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The profile of executive function (EF) in adults with Schizophrenia (SCZ) and autism spectrum disorder (ASD) remains unclear. This study aims to ascertain if distinct EF patterns can be identified between each clinical condition by comparing the neuropsychological profile of adults with SCZ and ASD, for whom the differential diagnosis is still highly challenging. Forty-five individuals (15 SCZ, 15 ASD, 15 controls) matched for age, sex, education level, and handedness underwent intelligence evaluation and neuropsychological testing for working memory, inhibition, planning and set-shifting, and verbal fluency subdomains. Principal component analysis (2D-PCA) using variables representing 4 domains was employed to identify patterns in neuropsychological profiles. The ASD group had lower scores on the Digits Forward subtest compared to the SCZ group (7.2 ± 2.1 vs. 9.3 ± 1.9, p = 0.003; Cohen's d: 1.05). ASD also performed significantly worse on the Stroop Word Test compared to the control group (77.7± 17.9 vs. 98.0 ± 12.7, p = 0.009; Cohen's d: 1.31). No significant differences were observed between ASD and SCZ on other EF measures. The larger contributors for the dimensions in 2D-PCA were the Digits Forward subtest and Stroop Word Test. Still, there was substantial overlap between the clinical groups. This study suggests a high degree of similarity of EF between SCZ and ASD. Through four EF measures, the discrimination of low and high-functioning EF groups spanning both diagnostic categories may help to identify the individuals who could better benefit from cognitive rehabilitation strategies.
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Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF), a training method for the self-regulation of brain activity, has shown promising results as a neurorehabilitation tool, depending on the ability of the patient to succeed in neuromodulation. This study explores connectivity-based structural and functional success predictors in an NF n-back working memory paradigm targeting the dorsolateral prefrontal cortex (DLPFC). We established as the NF success metric the linear trend on the ability to modulate the target region during NF runs and performed a linear regression model considering structural and functional connectivity (intrinsic and seed-based) metrics. We found a positive correlation between NF success and the default mode network (DMN) intrinsic functional connectivity and a negative correlation with the DLPFC-precuneus connectivity during the 2-back condition, indicating that success is associated with larger uncoupling between DMN and the executive network. Regarding structural connectivity, the salience network emerges as the main contributor to success. Both functional and structural classification models showed good performance with 77% and 86% accuracy, respectively. Dynamic switching between DMN, salience network and central executive network seems to be the key for neurofeedback success, independently indicated by functional connectivity on the localizer run and structural connectivity data.
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BACKGROUND: Deficits in executive function (EF) are consistently reported in autism spectrum disorders (ASD). Tailored cognitive training tools, such as neurofeedback, focused on executive function enhancement might have a significant impact on the daily life functioning of individuals with ASD. We report the first real-time fMRI neurofeedback (rt-fMRI NF) study targeting the left dorsolateral prefrontal cortex (DLPFC) in ASD. METHODS: Thirteen individuals with autism without intellectual disability and seventeen neurotypical individuals completed a rt-fMRI working memory NF paradigm, consisting of subvocal backward recitation of self-generated numeric sequences. We performed a region-of-interest analysis of the DLPFC, whole-brain comparisons between groups and, DLPFC-based functional connectivity. RESULTS: The ASD and control groups were able to modulate DLPFC activity in 84% and 98% of the runs. Activity in the target region was persistently lower in the ASD group, particularly in runs without neurofeedback. Moreover, the ASD group showed lower activity in premotor/motor areas during pre-neurofeedback run than controls, but not in transfer runs, where it was seemingly balanced by higher connectivity between the DLPFC and the motor cortex. Group comparison in the transfer run also showed significant differences in DLPFC-based connectivity between groups, including higher connectivity with areas integrated into the multidemand network (MDN) and the visual cortex. CONCLUSIONS: Neurofeedback seems to induce a higher between-group similarity of the whole-brain activity levels (including the target ROI) which might be promoted by changes in connectivity between the DLPFC and both high and low-level areas, including motor, visual and MDN regions.
