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Purpose: This study aimed to determine the prevalence of anxiety and depression among patients with glaucoma compared to the average Brazilian prevalence (9.8% of anxiety and 5.8% of depression, according to the World Health Organization) and its correlation with the severity of the disease. Methods: This was a transversal, single-arm trial of patients from four glaucoma centers in São Paulo and Curitiba-Brazil. Patients comprised adults at least 18 years of age with glaucoma diagnosis under treatment for at least 6 months. All subjects of the study answered two questionnaires (PHQ-9 and GAD-7) to evaluate the presence of anxiety and depression, and the results were analyzed accordingly to clinical and demographic characteristics. Results: The protocol included a total of 210 patients. The average age was 61.6 ± 15.3 years, and the female gender was more common (68.86%). Primary open-angle glaucoma was the most common diagnosis (59.90%). The average IOP was 18.5 mmHg, and 1.5 anti-glaucoma drops were the mean treatment. The prevalence of depression and anxiety was 26.90 and 25.71%, respectively. Most patients with anxiety were classified as early glaucoma, while those with depression had severe glaucoma. Conclusion: This study found that the prevalence of anxiety and depression among patients with glaucoma is higher than in the general population in our country.

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Breast cancer is the most prevalent cancer among women worldwide. Therapeutic strategies to control tumors and metastasis are still challenging. Three-dimensional (3D) spheroid-type systems more accurately replicate the features of tumors in vivo, working as a better platform for performing therapeutic response analysis. This work aimed to characterize the epithelial-mesenchymal transition and doxorubicin (dox) response in a mammary tumor spheroid (MTS) model. We evaluated the doxorubicin treatment effect on MCF-7 spheroid diameter, cell viability, death, migration and proteins involved in the epithelial-mesenchymal transition (EMT) process. Spheroids were also produced from tumors formed from 4T1 and 67NR cell lines. MTSs mimicked avascular tumor characteristics, exhibited adherens junction proteins and independently produced their own extracellular matrix. Our spheroid model supports the 3D culturing of cells isolated from mice mammary tumors. Through the migration assay, we verified a reduction in E-cadherin expression and an increase in vimentin expression as the cells became more distant from spheroids. Dox promoted cytotoxicity in MTSs and inhibited cell migration and the EMT process. These results suggest, for the first time, that this model reproduces aspects of the EMT process and describes the potential of dox in inhibiting the metastatic process, which can be further explored.

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A three-dimensional (3D) cell culture can more precisely mimic tissues architecture and functionality, being a promising alternative model to study disease pathophysiology and drug screening. Chagas disease (CD) is a neglected parasitosis that affects 7 million people worldwide. Trypanosoma cruzi's (T. cruzi) mechanisms of invasion/persistence continue to be elucidated. Benznidazole (BZ) and Nifurtimox (NF) are trypanocidal drugs with few effects on the clinical manifestations of the chronic disease. Chronic Chagas cardiomyopathy (CCC) is the main manifestation of CD due to its frequency and severity. The development of fibrosis and hypertrophy in cardiac tissue can lead to heart failure and sudden death. Thus, there is an urgent need for novel therapeutic options. Our group has more than fifteen years of expertise using 3D primary cardiac cell cultures, being the first to reproduce fibrosis and hypertrophy induced by T. cruzi infection in vitro. These primary cardiac spheroids exhibit morphological and functional characteristics that are similar to heart tissue, making them an interesting model for studying CD cardiac fibrosis. Here, we aim to demonstrate that our primary cardiac spheroids are great preclinical models which can be used to develop new insights into CD cardiac fibrosis, presenting advances already achieved in the field, including disease modeling and drug screening.

