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Recently, there has been a resurgence in experimental and conceptual efforts to understand how brain rhythms can serve to organize visual information. Oscillations can provide temporal structure for neuronal processing and form a basis for integrating information across brain areas. Here, we use a bistable paradigm and a data-driven approach to test the hypothesis that oscillatory modulations associate with the integration or segregation of visual elements. Spectral signatures of perception of bound and unbound configurations of visual moving stimuli were studied using magnetoencephalography (MEG) in ambiguous and unambiguous conditions. Using a 2 × 2 design, we were able to isolate correlates from visual integration, either perceptual or stimulus-driven, from attentional and ambiguity-related activity. Two frequency bands were found to be modulated by visual integration: an alpha/beta frequency and a higher frequency gamma-band. Alpha/beta power was increased in several early visual cortical and dorsal visual areas during visual integration, while gamma-band power was surprisingly increased in the extrastriate visual cortex during segregation. This points to an integrative role for alpha/beta activity, likely from top-down signals maintaining a single visual representation. On the other hand, when more representations have to be processed in parallel gamma-band activity is increased, which is at odds with the notion that gamma oscillations are related to perceptual coherence. These modulations were confirmed in intracranial EEG recordings and partially originate from distinct brain areas. Our MEG and stereo-EEG data confirms predictions of binding mechanisms depending on low-frequency activity for long-range integration and for organizing visual processing while refuting a straightforward correlation between gamma-activity and perceptual binding. PRACTITIONER POINTS: Distinct neurophysiological signals underlie competing bistable percepts. Increased alpha/beta activity correlate with visual integration while gamma correlates with segmentation. Ambiguous percepts drive alpha/beta activity in the posterior cingulate cortex., (© 2024 The Author(s). Human Brain Mapping published by Wiley Periodicals LLC.)

Research Background: Açaí berry is rich in antioxidant compounds and is therefore closely associated with beneficial health effects. In this study, we aim to investigate the potential of using Lacticaseibacillus rhamnosus HN001 as a probiotic culture on açaí flan., Experimental Approach: The chemical composition, physicochemical and microbiological characteristics, and sensory acceptance during refrigerated storage (5 °C for 42 days) of flan were investigated. In addition, the consumer perception of the product was evaluated using word association when consumers were shown a photo of the product with or without the added ingredients accompanied with a brief description of the product., Results and Conclusions: The flan had a suitable chemical composition, mainly carbohydrates and proteins, probiotic viability reached 8 log CFU/g in the product and 4 log CFU/g after gastrointestinal simulation, typical açaí coloration, significant antioxidant activity and high sensory acceptability. The information about the ingredients and properties of the products increased the health value and positive feelings of the consumers towards the product., Novelty and Scientific Contribution: Açaí flan has proven to be a suitable carrier for L. rhamnosus HN001 as a probiotic culture, further enhancing the characteristic beneficial properties of the fruit. Therefore, combining this information with marketing strategies that inform consumers about the benefits of the product can further improve its acceptance. As far as we know, this is the first study on açaí flan with added probiotic culture., Competing Interests: CONFLICT OF INTEREST The authors declare no conflict of interest., (Authors.)

A model based on inhibitory coupling has been proposed to explain perceptual oscillations. This 'adapting reciprocal inhibition' model postulates that it is the strength of inhibitory coupling that determines the fate of competition between percepts. Here, we used an fMRI-based adaptation technique to reveal the influence of neighboring neuronal populations, such as reciprocal inhibition, in motion-selective hMT+/V5. If reciprocal inhibition exists in this region, the following predictions should hold: 1. stimulus-driven response would not simply decrease, as predicted by simple repetition-suppression of neuronal populations, but instead, increase due to the activity from adjacent populations; 2. perceptual decision involving competing representations, should reflect decreased reciprocal inhibition by adaptation; 3. neural activity for the competing percept should also later on increase upon adaptation. Our results confirm these three predictions, showing that a model of perceptual decision based on adapting reciprocal inhibition holds true. Finally, they also show that the net effect of the well-known repetition suppression phenomenon can be reversed by this mechanism., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023. Published by Elsevier Inc.)

Objectives: Non-alcoholic fatty liver disease (NAFLD) is related to obesity, insulin resistance, dyslipidemia, and metabolic syndrome. The increasing prevalence of NAFLD results in a significant number of patients manifesting chronic liver disease over time. The aim of this study was to analyze the predictive factors to estimate NAFLD severity in patients who are candidates for Roux-en-Y gastric bypass., Methods: This descriptive observational study was conducted with 136 obese patients who were candidates for Roux-en-Y gastric bypass and had mild, moderate, or severe NAFLD., Results: Severe NAFLD was more prevalent among the men (P = 0.007), and mild NAFLD was more prevalent among the women (P = 0.007). Hyperferritinemia was observed in the group with severe NAFLD (P = 0.01). Neck circumference and waist-to-height ratio were associated with an increased risk when comparing the groups with mild and severe NAFLD and those with moderate and severe NAFLD (P = 0.023 and P = 0.001, respectively); the alanine aminotransferase (ALT) and aspartate aminotransferase ratio values were >1 (P = 0.002) in the same comparisons. The regression analyses showed that an increase of 1 ng/mL in vitamin D reduced the chances of severe steatosis by 10% (P = 0.043), and an increase of 1 U/L ALT increased the chances of severe steatosis by 13% (P = 0.002)., Conclusion: High neck circumference and low waist-to-height ratio values, male sex, hyperferritinemia, increased serum ALT values, and decreased vitamin D levels were related to the risk for severe NAFLD., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: co-author is Editors Emeritus of the Nutrition Journal - A.C.L.C., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Background: Concomitant tricuspid repair in MR surgery is indicated in patients with severa tricuspid regurgitation, however, concomitant repair in less-than-severe TR patients is still a matter of debate., Methods: In December 2021, we systematically searched PubMed, Embase and Cochrane databases for randomised control trials (RCTs) comparing isolated MR surgery versus MR surgery with concomitant TR annuloplasty. Four studies were included, resulting in 651 patients (323 in the prophylactic tricuspid intervention group and 328 in the no tricuspid intervention group)., Results: Our meta-analysis showed a similar all-cause mortality and perioperative mortality for concomitant prophylactic tricuspid repair when compared with no tricuspid intervention (pooled odds ratio (OR), 0.54; 95% confidence interval (CI): 0.25-1.15, P = 0.11; I 2  = 0% and pooled OR, 0.54; 95% CI: 0.25-1.15, P = 0.11; I 2  = 0%, respectively) in patients undergoing MV surgery. despite a significantly lower TR progression (pooled OR, 0.06; 95% CI: 0.02-0.24, P < 0.01; I 2  = 0%). Additionally, similar New York Heart Association (NYHA) classes III and IV were identified in both concomitant prophylactic tricuspid repair and no tricuspid intervention, despite a lower trend in the tricuspid intervention group (pooled OR, 0.63; 95% CI: 0.38-1.06, P = 0.08; I 2  = 0%)., Conclusions: Our pooled analyses suggested that TV repair at the time of MV surgery in patients with moderate or less-than-moderate TR did not impact on perioperative or postoperative all-cause mortality, despite reducing TR severity and TR progression following the intervention., (© 2023. The Author(s).)