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Trastorno del Espectro Autista , Neurorretroalimentación , Humanos , Función Ejecutiva , Trastorno del Espectro Autista/terapia , Encéfalo/diagnóstico por imagen , Mapeo EncefálicoRESUMEN
This work studied the potential of a combination of pungent spices (capsicum, black pepper, ginger, and cinnamaldehyde) to be used as a supplement in diets of gilthead seabream (Sparus aurata; 44.1 ± 4.2 g). During 90 days, fish were fed three experimental diets with low inclusion of fish oil and containing poultry fat as the main source of lipids, supplemented with graded levels of the tested supplement: 0 (control), 0.1 (SPICY0.1%), and 0.15% (SPICY0.15%). As a result, the pungent spices enhanced the growth performance, the activity of the bile-salt-activated lipase in the intestine, and decreased fat deposit levels within enterocytes. The SPICY0.1% diet reduced the feed conversion ratio and the perivisceral fat index and lipid deposits in the liver. Moreover, the ratio of docosahexaenoic acid/eicosapentaenoic acid in fillet increased in fish fed the SPICY0.1% diet, while the hepatic levels of docosahexaenoic acid and total n-3 polyunsaturated fatty acids increased in fish fed the SPICY0.15% diet. Furthermore, there was an effect on the expression of some biomarkers related to lipid metabolism in 2-h postprandial fish (fasn, elovl6, scd1b, cyp7a1, lpl, and pparß), and in 48 h fasted-fish fed with the SPICY0.1% diet, a regulation of the intestinal immune response was indicated. However, no significant differences were found in lipid apparent digestibility and proximate macronutrient composition. The spices did not affect biomarkers of hepatic or oxidative stress. No differences in microbial diversity were found, except for an increase in Simpson's Index in the posterior intestine of fish fed the SPICY0.1% diet, reflected in the increased relative abundance of the phylum Chloroflexi and lower relative abundances of the genera Campylobacter, Corynebacterium, and Peptoniphilus. In conclusion, the supplementation of gilthead seabream diets with pungent spices at an inclusion of 0.1% was beneficial to enhance growth performance and feed utilization; reduce fat accumulation in the visceral cavity, liver, and intestine; and improve the fish health status and condition. Results suggest that the tested supplement can be used as part of a nutritional strategy to promote a more judicious use of fish oil in fish diets due to its decreasing availability and rising costs.
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Aceites de Pescado , Dorada , Animales , Dorada/metabolismo , Ácidos Docosahexaenoicos/metabolismo , Ácidos Grasos/metabolismo , Suplementos Dietéticos , Dieta , Ácidos Grasos Insaturados/metabolismo , Biomarcadores/metabolismoRESUMEN
INTRODUCTION: Neurodevelopmental disorders are characterized by delay or variation in the acquisition of abilities or skills in several domains of development: motor, social, language, and cognitive. These disorders can manifest from childhood to adulthood, and therefore continuity of care is essential throughout these various developmental periods. However, several studies show that there is limited access to adult health care in this clinical domain. METHODS: A cross-sectional observational study was carried out by distributing an anonymous survey among psychiatry physicians, at a national level, in the period between October 6 and December 6, 2020. RESULTS: Data was collected from 83 psychiatry physicians (43 residents and 40 specialists). At the national level, only 16.9% of psychiatric departments had a subspecialized neurodevelopment clinic. Physicians reported that they observed few patients with neurodevelopment disorders: 72.3% observed one or none per week. When there was a neurodevelopmental disorders clinic in the psychiatry department, 64.3% of physicians reported that this clinic did not include a multidisciplinary team. The transition of these patients from the pediatric/child and adolescent psychiatry department to the psychiatric department occurred through regular intrahospital transfer in 51.8% of cases, but it occurred through a specific protocol or with a transitional medical appointment in only 15.7% of cases. Finally, 88% of psychiatry physicians considered the existence of a neurodevelopmental disorders clinic in adults to be pertinent and reported not having specialized training in the field of neurodevelopment. CONCLUSION: This study made it possible to identify some difficulties and barriers regarding adequate access for patients with neurodevelopmental disorders throughout the various developmental stages, from childhood to adulthood: lack of training in this clinical field, need of better communication between departments, lack of specific protocols, shortage of multidisciplinary teams, and asymmetry in the distribution of differentiated care.
