A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis.

OBJECTIVES: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. METHODS: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. RESULTS: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). CONCLUSION: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

A dopamine receptor D2 genetic polymorphism associated with transition to mental disorders in a cohort of individuals with at-risk mental state for psychosis

Objectives: To test the association of 45 single nucleotide polymorphisms (SNPs) with transition to psychiatric disorders in a cohort of individuals at ultrahigh risk (UHR) mental state for psychosis. Methods: Through general population screening, 88 non-help-seeking UHR subjects and 130 healthy control individuals were genotyped for 45 SNPs related to psychosis. They were followed for a mean of 2.5 years, and conversion to psychotic and to general psychiatric disorders was assessed. Genotype frequencies between controls, converters, and non-converters were analyzed. Results: There were no differences in sociodemographics between controls and UHR. Also, UHR converters and non-converters had no differences in their baseline symptoms scores. The dopamine receptor D2 gene (DRD2) SNP rs6277 was significantly more common among UHR who transitioned to psychosis (p < 0.001) and to UHR who transitioned to any psychiatric disorders (p = 0.001) when compared to UHR who did not transition. The rs6277 T allele was related to psychiatric morbidity in a dose-response fashion, being significantly more frequent in UHR converters than UHR non-converters and control subjects (p = 0.003). Conclusion: Our findings suggest that rs6277 could potentially constitute a genetic marker of transition to psychiatric disorders in subjects with at-risk mental states, warranting further investigation in larger samples.

Motion energy analysis during speech tasks in medication-naïve individuals with at-risk mental states for psychosis.

Movement abnormalities are commonly observed in schizophrenia and at-risk mental states (ARMS) for psychosis. They are usually detected with clinical interviews, such that automated analysis would enhance assessment. Our aim was to use motion energy analysis (MEA) to assess movement during free-speech videos in ARMS and control individuals, and to investigate associations between movement metrics and negative and positive symptoms. Thirty-two medication-naïve ARMS and forty-six healthy control individuals were filmed during speech tasks. Footages were analyzed using MEA software, which assesses movement by differences in pixels frame-by-frame. Two regions of interest were defined-head and torso-and mean amplitude, frequency, and coefficient of variability of movements for them were obtained. These metrics were correlated with the Structured Interview for Prodromal Syndromes (SIPS) symptoms, and with the risk of conversion to psychosis-inferred with the SIPS risk calculator. ARMS individuals had significantly lower mean amplitude of head movement and higher coefficients of movement variability for both head and torso, compared to controls. Higher coefficient of variability was related to higher risk of conversion. Negative correlations were seen between frequency of movement and most SIPS negative symptoms. All positive symptoms were correlated with at least one movement variable. Movement abnormalities could be automatically detected in medication-naïve ARMS subjects by means of a motion energy analysis software. Significant associations of movement metrics with symptoms were found, supporting the importance of movement analysis in ARMS. This could be a potentially important tool for early diagnosis, intervention, and outcome prediction.

Cognitive Patterns and Conversion in a Representative Sample of Individuals at Risk for Psychosis.

ABSTRACT: Clinical high-risk (CHR) individuals belong to a heterogeneous group, of which only a few will cross the threshold for a clinical diagnosis. Cognitive disturbances are present in CHR subjects and may be indicative of transition. Our study aims to identify such deficits in a representative CHR for psychosis sample. Our sample comprised 92 CHR individuals and 54 controls from a representative cohort of the general population. They were followed up for a mean of 2.5 years, with 15 individuals converting to schizophrenia or other Diagnostic and Statistical Manual of Mental Disorders, 5th Edition diagnoses. Neurocognitive assessment was performed with the University of Pennsylvania Computerized Neuropsychological Testing, and CHR status was assessed with the Structured Interview for Prodromal Syndromes (SIPS). Baseline scores were entered in a latent profile analysis model. Our study brought forward a four-class model on cognitive performance. One class displayed better performance, whereas the other three performed worse, all compared with controls. The class with lower executive function also had the highest score on disorganized communication (SIPS P5 = 1.36, p < 0.05), although unrelated to conversion. Among the low performers, the class significantly related to conversion (p = 0.023) had the highest score in decreased expression of emotion (SIPS N3 = 0.85, p < 0.05). Our study brings new and relevant data on non-help-seeking CHR individuals and the relationship between cognitive patterns and conversion. We have highlighted a specific cognitive signature, associated with negative symptoms, which represents a stable trait with presumed lower conversion to a psychiatric illness.

