Anti-Leishmania compounds can be screened using Leishmania spp. expressing red fluorescence (tdTomato).

The main challenges associated with leishmaniasis chemotherapy are drug toxicity, the possible emergence of resistant parasites, and a limited choice of therapeutic agents. Therefore, new drugs and assays to screen and detect novel active compounds against leishmaniasis are urgently needed. We thus validated Leishmania braziliensis (Lb) and Leishmania infantum (Li) that constitutively express the tandem tomato red fluorescent protein (tdTomato) as a model for large-scale screens of anti-Leishmania compounds. Confocal microscopy of Lb and Li::tdTomato revealed red fluorescence distributed throughout the entire parasite, including the flagellum, and flow cytometry confirmed that the parasites emitted intense fluorescence. We evaluated the infectivity of cloned promastigotes and amastigotes constitutively expressing tdTomato, their growth profiles in THP-1 macrophages, and susceptibility to trivalent antimony, amphotericin, and miltefosine in vitro. The phenotypes of mutant and wild-type parasites were similar, indicating that the constitutive expression of tdTomato did not interfere with the evaluated parameters. We applied our validated model to a repositioning strategy and assessed the susceptibility of the parasites to eight commercially available drugs. We also screened 32 natural plant and fungal extracts and 10 pure substances to reveal new active compounds. The infectivity and Glucantime treatment efficacy of BALB/c mice and golden hamsters infected with Lb and Li::tdTomato mutant lines, respectively, were very similar compared to animals infected with wild-type parasites. Standardizing our methodology would offer more rapid, less expensive, and easier assays to screen of compounds against L. braziliensis and L. infantum in vitro and in vivo. Our method could also enhance the discovery of active compounds for treating leishmaniasis.

Metabolic Plasticity and Virulence-Associated Factors of Sporothrix brasiliensis Strains Related to Familiar Outbreaks of Cat-to-Human Transmitted Sporotrichosis.

Sporothrix brasiliensis is the main agent of zoonotic sporotrichosis transmitted by domestic cats in South America. In humans, sporotrichosis commonly presents with cutaneous or lymphocutaneous lesions, and in cats, with multiple ulcerated skin lesions associated with enlarged lymph nodes and respiratory signs. Fungal virulence factors may affect the clinical presentation of the mycoses. Sporothrix spp. present some virulence factors. This study aims to compare 24 S. brasiliensis strains from 12 familiar outbreaks of cat-to-human transmitted sporotrichosis. Fungal growth in different substrates, thermotolerance, resistance to oxidative stress, and production of enzymes were evaluated. An invertebrate model of experimental infection was used to compare the virulence of the strains. The strains grew well on glucose and N-acetyl-D-glucosamine but poorly on lactate. Their thermotolerance was moderate to high. All strains were susceptible to hydrogen peroxide, and the majority produced hemolysins but not phospholipase and esterase. There was no significant difference in the putative virulence-associated factors studied among the different hosts. Moreover, strains isolated from a human and a cat from four familiar outbreaks presented a very similar profile of expression of these factors, reinforcing the zoonotic transmission of S. brasiliensis in Brazil and demonstrating the plasticity of this species in the production of virulence factors.

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.

Immune response of BV-2 microglial cells is impacted by peroxisomal beta-oxidation.

Microglia are crucial for brain homeostasis, and dysfunction of these cells is a key driver in most neurodegenerative diseases, including peroxisomal leukodystrophies. In X-linked adrenoleukodystrophy (X-ALD), a neuroinflammatory disorder, very long-chain fatty acid (VLCFA) accumulation due to impaired degradation within peroxisomes results in microglial defects, but the underlying mechanisms remain unclear. Using CRISPR/Cas9 gene editing of key genes in peroxisomal VLCFA breakdown (Abcd1, Abcd2, and Acox1), we recently established easily accessible microglial BV-2 cell models to study the impact of dysfunctional peroxisomal ß-oxidation and revealed a disease-associated microglial-like signature in these cell lines. Transcriptomic analysis suggested consequences on the immune response. To clarify how impaired lipid degradation impacts the immune function of microglia, we here used RNA-sequencing and functional assays related to the immune response to compare wild-type and mutant BV-2 cell lines under basal conditions and upon pro-inflammatory lipopolysaccharide (LPS) activation. A majority of genes encoding proinflammatory cytokines, as well as genes involved in phagocytosis, antigen presentation, and co-stimulation of T lymphocytes, were found differentially overexpressed. The transcriptomic alterations were reflected by altered phagocytic capacity, inflammasome activation, increased release of inflammatory cytokines, including TNF, and upregulated response of T lymphocytes primed by mutant BV-2 cells presenting peptides. Together, the present study shows that peroxisomal ß-oxidation defects resulting in lipid alterations, including VLCFA accumulation, directly reprogram the main cellular functions of microglia. The elucidation of this link between lipid metabolism and the immune response of microglia will help to better understand the pathogenesis of peroxisomal leukodystrophies.