Introdução: As perturbações do neurodesenvolvimento são caracterizadas pelo atraso ou alteração na aquisição de capacidades em vários domínios do desenvolvimento: motor, social, de linguagem e cognitivo. Deste modo, estas perturbações podem manifestar-se desde a infância até à vida adulta, exigindo a continuidade dos cuidados de saúde. Contudo, vários estudos mostram que existem limitações de acesso dos adultos aos cuidados de saúde nesta área clínica. Métodos: Foi realizado um estudo observacional descritivo transversal através da aplicação de um questionário anónimo a médicos de Psiquiatria, a nível nacional, no período compreendido entre 6 de outubro e 6 de dezembro de 2020. Resultados: Foram recolhidos dados de 83 médicos de Psiquiatria (43 internos de especialidade e 40 especialistas). A nível nacional, apenas 16,9% dos serviços de Psiquiatria tinham uma consulta diferenciada de neurodesenvolvimento. Os médicos respondentes reportaram ter observado poucos doentes com perturbações do neurodesenvolvimento: 72,3% observaram um ou nenhum por semana. Dos médicos que referiram ter consulta de neurodesenvolvimento no seu serviço, a maioria (64,3%) não dispunha de equipa multidisciplinar. A transição destes doentes da consulta de Pediatria do Neurodesenvolvimento/Pedopsiquiatria para a de Psiquiatria ocorria em 51,8% por transferência regular intra-hospitalar, contudo em apenas 15,7% ocorria através de protocolo específico ou com a realização de consulta de transição. Por fim, 88% dos médicos de Psiquiatria consideraram ser pertinente a existência de uma consulta de perturbações do neurodesenvolvimento no adulto e relataram não possuir formação especializada na área do neurodesenvolvimento. Conclusão: Este estudo possibilitou enumerar alguns obstáculos para que os doentes com perturbações do neurodesenvolvimento usufruam de uma transição de cuidados de saúde para a vida adulta favorável: carência de conhecimento na área, necessidade de melhor comunicação entre serviços, falta de protocolos específicos, escassez de equipas multidisciplinares e assimetria na distribuição de cuidados de saúde diferenciados.
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Trastornos del Neurodesarrollo , Médicos , Psiquiatría , Adulto , Adolescente , Humanos , Niño , Adulto Joven , Estudios Transversales , Trastornos del Neurodesarrollo/diagnóstico , Derivación y ConsultaRESUMEN
BACKGROUND AND OBJECTIVES: Schizophrenia-spectrum disorders (SSD) are characterized by impaired emotion processing and attention. SSD patients are more sensitive to the presence of emotional distractors. But despite growing interest on the emotion-attention interplay, emotional interference in SSD is far from fully understood. Moreover, research to date has not established the link between emotional interference and attentional control in SSD. This study thus aimed to investigate the effects of facial expression and attentional control in SSD, by manipulating perceptual load. METHODS: Twenty-two SSD patients and 22 healthy controls performed a target-letter discrimination task with task-irrelevant angry, happy, and neutral faces. Target-letter was presented among homogenous (low load) or heterogenous (high load) distractor-letters. Accuracy and RT were analysed using (generalized) linear mixed-effect models. RESULTS: Accuracy was significantly lower in SSD patients than controls, regardless of perceptual load and facial expression. Concerning RT, SSD patients were significantly slower than controls in the presence of neutral faces, but only at high load. No group differences were observed for angry and happy faces. LIMITATIONS: Heterogeneity of SSD, small sample size, lack of clinical control group, medication. CONCLUSIONS: One possible explanation is that neutral faces captured exogenous attention to a greater extent in SSD, thus challenging attentional control in perceptually demanding conditions. This may reflect abnormal processing of neutral faces in SSD. If replicated, these findings will help to understand the interplay between exogenous attention, attentional control, and emotion processing in SSD, which may unravel the mechanism underlying socioemotional dysfunction in SSD.