Objective: Sufficient vitamin D (25-hydroxyvitamin D [25(OH)D]) serum levels are associated with decreased asthma symptoms. Our aim was to investigate associations between vitamin D and atopy, asthma, asthma severity, and asthma phenotypes in Brazilian teenagers., Methods: This cross-sectional study involved 942 individuals (11-19 years old) engaged in an asthma cohort. The ISAAC questionnaire was employed to diagnosis asthma and asthma severity. Serum allergen-specific immunoglobulin E (sIgE) was measured by ImmunoCap and serum 25(OH)D was measured by ELISA. We calculated the correlation between sIgE and 25(OH)D. We used multivariate logistic regression analysis to assess associations of interest., Results: We found that 25(OH)D deficiency was positively associated with atopy (OR 1.45, confidence interval [CI] 1.05-2.00) and high levels of this vitamin negatively correlated with sIgE to Dermatophagoides pteronyssinus (r = -0.11, p = 0.019). The average 25(OH)D serum level was 27.0 ± 9.5 ng/ml; 366 individuals (38.8%) had a sufficient level. There was no association between 25(OH)D and asthma, asthma severity or asthma phenotypes in the population. However, sex was a possible effect modifier of the association between vitamin D and asthma: insufficiency in asthmatic women (86%) was higher than in asthmatic men (42%), and there was an association between insufficient vitamin D levels and greater asthma risk only in women (OR = 3.06, 95% CI 1.16-8.07)., Conclusion: We have shown that vitamin D deficiency was associated with greater risk of atopy in both sexes and vitamin D insufficiency was associated with asthma only in women. There was no association between vitamin D levels and asthma phenotypes or asthma severity., (© 2022 Wiley Periodicals LLC.)

Introduction: Jaccoud arthropathy (JA) is a nonerosive and deforming arthropathy experienced frequently by patients with systemic lupus erythematosus (SLE). Although genetic polymorphisms are associated with SLE development, the association between genetic polymorphisms and JA has not been studied to date. The main objective of this study was to evaluate an association between HLA, STAT4, IRF5, and BLK polymorphisms and the presence of JA in Brazilian individuals with SLE., Methods: Patients were selected from a cohort of individuals with SLE followed at 2 rheumatology reference centers in Salvador, Bahia, Brazil. The JA diagnosis was based on clinical and radiological criteria. The participants were genotyped for rs9271100, rs7574865, rs10488631, and rs13277113 polymorphisms in the HLA, STAT4, IRF5, and BLK genes, respectively, using real-time polymerase chain reaction. The presence of JA was correlated with allele frequencies, and clinical and laboratory data., Results: One hundred forty-four individuals with SLE (38 with JA and 106 with SLE without JA) were studied. The mean age of the patients was 45 ± 12 years; the majority were women and had brown skin. Patients with JA had a longer disease duration than patients without JA. Serositis and neuropsychiatric manifestations were more frequent in the JA population. The A allele of rs13277113 in the BLK gene was associated with the presence of JA., Conclusions: The rs13277113 polymorphism in the BLK gene was found to be a possible genetic risk for JA development. However, further studies in larger populations should be performed to confirm this finding., Competing Interests: The authors declare no conflict of interest., (Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.)

Neuroimaging studies have suggested that hMT+ encodes global motion interpretation, but this contradicts the notion that BOLD activity mainly reflects neuronal input. While measuring fMRI responses at 7 Tesla, we used an ambiguous moving stimulus, yielding the perception of two incoherently moving surfaces-component motion-or only one coherently moving surface-pattern motion, to induce perceptual fluctuations and identify perceptual organization size-matched domains in hMT+. Then, moving gratings, exactly matching either the direction of component or pattern motion percepts of the ambiguous stimulus, were shown to the participants to investigate whether response properties reflect the input or decision. If hMT+ responses reflect the input, component motion domains (selective to incoherent percept) should show grating direction stimulus-dependent changes, unlike pattern motion domains (selective to the coherent percept). This hypothesis is based on the known direction-selective nature of inputs in component motion perceptual domains versus non-selectivity in pattern motion perceptual domains. The response amplitude of pattern motion domains did not change with grating direction (consistently with their non-selective input), in contrast to what happened for the component motion domains (consistently with their selective input). However, when we analyzed relative ratio measures they mirrored perceptual interpretation. These findings are consistent with the notion that patterns of BOLD responses reflect both sensory input and perceptual read-out., (© 2021 The Authors. Human Brain Mapping published by Wiley Periodicals LLC.)

In this research communication we evaluate the impact of the addition of prebiotic components (inulin, polydextrose, and modified starch, 40 g/l) as fat substitutes on the physicochemical characteristics, probiotic survival, and sensory acceptance of probiotic (Lacticaseibacillus casei 01, 108 CFU/ml) Greek yogurts during storage (7 °C, 28 d). All formulations had probiotic counts higher than 107 CFU/ml during storage and simulated gastrointestinal conditions (SGIC). The prebiotic components increased the probiotic survival to the enteric phase of the SGIC, with inulin producing the most pronounced effect. Inulin addition resulted in products with lower pH values and consistency and higher titratable acidity during storage, with negative impact on the sensory acceptance (flavor, texture, and overall impression) at the end of the storage period. Modified starch addition impacted negatively on the acceptance of the products (appearance, flavor, texture, and overall impression). Polydextrose addition resulted in products with lower consistency, but similar sensory acceptance to the full-fat yogurt. It can be concluded that it is possible to prepare potentially synbiotic Greek yogurts by desorption technique using L. casei as probiotic culture and inulin, polydextrose or modified starch as prebiotic components, with the utilization of polydextrose being advisable.