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.

Desarrollo de los cuidados paliativos pediátricos en Uruguay, 2008-2020: informe de avances / Development of pediatric palliative care in Uruguay, 2008-2020: progress report / Desenvolvimento dos cuidados paliativos pediátricos no Uruguai nos anos 2008-2020: relatório de progresso

Desde el año 2007 en Uruguay los cuidados paliativos (CP) son parte de las prestaciones de salud que todos los ciudadanos que los necesitan tienen derecho a recibir y, desde entonces, ha aumentado significativamente la accesibilidad a estos. Objetivo: describir la situación actual del desarrollo organizativo de servicios de cuidados paliativos pediátricos (CPP) en el país y los pacientes por ellos asistidos desde el inicio de sus actividades hasta el 31/12/2020, las principales fortalezas y desafíos percibidos por los profesionales de dichos equipos. Metodología: se realizó una consulta mediante encuesta online auto administrada enviada a los coordinadores de servicios de CPP del Uruguay. Resultados: se confirmaron 19 equipos en 9/19 departamentos, 5/19 están integrados por profesionales de las cuatro disciplinas básicas recomendadas, el resto por distintas combinaciones de disciplinas, con cargas horarias muy variables. Brindan asistencia en: hospitalización 19/19, policlínica 18/19, atención domiciliaria coordinada 13/19 y retén telefónico 10/19. Fueron asistidos 2957 niños, 23% de los mismos fallecieron. 16/19 equipos reportan como principales fortalezas los valores compartidos y el trabajo en equipo interdisciplinario y 15/19 como principal desafío los déficits de recursos humanos. Conclusiones: persisten importantes inequidades en el acceso a los CPP. Se constató gran variabilidad en la integración de los equipos y la carga horaria de los profesionales. Es necesario que las autoridades sanitarias continúen promoviendo y exigiendo el desarrollo de equipos de CPP en las instituciones y departamentos que no los tienen y el cumplimiento de estándares mínimos de calidad en los ya existentes.

Since 2007, palliative care (PC) has been a part of the health benefits that all Uruguayan citizens are entitled to receive and, since then, accessibility has increased significantly. Objective: to describe the present development of pediatric palliative care services (PPC) in Uruguay and the patients assisted by health providers since the beginning of their services until 12/31/2020 and the key strengths and challenges perceived by these palliative care teams. Methodology: a consultation was carried out through a self-administered online survey and sent to the PPC service coordinators in Uruguay. Results: 19 teams were confirmed in 9/19 departments, 5/19 are integrated by professionals from the four recommended basic disciplines, the rest by different combinations of disciplines, with highly variable workloads. They provide assistance in: hospitalization 19/19, clinics 18/19, coordinated home care 13/19 and telephone assistance 10/19. 2957 children were assisted, 23% of them died. 16/19 teams report shared values and interdisciplinary teamwork as their main strengths, and 15/19 report human resource shortage as their main challenge. Conclusions: significant inequality persist regarding access to PPCs. We confirmed a high variability in teams' integration and professional workload. It is necessary for the health authorities to continue to promote and demand the development of PPC teams in the institutions and departments that do not yet have them and the compliance with minimum quality standards in those that already operate.

Desde 2007, os cuidados paliativos (CP) fazem parte dos benefícios de saúde que todos os cidadãos têm direito a receber no Uruguai e, desde então, a acessibilidade a eles tem aumentado significativamente. Objetivo: descrever a situação atual do desenvolvimento organizacional dos serviços de cuidados paliativos pediátricos (CPP) no Uruguai e dos pacientes atendidos desde o início de suas atividades até 31/12/2020 e as principais fortalezas e desafios percebidos pelos profissionais das referidas equipes. Metodologia: foi realizada uma consulta por meio de uma pesquisa online autoaplicável enviada aos coordenadores dos serviços do CPP no Uruguai. Resultados: 19 equipes foram confirmadas em 19/09 departamentos, 19/05 compostas por profissionais das quatro disciplinas básicas recomendadas, o restante por diferentes combinações de disciplinas, com cargas horárias altamente variáveis. Elas atendem em: internação 19/19, policlínica 18/19, atendimento domiciliar coordenado 13/19 e posto telefônico 19/10. 2.957 crianças foram atendidas, 23% delas faleceram. 16/19 equipes relatam valores compartilhados e trabalho em equipe interdisciplinar como suas principais fortalezas, e 15/19 relatam déficits de recursos humanos como seu principal desafio. Conclusões: persistem desigualdades significativas no acesso aos CPP. Verificou-se: grande variabilidade na integração das equipes e na carga de trabalho dos profissionais. É necessário que as autoridades de saúde continuem promovendo e exigindo o desenvolvimento de equipes de CPP nas instituições e departamentos que não as possuem e o cumprimento de padrões mínimos de qualidade nas que já existem.