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Esquizofrenia , Humanos , Ira , Emociones , Expresión Facial , Felicidad , Tiempo de Reacción , Estudios de Casos y ControlesRESUMEN
High dietary SBM content is known to induce important physiological alterations, hampering its use as a major FM alternative. Rainbow trout (Oncorhynchus mykiss) juveniles were fed two experimental diets during 9 weeks: (i) a FM diet containing 12% FM; and (ii) a vegetable meal (VM) diet totally devoid of FM and based on SBM (26%). Fish fed the VM diet did not show reduced growth performance when compared with fish fed the FM diet. Nevertheless, fish fed the VM diet had an increased viscerosomatic index, lower apparent fat digestibility, higher aminopeptidase enzyme activity and number of villi fusions, and lower α-amylase enzyme activity and brush border integrity. Small RNA-Seq analysis identified six miRs (omy-miR-730a-5p, omy-miR-135c-5p, omy-miR-93a-3p, omy-miR-152-5p, omy-miR-133a-5p, and omy-miR-196a-3p) with higher expression in blood plasma from fish fed the VM diet. Bioinformatic prediction of target mRNAs identified several overrepresented biological processes known to be associated with high dietary SBM content (e.g., lipid metabolism, epithelial integrity disruption, and bile acid status). The present research work increases our understanding of how SBM dietary content has a physiological impact in farmed fish and suggests circulating miRs might be suitable, integrative, and less invasive biomarkers in fish.
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INTRODUÇÃO: O transplante cardíaco (TxC) é uma opção terapêutica considerada em pacientes com insuficiência cardíaca avançada e refratária ao tratamento otimizado. No primeiro semestre de 2022, foram registradas 176 doações de coração para 32 centros espalhados pelo país. O paciente adolescente traz particularidades e uma fase da vida marcada pelo desejo de liberdade e independência, o adoecimento vem como um importante fator limitante, mesmo após a realização do transplante e re-inserção nas atividades diárias. OBJETIVO: Inserir a paciente como protagonista do seu próprio cuidado dentro do processo saúde-doença que envolve o TxC. MÉTODO: Paciente feminina, 14 anos, previamente hígida e sem antecedentes familiares, internada em enfermaria pediátrica após o diagnóstico de miocardiopatia dilatada. Foi inserida na fila de TxC. Frente ao prognóstico, foram levantadas pela paciente, dúvidas sobre o adoecimento e o tratamento proposto. As questões foram resgatadas pela equipe de psicologia e enfermagem numa roda de conversa na qual estavam presentes a paciente e sua mãe e foram utilizados elementos lúdicos - bexigas de diferentes tamanhos, para elucidar o processo de adoecimento e ensinar a partir da perspectiva da paciente. RESULTADOS: A intervenção foi embasada no referencial teórico de David Ausubel, que valoriza o aprendizado prévio do cliente. Foi percebido um esclarecimento e um levantamento de indagações ainda mais direcionadas para o processo que envolve o TxC. CONCLUSÕES: A intervenção obteve consonância com o registrado na literatura acerca da importância da educação em saúde que possibilita assistência com maior qualidade e coordenando seu próprio cuidado, ocupando um espaço independente no qual é estimulado seu protagonismo.
