Revista Brasileira de Psiquiatria最新文献

{"title":"Cannabis use patterns and different phenotypes in relation to other drugs use: latent class analyses from the Sao Paulo Megacity Mental Health Survey.","authors":"Camila Magalhães Silveira, João Maurício Castaldelli-Maia, Erica Rosanna Siu, Maria Carmen Viana, Yuan-Pang Wang, Laura Helena Andrade","doi":"10.47626/1516-4446-2024-3833","DOIUrl":"https://doi.org/10.47626/1516-4446-2024-3833","url":null,"abstract":"<p><p>Cannabis is the most widely used substance in Brazil. This study examined subtypes of individuals who use cannabis based on usage characteristics and correlates with other substance consumption and harms. Data are from the São Paulo Megacity Mental Health Survey (N = 5,037). Latent class analysis (LCA) was performed considering age of onset, use frequency , tobacco consumption, heavy episodic drinking (HED), alcohol use disorder (AUD) and substance use disorder. Logistic regression assessed class correlates, and further analysis compared socio-demographic, health and behavioral indicators. A 4-class model was optimal for 496 individuals. The 'Polydrug' class (26.2%) and the 'Former' class (5.9%) showed earlier onset and highest frequency of cannabis use, with strongest harm associations. 'Polydrug' class had higher odds of other drug use (OR=3.0), tobacco use (OR=2.5), HED (OR=1.8), and AUD (OR=1.5), compared to lighter-use groups. About 30% of those who use cannabis are at increased risk for negative outcomes, particularly those with early, frequent, and polydrug use patterns. Brazil's public health should prioritize targeted prevention on the risks associated with early and frequent cannabis, and polydrug use. Addressing this at-risk group is essential for harm reduction and a health-focused approach.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639676","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"No changes in plasma Brain-Derived Neurotrophic Factor (BDNF) levels in Treatment-Resistant Depression patients submitted to Convulsive Therapies.","authors":"Leonardo Afonso Dos Santos, Eric Cretaz, Helena Bellini, Adriana Munhoz Carneiro, José Gallucci-Neto, Leda Leme Tallib, André Russowsky Brunoni","doi":"10.47626/1516-4446-2024-3983","DOIUrl":"https://doi.org/10.47626/1516-4446-2024-3983","url":null,"abstract":"<p><strong>Background: </strong>Convulsive therapies are often effective for Treatment-Resistant Depression (TRD), although their mechanisms of action are unclear. Increases in Brain-Derived Neurotrophic Factor (BDNF) levels are observed after Electroconvulsive Therapy (ECT), but more recent evidence calls this claim into question. Moreover, Magnetic Seizure Therapy (MST), a new convulsive technique, has not yet been studied regarding possible neurotrophic modulation.</p><p><strong>Methods: </strong>We performed plasma BDNF measures before and throughout treatment of adult patients (18 to 65 years old) diagnosed with TRD and submitted to treatment with convulsive therapy (ECT or MST) in the arms of the EMCODE project.</p><p><strong>Results: </strong>We enrolled 31 participants (mean age = 38.4 years, SD = 11.88), 14 (45.16%) were submitted to ECT and 17 (54.84%) to MST. Notable improvements in depressive symptoms were observed in both groups, with no significant difference between them (p = 0.1046). Meanwhile, no significant changes in BDNF plasma levels were observed for any technique, pre and post-treatment (MD = -93.01 pg/ml, 95% CI -545.88 to 359.86), or over time (Coefficient = -67.95, SE = 37.75, p = 0.072).</p><p><strong>Conclusion: </strong>The findings suggested no significant changes in plasma BDNF following convulsive therapies, challenging the notion of BDNF as a biomarker for treatment-resistant depression.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-03-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639806","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copy Number Variations in the Brazilian High-Risk Cohort for Mental Conditions.","authors":"Júlia Arendt, Malú Zamariolli, Liriel Almodobar, Lucas Toshio Ito, Rafaella Ormond, Adrielle M Oliveira, Vanessa Ota, Luis Augusto Rohde, Euripedes Constantino Miguel, Pedro Pan, Rodrigo Bressan, Giovanni Salum, Sintia Belangero, Marcos Santoro","doi":"10.47626/1516-4446-2024-3765","DOIUrl":"https://doi.org/10.47626/1516-4446-2024-3765","url":null,"abstract":"<p><p>Copy number variations (CNVs) are genetic variants with a known major impact on the development of mental health disorders (MHDs). Here, we aim to characterize CNVs in a Brazilian cohort regarding frequency and inheritance pattern and verify the impact of CNVs previously associated with MHDs on the risk of developing these disorders