Use of a Bayesian Network Model to predict psychiatric illness in individuals with 'at risk mental states' from a general population cohort.

The 'at risk mental state' (ARMS) paradigm has been introduced in psychiatry to study prodromal phases of schizophrenia. With time it was seen that the ARMS state can also precede mental disorders other than schizophrenia, such as depression and anxiety. However, several problems hamper the paradigm's use in preventative medicine, such as varying transition rates across studies, the use of non-naturalistic samples, and the multifactorial nature of psychiatric disorders. To strengthen ARMS predictive power, there is a need for a holistic model incorporating-in an unbiased fashion-the small-effect factors that cause mental disorders. Bayesian networks, a probabilistic graphical model, was used in a populational cohort of 83 ARMS individuals to predict conversion to psychiatric illness. Nine predictors-including state, trait, biological and environmental factors-were inputted. Dopamine receptor 2 polymorphism, high private religiosity, and childhood trauma remained in the final model, which reached an 85.51% (SD = 0.1190) accuracy level in predicting conversion. This is the first time a robust model was produced with Bayesian networks to predict psychiatric illness among at risk individuals from the general population. This could be an important tool to strengthen predictive measures in psychiatry which should be replicated in larger samples to provide the model further learning.

Asymmetric Cation-Olefin Monocyclization by Engineered Squalene-Hopene Cyclases.

Squalene-hopene cyclases (SHCs) have great potential for the industrial synthesis of enantiopure cyclic terpenoids. A limitation of SHC catalysis has been the enzymes' strict (S)-enantioselectivity at the stereocenter formed after the first cyclization step. To gain enantio-complementary access to valuable monocyclic terpenoids, an SHC-wild-type library including 18 novel homologs was set up. A previously not described SHC (AciSHC) was found to synthesize small amounts of monocyclic (R)-γ-dihydroionone from (E/Z)-geranylacetone. Using enzyme and process optimization, the conversion to the desired product was increased to 79 %. Notably, analyzed AciSHC variants could finely differentiate between the geometric geranylacetone isomers: While the (Z)-isomer yielded the desired monocyclic (R)-γ-dihydroionone (>99 % ee), the (E)-isomer was converted to the (S,S)-bicyclic ether (>95 % ee). Applying the knowledge gained from the observed stereodivergent and enantioselective transformations to an additional SHC-substrate pair, access to the complementary (S)-γ-dihydroionone (>99.9 % ee) could be obtained.

Influence of migration on the thought process of individuals at ultra-high risk for psychosis

Objective: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. Methods: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. Results: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. Conclusions: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

Influence of migration on the thought process of individuals at ultra-high risk for psychosis.

OBJECTIVE: To assess the influence of migration on the psychopathological presentation of individuals at ultra-high risk for psychosis (UHR) in São Paulo, Brazil. METHODS: This study is part of the Subclinical Symptoms and Prodromal Psychosis (SSAPP) project, a cohort study in São Paulo, Brazil, designed to follow individuals at UHR. After screening with the Prodromal Questionnaire (PQ) and a clinical interview, the Global Assessment of Functioning (GAF) was administered, a neuropsychological assessment was performed, sociodemographic and migration data were obtained. We then analyzed UHR individuals who had migration data to see if migration had any effect on their cognition and psychopathology. Chi-square tests were used for categorical variables, and Student's t test or analysis of variance (ANOVA) were used for nonparametric and parametric distributions, respectively. RESULTS: The sample was composed of 42 at-risk subjects, of whom 5 had a migration history in the past two generations. Those with migration history showed significantly more formal thought disturbances (p = 0.012) and sleeping problems (p = 0.033) compared to those without. CONCLUSIONS: Our data reinforce migration as a risk factor for psychosis in developing countries as well, and highlights the importance of studying the specific effect of this factor in UHR psychopathology.

Relationship Between Symptomatic Dimensions and Global Functioning of Non-Help-Seeking Individuals at Risk for Psychosis.

This study aims to analyze the relationship between the symptomatic dimensions of psychosis and functioning of individuals at risk for psychosis (ultrahigh risk [UHR]) in a non-help-seeking UHR sample from the general population. The sample is the same as the one used in the Brazilian Subclinical Symptoms and Prodromal Psychosis cohort study. We applied questionnaires of functioning (Global Assessment of Functioning Scale) and symptomatic dimensions (Scale of Prodromal Symptoms). Next, we correlated the symptomatic dimensions with functioning. We found a significant relationship between avolition and uncommon thought content with poor functioning, whereas the remaining symptoms were not as relevant. Poor functioning was most related to avolition, a negative symptom, followed by unusual thought content, a positive symptom.