Physicochemical Profile, Antioxidant and Antimicrobial Activities of Honeys Produced in Minas Gerais (Brazil).

Honeys can be classified as polyfloral or monofloral and have been extensively studied due to an increased interest in their consumption. There is concern with the correct identification of their flowering, the use of analyses that guarantee their physicochemical quality and the quantification of some compounds such as phenolics, to determine their antioxidant and antimicrobial action. This study aims at botanical identification, physicochemical analyses, and the determination of total polyphenols, chromatographic profile and antiradical and antimicrobial activity of honey from different regions of Minas Gerais. Seven different samples were analyzed for the presence of pollen, and color determination. The physicochemical analyses performed were total acidity, moisture, HMF, reducing sugar, and apparent sucrose. The compound profile was determined by UHPLC/MS, the determination of total phenolics and antiradical activity (DPPH method) were performed by spectrophotometry, and minimum inhibitory and bacterial concentrations were determined for cariogenic bacteria. All honey samples met the quality standards required by international legislation, twenty compounds were detected as the main ones, the polyfloral honey was the only honey that inhibited all of the bacteria tested. Sample M6 (Coffee) was the one with the highest amount of total polyphenols, while the lowest was M4 (Cipó-uva). Regarding the antioxidant activity, M5 (Velame) had the best result and M4 (Cipó-uva) was the one that least inhibited oxidation. Of the polyfloral honeys, there was not as high a concentration of phenolic compounds as in the others. Coffee, Aroeira, Velame and Polyfloral have the best anti-radical actions. Betônica, Aroeira, Cipó-uva and Pequi inhibited only some bacteria. The best bacterial inhibition results are from Polyfloral.

Optimization of Resveratrol Used as a Scaffold to Design Histone Deacetylase (HDAC-1 and HDAC-2) Inhibitors.

Histone deacetylases (HDAC) are epigenetic enzymes responsible for repressing gene expression through the deacetylation of histone lysine residues. Therefore, inhibition of HDACs has become an interesting approach for the treatment of several diseases, including cancer, hematology, neurodegenerative, immune diseases, bacterial infections, and more. Resveratrol (RVT) has pleiotropic effects, including pan-inhibition of HDAC isoforms; however, its ability to interfere with membranes requires additional optimization to eliminate nonspecific and off-target effects. Thus, to explore RVT as a scaffold, we designed a series of novel HDAC-1 and -2 inhibitors containing the 2-aminobenzamide subunit. Using molecular modeling, all compounds, except unsaturated compounds (4) and (7), exhibited a similar mode of interaction at the active sites of HDAC 1 and 2. The docking score values obtained from the study ranged from -12.780 to -10.967 Kcal/mol. All compounds were synthesized, with overall yields ranging from 33% to 67.3%. In an initial screening, compounds (4), (5), (7), and (20)-(26), showed enzymatic inhibitory effects ranging from 1 to 96% and 6 to 93% against HDAC-1 and HDAC-2, respectively. Compound (5), the most promising HDAC inhibitor in this series, was selected for IC50 assays, resulting in IC50 values of 0.44 µM and 0.37 µM against HDAC-1 and HDAC-2, respectively. In a panel of selectivity against HDACs 3-11, compound (5) presented selectivity towards Class I, mainly HDAC-1, 2, and 3. All compounds exhibited suitable physicochemical and ADMET properties as determined using in silico simulations. In conclusion, the optimization of the RVT structure allows the design of selective HDAC inhibitors, mainly targeting HDAC-1 and HDAC-2 isoforms.

Searching for plant-derived antivirals against dengue virus and Zika virus.