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Humanos , Femenino , Adolescente , Grupo de Atención al PacienteRESUMEN
BACKGROUND: Preterm birth and congenital heart defects are two major causes of neonatal and infant mortality. However, the relationship between them has not yet been fully clarified. OBJECTIVE: To determine the prevalence and spectrum of congenital heart defects in preterms, the specific associations between categories of congenital heart defects and preterm birth and to establish the influence on outcomes. METHODS: Observational, case-control analysis that included 448 live births with congenital heart defects born between 2003 and 2017. Preterm with congenital heart defects were the case subjects and term neonates with congenital heart defects the control subjects. RESULTS: Of the newborns with congenital heart defects, 23% were preterm. The odds of congenital heart defects in preterm were twofold higher than for term neonates (p<0.0001), even when considering only those with severe congenital heart defects (p=0.0002). The odds in preterm were 9.2-fold higher for abnormalities of the atria and atrial septum (p<0.0001) and two-fold higher for abnormalities of the ventricles and ventricular septum (p<0.0001) compared with term neonates. The neonatal mortality rate in the preterm group was not statistically different from that of the term group with congenital heart defects (p=0.799) or severe congenital heart defects (p=0.554). CONCLUSION: Preterm have more than twice as many congenital heart defects as term neonates. Although the etiology of prematurity between infants with congenital heart defects is still uncertain, our findings highlight a possible relationship between prematurity and congenital heart defects.
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Cardiopatías Congénitas , Nacimiento Prematuro , Lactante , Femenino , Recién Nacido , Humanos , Nacimiento Prematuro/epidemiología , Nacimiento Prematuro/etiología , Recien Nacido Prematuro , Prevalencia , Derivación y Consulta , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/epidemiologíaRESUMEN
Executive functions and motivation have been established as key aspects for neurofeedback success. However, task-specific influence of cognitive strategies is scarcely explored. In this study, we test the ability to modulate the dorsolateral prefrontal cortex, a strong candidate for clinical application of neurofeedback in several disorders with dysexecutive syndrome, and investigate how feedback contributes to better performance in a single session. Participants of both neurofeedback (n = 17) and sham-control (n = 10) groups were able to modulate DLPFC in most runs (with or without feedback) while performing a working memory imagery task. However, activity in the target area was higher and more sustained in the active group when receiving feedback. Furthermore, we found increased activity in the nucleus accumbens in the active group, compared with a predominantly negative response along the block in participants receiving sham feedback. Moreover, they acknowledged the non-contingency between imagery and feedback, reflecting the impact on motivation. This study reinforces DLPFC as a robust target for neurofeedback clinical implementations and enhances the critical influence of the ventral striatum, both poised to achieve success in the self-regulation of brain activity.
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This study aimed to investigate the effects of supplementing broiler chicken diets with an encapsulated product based on capsicum and other spice (black pepper and ginger) extracts on growth performance, nutrient digestibility, digestive enzyme activity and antioxidant response. To this end, 480 1-day-old male chicks were randomly assigned to two experimental treatments (12 pens/treatment; 20 birds/pen). Dietary treatments included a basal diet with no additives (CONTROL) and a basal diet supplemented with 250 ppm of the spice additive (SPICY; Lucta S.A., Spain). Supplementation of SPICY increased body weight (p < 0.05) compared with CONTROL at 7 d of age and improved (p < 0.01) ADG from 0 to 7 d of age. The apparent ileal digestibility of dry matter, gross energy and crude protein was higher (p < 0.05) in birds fed the SPICY diet compared with the CONTROL diet. Birds fed SPICY showed lower (p < 0.05) plasma catalase (CAT) activity, and the hepatic gene expression of CAT and Nrf2 was down-regulated (p < 0.05) compared with the CONTROL. In conclusion, the inclusion of 250 ppm of SPICY in broiler diets improved growth performance at 7 d of age and positively affected nutrient digestibility and antioxidant response.
