GAPi: A description of the initiative for early psychosis intervention in Latin America and the short- to medium-term outcomes in early psychosis patients.

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.

Urban distance to mental healthcare units and public transport increases duration of untreated psychosis in first-episode patients.

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.

Deep Brain Stimulation Surgery Using a Mobile Intraoperative CT Scanner.

Introduction Deep brain stimulation (DBS) is widely used for the treatment of movement disorders. Precise placement of electrodes is critical for treatment success. The aim of this study was to analyze the accuracy of the intraoperative computer tomography (CT) images compared to that of a traditional fixed CT for patients undergoing DBS procedures. Methods We retrospectively analyzed the charts from 30 patients who underwent DBS. In group 1, 10 patients underwent electrode implantation surgery using a fixed CT scanner for pre- and post-operative (OP) images. In group 2, 20 patients underwent surgery using an intraoperative CT scanner for pre- and post-operative images, as well as a fixed CT scanner for post-operative images. We compared the average pre-operative localizer box registration error acquired in these two groups. We also analyzed, in group 2, the final electrode position given on each post-operative CT images. We compared the average Euclidean distances between each set of cartesian coordinates to assess target accuracy between both scanning methodologies. Results Thirty patients had ages ranging from 40 to 88 years, with a median of 69 years old. In the 20 patients who utilized an intraoperative CT scanner pre-operatively in group 2, the mean error, given by the Medtronic software (Medtronic Minimally Invasive Therapies, Minneapolis, MN) with the Leksell frame on, was 0.37. For the 10 pre-operative scans with the stealth fixed CT scanner in group 1, the mean error was 0.44 (p = 0.13). In group 2, the average of the 20 Euclidean distances for each target, in those 20 patients who had post-operative images with both scanners, was 0.36. Conclusion We concluded that the accuracy of the intraoperative CT scanner is comparable to the gold standard fixed CT scanner for DBS electrode planning and placement, as well as for positioning confirmation after the electrodes are in place.

Restoration of a malformed primary incisor using digital technology in a pediatric patient with congenital Zika virus syndrome: A case report.

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.

Differences of affective and non-affective psychoses in early intervention services from Latin America.

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.

Investigating the Dialysis Treatment Using Hollow Fiber Membrane: A New Approach by CFD.

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.

Longitudinal invariance of the positive and negative syndrome scale negative dimension in antipsychotic naïve first-episode schizophrenia.

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.

BDNF in antipsychotic naive first episode psychosis: Effects of risperidone and the immune-inflammatory response system.

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.

A New Design of Tubular Ceramic Membrane Module for Oily Water Treatment: Multiphase Flow Behavior and Performance Evaluation.

Petroleum has been extracted from oil reservoirs using different techniques. This activity is accompanied for a large amount of water and sometimes mixed with gas. This produced water has a high oil concentration and other toxic chemical compounds, thus, it must be treated to be reused or released to environment according to environmental protection regulations. Currently, ceramic membrane technology has been employed in the wastewater treatment, due to its high benefit-cost ratio. In this sense, this work aims to study the oil-water mixture separation process using a new configuration of tubular ceramic membrane module by computational fluid dynamic (ANSYS Fluent software). The proposed model is composed of mass and linear momentum conservation equations coupled to Darcy's law and SST k-ω turbulence model. Results of the volumetric fraction, pressure, and velocity distribution of the oil and water phases are presented and discussed. The results indicated that the proposed model and new device both have great potential to be used on the water/oil separation process and that the transmembrane pressure remains constant in the axial direction and decreases radially through the membranes, indicating an efficient system that favors the transport of clean water and oil retention.

LINE-1 hypomethylation is associated with poor risperidone response in a first episode of psychosis cohort.

Aim: We investigated the DNA methylation profile over LINE-1 in antipsychotic-naive, first-episode psychosis-patients (n = 69) before and after 2 months of risperidone treatment and in healthy controls (n = 62). Materials & methods: Patients were evaluated using standardized scales and classified as responders and nonresponders. DNA from blood was bisulfite converted and LINE-1 fragments were amplified and pyrosequencing was performed. Results: Lower LINE-1 methylation was observed in antipsychotic-naive first-episode psychosis patients than in healthy controls. Lower DNA methylation levels before treatment were associated with poor risperidone responses. A positive correlation was observed between LINE-1 methylation levels and positive symptoms response. Conclusion: Our study brings new insight regarding how epigenomic studies and clinical correlation studies can supplement psychosis treatment.