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Neurological commitment is a neglected manifestation of Chagas disease (CD). Meningoencephalitis mainly affects children and immunosuppressed patients, while stroke can occur with or without cardiac compromise. One of the possible causes of stroke development is microvascular commitment. Our group previously described that experimental Trypanossoma cruzi acute infection leads to cerebral microvasculopathy. This condition is characterized by decreased capillary density, increased leukocyte rolling and adhesion, and endothelial dysfunction. CD was discovered 114 years ago, and until today, only two drugs have been available for clinical treatment: benznidazole and nifurtimox. Both present a high cure rate for the acute phase (80%) and small cure rate for the chronic phase (20%). In addition, the high occurrence of side-effects, without proper medical follow-up, can result in treatment abandonment. Therefore, the search for new therapeutic schemes is necessary. Statins are drugs already used in the clinic that have several pleiotropic effects including endothelial function improvement, anti-inflammatory action, as well as trypanocidal effects, making them a potential alternative treatment for brain microvasculopathy in CD. Here, we investigate the effect of lovastatin (LOV) on brain microvasculopathy and inflammatory parameters. Swiss Webster mice were intraperitoneally inoculated with the Y strain of T. cruzi. Treatment with lovastatin (20 mg/kg/day) was initiated 24 h after the infection and continued for 14 consecutive days. We observed that LOV treatment did not affect parasitemia, brain microcirculation alterations, or the reduction in cerebral blood flow caused by T. cruzi infection. Also, LOV did not prevent the increased number of CD3+ cells and eNOS levels in the T. cruzi-infected brain. No alterations were observed on VCAM-1 and MCP-1 expressions, neither caused by infection nor LOV treatment. However, LOV prevented the increase in F4/80+ cells and ICAM-1 levels in the brain caused by acute infection with T. cruzi. These results suggest an anti-inflammatory activity of LOV, but more studies are needed to elucidate the role of LOV in CD acute infection.

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Selenium has been proven to influence several biological functions, showing to be an essential micronutrient. The functional studies demonstrated the benefits of a balanced selenium diet and how its deficiency is associated with diverse diseases, especially cancer and viral diseases. Selenium is an antioxidant, protecting the cells from damage, enhancing the immune system response, preventing cardiovascular diseases, and decreasing inflammation. Selenium can be found in its inorganic and organic forms, and its main form in the cells is the selenocysteine incorporated into selenoproteins. Twenty-five selenoproteins are currently known in the human genome: glutathione peroxidases, iodothyronine deiodinases, thioredoxin reductases, selenophosphate synthetase, and other selenoproteins. These proteins lead to the transport of selenium in the tissues, protect against oxidative damage, contribute to the stress of the endoplasmic reticulum, and control inflammation. Due to these functions, there has been growing interest in the influence of polymorphisms in selenoproteins in the last two decades. Selenoproteins' gene polymorphisms may influence protein structure and selenium concentration in plasma and its absorption and even impact the development and progression of certain diseases. This review aims to elucidate the role of selenoproteins and understand how their gene polymorphisms can influence the balance of physiological conditions. In this polymorphism review, we focused on the PubMed database, with only articles published in English between 2003 and 2023. The keywords used were "selenoprotein" and "polymorphism". Articles that did not approach the theme subject were excluded. Selenium and selenoproteins still have a long way to go in molecular studies, and several works demonstrated the importance of their polymorphisms as a risk biomarker for some diseases, especially cardiovascular and thyroid diseases, diabetes, and cancer.

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Chagas disease (CD) caused by Trypanosoma cruzi is a neglected illness and a major reason for cardiomyopathy in endemic areas. The existing therapy generally involves trypanocidal agents and therapies that control cardiac alterations. However, there is no treatment for the progressive cardiac remodeling that is characterized by inflammation, microvasculopathy and extensive fibrosis. Thus, the search for new therapeutic strategies aiming to inhibit the progression of cardiac injury and failure is necessary. Vascular Endothelial Growth Factor A (VEGF-A) is the most potent regulator of vasculogenesis and angiogenesis and has been implicated in inducing exacerbated angiogenesis and fibrosis in chronic inflammatory diseases. Since cardiac microvasculopathy in CD is also characterized by exacerbated angiogenesis, we investigated the effect of inhibition of the VEGF signaling pathway using a monoclonal antibody (bevacizumab) on cardiac remodeling and function. Swiss Webster mice were infected with Y strain, and cardiac morphological and molecular analyses were performed. We found that bevacizumab significantly increased survival, reduced inflammation, improved cardiac electrical function, diminished angiogenesis, decreased myofibroblasts in cardiac tissue and restored collagen levels. This work shows that VEGF is involved in cardiac microvasculopathy and fibrosis in CD and the inhibition of this factor could be a potential therapeutic strategy for CD.