Hysteresis is a well-known phenomenon in physics that relates changes in a system with its prior history. It is also part of human visual experience (perceptual hysteresis), and two different neural mechanisms might explain it: persistence (a cause of positive hysteresis), which forces to keep a current percept for longer, and adaptation (a cause of negative hysteresis), which in turn favors the switch to a competing percept early on. In this study, we explore the neural correlates underlying these mechanisms and the hypothesis of their competitive balance, by combining behavioral assessment with fMRI. We used machine learning on the behavioral data to distinguish between positive and negative hysteresis, and discovered a neural correlate of persistence at a core region of the ventral attention network, the anterior insula. Our results add to the understanding of perceptual multistability and reveal a possible mechanistic explanation for the regulation of different forms of perceptual hysteresis., Competing Interests: Declaration of competing interest The authors declare no competing interests., (Copyright © 2020 The Author(s). Published by Elsevier Inc. All rights reserved.)

This research communication addresses the impact of the addition of Lactobacillus casei and/or carbonation (CO2) on the chemical composition, physicochemical characteristics, probiotic survival, and sensory acceptance of passion-fruit flavored whey dairy beverages (70% milk/30% whey) during storage (30 d/4°C). The addition of Lactobacillus casei and/or carbonation did not impact on the chemical composition, pH values, and acceptance (flavor and overall impression) of the products, but increased the acidity, and decreased the aroma acceptance. The carbonation process did not affect the probiotic survival but decreased the acidity of the products during storage. It can be concluded that it is possible to develop a probiotic passion-fruit flavored carbonated whey dairy beverage with suitable chemical composition, acidity, sensory acceptance (>6 in 9-point hedonic scale) and probiotic viability (>7 log cfu/ml) that could be refrigerated stored for 30 d. This is the first report considering a probiotic non-fermented carbonated whey dairy beverage.

Synbiotic supplements contain pre- and probiotics and are used to modulate gut microbiota composition. This study aimed to investigate effects of two synbiotic mixtures on human faecal bacteria in vitro. Short chain fructooligosaccharides (FOS) (1% w/v) combined with either Bifidobacterium lactis Bb12 or Bifidobacterium lactis HN019 (10 6 colony-forming units (CFU)/mL)] were added to pH-controlled anaerobic batch cultures inoculated with human faeces. Maltodextrin (1% w/v), FOS (1% w/v) and the probiotic strains were also tested individually. Effects on bacteria, short-chain fatty acids (SCFAs) and branched-chain fatty acids (BCFAs) were assessed over 48 h. With maltodextrin, FOS and the synbiotic mixtures, there was a significant increase in total bacteria and bifidobacteria numbers, compared to the negative control or probiotics alone. Increases in Atopobium cluster and Clostridium coccoides-Eubacterium rectale group occurred with FOS and maltodextrin, respectively. Additionally, maltodextrin, FOS and synbiotics resulted in a greater production of acetate and butyrate (SCFAs) compared to the negative control and probiotics alone, whereas concentrations of iso-valerate (BCFA) were lower with these treatments. In conclusion, synbiotic-induced in vitro bacterial changes and changes in SCFAs concentrations were not different from those observed with FOS alone. These data suggest that metabolic effects of these synbiotics are largely driven by the prebiotic component., (Copyright © 2019. Published by Elsevier Ltd.)

Schizophrenia is believed to be a neurodevelopmental disease with high heritability. Differential diagnosis is often challenging, especially in early phases, namely with other psychotic disorders or even mood disorders. such as bipolar disorder with psychotic symptoms. Key pathophysiological changes separating these two classical psychoses remain poorly understood, and current evidence favors a more dimensional than categorical differentiation between schizophrenia and bipolar disorder. While established biomarkers like cortical thickness and grey matter volume are heavily influenced by post-onset changes and thus provide limited possibility of accessing early pathologies, gyrification is assumed to be more specifically determined by genetic and early developmental factors. The aim of our study was to compare both classical and novel morphometric features in these two archetypal psychiatric disorders. We included 20 schizophrenia patients, 20 bipolar disorder patients and 20 age- and gender-matched healthy controls. Data analyses were performed with CAT12/SPM12 applying general linear models for four morphometric measures: gyrification and cortical thickness (surface-based morphometry), and whole-brain grey matter/grey matter volume (voxel-based morphometry - VBM). Group effects were tested using age and gender as covariates (and total intracranial volume for VBM). Voxel-based morphometry analysis revealed a schizophrenia vs. control group effect on regional grey matter volume (p < 0.05, familywise error correction) in the right globus pallidus. There was no group effect on white matter volume when correcting for multiple comparisons neither on cortical thickness. Gyrification changes in clinical samples were found in the left supramarginal gyrus (BA40) - increased and reduced gyrification, respectively, in BPD and SCZ patients - and in the right inferior frontal gyrus (BA47), with a reduction in gyrification of the SCZ group when compared with controls. The joint analysis of different morphometric features, namely measures such as gyrification, provides a promising strategy for the elucidation of distinct phenotypes in psychiatric disorders. Different morphological change patterns, highlighting specific disease trajectories, could potentially generate neuroimaging-derived biomarkers, helping to discriminate schizophrenia from bipolar disorder in early phases, such as first-episode psychosis patients., Competing Interests: Declarations of Competing Interest The authors have no conflict of interest to report., (Copyright © 2020 The Authors. Published by Elsevier Inc. All rights reserved.)

The worldwide prevalence of type 2 diabetes mellitus (T2DM) is constantly increasing, and it has become a major concern, with several implications for public health, economy, and social well-being. It is well-known that several factors such as lifestyle, increased intake of fat and sugar-rich foods, and host genetics can lead to T2DM. Some recent studies have suggested that the composition of the intestinal microbiota can trigger T2DM. Since then, considerable effort has been made to understand the link between the composition of intestinal microbiota and T2DM, as well as the role of probiotics in modulation of intestinal microbiota. This mini-review summarizes the major findings and discusses the close relationship between intestinal microbiota, probiotics, and T2DM.