The Impact of Mental Illness Stigma on Psychiatric Emergencies.

Psychiatric emergencies are severe behavioral changes secondary to worsening mental illness. Such situations present a risk to the patient and other people, so they need immediate therapeutic intervention. They are associated with feelings of fear, anger, prejudice, and even exclusion. The attitudes of professionals and factors related to the workplace culture in health can help to perpetuate stereotypes and interfere with the quality of care. Stigma has undesirable consequences in patients with mental disorders. Certain measures can reduce stigma and provide a more dignified way for patients to recover from the crisis. This article aims to discuss the causes of stigma, ways of dealing with it, and achievements that have been made in psychiatric emergency care settings.

Impact of duration of untreated psychosis in short-term response to treatment and outcome in antipsychotic naïve first-episode psychosis.

AIM: Duration of untreated psychosis (DUP) is one of the few potentially modifiable outcome predictors in psychosis. Previous studies have associated a longer DUP with a poor prognosis, but few of them were performed in countries with low and middle level of income. This study aimed to investigate the DUP in a Brazilian sample of antipsychotic-naïve first-episode psychosis (AN-FEP) patients and its association with clinical characteristics and treatment outcomes in a short-term follow-up. METHODS: One hundred forty-five AN-FEP patients between 16 and 40 years were enrolled and were reassessed 10 weeks after risperidone treatment. We investigated the association between DUP and symptom severity, functionality and response to treatment, using the Positive and Negative Syndrome Scale (PANSS), the Clinical Global Impression-Severity Scale (CGI) and the Global Assessment of Functionality (GAF) scale. DUP was defined as the period between the onset of the first psychotic symptoms and the first effective antipsychotic treatment. For the analysis, we performed multivariate linear regressions. RESULTS: The DUP's median was 61 days. At baseline, we did not find any significant association between DUP and clinical characteristics. After treatment, the longer DUP predicted worse positive and negative symptom dimensions, worse total PANSS, GAF and CGI scores and poorer response to treatment. CONCLUSION: Our results showed that DUP is associated with worse outcomes after short treatment, but it does not modify the baseline clinical profile of the AN-FEP patients. Such results reinforce the need to develop early intervention strategies, reducing DUP.

Endoscopic Versus Microscopic Transcallosal Excision of Colloid Cysts: A Systematic Review in the Era of Complete Endoscopic Excision.

OBJECTIVE: Transcallosal microscopic and endoscopic excisions are both well established approaches to colloid cyst resection; however, there has been no clear consensus regarding the favored approach. We performed a systematic review comparing the transcallosal microscopic and endoscopic transcortical approaches for colloid cyst excision. METHODS: We performed a systematic review from 2000-2018 of patients undergoing colloid cyst excision via a microscopic transcallosal or endoscopic transcortical approach where the surgical intent was gross total resection. Studies that included multiple approaches were included if the reported results were stratified by approach. RESULTS: The microsurgical transcallosal approach had a higher rate of gross total resection when compared with endoscopic excision (96% for transcallosal vs. 78.5% endoscopic; P < 0.0001). There was also a lower recurrence rate with the transcallosal approach (0.98% vs. 2.16%; P = 0.0036); however, there was no difference in reoperation rates with similar length of follow-up (0.33% transcallosal, 0.61% endoscopic; P = 1.000). Endoscopy had lower overall morbidity when compared with transcallosal approaches (8.7% vs. 18.6%; P = 0.0001), including statistically significant lower rates of infection, infarct, and seizures in the endoscopic cohort. Rates of permanent memory deficit were similar (6.55% transcallosal vs. 4.5% endoscopic; P = 0.52). Shunt dependency was 9.8% after transcallosal excision versus 3.5% after endoscopic excision (P = 0.0002). CONCLUSIONS: Modern series of colloid cyst excision continue to favor transcallosal approaches in achieving gross total resection. Nevertheless, endoscopic techniques have significantly reduced morbidity compared to transcallosal approaches, including lower rates of infection, infarct, and seizure. Endoscopic approaches also have a statistically significant decreased rate of shunt dependency-arguably the most important primary endpoint of surgery. With improving endoscopic technology and mastery of the technique, endoscopic excision is maturing into a standard first-line approach for colloid cyst excision.

Role of dorsal raphe nucleus GHS-R1a receptors in the regulation of inhibitory avoidance and escape behaviors in rats.