Childhood maltreatment in individuals at risk of psychosis: Results from the Brazilian SSAPP cohort.

BACKGROUND: Childhood maltreatment is a known risk factor for the development of mental disorders, such as psychotic symptoms. An extensive body of literature about childhood maltreatment and mental health has been developed in wealthy countries, but information about this connection is lacking in developing countries. AIMS: To explore a possible relationship between childhood maltreatment and ultra-high risk of psychosis in a non-help-seeking population in a low- and middle-income country. METHODS: A household survey was conducted in Sao Paulo, Brazil, involving over 2,500 individuals aged 18-30 years who were randomly selected from the general population. The participants underwent screening with the Prodromal Questionnaire. Ultra-high risk status was assessed using the Structured Interview for Prodromal Syndromes, and childhood maltreatment was assessed using the Childhood Trauma Questionnaire. The final sample comprised 87 ultra-high risk individuals and 115 controls. RESULTS: Childhood maltreatment was significantly more present among ultra-high risk individuals. In ultra-high risk individuals, physical and emotional neglect were inversely related to grandiosity symptoms, physical abuse was related to perceptual abnormalities and physical neglect was related to disorganized speech and thought. CONCLUSION: This is the first study to investigate the relationship between childhood maltreatment and ultra-high risk status and psychopathological features in a large Latin American sample. Further studies in this field are necessary to better understand the specific influence of various early life adversities on psychosis risk.

Simultaneous hydrolysis of cheese whey and lactulose production catalyzed by ß-galactosidase from Kluyveromyces lactis NRRL Y1564.

ß-Galactosidase was produced by the yeast Kluyveromyces lactis NRRL Y1564 in cheese whey supplemented with yeast extract under the optimal temperature of 30 °C, delivering an enzymatic activity of 4418.37 U/gcell after 12 h of process. In order to develop more stable biocatalysts, the enzyme produced by fermentation was immobilized on 2.0% w/v chitosan activated with glutaraldehyde, epichlorohydrin or glycidol, producing a highly active and stable biocatalyst capable of hydrolyzing lactose and producing lactulose simultaneously. The biocatalyst obtained by immobilization in chitosan-glutaraldehyde showed high storage stabilities (100% of its activity when stored at 4 °C 105 days). Regarding the milk lactose hydrolysis by both the soluble and the immobilized enzyme, the conversions obtained were 38.0% and 42.8%, respectively. In this study, by using a biocatalyst deriving from enzyme immobilization to chitosan support, a lactulose production of 17.32 g/L was also possible.

Hearing spirits? Religiosity in individuals at risk for psychosis-Results from the Brazilian SSAPP cohort.

In the last decades, biological and environmental factors related to psychosis were investigated in individuals at ultra-risk for psychosis (UHR) to predict conversion. Although religion relates to psychosis in a variety of ways, it is understudied in subclinical samples. Therefore, we assessed the interplay between religion and prodromal symptoms in 79 UHR and 110 control individuals. They were interviewed with the Duke University Religion Index and the Structured Interview for Prodromal Syndromes (SIPS). Organizational religious activity, a measure of how often someone attends churches/temples, was positively related to perceptual abnormalities/hallucinations (Spearman's rho = 0.262, p = 0.02). This relationship was replicated in a path analysis model (ß = 0.342, SE = 0.108, p = 0.002), as well as a link between organizational religious activity and lower ideational richness (ß = 0.401, SE = 0.105, p = 0.000) with no influence of sex, age, religious denomination, or socioeconomic class. Intrinsic religious activity was negatively correlated with suspiciousness (SIPS P2) (ß = -0.028, SE = 0.009, p = 0.002), and non-organizational religious activity was correlated with higher ideational richness (N5) (ß = -0.220, SE = 0.097, p = 0.023). We hypothesize that subjects with subclinical psychosis may possibly use churches and other religious organizations to cope with hallucinations. Indeed, Brazil is characterized by a religious syncretism and a strong influence of Spiritism in the popular culture. The mediumistic idea that some might be able to hear and/or see spirits is probably employed to explain subclinical hallucinations in the lay knowledge. Our results emphasize the importance of assessing religion and other region-specific aspects of various cultures when studying UHR individuals. This sort of assessment would enhance understanding of differences in conversion rates, and would help to transpose prevention programs from high-income countries to other settings.

Poverty, low education, and the expression of psychotic-like experiences in the general population of São Paulo, Brazil.