in the cohort. A total of 2,250 probands and 3,174 parents (897 trios) from the Brazilian High-Risk Cohort Study for Mental Conditions (BHRCS) were genotyped and CNVs were detected using PennCNV software. In total, 56.03% of the CNVs were inherited. Among the distinct CNVs, 96.15% were rare (frequency lower than 1% in the BHRCS). Duplications at 2q13 and 15q13.3 showed lower frequencies, while those at 2q11.2 and 16p11.2 exhibited higher frequencies in the BHRCS when compared to databases such as the Database of Genomic Variants (DGV) and the Genome Aggregation Database (gnomAD). Of 40 previously associated CNVs with MHDs, 18 were identified in the sample. While the 7q11.2 duplication has been considered protective for Schizophrenia, we identified that 7q11.2 deletion was protective for MHDs in BHRCS (p-value=0.033, OR=0.103). For the other CNVs, no statistical significance was identified, even with mild effect sizes. This is one of the largest CNV studies in a Brazilian sample and will be a valuable resource for future meta-analysis to advance the understanding of the genetics of MHDs, especially regarding diverse populations.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143524160","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Subjective Sleep Quality and Its Subcomponents Among Homeless Individuals in São Paulo.","authors":"Rafael Eduardo Benavides Gélvez, Debora Cristina Hipolide, Julia Ribeiro da Silva Vallim, Juliana Garcia Cespedes, Anderson da Silva Rosa","doi":"10.47626/1516-4446-2024-4078","DOIUrl":"https://doi.org/10.47626/1516-4446-2024-4078","url":null,"abstract":"<p><strong>Objective: </strong>Sleep quality is essential for health, with sleep deprivation linked to physical and mental issues. Homeless populations face additional sleep challenges, yet this topic remains underexplored. This study assessed sleep quality among homeless individuals in São Paulo, Brazil, considering demographics and substance use.</p><p><strong>Methods: </strong>A psychiatrist conducted interviews to collect demographic and substance use data assessing sleep quality using the Pittsburgh Sleep Quality Index (PSQI). A Generalized Linear Model analyzed PSQI scores, considering sleeping location, gender, substance use, and interactions as fixed factors, with homelessness duration as a covariate. The sample comprised 177 participants (22% female, 7 transgenders; mean age: 42.8 ± 11.4 years), with an average homelessness duration of 10.5 ± 8.4 years (range: 1-40). Among them, 33% slept in shelters, 83% used depressants, 83% stimulants, and 59% hallucinogens.</p><p><strong>Results: </strong>Approximately 67% reported good subjective sleep quality (mean PSQI: 4.9 ± 2.7). Depressant and stimulant use correlated with poorer sleep. Women had poorer sleep, longer sleep latency, and greater daytime dysfunction than men.</p><p><strong>Conclusions: </strong>Positive sleep quality reports may reflect adaptive expectations from prolonged adversity and substance use. The findings highlight the need for improved shelters and targeted interventions to address sleep challenges in this vulnerable population.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143639814","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive changes in post-stroke depression patients undergoing treatment with transcranial direct current stimulation (tDCS): an exploratory, ancillary analysis of a randomized, sham-controlled clinical trial.","authors":"Tamires Zanão, Roberta A M P F D Mattar, Bianca S Pinto, Janaina Oliveira, Renata R Vaughan, Isabela M Benseñor, Alessandra Goulart, André R Brunoni, Leandro Valiengo","doi":"10.47626/1516-4446-2024-3847","DOIUrl":"https://doi.org/10.47626/1516-4446-2024-3847","url":null,"abstract":"<p><strong>Objective: </strong>Post-stroke depression (PSD) affects approximately 40% of stroke survivors, with cognitive deficits being frequently observed. Transcranial Direct Current Stimulation (tDCS) has shown promise in improving cognitive performance in stroke patients. We explored the effects of tDCS on cognitive performance in PSD.</p><p><strong>Methods: </strong>An exploratory analysis was conducted in 48 patients from a double-blinded, sham-controlled, randomized clinical trial that investigated the effects of tDCS for treating PSD. A neuropsychological battery was applied at baseline and endpoint. We assessed three key domains: (1) Stroop effect, measured by the Stroop test components (color naming, word-reading and word-color interference); (2) processing speed, assessed using the Trail Making Test and the Digit Symbol coding test; (3) executive function, evaluated with the Digit Span test and the Frontal Assessment Battery (FAB). A Linear mixed regression models were used to evaluate changes according to groups.