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Chagas disease (CD) is caused by the flagellate protozoan Trypanosoma cruzi. It is endemic in Latin America. Nowadays around 6 million people are affected worldwide, and 75 million are still at risk. CD has two evolutive phases, acute and chronic. The acute phase is mostly asymptomatic, or presenting unspecific symptoms which makes it hard to diagnose. At the chronic phase, patients can stay in the indeterminate form or develop cardiac and/or digestive manifestations. The two trypanocide drugs available for the treatment of CD are benznidazole (BZ) and nifurtimox (NFX), introduced in the clinic more than five decades ago. WHO recommends treatment for patients at the acute phase, at risk of congenital infection, for immunosuppressed patients and children with chronic infection. A high cure rate is seen at the CD acute phase but better treatment schemes still need to be investigated for the chronic phase. There are some limitations within the use of the trypanocide drugs, with side effects occurring in about 40% of the patients, that can lead patients to interrupt treatment. In addition, patients with advanced heart problems should not be treated with BZ. This is a neglected disease, discovered 114 years ago that still has no drug effective for their chronic phase. Multiple social economic and cultural barriers influence CD research. The high cost of the development of new drugs, in addition to the low economical return, results in the lack of investment. More economic support is required from governments and pharmaceutical companies on the development of more research for CD treatment. Two approaches stand out: repositioning and combination of drugs, witch drastically decrease the cost of this process, when compared to the development of a new drug. Here we discuss the progress of the clinical trials for the etiological and pathophysiological treatment for CD. In summary, more studies are needed to propose a new drug for CD. Therefore, BZ is still the best option for CD. The trials in course should clarify more about new treatment regimens, but it is already possible to indicate that dosage and time of treatment need to be adjusted.

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BACKGROUND: Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear. OBJECTIVES: The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD. METHODS: The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting. FINDINGS: In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium. MAIN CONCLUSIONS: We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.

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Forest fires can threaten amphibians because ash-associated contaminants transported by post-fire runoff impact both terrestrial and aquatic ecosystems. Still, the effects of these contaminants on the skin microbiome of amphibians have been overlooked. Thus, the main objective of this study was to assess the effects of ash from different severity wildfires (moderate and high) on the skin microbiome of the Iberian frog (Rana iberica). Bacterial isolates sampled from R. iberica skin microbiome were tested for their antimicrobial activity against the pathogen Aeromonas salmonicida. The isolates with antimicrobial activity were identified and further exposed to several concentrations (0, 6.25, 12.5, 25, 50, 75, and 100%) of Eucalypt (Eucalyptus globulus) aqueous extracts (AAEs) of ash from both a moderate and a high severity wildfire. The results showed that 53% of the bacterial isolates presented antimicrobial activity, with Pseudomonas being the most common genus. Exposure to AAEs had diverse effects on bacterial growth since a decrease, an increase or no effects on growth were observed. For both ash types, increasing AAEs concentrations led to an increase in the number of bacteria whose growth was negatively affected. Ash from the high severity fire showed more adverse effects on bacterial growth than those from moderate severity, likely due to the higher metal concentrations of the former. This study revealed that bacteria living in Iberian frogs' skin could be impaired by ash-related contaminants, potentially weakening the individual's immune system. Given the foreseen increase in wildfires' frequency and severity under climate change, this work raises awareness of the risks faced by amphibian communities in fire-prone regions, emphasising the importance of a rapid implementation of post-fire emergency measures for the preservation and conservation of this group of animals.