BACKGROUND: The worldwide epidemics of diseases as dengue and Zika have triggered an intense effort to repurpose drugs and search for novel antivirals to treat patients as no approved drugs for these diseases are currently available. Our aim was to screen plant-derived extracts to identify and isolate compounds with antiviral properties against dengue virus (DENV) and Zika virus (ZIKV). METHODS: Seven thousand plant extracts were screened in vitro for their antiviral properties against DENV-2 and ZIKV by their viral cytopathic effect reduction followed by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method, previously validated for this purpose. Selected extracts were submitted to bioactivity-guided fractionation using high- and ultrahigh-pressure liquid chromatography. In parallel, high-resolution mass spectrometric data (MSn) were collected from each fraction, allowing compounds into the active fractions to be tracked in subsequent fractionation procedures. The virucidal activity of extracts and compounds was assessed by using the plaque reduction assay. EC50 and CC50 were determined by dose response experiments, and the ratio (EC50/CC50) was used as a selectivity index (SI) to measure the antiviral vs. cytotoxic activity. Purified compounds were used in nuclear magnetic resonance spectroscopy to identify their chemical structures. Two compounds were associated in different proportions and submitted to bioassays against both viruses to investigate possible synergy. In silico prediction of the pharmacokinetic and toxicity (ADMET) properties of the antiviral compounds were calculated using the pkCSM platform. RESULTS: We detected antiviral activity against DENV-2 and ZIKV in 21 extracts obtained from 15 plant species. Hippeastrum (Amaryllidaceae) was the most represented genus, affording seven active extracts. Bioactivity-guided fractionation of several extracts led to the purification of lycorine, pretazettine, narciclasine, and narciclasine-4-O-ß-D-xylopyranoside (NXP). Another 16 compounds were identified in active fractions. Association of lycorine and pretazettine did not improve their antiviral activity against DENV-2 and neither to ZIKV. ADMET prediction suggested that these four compounds may have a good metabolism and no mutagenic toxicity. Predicted oral absorption, distribution, and excretion parameters of lycorine and pretazettine indicate them as candidates to be tested in animal models. CONCLUSIONS: Our results showed that plant extracts, especially those from the Hippeastrum genus, can be a valuable source of antiviral compounds against ZIKV and DENV-2. The majority of compounds identified have never been previously described for their activity against ZIKV and other viruses.

Natural Occurring Phenolic Derivatives from Mauritia flexuosa (Buriti) Stems and Their Potential Antibacterial Activity against Methicillin-Resistant Staphylococcus aureus (MRSA).

Mauritia flexuosa Linnaeus filius (buriti or aguage; Arecaceae) is a palm used by traditional medicine in Brazil to treat dysentery and diarrhea. Our group showed that the soluble dichloromethane (CH2 Cl2 ) fraction from EtOH extract from M. flexuosa stems inhibited the growth of methicillin-susceptible Staphylococcus aureus (MSSA) and methicillin-resistant S. aureus (MRSA) and it is rich in phenolic compounds. This study aimed to isolate new phenolic compounds from CH2 Cl2 fraction from M. flexuosa stems with in vitro antibacterial activity. The crude CH2 Cl2 fraction was fractionated by gel permeation chromatography (GPC) followed by semi-preparative RP-HPLC. The antibacterial activity was evaluated using the broth microdilution method against MSSA (ATCC 29213) and MRSA (clinical isolate 155). All compounds were also tested against Gram-negative (Escherichia coli; ATCC 35218) bacteria and two fungi species (Candida albicans; ATCC 14053 and Trichophyton rubrum; ATCC MYA 4438). The chemical structures of isolated compounds were determined by analysis and comparison with literature data of their NMR and HRMS spectra and optical activity. The chemical investigation yielded seven aromatic compounds, of which four, (2S,15S)-2,15-dimethyl-2,15-dioxa-1,8(1,4)-dibenzenacyclotetradecaphane (1), (2S,5S)-1-(4-hydroxyphenyl)hexane-2,5-diol (3), bruguierol E (4), and buritin (5) were previously unreported and three are known compounds identified as 6-(4'-hydroxyphenyl) hexan-2-one (2), (+)-(2R,3R)-dihydrokaempferol (6), and (+)-(2R)-naringenin (7). Compounds 1 and 7 showed antibacterial activity against MRSA and MSSA with minimum inhibitory concentrations (MICs) of between 62.5 and 31.3 µg/mL, respectively. Our preliminary findings support that CH2 Cl2 fraction from buriti, a typical species of flooded areas of Brazilian savanna, and its aromatic phenolic compounds are active against MSSA and MRSA contributing with understanding about the traditional use of this species.

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.

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.

Decision-making executive function profile and performance in older adults with major depression: a case-control study.