</p><p><strong>Results: </strong>We found that the active tDCS group worsened slightly, while the sham group improved in Executive Function for the adjusted models. Significant interactions were also found for FAB.</p><p><strong>Conclusions: </strong>We found no consistent evidence that tDCS significantly improved the cognitive domains. The bidirectional association with cognition analysis suggest that tDCS effects may vary based on depression severity and task complexity.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":""},"PeriodicalIF":3.6,"publicationDate":"2025-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142966406","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Higher risks of hyperopia, myopia, astigmatism, and strabismus in children with autism spectrum disorder: a nationwide, population-based cohort study.","authors":"Yi-Lung Chen, Cheng-Fang Yen, Yu-Hung Lai, Ray C Hsiao, Wei-Po Chou","doi":"10.47626/1516-4446-2023-3515","DOIUrl":"10.47626/1516-4446-2023-3515","url":null,"abstract":"<p><strong>Objective: </strong>In this population-based cohort study, we compared the risks of incident hyperopia, myopia, astigmatism, and strabismus between children with autism spectrum disorder (ASD) and those without ASD.</p><p><strong>Methods: </strong>This study included children who were born in Taiwan at any time between 2004 and 2017, using data from the Taiwan Maternal and Child Health Database (TMCHD). We included 20,688 children with ASD and 2,062,120 matched controls to estimate the risks of incident hyperopia, myopia, astigmatism, and strabismus. Cox proportional hazards regression models were conducted for risk assessment. Models were adjusted for sex, calendar year of birth, and gestational age at birth. Statistical significance was determined through adjusted hazard ratios (aHRs) and 95%CIs.</p><p><strong>Results: </strong>Children with ASD had higher risks of incident hyperopia (aHR: 1.78; 95%CI 1.70-1.86), myopia (aHR: 1.27; 95%CI 1.24-1.30), astigmatism (aHR: 1.51; 95%CI 1.46-1.56), and strabismus (aHR: 2.18; 95%CI 2.05-2.32) compared to children without ASD.</p><p><strong>Conclusion: </strong>Clinicians should screen children with ASD for potential eye conditions. Further studies are required to elucidate the mechanisms linking ASD with eye diseases. In addition, studies should explore how the type and severity of ASD symptoms influence the detection of these eye conditions.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":"e20233515"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142294253","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A hybrid model for predicting response to risperidone after first-episode psychosis.","authors":"Giovany Oliveira Costa, Vanessa K Ota, Matheus Rodrigues Luiz, Joice Santos Rosa, Gabriela Xavier, Jessica Honorato-Mauer, Marcos L Santoro, Carolina Muniz Carvalho, Daniel A Cavalcante, Amanda V G Bugiga, Rodrigo A Bressan, Gerome Breen, Ary Gadelha, Cristiano Noto, Diego R Mazzotti, Sintia I Belangero","doi":"10.47626/1516-4446-2024-3608","DOIUrl":"10.47626/1516-4446-2024-3608","url":null,"abstract":"<p><strong>Objective: </strong>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 patients in first-episode psychosis (FEP) to the antipsychotic risperidone.</p><p><strong>Methods: </strong>We evaluated 141 antipsychotic-naive 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 (PANSS) 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.</p><p><strong>Results: </strong>Clinical models presented greater balanced accuracy (63.3%; 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 (CGI-S) scale scores, age, cannabis use, and 406 SNVs, showed the best performance (balanced accuracy: 72.9% [CI 0.62-0.84], RF algorithm).</p><p><strong>Conclusion: </strong>A hybrid model including clinical and genetic predictors can enhance prediction of response to antipsychotic treatment.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":"e20243608"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141793325","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mind the gap: the inconceivable void on the epidemiology of autism spectrum disorders in Brazil.","authors":"Lucas Dellazari, Érica Bonganhi de Bem, Arthur Bezerra Falcão, Felipe de Moura Manjabosco, Gabriela Bezerra Sorato, Laura Fernandes Berto, Vitor Azevedo Dantas, André Luiz Schuh Teixeira da Rosa, Ana Soledade Graeff-Martins, Renata Rocha Kieling, Giovanni Abrahão Salum Junior, Luis Augusto Rohde, Arthur Caye","doi":"10.47626/1516-4446-2024-3956","DOIUrl":"10.47626/1516-4446-2024-3956","url":null,"abstract":"","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":"e20243956"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971973","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A