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Environmental contamination influences the diversity of the resident skin microbial community of amphibians, ultimately affecting the individual's immune system. Wildfires are expected to impact the skin microbiome, since post-fire runoff typically transports hazardous substances, that can affect terrestrial and aquatic ecosystems. The present study is the first to assess the effects of Eucalypt and Pine wildfire ash on cultivable bacterial isolates from the skin microbiome of amphibians, in particular the fire salamander (Salamandra salamandra), a common species in fire-prone Mediterranean ecosystems. To achieve this goal, samples of skin bacteria of adult individuals of S. salamandra were collected at a site without influence of wildfires. The bacterial isolates were tested against the pathogenic agent Aeromonas salmonicida for assessing their antimicrobial activity, before exposing them to a series of dilutions of aqueous extracts of Eucalypt and Pine ashes (AAEs) from high severity wildfires. From the 80 bacterial isolates collected, 48 (mostly Pseudomonas spp.) showed antimicrobial activity. Exposure of bacteria with antimicrobial activity to the Eucalypt and Pine AAEs at concentrations of 0, 6.25, 12.5, 25, 50, 75, and 100%, revealed that bacterial growth could be significantly inhibited, stimulated or unaffected by ash. Growth inhibition was found for Pine and Eucalypt AAEs at concentrations as low as 6.25% and 12.5%, respectively, but were more expressive at concentrations equal or above 50%. Eucalypt AAEs had a higher negative impact on bacterial growth than Pine AAEs, likely due to differences in metal concentrations between ash types. These findings raise concern about the future of amphibians in fire-prone regions since the foreseen increase in fire frequency and severity owing to climate changes are likely to alter the skin microbiome of amphibians, weaken the immune system and consequently increasing the incidence of infections or diseases, further contributing to the decline of the populations.

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PURPOSE: Late hypotony is an undesirable and challenging complication of glaucoma surgery. We describe our use of the Ologen Collagen Matrix to treat late hypotony developing after trabeculectomy. STUDY DESIGN: A retrospective study performed at three eye surgery centers in Brazil. PARTICIPANTS: Eighteen patients who underwent 19 eye surgeries. INTERVENTION: Subconjunctival Ologen was implanted at the trabeculectomy sites to treat over-filtering or leaking blebs in patients experiencing late hypotony after trabeculectomy (obtained 6 months after glaucoma surgery). The primary outcome was the intraocular pressure (IOP); we gathered preoperative data records from 19 Ologen treated eyes and days 1, 7, 30, 60, and 180 postoperatively. The secondary outcomes included visual acuity and macular thickness measured via optical coherence tomography; we compared preoperative data to subsequent ones up to sixth-month-evolution. RESULTS: Over the 6-month period, the IOP rose from 2.89 ± 1.59 mmHg preoperatively to 8.21 ± 3.46 mmHg (p = 0.0001). Visual acuity improved from 0.33 ± 0.29 to 0.21 ± 0.31 LogMar (p = 0.0013). Macular thickness fell from 325.62 ± 58.7 to 283.08 ± 47.35 µm (p = 0.0097). We encountered two complications: one related to suture dehiscence following an ocular trauma and one instance of transitory choroidal detachment. CONCLUSION: Subconjunctival Ologen implants preserved bleb function and successfully treated post-trabeculectomy hypotony as revealed by data collected at the 6-month follow-up. Longer follow-up is necessary to confirm long-term efficacy and safety. There are no financial conflicts of interest to disclose.

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BACKGROUND Angiogenesis has been implicated in tissue injury in several noninfectious diseases, but its role in Chagas disease (CD) physiopathology is unclear. OBJECTIVES The present study aimed to investigate the effect of Trypanosoma cruzi infection on cardiac angiogenesis during the acute phase of experimental CD. METHODS The signalling pathway involved in blood vessel formation and cardiac remodelling was evaluated in Swiss Webster mice infected with the Y strain of T. cruzi. The levels of molecules involved in the regulation of angiogenesis, such as vascular endothelial growth factor-A (VEGF-A), Flk-1, phosphorylated extracellular-signal-regulated protein kinase (pERK), hypoxia-inducible factor-1α (HIF-1α), CD31, α-smooth muscle actin (α-SMA) and also the blood vessel growth were analysed during T. cruzi infection. Hearts were analysed using conventional histopathology, immunohistochemistry and western blotting. FINDINGS In this study, our data demonstrate that T. cruzi acute infection in mice induces exacerbated angiogenesis in the heart and parallels cardiac remodelling. In comparison with noninfected controls, the cardiac tissue of T. cruzi-infected mice presented higher levels of (i) HIF-1α, VEGF-A, Flk-1 and pERK; (ii) angiogenesis; (iii) α-SMA+ cells in the tissue; and (iv) collagen -1 deposition around blood vessels and infiltrating throughout the myocardium. MAIN CONCLUSIONS We observed cardiac angiogenesis during acute experimental T. cruzi infection parallels cardiac inflammation and remodelling.