Background: Asthma is a complex disease with worldwide public health relevance, is related to environmental causes and a genetic predisposition. The chromosomal 17q12-21 locus has been consistently demonstrated to be associated with asthma risk. The effects of variants in the 17q12-21 locus on childhood asthma were first identified in a genome wide- association study. Since that time, those findings have been replicated in different populations but not in South American populations., Objective: This study aimed to investigate the role of variants in the 17q12-21 locus on asthma in a sample of Brazilian children., Methods: This was a cross-sectional study conducted on a cohort of 1247 children. These analyses used 50 Single Nucleotide Variants (SNVs) in the 17q12-21 locus were genotyped as part of a genome wide association study (GWAS)., Results: Four SNVs (rs4065275, rs12603332, rs73985228 and rs77777702) were associated with childhood asthma. The rs73985228 exhibited the strongest association across the different genetic models (OR, 95%CI 2.8, 1.44-3.21, p < 0.01). In an analysis that was stratified by atopy, two SNVs (rs73985228 and rs2715555) were found to be associated with atopic and non-atopic asthma. For the first time, we observed a significant interaction with seropositivity for the Varicella zoster virus (for rs4065275, p = 0.02, and for rs12603332, p = 0.04); i.e., the association was found in those who were seropositive but not in those who were seronegative for this virus., Conclusions: We confirmed the associations of variants in the 17q12-21 locus with atopic and non-atopic asthma and identified an interaction with seropositivity for the Varicella zoster virus., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Background: Grape seed pomace is a valuable by-product from winery/oil extraction industries and a potential source of bioactive compounds. Hot water extraction is the most widely used technology for polysaccharide recovery from plant and seed sources. To obtain an antioxidant fiber-rich extract (AFE) from defatted grape seed pomace, seed:water ratio (1:10-1:20) and extraction temperature (70-90 °C) effects on extraction yield, total sugars, total phenolic compounds and condensed tannins were investigated., Results: The best extraction results were achieved at the highest seed:water ratio and temperature. At these conditions, the extraction yield and total sugar content of the freeze-dried AFE were 100.1 g kg -1 and 725.3 g kg -1 , respectively. The AFE presented high total phenolic content (16.2 g GAE kg -1 ), condensed tannins (515.1 mg CAT kg -1 ), soluble (219.1 g kg -1 ) and insoluble fibers (132.4 g kg -1 ), besides protein (171.1 g kg -1 ) and ash (152.6 g kg -1 ). The antioxidant capacity of the AFE was 382.7, 823.7 and 1439.4 μmol Trolox g -1 for DPPH, ABTS and ORAC methods., Conclusion: The AFE was shown to be not only an interesting source of fiber with antioxidant capacity, which could become a potential foodstuff, but also an ecofriendly and sustainable alternative to use grape seed pomace. © 2019 Society of Chemical Industry., (© 2019 Society of Chemical Industry.)

The role of long-range integration mechanisms underlying visual perceptual binding and their link to interhemispheric functional connectivity, as measured by fMRI, remains elusive. Only inferences on anatomical organization from resting state data paradigms not requiring coherent binding have been achieved. Here, we used a paradigm that allowed us to study such relation between perceptual interpretation and functional connectivity under bistable interhemispheric binding vs. non-binding of visual surfaces. Binding occurs by long-range perceptual integration of motion into a single object across hemifields and non-binding reflects opponent segregation of distinct moving surfaces into each hemifield. We hypothesized that perceptual integration vs. segregation of surface motion, which is achieved in visual area hMT+, is modulated by changes in interhemispheric connectivity in this region. Using 7T fMRI, we found that perceptual long-range integration of bistable motion can be tracked by changes in interhemispheric functional connectivity between left/right hMT+. Increased connectivity was tightly related with long-range perceptual integration. Our results indicate that hMT+ interhemispheric functional connectivity reflects perceptual decision, suggesting its pivotal role on long-range disambiguation of bistable physically constant surface motion. We reveal for the first time, at the scale of fMRI, a relation between interhemispheric functional connectivity and decision based perceptual binding.

In the field of medical education, it is possible to consider that the acquisition of professional competences can gain new contours when considering the use of active methodologies. It is important to analyze the perception of the students about the use of them in medical courses, as well as to reflect on their challenges and potentials. In the present study, a semistructured questionnaire of student perception was applied immediately after the execution of different types of active methodologies in the discipline of physiology in two medical courses. The results suggest a highly positive evaluation of the use of active methodologies by the student body of the two institutions. The students evaluated positively the application of the method (94.6%) and the perception about the learning (84.1%). On the other hand, when questioned about the substitution of the traditional expository method by the active methodologies, there was a tendency to the centrality of the answers, with 84.0% of the responses concentrated at positions 2, 3, and 4 on a scale of 1 (minimum) to 5 (maximum) on the Likert scale. There were no statistically significant differences when comparing variables of age, sex, and previous graduation. Although there was no consensus regarding the full replacement of traditional for active methodologies, one can conclude that the students' perception about the introduction of said methodologies in the teaching of physiology in medical courses is positive, regardless of the subgroups evaluated. These results encourage the insertion of these and other methodologies into medical courses.

Visual adaptation describes the processes by which the visual system alters its operating properties in response to changes in the environment. It is one of the mechanisms controlling visual perceptual bistability - when two perceptual solutions are available - by controlling the duration of each percept. Moving plaids are an example of such ambiguity. They can be perceived as two surfaces sliding incoherently over each other or as a single coherent surface. Here, we investigated, using fMRI, whether activity in the human motion complex (hMT+), a region tightly related to the perceptual integration of visual motion, is modulated by distinct forms of visual adaptation to coherent or incoherent perception of moving plaids. Our hypothesis is that exposure to global coherent or incoherent moving stimuli leads to different levels of measurable adaptation, reflected in hMT+ activity. We found that the strength of the measured visual adaptation effect depended on whether subjects integrated (coherent percept) or segregated (incoherent percept) surface motion signals. Visual motion adaptation was significant both for coherent motion and globally incoherent surface motion. Although not as strong as to the coherent percept, visual adaptation due to the incoherent percept also affects hMT+. This shows that adaptation can contribute to regulate percept duration during visual bistability, with distinct weights, depending on the type of percept. Our findings suggest a link between bistability and adaptation mechanisms, both due to coherent and incoherent motion percepts, but in an asymmetric manner. These asymmetric adaptation weights have strong implications in models of perceptual decision and may explain asymmetry of perceptual interpretation periods., (Copyright © 2018. Published by Elsevier Inc.)