call for greater diversity and representativeness within countries in psychiatric research: lessons and challenges from a systematic review of schizophrenia research in Brazil.","authors":"Thiago Holanda Freitas, Carolina Ziebold, Marcos Leite Santoro, Sintia Iole Nogueira Belangero, Pedro Gabriel Lorencetti, Larissa Medeiros Barros Leal, Gustavo Magalhães de Almeida E Vasconcelos, Lucas de Castro Quarantini, Mateus Jose Abdalla Diniz, Saulo Giovanni Castor Albuquerque, Nayana Holanda de Oliveira, André Luiz de Souza Rodrigues, Ary Gadelha","doi":"10.47626/1516-4446-2024-3834","DOIUrl":"10.47626/1516-4446-2024-3834","url":null,"abstract":"<p><strong>Objective: </strong>To systematically review studies on schizophrenia in Brazil, addressing geographical coverage as an indicator of sampling representativeness - an essential precondition for inferences regarding the generalizability of findings - and, secondarily, of variation in research funding across different regions.</p><p><strong>Methods: </strong>We searched for studies carried out until July 2023. The inclusion criteria were studies of patients diagnosed with schizophrenia (or its spectrum) recruited in Brazil. The following parameters were extracted: geographic region of the first and last authors, recruitment setting, research subfield, and funding sources. This review followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.</p><p><strong>Results: </strong>Of 296 studies reviewed, most (63.18%) took place in the Southeast region, particularly the state of São Paulo (48.98%). Clinical trials comprised the majority (41.6%); genetic studies were primarily conducted in the Southeast or South (81.5%). Funding was reported in 64% of papers. The Northeast region was less likely to receive study funding compared to the Southeast.</p><p><strong>Conclusion: </strong>Schizophrenia research in Brazil shows a clear geographic concentration, with significant disparities in funding allocation and underrepresentation of certain regions. Broadening research coverage through equitable distribution of funding opportunities and fostering collaborations with local institutions are of utmost importance to enhance the understanding and treatment of schizophrenia within Brazil's diverse socioeconomic and ethnic landscape.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":"e20243834"},"PeriodicalIF":2.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142971694","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mental health predictors of Internet Gaming Disorder: a longitudinal study.","authors":"Guilherme Borges, Ricardo Orozco, Raúl Gutierrez-Garcia, Yesica Albor, Ana Lucía Jiménez Pérez, Karla Patrica Valdés-García, Patricia M Baez Mansur, María Anabell Covarrubias Dýaz-Couder, Corina Benjet","doi":"10.47626/1516-4446-2024-3816","DOIUrl":"10.47626/1516-4446-2024-3816","url":null,"abstract":"<p><strong>Objective: </strong>We investigated whether a wide range of baseline mental disorders among university students predict Internet gaming disorder (IGD) 1 to 3 years later.</p><p><strong>Methods: </strong>This prospective cohort study was conducted in six Mexican universities and had a 1- to 3-year follow-up period (September 2018 to June 2022). Participants were 1st-year university students (n=2,144) free of symptoms indicative of IGD at entry (baseline). Ten mental disorders (bipolar, major depressive disorder, generalized anxiety disorder, panic disorder, alcohol use disorder, drug use disorder, binging and/or purging, intermittent explosive disorder, psychotic experiences, and attention deficit hyperactivity disorder) at baseline were investigated as risk factors for IGD at the end of the follow-up. We used Cox regression to model the IGD incidence rate.</p><p><strong>Results: </strong>Any baseline mental disorder was associated with a 2.33 times (1.26-4.31) higher rate of IGD 1 to 3 years later. Several individual disorders were associated with rates of IGD in multiple models, with comorbid conditions diminishing most of these associations.</p><p><strong>Conclusion: </strong>Only major depressive disorder and bipolar disorder remained associated with new cases of IGD. The discrepant results of longitudinal studies on the role of specific mental disorders in the development of IGD should be further investigated.</p>","PeriodicalId":21244,"journal":{"name":"Revista Brasileira de Psiquiatria","volume":" ","pages":"e20243816"},"PeriodicalIF":3.6,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142352903","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}