Ghrelin is a recently discovered peptide, mainly produced in the stomach and involved in body's energy-maintenance processes. Ghrelin exerts its actions by activating the growth hormone secretagogue receptor (GHS-R). Recent analyses indicate that ghrelin targets the brain to regulate a wealth of functions, including behavioral responses that have been associated with stress and anxiety mechanisms. In this context, evidence shows the presence of GHS-R receptors in the dorsal raphe nucleus (DRN), the main source of serotonergic neurons that innervate encephalic structures involved in emotional control. Our study aims to evaluate the effects of the pharmacological manipulation of ghrelin receptors located in the DRN on the expression of the behavioral responses of Wistar rats. Such responses were assessed in the elevated T maze (ETM), an experimental model that allows the measurement, in the same animal, of two defensive tasks, inhibitory avoidance and escape. Our results showed that the intra-DRN infusion of ghrelin impaired the acquisition of inhibitory avoidance, an anxiolytic-like effect, and facilitated the expression of escape response in the ETM, indicating a panicogenic-like effect. The intra-DRN administration of the ghrelin receptor (GHS-R1a) antagonist PF-04628935 did not alter the behavioral tasks assessed in the ETM. Finally, our results revealed that intra-DRN infusions of PF-04628935 prior to the administration of ghrelin into this area neutralized the behavioral effects obtained in the ETM. Taken together, our data reveal the involvement of DRN GHS-R1a receptors in the regulation of defensive tasks that have been associated with generalized anxiety and panic disorders.

Prostatic adenocarcinoma CNS parenchymal and dural metastases: alterations in ERG, CHD1 and MAP3K7 expression.

BACKGROUND: Prostatic carcinoma metastatic to dura is commonly encountered at autopsy, but presenting as a dural or, especially parenchymal, brain metastasis during life is far less common. Our group has been interested in two immunohistochemical (IHC) markers previously shown to be downregulated in particularly aggressive primary prostatic carcinomas: CHD1 and MAP3K7. Here we assess protein expression in clinically-relevant CNS metastases. We also assessed how these two markers correlated with the most common genetic alteration in prostate cancer: TMPRSS2 fusion to ERG (40-60% of carcinomas at the primary site), which places ERG expression under the control of the androgen-regulated TMPRSS2 gene, increasing expression. DESIGN: Database query, 2000-2016, identified 16 metastases to dura, 5 to brain parenchyma. RESULTS: Four of five intraparenchymal metastases and 15/16 informative dural-based metastases were ERG-negative (90.5% overall). There was reduced expression of CHD1 in 8/21 and reduced MAP3K7 in 17/21 cases; 7/19 (37%) ERG-negative metastases had dual low expression of CHD1/MAP3K7. ERG-positive cases had high expression of one or both markers. CONCLUSION: Metastatic prostatic carcinoma to CNS demonstrates expression patterns consistent with particularly aggressive behavior. Lower ERG expression in dural and intraparenchymal metastases suggests a possibility that ERG-negative tumors with loss of MAP3K7 may become resistant to standard therapies and diffusely metastasize.

Cannabis acute use impacts symptoms and functionality in a cohort of antipsychotic naïve First Episode of Psychosis individuals.

INTRODUCTION: Cannabis use increases the risk of developing psychosis, and subjects with psychosis are more likely to use cannabis. However, studies on the influence of cannabis on psychotic dimensions, response to treatment, and functional outcomes showed conflicting results. Such heterogeneity may be due the inclusion of patients who were already under treatment, and lack of specificity in evaluations. We investigated whether cannabis use yields distinct symptom profiles and functionality in a cohort of antipsychotic-naïve patients at first episode of psychosis (FEP). METHODS: This research is part of a prospective cohort study performed in Sao Paulo, Brazil. The baseline assessment was completed by 175 individuals, and 99 of them were reassessed in a ten-week follow up. We investigated the relationship between cannabis exposure variables (acute use, lifetime use and age at first use) and outcomes: symptom dimensions and functioning. RESULTS: Individuals who reported acute use of cannabis had higher excitement symptoms at baseline, higher excitement and positive response rates, but no significant differences at follow-up. Additionally, more days of cannabis use in the last month predicted worse functionality and clinical impression at baseline but not at follow-up. DISCUSSION: The acute use of cannabis influenced the clinical presentation at our FEP baseline assessment, but did not to influence symptoms or functional outcomes at 10-week follow-up. Additionally, acute cannabis users had a better response for excitement and positive symptoms. Higher excitement symptoms at presentation of FEP should raise concerns of possible acute use of cannabis. Longer follow-up times may elucidate whether the effects on functionality would be more evident later in disease development.