Beneficial effects of probiotics have been reported on body weight, lipid and carbohydrate metabolism, inflammatory state and oxidative stress in healthy subjects and in many metabolic and inflammatory diseases. The aim of this study was to evaluate the effects of Bifidobacterium lactis HN019 on inflammatory state and nitro-oxidative stress in patients with and without the metabolic syndrome (MetS). The usual diets of the thirty-three subjects were supplemented with probiotic milk for 90 d. Inflammatory markers and oxidative measurements were performed. In relation to the baseline values, subjects in both groups showed a decrease in homocysteine (P=0·02 and P=0·03, respectively), hydroperoxides (P=0·02 and P=0·01, respectively) and IL-6 levels (P=0·02). Increases in adiponectin (P=0·04) and nitric oxide metabolites (NOx, P=0·001) levels were only seen in the group with the MetS in relation to the baseline values, whereas only the individuals without the MetS had increases in total radical-trapping antioxidant parameter levels (P=0·002). In conclusion, B. lactis HN019 have several beneficial effects on inflammatory and oxidative biomarkers in healthy subjects and the MetS patients. Patients with the MetS showed a specific improvement in adiponectin and NOx levels, whereas a specific favourable effect was shown in the antioxidant defenses in healthy subjects. If the results obtained in the present study are confirmed, supplementation of fermented milk with probiotics in healthy subjects and patients with the MetS must be further discussed.

EPIGEN-Brazil is one of the largest Latin American initiatives at the interface of human genomics, public health, and computational biology. Here, we present two resources to address two challenges to the global dissemination of precision medicine and the development of the bioinformatics know-how to support it. To address the underrepresentation of non-European individuals in human genome diversity studies, we present the EPIGEN-5M+1KGP imputation panel-the fusion of the public 1000 Genomes Project (1KGP) Phase 3 imputation panel with haplotypes derived from the EPIGEN-5M data set (a product of the genotyping of 4.3 million SNPs in 265 admixed individuals from the EPIGEN-Brazil Initiative). When we imputed a target SNPs data set (6487 admixed individuals genotyped for 2.2 million SNPs from the EPIGEN-Brazil project) with the EPIGEN-5M+1KGP panel, we gained 140,452 more SNPs in total than when using the 1KGP Phase 3 panel alone and 788,873 additional high confidence SNPs ( info score ≥ 0.8). Thus, the major effect of the inclusion of the EPIGEN-5M data set in this new imputation panel is not only to gain more SNPs but also to improve the quality of imputation. To address the lack of transparency and reproducibility of bioinformatics protocols, we present a conceptual Scientific Workflow in the form of a website that models the scientific process (by including publications, flowcharts, masterscripts, documents, and bioinformatics protocols), making it accessible and interactive. Its applicability is shown in the context of the development of our EPIGEN-5M+1KGP imputation panel. The Scientific Workflow also serves as a repository of bioinformatics resources., (© 2018 Magalhães et al.; Published by Cold Spring Harbor Laboratory Press.)

In vision, perceptual features are processed in several regions distributed across the brain. Yet, the brain achieves a coherent perception of visual scenes and objects through integration of these features, which are encoded in spatially segregated brain areas. How the brain seamlessly achieves this accurate integration is currently unknown and is referred to as the "binding problem." Among the proposed mechanisms meant to resolve the binding problem, the binding-by-synchrony hypothesis proposes that binding is carried out by the synchronization of distant neuronal assemblies. This study aimed at providing a critical test to the binding-by-synchrony hypothesis by evaluating long-range connectivity using EEG during a motion integration visual task that entails binding across hemispheres. Our results show that large-scale perceptual binding is not associated with long-range interhemispheric gamma synchrony. However, distinct perceptual interpretations were found to correlate with changes in beta power. Increased beta activity was observed during binding under ambiguous conditions and originates mainly from parietal regions. These findings reveal that the visual experience of binding can be identified by distinct signatures of oscillatory activity, regardless of long-range gamma synchrony, suggesting that such type of synchrony does not underlie perceptual binding.

It remains an open question whether long-range disambiguation of ambiguous surface motion can be achieved in early visual cortex or instead in higher level regions, which concerns object/surface segmentation/integration mechanisms. We used a bistable moving stimulus that can be perceived as a pattern comprehending both visual hemi-fields moving coherently downward or as two widely segregated nonoverlapping component objects (in each visual hemi-field) moving separately inward. This paradigm requires long-range integration across the vertical meridian leading to interhemispheric binding. Our fMRI study (n = 30) revealed a close relation between activity in hMT+ and perceptual switches involving interhemispheric segregation/integration of motion signals, crucially under nonlocal conditions where components do not overlap and belong to distinct hemispheres. Higher signal changes were found in hMT+ in response to spatially segregated component (incoherent) percepts than to pattern (coherent) percepts. This did not occur in early visual cortex, unlike apparent motion, which does not entail surface segmentation. We also identified a role for top-down mechanisms in state transitions. Deconvolution analysis of switch-related changes revealed prefrontal, insula, and cingulate areas, with the right superior parietal lobule (SPL) being particularly involved. We observed that directed influences could emerge either from left or right hMT+ during bistable motion integration/segregation. SPL also exhibited significant directed functional connectivity with hMT+, during perceptual state maintenance (Granger causality analysis). Our results suggest that long-range interhemispheric binding of ambiguous motion representations mainly reflect bottom-up processes from hMT+ during perceptual state maintenance. In contrast, state transitions maybe influenced by high-level regions such as the SPL. Hum Brain Mapp 38:4882-4897, 2017. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

Several genome-wide association studies have been conducted to investigate the influence of genetic polymorphisms in the development of allergic diseases, but few of them have included the X chromosome. The aim of present study was to perform an X chromosome-wide association study (X-WAS) for asthma symptoms. The study included 1307 children of which 294 were asthma cases. DNA was genotyped using 2.5 HumanOmni Beadchip from Illumina. Statistical analyses were performed in PLINK 1.9, MACH 1.0 and Minimac2. The variant rs12007907 (g.29483892C>A) in IL1RAPL gene was suggestively associated with asthma symptoms in discovery set (odds ratio (OR)=0.49, 95% confidence interval (CI): 0.37-0.67; P=3.33 × 10 - 6 ). This result was replicated in the ProAr cohort in men only (OR=0.45, 95% CI: 0.21-0.95; P=0.038). Furthermore, investigating the functional role of the rs12007907 on the production a Th2-type cytokine, IL-13, we found a negative association between the minor allele A with IL-13 production in the discovery set (P=0.044). Gene-based analysis revealed that NUDT10 was the most consistently associated with asthma symptoms in discovery sample. In conclusion, the rs12007907 variant in IL1RAPL gene was negatively associated with asthma and IL-13 production in our study and a sex-specific association was observed in one of the validation samples. It suggests an effect on asthma susceptibility and may explain differences in severe asthma frequency between women and men.