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Chagas disease is responsible for more than 10,000 deaths per year and about 6 to 7 million infected people worldwide. In its chronic stage, patients can develop mega-colon, mega-esophagus, and cardiomyopathy. Differences in clinical outcomes may be determined, in part, by the genetic background of the parasite that causes Chagas disease. Trypanosoma cruzi has a high genetic diversity, and each group of strains may elicit specific pathological responses in the host. Conflicting results have been reported in studies using various combinations of mammalian host-T. cruzi strains. We previously profiled the transcriptomic signatures resulting from infection of L6E9 rat myoblasts with four reference strains of T. cruzi (Brazil, CL, Y, and Tulahuen). The four strains induced similar overall gene expression alterations in the myoblasts, although only 21 genes were equally affected by all strains. Cardiotrophin-like cytokine factor 1 (Clcf1) was one of the genes found to be consistently upregulated by the infection with all four strains of T. cruzi. This cytokine is a member of the interleukin-6 family that binds to glycoprotein 130 receptor and activates the JAK/STAT signaling pathway, which may lead to muscle cell hypertrophy. Another commonly upregulated gene was tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein theta (Ywhaq, 14-3-3 protein Θ), present in the Cell Cycle Pathway. In the present work, we reanalyzed our previous microarray dataset, aiming at understanding in more details the transcriptomic impact that each strain has on JAK/STAT signaling and Cell Cycle pathways. Using Pearson correlation analysis between the expression levels of gene pairs in biological replicas from each pathway, we determined the coordination between such pairs in each experimental condition and the predicted protein interactions between the significantly altered genes by each strain. We found that although these highlighted genes were similarly affected by all four strains, the downstream genes or their interaction partners were not necessarily equally affected, thus reinforcing the idea of the role of parasite background on host cell transcriptome. These new analyses provide further evidence to the mechanistic understanding of how distinct T. cruzi strains lead to diverse remodeling of host cell transcriptome.

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BACKGROUND: Although previous studies have evaluated the effect of anti-VEGF therapies for central retinal vein occlusion (CRVO) patients, the majority of previous studies have excluded or included a very small number of patients with ischemic CRVO (iCRVO). The aim of our study is to examine the effects of bevacizumab on macular edema secondary to ischemic central retinal vein occlusion, as well as the effects on central choroidal thickness and best-corrected visual acuity. METHODS: In this prospective, interventional case series, iCRVO was defined by the presence of ≥ 10 or more disc diameter areas of retinal nonperfusion by fluorescein angiography (FA) and by the presence of a b/a ratio less than 1.5 by full-field electroretinogram (ffERG). Nine eyes with iCRVO received monthly bevacizumab 0.5 mg injections at baseline and months 1 to 5 for a maximum of six injections. Main outcome measures were visual acuity (Snellen), central foveal thickness, and central choroidal thickness as measured by Spectral-Domain Optical Coherence Tomography (SD-OCT) at baseline and at 6 month following initial intravitreal bevacizumab injection. Pairwise t-tests and the Wilcoxon signed-rank test were conducted to compare the outcome measures. RESULTS: After intravitreal administration of bevacizumab, there was a significant reduction of central foveal thickness from 858 ± 311 µm at baseline to 243 ± 106 µm at the 6-month follow-up, as well as a significant reduction of central choroidal thickness from 282 ± 38 µm at baseline to 227 ± 56 µm at the 6-month follow-up (p = 0.0006, p = 0.0003 respectively). The visual acuity worsened from a median of 1.3 to 1.7 (p = 0.02). CONCLUSION: In patients with iCRVO, intravitreal bevacizumab led to a reduction of central macular edema and central choroidal thickness, but a worsening of visual acuity. Intravitreal bevacizumab reduces macular edema but is not able to overcome the poor prognosis of iCRVO.