The aim of our study was to assess psychotic-like experiences in the general population aged 18-30 years old of the city of São Paulo, Brazil. A household survey was conducted with 1950 young-adults randomly drawn from the city's general population. The validated 92-item Portuguese version of the Prodromal Questionnaire (PQ) was used for face-to-face interviews. Latent class analysis was conducted. Mean age was of 24 years; 51.1% of the sample was of women. Mean total score on the PQ was 22.06 (SD=17.16). Considering a suggested cut-off of 14 in the positive subscale, 30.8% of individuals were above the threshold for ultra-high risk for psychosis detection. Latent class analysis resulted in a three classes clusterization. Class 1 (20%; n=390) had the highest overall PQ scores (mean=49.31,SD=10.783), class 2 (43%; n=835) had intermediate scores (mean=23.37,SD=6.56), and class 3 (37%; n=721) had the lowest scores (mean=5.81,SD=3.74). Class 1 had significantly more individuals with less education and significantly more individuals with lower socioeconomic class. Poverty and low education might be associated with the psychotic expression in the general population, amplifying their actions on the psychosis gradient in developing countries. The psychosis continuum might be constituted by three distinct quantitatively different classes.

Conduta cirúrgica do derrame pleural parapneumônico em adultos / Surgical treatment for parapneumonic pleural effusion in adults

Cerca de 40% dos pacientes portadores de pneumoniadesenvolverão derrame pleural parapneumônico (DPP), o que está associado a considerável morbimortalidade. O DPP possui três fases: exsudativa, fibrino-purelenta e de organização, que representam o progresso da doença. Apesar das várias opções de tratamento existentes, a conduta terapêutica não está bemestabelecida, visto que para cada fase a eficácia de cada método é variável. Procurou-se, nesta revisão de literatura, analisar as diversas opções disponíveis e os critérios que determinam suaindicação. De modo geral, o uso da toracocentese terapêutica deve ser restrito a casos de DPP simples pequenos, que ocupam até metade do hemitórax. Já a toracostomia com drenagem fechada apresenta indicação mais ampla: DPP simples volumosos ouDPP complicados e empiema livres na cavidade. Para tais casos com múltiplas loculações, a decorticação vídeo-assistida (VATS) constitui o tratamento ideal. Por fim, a decorticação por toracotomia está indicada em casos mais crônicos com encarceramentopulmonar, embora existam evidências de que a VATS também pode ser empregada nesses casos e, em caso de necessidade, convertida no intra-operatório para toracotomia. Em relação aos agentes fibrinolíticos, os dados existentes sobre sua eficácia sãocontraditórios, de modo que seu uso ainda é restrito...

At least, 40% of all patients with pneumonia will have a parapneumonic pleural effusion (PPE), which is associated to considerable morbidity and mortality. The PPE has three phases: exsudative, fibrinopurulent and organizing, which represent the development of the disease. Despite the great number of therapeutic methods, the PPE management is not well established, because for each phase the success rate of each technique is variable. The objective of this review of literature was to analyzeeach method available and its indications. Briefly, the use oftherapeutic thoracocentesis is restricted to small simple PPE, which are limited to half of the hemithorax. On the other hand, tube thoracostomy has a wider indication: large simple effusions and free-flowing complicated PPE or empyema. For multiloculated cases, the Video-assisted Thoracoscopic Surgery (VATS) is recommendable. Finally, the decortication through thoracotomy isindicated for chronic cases with lung entrapment, although there areevidences that VATS can be used too and, if needed, converted tothoracotomy in the operation room. Regarding thrombolytics, the data available about its efficacy is controversial, thereby its use isstill very restricted...

Cardiothoracic Surgery League from University of São Paulo Medical School: twelve years in medical education experience / Doze anos de experiência em Educação Médica da Liga de Cirurgia Cardiotorácica da Universidade de São Paulo

