Stimulation of microvesicle secretion in Trichomonas vaginalis.

Trichomonas vaginalis is an extracellular flagellate protozoan and the etiological agent of human trichomoniasis, a sexually transmitted infection (STI) with a high incidence. Several reports have shown that this protozoan releases microvesicles into the culture medium, which show high potential in modulating cell-to-cell communication and the host response to infections. However, the biogenesis of these vesicles has not been analyzed in detail. In the present study, high-resolution ion scanning microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze the surface of control cells and cells incubated in the presence of Ca2+ alone or with A 23187 calcium ionophore. Two different strains of T. vaginalis were analyzed. Most control cells displayed relatively smooth surfaces, whereas cells incubated with Ca2+ had many surface projections of variable shape and size (from 40 nm to around 1 µm). Quantitative analyses were performed directly in the scanning electron microscope and showed a significant increase in the number of cells with surface projections after incubation in the presence of calcium. TEM showed that treated cells presented several cytoplasmic multivesicular structures, suggesting membrane fusion and exosomes in the extracellular medium. The amount and size of the released vesicles were quantitatively analyzed using light scattering and TEM on negatively stained samples. The observations show that incubation of both parasite strains in the presence of Ca2+ significantly increased the release of microvesicles into the extracellular medium in a time-dependent process. Sequential incubation in the presence of Ca2+ and the calcium ionophore A23187 increases the presence of vesicles on the parasite surface only at a short incubation time (5 min). Transmission electron microscopy showed that at least part of the vesicles are originated from cytoplasmic multivesicular structures. This information contributes to a better understanding of the biogenesis of extracellular vesicles secreted by T. vaginalis.

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.

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.

Expression profiles of sugarcane under drought conditions: Variation in gene regulation.

Drought is a major factor in decreased sugarcane productivity because of the resulting morphophysiological effects that it causes. Gene expression studies that have examined the influence of water stress in sugarcane have yielded divergent results, indicating the absence of a fixed pattern of changes in gene expression. In this work, we investigated the expression profiles of 12 genes in the leaves of a drought-tolerant genotype (RB72910) of sugarcane and compared the results with those of other studies. The genotype was subjected to 80-100% water availability (control condition) and 0-20% water availability (simulated drought). To analyze the physiological status, the SPAD index, Fv/Fm ratio, net photosynthesis (A), stomatal conductance (gs) and stomatal transpiration (E) were measured. Total RNA was extracted from leaves and the expression of SAMDC, ZmPIP2-1 protein, ZmTIP4-2 protein, WIP protein, LTP protein, histone H3, DNAj, ferredoxin I, ß-tubulin, photosystem I, gene 1 and gene 2 was analyzed by quantitative real-time PCR (RT-PCR). Important differences in the expression profiles of these genes were observed when compared with other genotypes, suggesting that complex defense mechanisms are activated in response to water stress. However, there was no recognizable pattern for the changes in expression of the different proteins associated with tolerance to drought stress.

Cannabis use influences disorganized symptoms severity but not transition in a cohort of non-help-seeking individuals at-risk for psychosis from São Paulo, Brazil.

BACKGROUND: Cannabis use is associated with an increased risk of developing a psychotic disorder. However, in individuals with at-risk mental states for psychosis (ARMS) this association is not clear, as well as the impact of cannabis use on symptom severity. The objective of this study was to evaluate the association of cannabis use patterns and ARMS risk status, transition to psychotic and psychiatric disorders, and psychopathology. METHOD: A sample of 109 ARMS and 197 control individuals was drawn from the general population. Lifetime, maximum and current amount of cannabis use were assessed with the South Westminster modified questionnaire. Participants were followed-up for a mean of 2.5 years and reassessed for transition to any psychiatric disorder. RESULTS: There were no differences between ARMS and controls regarding lifetime use, current amount of use, or maximum amount of cannabis use. There were also no differences between those who transitioned to a psychiatric disorder and those who did not regarding cannabis use variables. In ARMS individuals, cannabis use was significantly related to disorganization symptoms. CONCLUSION: The results of this study suggest that cannabis plays a role in the psychopathology of ARMS individuals, leading to more severe symptomatology.

Natural language processing in at-risk mental states: enhancing the assessment of thought disorders and psychotic traits with semantic dynamics and graph theory.

OBJECTIVE: Verbal communication has key information for mental health evaluation. Researchers have linked psychopathology phenomena to some of their counterparts in natural-language-processing (NLP). We study the characterization of subtle impairments presented in early stages of psychosis, developing new analysis techniques and a comprehensive map associating NLP features with the full range of clinical presentation. METHODS: We used NLP to assess elicited and free-speech of 60 individuals in at-risk-mental-states (ARMS) and 73 controls, screened from 4,500 quota-sampled Portuguese speaking citizens in Sao Paulo, Brazil. Psychotic symptoms were independently assessed with Structured-Interview-for-Psychosis-Risk-Syndromes (SIPS). Speech features (e.g.sentiments, semantic coherence), including novel ones, were correlated with psychotic traits (Spearman's-ρ) and ARMS status (general linear models and machine-learning ensembles). RESULTS: NLP features were informative inputs for classification, which presented 86% balanced accuracy. The NLP features brought forth (e.g. Semantic laminarity as 'perseveration', Semantic recurrence time as 'circumstantiality', average centrality in word repetition graphs) carried most information and also presented direct correlations with psychotic symptoms. Out of the standard measures, grammatical tagging (e.g. use of adjectives) was the most relevant. CONCLUSION: Subtle speech impairments can be grasped by sensitive methods and used for ARMS screening. We sketch a blueprint for speech-based evaluation, pairing features to standard thought disorder psychometric items.