Considering the variety of implant connection systems available in the market and the contrasting literature regarding tapered connection systems in terms of bacterial leakage, the aim of this in vitro study was to compare the effectiveness of the bacterial seal at the implant/abutment interface between an external hexagon and a tapered connection system. Twelve sets of indexed tapered connection components and twelve sets of external hexagon connection components were used for microbiological analysis. In addition, for each model, an implant with its respective prosthetic abutment was used as a negative control and another as a positive control of microbial contamination. Failure of the abutment/implant interface seal was observed via turbidity or presence of deposits in the culture. Descriptive analysis of the data and relative frequency (percentage) as well as Fisher's exact test were used at a significance level of 5%. Two of ten (20%) external hexagon specimens showed contamination against 0/10 (0%) tapered connection implants. In conclusion, both implant/abutment connections were able to prevent bacterial leakage in vitro., Competing Interests: The authors declare that they have no competing interests.

Snake venom serine proteases (SVSPs) are enzymes capable of interfering at several points of hemostasis. Some serine proteases present thrombin-like activity, which makes them targets for the development of therapeutics agents in the treatment of many hemostatic disorders. In this study, a recombinant thrombin-like serine protease, denominated rBpSP-II, was obtained from cDNA of the Bothrops pauloensis venom gland and was characterized enzymatically and biochemically. The enzyme rBpSP-II showed clotting activity on bovine plasma and proteolytic activity on fibrinogen, cleaving exclusively the Aα chain. The evaluation of rBpSP-II activity on chromogenic substrates demonstrated thrombin-like activity of the enzyme due to its capacity to hydrolyze the thrombin substrate. These characteristics make rBpSP-II an attractive molecule for additional studies. Further research is needed to verify whether rBpSP-II can serve as a template for the synthesis of therapeutic agents to treat hemostatic disorders., (Copyright © 2016 Elsevier Ltd. All rights reserved.)

Objective: Human studies have shown the beneficial effects of probiotic microorganisms on the parameters of metabolic syndrome (MetS) and other cardiovascular risks, but to our knowledge the effect of Bifidobacterium lactis has not yet been reported. The aim of this study was to evaluate the effect of consumption of milk containing the probiotic B. lactis HN019 on the classical parameters of MetS and other related cardiovascular risk factors., Methods: Fifty-one patients with MetS were selected and divided into a control group (n = 25) and a probiotic group (n = 26). The probiotic group consumed fermented milk with probiotics over the course of 45 d. The effects of B. lactis on lipid profile, glucose metabolism, and proinflammatory cytokines (tumor necrosis factor-α and interleukin-6) were assessed in blood samples of the individuals at the baseline and after 45 d., Results: Daily ingestion of 80 mL fermented milk with 2.72 × 10(10) colony-forming units of B. lactis HN019 showed significant reduction in body mass index (P = 0.017), total cholesterol (P = 0.009), and low-density lipoprotein (P = 0.008) compared with baseline and control group values. Furthermore, a significant decrease in tumor necrosis factor-α (P = 0.033) and interleukin-6 (P = 0.044) proinflammatory cytokines was observed., Conclusion: These data showed potential effects of B. lactis HN019 in reducing obesity, blood lipids, and some inflammatory markers, which may reduce cardiovascular risk in patients with MetS., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The limited capacity of the human brain to process the full extent of visual information reaching the visual cortex requires the recruitment of mechanisms of information selection through attention. Neurofibromatosis type-1 (NF1) is a neurodevelopmental disease often exhibiting attentional deficits and learning disabilities, and is considered to model similar impairments common in other neurodevelopmental disorders such as autism. In a previous study, we found that patients with NF1 are more prone to miss targets under overt attention conditions. This finding was interpreted as a result of increased occipito-parietal alpha oscillations. In the present study, we used electroencephalography (EEG) to study alpha power modulations and the performance of patients with NF1 in a covert attention task. Covert attention was required in order to perceive changes (target offset) of a peripherally presented stimulus. Interestingly, alpha oscillations were found to undergo greater desynchronization under this task in the NF1 group compared with control subjects. A similar pattern of desynchronization was found for beta frequencies while no changes in gamma oscillations could be identified. These results are consistent with the notion that different attentional states and task demands generate different patterns of abnormal modulation of alpha oscillatory processes in NF1. Under covert attention conditions and while target offset was reported with relatively high accuracy (over 90% correct responses), excessive desynchronization was found. These findings suggest an abnormal modulation of oscillatory activity and attentional processes in NF1. Given the known role of alpha in modulating attention, we suggest that alpha patterns can show both abnormal increases and decreases that are task and performance dependent, in a way that enhanced alpha desynchronization may reflect a compensatory mechanism to keep performance at normal levels. These results suggest that dysregulation of alpha oscillations may occur in NF1 both in terms of excessive or diminished activation patterns.

Background: Asthma is a chronic disease of the airways and, despite the advances in the knowledge of associated genetic regions in recent years, their mechanisms have yet to be explored. Several genome-wide association studies have been carried out in recent years, but none of these have involved Latin American populations with a high level of miscegenation, as is seen in the Brazilian population., Methods: 1246 children were recruited from a longitudinal cohort study in Salvador, Brazil. Asthma symptoms were identified in accordance with an International Study of Asthma and Allergies in Childhood (ISAAC) questionnaire. Following quality control, 1,877,526 autosomal SNPs were tested for association with childhood asthma symptoms by logistic regression using an additive genetic model. We complemented the analysis with an estimate of the phenotypic variance explained by common genetic variants. Replications were investigated in independent Mexican and US Latino samples., Results: Two chromosomal regions reached genome-wide significance level for childhood asthma symptoms: the 14q11 region flanking the DAD1 and OXA1L genes (rs1999071, MAF 0.32, OR 1.78, 95% CI 1.45-2.18, p-value 2.83 × 10(-8)) and 15q22 region flanking the FOXB1 gene (rs10519031, MAF 0.04, OR 3.0, 95% CI 2.02-4.49, p-value 6.68 × 10(-8) and rs8029377, MAF 0.03, OR 2.49, 95% CI 1.76-3.53, p-value 2.45 × 10(-7)). eQTL analysis suggests that rs1999071 regulates the expression of OXA1L gene. However, the original findings were not replicated in the Mexican or US Latino samples., Conclusions: We conclude that the 14q11 and 15q22 regions may be associated with asthma symptoms in childhood.