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BACKGROUND: Cardiac fibrosis is a consequence of chronic chagasic cardiomyopathy (CCC). In other cardiovascular diseases, the protagonist role of fibroblasts in cardiac fibrosis is well established. However, the role of cardiac fibroblasts (CFs) in fibrosis during the CCC is not clear. Here, our aim was to investigate the effect of Trypanosoma cruzi, the etiological agent of Chagas disease on CFs activation. METHODS: Cardiac fibroblasts were purified from primary cultures of mouse embryo cardiac cells. After two passages, cells were infected with T. cruzi (Y strain) and analyzed at different times for determination of infectivity, activation and production of extracellular matrix components (fibronectin, laminin and collagen IV) by immunofluorescence and western blot. RESULTS: At second passage, cultures were enriched in CFs (95% of fibroblasts and 5% of cardiomyocytes), as revealed by presence of alpha-smooth muscle actin (α-SMA) and discoidin domain receptor 2 (DDR2) and absence of sarcomeric tropomyosin (ST) protein expression. Trypanosoma cruzi infection induced fibroblast-myofibroblast transition, with increased expression of α-SMA after 6 and 24 h post-infection (hpi). Fibronectin was increased at 6, 24 and 48 hpi, laminin was increased at 6 and 24 hpi and collagen IV was increased at 6 hpi. CONCLUSIONS: Our results showed that T. cruzi activates CFs, inducing activation and exacerbates ECM production. Furthermore, our data raise the possibility of the involvement of CFs in heart fibrosis during Chagas disease.

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Although the current treatment for anxiety is effective, it promotes a number of adverse reactions and medical interactions. Inhaled essential oils have a prominent action on the central nervous system, with minimal systemic effects, primarily because of reduced systemic bioavailability. The effects of drugs on the consolidation of fear conditioning reflects its clinical efficacy in preventing a vicious cycle of anticipatory anxiety leading to fearful cognition and anxiety symptoms. In this study, we investigated the effects of inhaled Lavandula angustifolia essential oil on the consolidation of aversive memories and its influence on c-Fos expression. Adult male Wistar rats were subjected to a fear conditioning protocol. Immediately after the training session, the rats were exposed to vaporized water or essential oil (1%, 2.5% and 5% solutions) for 4h. The next day, the rats underwent contextual- or tone-fear tests and 90min after the test they were euthanized and their brains processed for c-Fos immunohistochemistry. In the contextual-fear test, essential oil at 2.5% and 5% (but not 1%) reduced the freezing response and its respective c-Fos expression in the ventral hippocampus and amygdala. In the tone-fear test, essential oil did not reduce the freezing response during tone presentation. However, rats that inhaled essential oil at 2.5% and 5% (but not 1%) showed decreased freezing in the three minutes after tone presentation, as well as reduced c-Fos expression in the prefrontal cortex and amygdala. These results show that the inhalation of L. angustifolia essential oil inhibited the consolidation of contextual- but not tone-fear conditioning and had an anxiolytic effect in a conditioned animal model of anxiety.