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A 10-week growth trial was conducted to investigate the effects of a phytogenic feed additive (PFA) containing olive by-products and green tea extracts supplemented to a reduced fishmeal/high soybean meal diet on the growth performance, hepatic antioxidant capacity, lipid metabolism, and liver health of largemouth bass (Micropterus salmoides). Three experimental diets were tested: (1) a control high fishmeal (40%) and low soybean meal (15.57%) diet (named HFM), (2) a reduced fishmeal (30%) and high soybean meal (30.97%) diet (named HSB), and (3) a HSB diet supplemented with the PFA at 500 mg/kg (named HSB+P). Each diet was assigned to four replicate tanks, each containing 30 largemouth bass (initial body weight, IBW = 48.33 ± 0.01 g). The results showed that increasing the soybean meal content in the diet did not negatively affect growth performance, whereas supplementation with PFA significantly increased weight gain and specific growth rate of largemouth bass compared to both HFM and HSB groups. Reducing fishmeal and increasing soybean meal in the diet caused oxidative stress with a higher content of ROS in the liver. However, the hepatic antioxidant capacity was enhanced, with reduced ROS and increased GSH-Px levels in the HSB+P group. Moreover, the decrease of plasma TG, LDL-C, and LDL-C/TC, and downregulation of lipogenesis and cholesterol synthesis gene expression in liver, indicated that supplementation with the PFA improved fish lipid metabolism. Protein retention efficiency was also significantly increased in largemouth bass fed the diet with PFA supplementation, which regulated (enhanced) AKT-mTOR phosphorylation. These results clearly indicated that a PFA containing olive by-product and green tea extracts can positively improve growth performance, protein retention efficiency, antioxidant capacity, and lipid metabolism of largemouth bass fed a reduced fishmeal/high soybean meal diet.
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In this study, we investigated the transcriptional spatio-temporal dynamics of the taste 1 receptor (T1R) gene family repertoire in seabream (Sparus aurata [sa]), during larval ontogeny and in adult tissues. In early larval development, saT1R expression arises heterochronously, i.e. the extraoral taste-related perception in the gastrointestinal tract (GIT) anticipates first exogenous feeding (at 9 days post hatching [dph]), followed by the buccal/intraoral perception from 14 dph onwards, supporting the hypothesis that the early onset of the molecular machinery underlying saT1R expression in the GIT is not induced by food but rather genetically hardwired. During adulthood, we characterized the expression patterns of sa T1R within specific tissues (n = 4) distributed in oropharingeal, GIT and brain regions substantiating their functional versatility as chemosensory signaling players to a variety of biological functions beyond oral taste sensation. Further, we provided for the first time direct evidences in fish for mRNA co-expression of a subset of saT1R genes (mostly sa T1R3, i.e. the common subunit of the heterodimeric T1R complexes for the detection of "sweet" and "umami" substances), with the selected gut peptides ghrelin (ghr), cholecystokinin (cck), hormone peptide yy (pyy) and proglucagon (pg). Each peptide defines the enteroendocrine cells (ECCs) identity, and establishes on morphological basis, a direct link for T1R chemosensing in the regulation of fish digestive processes. Finally, we analyzed the spatial gene expression patterns of 2 taste signaling components functionally homologous to the mammalian G(i)α subunit gustducin, namely sa G( i )α1 and sa G( i )α2, and demonstrated their co-localization with the saT1R3 in EECs, thus validating their direct involvement in taste-like transduction mechanisms of the fish GIT. In conclusion, data provide new insights in the evolutionary conservation of gut sensing in fish suggesting a conserved role for nutrient sensors modulating entero-endocrine secretion.
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Theobromine is a caffeine metabolite most abundant in dark chocolate, of which consumption is linked with a lower risk of cognitive decline. However, the mechanisms through which theobromine affects neuronal function remain ill-defined. Using electrophysiological recordings in mouse hippocampal synapses, we now characterized the impact of a realistic concentration of theobromine on synaptic transmission and plasticity. Theobromine (30 µM) facilitated synaptic transmission while decreasing the magnitude of long-term potentiation (LTP), with both effects being blunted by adenosine deaminase (2 U/mL). The pharmacological blockade of A1R with DPCPX (100 nM) eliminated the theobromine-dependent facilitation of synaptic transmission, whereas the A2AR antagonist SCH58261 (50 nM), as well as the genetic deletion of A2AR, abrogated the theobromine-induced impairment of LTP. Furthermore, theobromine prevented LTP deficits and neuronal loss, respectively, in mouse hippocampal slices and neuronal cultures exposed to Aß1-42 peptides, considered a culprit of Alzheimer's disease. Overall, these results indicate that theobromine affects information flow via the antagonism of adenosine receptors, normalizing synaptic plasticity and affording neuroprotection in dementia-related conditions in a manner similar to caffeine.