INTRODUCTION: Academic Leagues (Academic Interest Group) are entities that belong to medical schools and their hospitals. Their goals are research, medical education and health care. The cardiothoracic Surgery League (Liga de Cirurgia Cardiotorácica - LCCT), University of São Paulo Medical School, was founded 12 years ago, aimed at providing undergraduate medical students an opportunity to expand knowledge in cardiothoracic surgery and to take part in scientific studies in the field. OBJECTIVE: To evaluate the experience gained through LCCT implementation. METHODS: Current students and former members of LCCT were submitted to a specific evaluation form, delivered personally or by email, which provided data on the general opinion regarding LCCT's activities, the reasons for answers provided and choice of medical specialties. Furthermore, LCCT's total scientific production was evaluated. Results: Most undergraduate medical students 51/65 (78.5 percent) and former members 94/121 (77.7 percent) completed the form. The interest in Cardiothoracic Surgery was the most common reason for joining LCCT 44/161 (27.3 percent). Most students 32/51 (62.7 percent) - reported their initial expectations were partially met. Almost every member would recommend a fellow medical student to join LCCT 50/51 (98 percent) and 25/51 (49 percent) of them participated in a scientific project linked to LCCT. In total, 47 scientific papers were published having LCCT's medical students as authors or co-authors during the existence of the league. Of the former members who chose a surgical career, 7/52 (13.4 percent) chose thoracic or cardiovascular surgery. CONCLUSION: LCCT has met its goals, since most current and former members recognized its role in their medical training, besides it is a good way to produce scientific initiation.

INTRODUÇÃO: Ligas acadêmicas são entidades pertencentes a faculdades de Medicina e seus hospitais. Compartilham os objetivos: pesquisa, ensino e assistência à saúde. Há doze anos, fundou-se a Liga de Cirurgia Cardiotorácica (LCCT) pela Faculdade de Medicina da USP, com o objetivo de fornecer aos estudantes de Medicina a oportunidade de ter conhecimento mais profundo em Cirurgia Cardiovascular e para participar de iniciação científica nesse campo. OBJETIVO: Avaliar a experiência adquirida nos 12 anos de existência da LCCT. Métodos: Membros atuais e antigos da LCCT responderam a um formulário entregue pessoalmente ou por e-mail, fornecendo opinião geral (e suas razões) sobre atividades da LCCT e escolha de especialidades médicas. O total de produção científica da LCCT foi também contabilizado. RESULTADOS: A maioria dos atuais estudantes 51/65 (78,5 por cento) e ex-membros 94/121 (77,7 por cento) respondeu ao formulário. O interesse em Cirurgia Cardiovascular foi o motivo mais apontado para ingressar na LCCT, representrando 44/161 (27,3 por cento). A maioria dos estudantes - 32/51 (62,7 por cento) - relatou que suas perspectivas iniciais foram parcialmente preenchidas. Quase todos os membros recomendariam a um colega participar da liga 50/51 (98 por cento) e 25/51 (49 por cento) deles participaram de uma iniciação científica vinculada à LCCT. No total, 47 trabalhos científicos com alunos da LCCT como autores ou coautores foram publicados. Dentre os exmembros que optaram por uma carreira cirúrgica, 7/52 (13,4 por cento) deles escolheram Cirurgia Torácica ou Cardiovascular. CONCLUSÃO: LCCT cumpriu seus objetivos, os alunos reconheceram a colaboração da LCCT na sua formação médica, além de ter se mostrado um bom meio de realizar iniciação científica.

Cardiothoracic Surgery League from University of São Paulo Medical School: twelve years in medical education experience.

INTRODUCTION: Academic Leagues (Academic Interest Group) are entities that belong to medical schools and their hospitals. Their goals are research, medical education and health care. The cardiothoracic Surgery League (Liga de Cirurgia Cardiotorácica--LCCT), University of São Paulo Medical School, was founded 12 years ago, aimed at providing undergraduate medical students an opportunity to expand knowledge in cardiothoracic surgery and to take part in scientific studies in the field. OBJECTIVE: To evaluate the experience gained through LCCT implementation. METHODS: Current students and former members of LCCT were submitted to a specific evaluation form, delivered personally or by email, which provided data on the general opinion regarding LCCT's activities, the reasons for answers provided and choice of medical specialties. Furthermore, LCCT's total scientific production was evaluated. RESULTS: Most undergraduate medical students 51/65 (78.5%) and former members 94/121 (77.7%) completed the form. The interest in Cardiothoracic Surgery was the most common reason for joining LCCT 44/161 (27.3%). Most students 32/51 (62.7%)--reported their initial expectations were partially met. Almost every member would recommend a fellow medical student to join LCCT 50/51 (98%) and 25/51 (49%) of them participated in a scientific project linked to LCCT. In total, 47 scientific papers were published having LCCT's medical students as authors or co-authors during the existence of the league. Of the former members who chose a surgical career, 7/52 (13.4%) chose thoracic or cardiovascular surgery. CONCLUSION: LCCT has met its goals, since most current and former members recognized its role in their medical training, besides it is a good way to produce scientific initiation.