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BACKGROUND: We aimed to investigate the effects of chronic oral treatment with centrally acting antihypertensive drugs, such as clonidine (CLO), an α2-adrenoceptor agonist, or LNP599, a selective I1 imidazoline receptor agonist, on brain microvascular function in rats with high-fat diet (HFD)-induced metabolic syndrome. METHODS: Male Wistar Kyoto rats were maintained on a normal diet (CON) or a HFD for 20 weeks. After this period, the HFD group received oral CLO (0.1 mg/kg), LNP599 (20 mg/kg), or vehicle daily for 4 weeks. Systolic blood pressure and heart rate (HR) were evaluated by photoplethysmography. Functional capillary density, endothelial function, and endothelial-leukocyte interactions in the brain were investigated by intravital video microscopy. Cerebral microcirculatory flow was evaluated by laser speckle contrast imaging. Brain tissue endothelial nitric oxide synthase, oxidative enzyme, and inflammatory marker expression levels were analyzed. RESULTS: Metabolic syndrome decreased brain functional capillary density and microvascular blood perfusion, changes accompanied by deficient brain microcirculation vasodilatory responses to acetylcholine. Significant numbers of rolling and adherent leukocytes were also observed in the brain venules. Chronic sympathetic inhibition with clonidine and LNP599 reduced blood pressure and HR. These effects were accompanied by reversals of cerebral capillary rarefaction, improvements in cerebral microvascular blood flow and endothelial function, and decreases in endothelial-leukocyte interactions in the cerebral venules. CONCLUSIONS: Our results suggest that central sympathetic inhibition exerts beneficial effects by increasing perfusion and reducing inflammatory marker expression and oxidative stress in the brains of rats with metabolic syndrome. Centrally acting antihypertensive drugs may be helpful in regulating cerebral microcirculatory function and vascular inflammation in metabolic syndrome.

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Drug addiction can be viewed as a pathological memory that is constantly retrieved and reconsolidated. Since drug abuse takes place in different contexts, it could be considered that reconsolidation plays a role in memory updating. There is consistent evidence supporting the role of reconsolidation in the strength and maintenance of contextual memories induced by drugs of abuse. However, this role is not well established in memory update. The purpose of the current study was to assess the reconsolidation process over memory update. C57BL6 mice were subjected to a morphine-induced, conditioned place preference (CPP) paradigm. Based on CPP results, animals were divided into distinct experimental groups, according to the contextual characteristics of the re-exposure and a second CPP Test. Re-exposure in the original context was important for memory maintenance and re-exposure under discrete contextual changes resulted in memory updating, although original memory was maintained. Interestingly, cycloheximide, an inhibitor of protein synthesis, had different outcomes in our protocol. When the re-exposure was done under discrete contextual changes, cycloheximide treatment just after re-exposure blocked memory updating, without changes in memory maintenance. When re-exposure was done under the original context, only two subsequent cycloheximide injections (3 and 6h) disrupted later CPP expression. Considering the temporal window of protein synthesis in consolidation and reconsolidation, these findings suggest that re-exposure, according to the contextual characteristics in our protocol, could trigger both phenomena. Furthermore, when new information is present on retrieval, reconsolidation plays a pivotal role in memory updating.

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Resumo Recusa Escolar é o termo que refere-se à dificuldade do estudante (criança ou adolescente) em permanecer total ou parcialmente no ambiente escolar, gerando angústia e sofrimento. Ludoterapia comportamental foi utilizada no atendimento de Rita, uma menina (oito anos) que recusava ir à escola. O atendimento consistiu em avaliação (entrevistas e observação) e intervenções (alteração do padrão de brincar e orientações aos pais). Rita apresentou mudanças em termos de complexidade do lúdico e aceitação da escola. Teoria da motivação de Dember e Earl foi utilizada para explicar as escolhas lúdicas na direção hipotetizada; foi discutida a carência de detalhamento sobre a tomada de decisão em ludoterapia comportamental. É sugerido um modelo de tomada de decisão clínica que descreva como o psicólogo analisa as interações da criança com seu ambiente. Tal modelo de tomada de decisão deve ser capaz de incluir as características principais do conceito de lúdico presentes na teoria de Dember-Earl....(AU)

Abstract “School refusal” is the term that is used to express students (child or adolescent) struggling with staying wholly or partly within the school environment, generating anguish and suffering. Behavioral Play Therapy was used to treat Rita, a girl (8 years old) who refused to go to school. Treatment consisted of assessment (interviews and observation) and interventions (change in the pattern of play and guidelines to parents). Rita showed changes in the complexity of play and agreed to go to school. The Motivation Theory by Dember and Earl was used to explain ludic choices in the hypothesized direction; the lack of details on the decision making in Behavioral Play Therapy was also discussed. A model of clinical decision-making that describes how the psychologist analyzes the child’s interactions with his environment is suggested. This decision-making model should be able to include the main features of the concept of play presented by Dember and Earl in their theory....(AU)