While South Americans are underrepresented in human genomic diversity studies, Brazil has been a classical model for population genetics studies on admixture. We present the results of the EPIGEN Brazil Initiative, the most comprehensive up-to-date genomic analysis of any Latin-American population. A population-based genome-wide analysis of 6,487 individuals was performed in the context of worldwide genomic diversity to elucidate how ancestry, kinship, and inbreeding interact in three populations with different histories from the Northeast (African ancestry: 50%), Southeast, and South (both with European ancestry >70%) of Brazil. We showed that ancestry-positive assortative mating permeated Brazilian history. We traced European ancestry in the Southeast/South to a wider European/Middle Eastern region with respect to the Northeast, where ancestry seems restricted to Iberia. By developing an approximate Bayesian computation framework, we infer more recent European immigration to the Southeast/South than to the Northeast. Also, the observed low Native-American ancestry (6-8%) was mostly introduced in different regions of Brazil soon after the European Conquest. We broadened our understanding of the African diaspora, the major destination of which was Brazil, by revealing that Brazilians display two within-Africa ancestry components: one associated with non-Bantu/western Africans (more evident in the Northeast and African Americans) and one associated with Bantu/eastern Africans (more present in the Southeast/South). Furthermore, the whole-genome analysis of 30 individuals (42-fold deep coverage) shows that continental admixture rather than local post-Columbian history is the main and complex determinant of the individual amount of deleterious genotypes.

The degree of admixture in Brazil between historically isolated populations is complex and geographically variable. Studies differ as to what the genetic and phenotypic consequences of this mixing have been. In Northeastern Brazil, we enrolled 522 residents of Salvador and 620 of Fortaleza whose distributions of self-declared color were comparable to those in the national census. Using the program Structure and principal components analysis there was a clear correlation between biogeographic ancestry and categories of skin color. This correlation with African ancestry was stronger in Salvador (r=0.585; P<0.001) than in Fortaleza (r=0.236; P<0.001). In Fortaleza, although self-declared blacks had a greater proportion of European ancestry, they had more African ancestry than the other categories. When the populations were analyzed without pseudoancestors, as in some studies, the relationship of 'race' to genetic ancestry tended to diffuse or disappear. The inclusion of different African populations also influenced ancestry estimates. The percentage of unlinked ancestry informative markers in linkage disequilibrium, a measure of population structure, was 3-5 times higher in both Brazilian populations than expected by chance. We propose that certain methods, ascertainment bias and population history of the specific populations surveyed can result in failure to demonstrate a correlation between skin color and genetic ancestry. Population structure in Brazil has important implications for genetic studies, but genetic ancestry is irrelevant for how individuals are treated in society, their health, their income or their inclusion. These track more closely with perceived skin color than genetic ancestry.

Lactobacillus plantarum has been used in human clinical trials to promote beneficial effects in the immune system, to alleviate intestinal disorders, and to reduce the risk of cardiovascular disease. It is also involved in many fermentation processes in the food industry. However, information on the fate of ingested L. plantarum is limited. In this study, 61 subjects received daily doses of fermented milk containing 2 × 10(11) cells of L. plantarum Lp115 for different periods of time. The target microorganism was monitored in the fecal microbiota via quantitative PCR (qPCR). L. plantarum was detected and quantified in all of the subjects during the ingestion periods. The differences between the L. plantarum levels at time zero and during all the different ingestion periods were statistically significant (P = 0.001). However, at 15 and 45 days after discontinuing supplementation, the number of lactobacilli was reduced to the baseline level (those at time zero). A longer period with L. plantarum in the diet did not result in increased levels of this bacterium in the stool, based on postconsumption evaluations (P = 0.001). The qPCR method was specific and sensitive for L. plantarum quantification in such a complex microbial environment as the gastrointestinal tract.

The early stages of diabetic retinopathy (DR) are characterized by alterations similar to neurodegenerative and inflammatory conditions such as increased neural apoptosis, microglial cell activation and amplified production of pro-inflammatory cytokines. Adenosine regulates several physiological functions by stimulating four subtypes of receptors, A1AR, A2AAR, A2BAR, and A3AR. Although the adenosinergic signaling system is affected by diabetes in several tissues, it is unknown whether diabetic conditions in the retina can also affect it. Adenosine delivers potent suppressive effects on virtually all cells of the immune system, but its potential role in the context of DR has yet to be studied in full. In this study, we used primary mixed cultures of rat retinal cells exposed to high glucose conditions, to mimic hyperglycemia, and a streptozotocin rat model of type 1 diabetes to determine the effect diabetes/hyperglycemia have on the expression and protein levels of adenosine receptors and of the enzymes adenosine deaminase and adenosine kinase. We found elevated mRNA and protein levels of A1AR and A2AAR, in retinal cell cultures under high glucose conditions and a transient increase in the levels of the same receptors in diabetic retinas. Adenosine deaminase and adenosine kinase expression and protein levels showed a significant decrease in diabetic retinas 30 days after diabetes induction. An enzymatic assay performed in retinal cell cultures revealed a marked decrease in the activity of adenosine deaminase under high glucose conditions. We also found an increase in extracellular adenosine levels accompanied by a decrease in intracellular levels when retinal cells were subjected to high glucose conditions. In conclusion, this study shows that several components of the retinal adenosinergic system are affected by diabetes and high glucose conditions, and the modulation observed may uncover a possible mechanism for the alleviation of the inflammatory and excitotoxic conditions observed in diabetic retinas.

Surfactants have long been known to have microbicidal action and have been extensively used as antiseptics and disinfectants for a variety of general hygiene and clinical purposes. Among surfactants, quaternary ammonium compounds (QAC) are known to be the most useful antiseptics and disinfectants. However, our previous toxicological studies showed that QAC are also the most toxic surfactants for mammalian cells. An understanding of the mechanisms that underlie QAC toxicity is a crucial first step in their rational use and in the design and development of more effective and safer molecules. We show that QAC-induced toxicity is mediated primarily through mitochondrial dysfunction in mammalian columnar epithelial cell cultures in vitro. Toxic effects begin at sublethal concentrations and are characterized by mitochondrial fragmentation accompanied by decreased cellular energy charge. At very low concentrations, several QAC act on mitochondrial bioenergetics through a common mechanism of action, primarily by inhibiting mitochondrial respiration initiated at complex I and, to a lesser extent, by slowing down coupled ADP phosphorylation. The result is a reduction of cellular energy charge which, when reduced below 50% of its original value, induces apoptosis. The lethal effects are shown to be primarily a result of this process. At higher doses (closer to the critical micellar concentration), QAC induce the complete breakdown of cellular energy charge and necrotic cell death.