Plasma levels of neurotrophin 4/5, NGF and pro-BDNF influence transition to mental disorders in a sample of individuals at ultra-high risk for psychosis.

BACKGROUND: Neurotrophins (NTs) and their precursors (pro-NTs) are polypeptides with important roles in neuronal development, differentiation, growth, survival and plasticity, as well as apoptosis and neuronal death. Imbalance in NT levels were observed in schizophrenia spectrum disorders, but evidence in ultra-high risk for psychosis (UHR) samples is scarce. METHODS: A naturalistic sample of 87 non-help-seeking UHR subjects and 55 healthy controls was drawn from the general population. Blood samples were collected and NT-3, NT-4/5, BDNF, pro-BDNF, NGF, pro-NGF were analyzed through enzyme linked immunosorbent assay (ELISA). Information on cannabis and tobacco use was also collected. Logistic regression models and path analysis were used to control for confounders (tobacco, age, cannabis use). RESULTS: NT-4/5 was significantly decreased, and pro-BDNF was significantly increased in UHR individuals compared to controls. Cannabis use and higher NGF levels were significantly related to transition to psychiatric disorders among UHR subjects. Increased pro-BDNF and decreased NT-4/5 influenced transition by the mediation of perceptual abnormalities. CONCLUSIONS: Our study shows for the first time that NTs are altered in UHR compared to healthy control individuals, and that they can be a predictor of transition to psychiatric illnesses in this population. Future studies should employ larger naturalistic samples to confirm the findings.

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.

Detecting at-risk mental states for psychosis (ARMS) using machine learning ensembles and facial features.

AIMS: Our study aimed to develop a machine learning ensemble to distinguish "at-risk mental states for psychosis" (ARMS) subjects from control individuals from the general population based on facial data extracted from video-recordings. METHODS: 58 non-help-seeking medication-naïve ARMS and 70 healthy subjects were screened from a general population sample. At-risk status was assessed with the Structured Interview for Prodromal Syndromes (SIPS), and "Subject's Overview" section was filmed (5-10 min). Several features were extracted, e.g., eye and mouth aspect ratio, Euler angles, coordinates from 51 facial landmarks. This elicited 649 facial features, which were further selected using Gradient Boosting Machines (AdaBoost combined with Random Forests). Data was split in 70/30 for training, and Monte Carlo cross validation was used. RESULTS: Final model reached 83 % of mean F1-score, and balanced accuracy of 85 %. Mean area under the curve for the receiver operator curve classifier was 93 %. Convergent validity testing showed that two features included in the model were significantly correlated with Avolition (SIPS N2 item) and expression of emotion (SIPS N3 item). CONCLUSION: Our model capitalized on short video-recordings from individuals recruited from the general population, effectively distinguishing between ARMS and controls. Results are encouraging for large-screening purposes in low-resource settings.

Gesticulation in individuals with at risk mental states for psychosis.

Nonverbal communication (NVC) is a complex behavior that involves different modalities that are impaired in the schizophrenia spectrum, including gesticulation. However, there are few studies that evaluate it in individuals with at-risk mental states (ARMS) for psychosis, mostly in developed countries. Given our prior findings of reduced movement during speech seen in Brazilian individuals with ARMS, we now aim to determine if this can be accounted for by reduced gesticulation behavior. Fifty-six medication-naïve ARMS and 64 healthy controls were filmed during speech tasks. The frequency of specifically coded gestures across four categories (and self-stimulatory behaviors) were compared between groups and tested for correlations with prodromal symptoms of the Structured Interview for Prodromal Syndromes (SIPS) and with the variables previously published. ARMS individuals showed a reduction in one gesture category, but it did not survive Bonferroni's correction. Gesture frequency was negatively correlated with prodromal symptoms and positively correlated with the variables of the amount of movement previously analyzed. The lack of significant differences between ARMS and control contradicts literature findings in other cultural context, in which a reduction is usually seen in at-risk individuals. However, gesture frequency might be a visual proxy of prodromal symptoms, and of other movement abnormalities. Results show the importance of analyzing NVC in ARMS and of considering different cultural and sociodemographic contexts in the search for markers of these states.

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.

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.

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.

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.

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.

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.

Neoplasia maligna primária de fígado / Primary malignant neoplasm of the liver

Foram analisados no presente trabalho 21 pacientes com neoplasia maligna primária de fígado, 15 homens e seis mulheres, com idade média de 54,5 anos. Desses pacientes, 17 foram à laparotomia, quando duas ressecçöes puderam ser realizadas, e 14 fizeram apenas biópsias. Em quatro o diagnóstico foi feito por biópsia através de punçäo transparieto-hepática. O tempo médio de história foi de três meses e, por ocasiäo do diagnóstico, 95% dos pacientes tinham câncer avançado (estádios II e III). O tempo médio de sobrevida foi de seis meses, contado a partir do início dos sintomas, e de 2,5 meses a partir do diagnóstico. Nos oito pacientes que receberam quimioterapia, a sobrevida média foi de 3,5 meses (desde o diagnóstico) e, nos que näo receberam, de 27 dias. Os autores concluem que o prognóstico do câncer de fígado é muito pobre, a ressecabilidade muito baixa e, por ocasiäo do diagnóstico, a grande maioria dos doentes já se encontra em fase avançada da doença, sendo necessários esforços no sentido de se proceder ao diagnóstico mais precoce, com seguimento de populaçöes de risco