a good concordance was obtained. The simulation results showed that the proposed model can predict the fluid behavior inside the hollow fiber membrane adequately. In addition, it was found that the clearance decreases with increasing radial viscous resistance, with greater permeations in the vicinity of the lumen inlet region, as well as the emergence of the retrofiltration phenomenon, characteristic of this type of process. Herein, velocity, pressure, and volumetric fraction fields are presented and analyzed.

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AIM: Construct stability over time is required for reliable inference, but evidence regarding the longitudinal invariance of negative symptoms is still limited. Thus, we examined the longitudinal invariance of the negative dimension using the positive and negative syndrome scale (PANSS) in an antipsychotic-naïve first-episode schizophrenia sample at baseline and after 10 weeks. METHODS: Our study was conducted at a specialized early intervention service. PANSS ratings were analysed for 138 patients, and two different models were specified and tested: a unidimensional and a two-correlated factor solution. RESULTS: The unidimensional model fulfilled criteria for longitudinal invariance, whilst the two-correlated did not. CONCLUSION: Our study provides support for the PANSS negative unidimensional model use to evaluate negative symptoms' longitudinal change following first-episode schizophrenia.

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Brain-derived neurotrophic factor (BDNF) and the immune-inflammatory response system (IRS) have been implicated in the pathophysiology of schizophrenia. However, no research examined the associations between BDNF and immune activation both before and after treatment in antipsychotic-naïve first episode psychosis (AN-FEP). This study aims to examine serum BDNF levels and their association with IRS and the compensatory immune-regulatory reflex system (CIRS) in AN-FEP before and after risperidone treatment. We included 31 AN-FEP and 22 healthy controls. AN-FEP showed reduced levels of BDNF as compared to controls, and BDNF levels normalized after treatment with risperidone. BDNF levels were inversely correlated with a greater IRS response. Higher levels of IRS/CIRS biomarkers were associated with lower levels of BDNF including M1 macrophage, T-helper (Th)-1, Th-2, and Th-17, and T-regulatory (Treg) cell responses. Our findings indicate that AN-FEP is characterized by decreased levels of BDNF, which are normalized after treatment with risperidone. BDNF levels were inversely associated with activated immune-inflammatory pathways. The findings support the hypothesis that, increased IRS is linked to neurotoxicity, and that a decrease in BDNF may be part of the IRS/CIRS responses in FEP and, thus, be involved in the development of psychosis.

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