Unlabelled: A dried tomato-flavored probiotic cream cheese (P) containing Lactobacillus paracasei Lpc-37 was developed for the purpose of this study. The same product, but without probiotic addition (C) was used as control. Lactococcus lactis subsp. lactis and Lactococcus lactis subsp. cremoris were used as lactic starter cultures. Chemical composition analyses and sensory tests were performed on days 1 and 7, respectively. Titratable acidity, pH value and L. paracasei population were determined every 7 d during the refrigerated storage (21 d) of the cream cheeses. The experiment and analyses were performed in triplicate, using standard methods. Probiotic population remained greater than 10(7) CFU/g throughout the storage period, thereby characterizing the product as potentially probiotic. Cream cheeses C and P did not differ on the sensory tests, both obtaining good overall acceptance by the consumers, of which 82.6% stated that they certainly or probably would buy the product., Practical Application: Lactobacillus paracasei Lpc-37 is a probiotic bacterium and clinical studies have shown that this microorganism beneficially affects its host. In general, dried tomato-flavored products and cream cheese are products with good acceptance by the consumers. Thus, regular consumption of the probiotic cream cheese developed in this study may have positive effects on health and well being of people if incorporated into their diet., (© 2012 Institute of Food Technologists®)

Background: Adverse drug reactions (ADRs) associated with anti-tuberculosis (anti-TB) drug regimens have considerable impact on anti-TB treatment, potentially leading to unsuccessful outcomes. Nevertheless, the risk factors that play a role in anti-TB drug-induced ADRs are not well established. It is well documented that genetic polymorphisms in drug-metabolizing enzymes (DMEs) result in considerably complex variability in anti-TB drug disposition. In addition, the impact of pharmacogenetic variation on the metabolism of anti-TB drugs may be modifiable by environmental exposure. Thus, an assessment of pharmacogenetic variability combined with biomarkers of environmental exposure may be helpful for demonstrating the effect of the gene-environment interaction on susceptibility to ADRs induced by anti-TB drug therapy., Objective: The aim of the study was to investigate the impact of the interaction between environmental risk factors and pharmacogenetic polymorphisms in four common DMEs--N-acetyltransferase 2 (arylamine N-acetyltransferase) [NAT2], glutathione S-transferase theta 1 [GSTT1], glutathione S-transferase mu 1 [GSTM1], and cytochrome P450 2E1 [CYP2E1]--on commonly reported ADRs to first-line anti-TB drugs in 129 patients receiving homogeneous TB treatment., Methods: TB patients monitored during drug treatment were divided into subgroups according to the presence or absence of ADRs. Additionally, the patients' clinical and demographic characteristics were collected in order to identify the environmental factors that are potential triggers for ADRs induced by anti-TB drug treatment. Pharmacogenetic variability was determined by gene sequencing, TaqMan® assays, or polymerase chain reaction., Results: The findings of this study suggest that the NAT2 slow acetylator haplotype, female sex, and smoking are important determinants of susceptibility to ADRs induced by anti-TB drugs. Patients carrying multiple, but not single, polymorphisms in the NAT2, GSTM1, GSTT1, and CYP2E1 genes were found to have an increased risk of ADRs, as revealed by gene-gene interaction analysis. Moreover, we also identified meaningful gene-environment interaction models that resulted in the highest levels of ADR risk., Conclusion: The study findings provide evidence of the clinical impact of the interaction between pharmacogenetic variability and environmental factors on ADRs induced by anti-TB drug therapy. Predictive pharmacogenetic testing and a comprehensive clinical history would therefore be helpful for identification and careful monitoring of patients at high risk of this complication.

Diabetic retinopathy (DR), a leading cause of vision loss and blindness among working-age adults, holds several hallmarks of an inflammatory disease. The increase in cell death in neural retina is an early event in the diabetic retina, preceding the loss of microvascular cells. Since tumor necrosis factor-α (TNF-α) has been shown to trigger the death of perycites and endothelial cells as well as the breakdown of the blood-retinal barrier, we set out to investigate whether TNF-α acting through tumor necrosis factor receptor 1 (TNFR1), the major receptor responsible for mediating TNF-induced cell death, could also be responsible for the early neuronal cell death observed in DR. We used retinal neural cell cultures exposed to high glucose conditions, to mimic hyperglycaemia, and evaluated the contribution of TNFR1 in neural cell death. TNFR1 was found to be present to a great extent in retinal neurons and the levels of this receptor were found to be altered in cells cultured in high glucose conditions. High glucose induced an early decrease in cell viability, an increase in apoptosis and a higher immunoreactivity for the cleaved caspase-3, indicating a high glucose-induced caspase-dependent cell death. These observations were correlated with an increase in TNF-α expression. Nonetheless, inhibiting the activation of TNFR1 was sufficient to prevent the decrease in cell viability and the increase in retinal cell death by apoptosis. In conclusion, our data indicate that TNF-α acting through TNFR1 is responsible for the high glucose-induced cell death and that blocking the activity of this receptor is an adequate strategy to avoid cell loss in such conditions., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Activation of purinergic P2 receptors, which are expressed in neurons and microglial cells, normally induces an increase in intracellular calcium concentration ([Ca(2+)](i)) and some of the inflammatory mediators and excitatory neurotransmitters found to be implicated in neuronal cell death observed in diabetic retinas are released in response to an increase in the [Ca(2+)](i). However, it is unknown whether hyperglycemia/high glucose has an effect in the [Ca(2+)](i) changes triggered by the activation of P2 receptors in retinal cells. Using single-cell calcium imaging studies, we found that [Ca(2+)](i) changes triggered by purinergic receptors activation, both in retinal neurons and microglial cells, were potentiated in cells that had been cultured in high glucose conditions. In retinal neurons the increase in [Ca(2+)](i) was mostly due to Ca(2+) influx through voltage sensitive calcium channels, whereas in microglial cells Ca(2+) influx occurred mainly through P2X receptor channels, while there was also a smaller component of [Ca(2+)](i) rise dependent on calcium release from intracellular stores, probably due to P2Y receptor activation. In conclusion, our results show that rat retinal neural cells cultured in high glucose conditions show increased calcium responses to P2 receptors activation. This augmented calcium response might account for the increase in the release of neurotransmitters and inflammatory mediators found in diabetic retinas and, therefore, be responsible for retinal cell death observed in the early stages of diabetic retinopathy., ((c) 2009 Elsevier B.V. All rights reserved.)