OBJECTIVES: Decision making (DM) is a component of executive functioning, essential for choosing appropriate decisions. Executive dysfunctioning is particularly common in late-life depression, however the literature is scarce on DM. This case-control study aimed to evaluate the DM profile and performance in participants with and without unipolar major depression. METHOD: The DM profile and performance were assessed by the Melbourne Decision Making Questionnaire and the Iowa Gambling Task (IGT), respectively, in three groups of older adults from a university-based geriatric psychiatry clinic, i.e. current depression (n = 30), remitted depression (n = 43) and healthy controls (n = 59). The Hamilton Depression scale (HAM-D) 21 items, the Hamilton Anxiety scale, and the Mini-Mental State Examination were used to access depressive symptoms, anxiety symptoms, and cognitive impairment, respectively. Multinomial, nominal and binary logistic regression was used to evaluate the associations between depression, depressive symptomatology and DM. RESULTS: In comparison to the control group, patients with current depression presented higher scores in buck-passing and proscratination DM profiles. In the hypervigilance profile, there was a significant difference between current and remitted depression groups. A higher value ​in the HAM-D scale increased the probability of disadvantageous DM profiles. Depressive patients showed a tendency of a higher mean score in both disadvantageous decks (A and B) of IGT. Patients with current depression showed a worse performance compared to the remitted depression group in the IGT netscore. CONCLUSION: Older adults with current depression showed DM profiles considered maladaptive or disadvantageous compared to both remitted depression and healthy controls groups.

Behavioral and brain morphological analysis of non-inflammatory and inflammatory rat models of preterm brain injury.

Investigations using preclinical models of preterm birth have much contributed, together with human neuropathological studies, for advances in our understanding of preterm brain injury. Here, we evaluated whether the neurodevelopmental and behavioral consequences of preterm birth induced by a non-inflammatory model of preterm birth using mifepristone would differ from those after inflammatory prenatal transient hypoxia-ischemia (TSHI) model. Pregnant Wistar rats were either injected with mifepristone, and pups were delivered on embryonic day 21 (ED21 group), or laparotomized on the 18th day of gestation for 60 min of uterine arteries occlusion. Rat pups were tested postnatally for characterization of developmental milestones and, after weaning, they were behaviorally tested for anxiety and for spatial learning and memory. One month later, brains were processed for quantification of doublecortin (DCX)- and neuropeptide Y (NPY)-immunoreactive cells, and cholinergic varicosities in the hippocampus. ED21 rats did not differ from controls with respect to neonatal developmental milestones, anxiety, learning and memory functions, and neurochemical parameters. Conversely, in TSHI rats the development of neonatal reflexes was delayed, the levels of anxiety were reduced, and spatial learning and memory was impaired; in the hippocampus, the total number of DCX and NPY cells was increased, and the density of cholinergic varicosities was reduced. With these results we suggest that a preterm birth, in a non-inflammatory prenatal environment, does not significantly change neonatal development and adult neurologic outcome. On other hand, prenatal hypoxia and ischemia (inflammation) modifies developmental trajectory, learning and memory, neurogenesis, and NPY GABAergic and cholinergic brain systems.

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.

Gray Matter Volume in Elderly adults With ADHD: Associations of Symptoms and Comorbidities With Brain Structures.

Objective: To investigate total and selected region-of-interest-based gray matter volume (GMV) in older adults with ADHD. Method: Twenty-five elderly (≥65 years old) patients with ADHD and 34 healthy controls underwent 1.5-T magnetic resonance imaging (MRI). We used voxel-based morphometry to compare GMV between groups and performed a correlation analysis with ADHD symptoms and comorbidities. Results: Findings revealed a smaller total GMV in males with ADHD and a smaller GMV in the right medial frontal orbital area extending toward the medial frontal superior, the frontal superior, and the subgenual anterior cingulate cortex (ACC) besides correlations between inattentiveness and ACC (bilaterally) and left cerebellum, hyperactivity/impulsivity and the left frontal inferior orbital, depression and caudate (bilaterally), and the right inferior parietal lobule. Conclusion: Neural correlates in regions related to attention, executive control, and affective processing suggest that impairments in frontostriatal and frontoparietal-cerebellar areas observed in adults with ADHD persist into old age.

A green metal-free "one-pot" microwave assisted synthesis of 1,4-dihydrochromene triazoles.

The synthesis of several 4-aryl-1,4-dihydrochromene-triazoles was achieved via a metal-free "one-pot" procedure using PEG400 as the sole solvent in an eco-friendly process. Using microwave irradiation, the triazole derivatives were obtained in good yields and short reaction times starting from readily accessible building blocks.