Resumen “Rechazo a la escuela” es el término que se utiliza para denotar la dificultad del alumno (niño o adolescente) para permanecer total o parcialmente en el ámbito escolar, generando angustia y sufrimiento. La ludoterapia del comportamiento se utilizó para tratar a Rita, una niña (8 años) que se negaba a ir a la escuela. El tratamiento consistió en una evaluación (entrevistas y observación) y algunas intervenciones (cambio en el patrón de juego y directrices para los padres). La niña mostró un cambio en el nivel de complejidad del juego y aceptó ir a la escuela. La Teoría de la Motivación de Dember y Earl se utilizó para explicar las opciones lúdicas empleadas en la dirección hipotética; se señaló la falta de detalle en la toma de decisiones en ludoterapia del comportamiento. Se sugiere un modelo de toma de decisiones clínicas que describa cómo el psicólogo analiza las interacciones del niño con su entorno. Este modelo de toma de decisiones debe ser capaz de incluir las principales características del concepto de juego presente en la teoría Dember-Earl....(AU)

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Resumo Recusa Escolar é o termo que refere-se à dificuldade do estudante (criança ou adolescente) em permanecer total ou parcialmente no ambiente escolar, gerando angústia e sofrimento. Ludoterapia comportamental foi utilizada no atendimento de Rita, uma menina (oito anos) que recusava ir à escola. O atendimento consistiu em avaliação (entrevistas e observação) e intervenções (alteração do padrão de brincar e orientações aos pais). Rita apresentou mudanças em termos de complexidade do lúdico e aceitação da escola. Teoria da motivação de Dember e Earl foi utilizada para explicar as escolhas lúdicas na direção hipotetizada; foi discutida a carência de detalhamento sobre a tomada de decisão em ludoterapia comportamental. É sugerido um modelo de tomada de decisão clínica que descreva como o psicólogo analisa as interações da criança com seu ambiente. Tal modelo de tomada de decisão deve ser capaz de incluir as características principais do conceito de lúdico presentes na teoria de Dember-Earl.(AU)

Abstract “School refusal” is the term that is used to express students (child or adolescent) struggling with staying wholly or partly within the school environment, generating anguish and suffering. Behavioral Play Therapy was used to treat Rita, a girl (8 years old) who refused to go to school. Treatment consisted of assessment (interviews and observation) and interventions (change in the pattern of play and guidelines to parents). Rita showed changes in the complexity of play and agreed to go to school. The Motivation Theory by Dember and Earl was used to explain ludic choices in the hypothesized direction; the lack of details on the decision making in Behavioral Play Therapy was also discussed. A model of clinical decision-making that describes how the psychologist analyzes the child’s interactions with his environment is suggested. This decision-making model should be able to include the main features of the concept of play presented by Dember and Earl in their theory.(AU)

Resumen “Rechazo a la escuela” es el término que se utiliza para denotar la dificultad del alumno (niño o adolescente) para permanecer total o parcialmente en el ámbito escolar, generando angustia y sufrimiento. La ludoterapia del comportamiento se utilizó para tratar a Rita, una niña (8 años) que se negaba a ir a la escuela. El tratamiento consistió en una evaluación (entrevistas y observación) y algunas intervenciones (cambio en el patrón de juego y directrices para los padres). La niña mostró un cambio en el nivel de complejidad del juego y aceptó ir a la escuela. La Teoría de la Motivación de Dember y Earl se utilizó para explicar las opciones lúdicas empleadas en la dirección hipotética; se señaló la falta de detalle en la toma de decisiones en ludoterapia del comportamiento. Se sugiere un modelo de toma de decisiones clínicas que describa cómo el psicólogo analiza las interacciones del niño con su entorno. Este modelo de toma de decisiones debe ser capaz de incluir las principales características del concepto de juego presente en la teoría Dember-Earl.(AU)

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