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Adenosina Desaminasa , Cafeína , Adenosina Desaminasa/metabolismo , Animales , Cafeína/metabolismo , Cafeína/farmacología , Hipocampo/metabolismo , Ratones , Plasticidad Neuronal , Receptor de Adenosina A2A/metabolismo , Sinapsis/metabolismo , Teobromina/farmacologíaRESUMEN
The molecular mechanisms underlying circuit re-wiring in the mature brain remains ill-defined. An eloquent example of adult circuit remodelling is the hippocampal mossy fiber (MF) sprouting found in diseases such as temporal lobe epilepsy. The molecular determinants underlying this retrograde re-wiring remain unclear. This may involve signaling system(s) controlling axon specification/growth during neurodevelopment reactivated during epileptogenesis. Since adenosine A2A receptors (A2AR) control axon formation/outgrowth and synapse stabilization during development, we now examined the contribution of A2AR to MF sprouting. A2AR blockade significantly attenuated status epilepticus(SE)-induced MF sprouting in a rat pilocarpine model. This involves A2AR located in dentate granule cells since their knockdown selectively in dentate granule cells reduced MF sprouting, most likely through the ability of A2AR to induce the formation/outgrowth of abnormal secondary axons found in rat hippocampal neurons. These A2AR should be activated by extracellular ATP-derived adenosine since a similar prevention/attenuation of SE-induced hippocampal MF sprouting was observed in CD73 knockout mice. These findings demonstrate that A2AR contribute to epilepsy-related MF sprouting, most likely through the reactivation of the ability of A2AR to control axon formation/outgrowth observed during neurodevelopment. These results frame the CD73-A2AR axis as a regulator of circuit remodeling in the mature brain.
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Adenosina , Epilepsia del Lóbulo Temporal , Receptor de Adenosina A2A/metabolismo , Animales , Epilepsia del Lóbulo Temporal/inducido químicamente , Ratones , Fibras Musgosas del Hipocampo , Pilocarpina/farmacología , Ratas , Sinapsis/fisiologíaRESUMEN
Antimicrobial resistance is a global threat that is worryingly rising in the livestock sector. Among the proposed strategies, immunostimulant development appears an interesting approach to increase animal resilience at critical production points. The use of nanoparticles based on cytokine aggregates, called inclusion bodies (IBs), has been demonstrated as a new source of immunostimulants in aquaculture. Aiming to go a step further, the objective of this study was to produce cytokine nanoparticles using a food-grade microorganism and to test their applicability to stimulate intestinal mucosa in swine. Four cytokines (IL-1ß, IL-6, IL-8, and TNF-α) involved in inflammatory response were produced recombinantly in Lactococcus lactis in the form of protein nanoparticles (IBs). They were able to stimulate inflammatory responses in a porcine enterocyte cell line (IPEC-J2) and alveolar macrophages, maintaining high stability at low pH and high temperature. In addition, an in vivo assay was conducted involving 20 piglets housed individually as a preliminary exploration of the potential effects of IL-1ß nanoparticles in piglet intestinal mucosa after a 7 d oral administration. The treated animals tended to have greater levels of TNF-α in the blood, indicating that the tested dose of nanoparticles tended to generate an inflammatory response in the animals. Whether this response is sufficient to increase animal resilience needs further evaluation.
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In order to contribute to knowledge of the epidemiology of American cutaneous leishmaniasis (ACL) among indigenous people living in sylvatic regions, we studied the sand fly fauna collected in areas of disease transmission in the Brazilian Amazon. Our two datasets reported here are comprised of occurrence data for sand flies from the Suruwaha Indigenous Land in the state of Amazonas collected between 2012-1013, and the Wajãpi Indigenous Land in the state of Amapá collected between 2013-2014. Sand flies were collected using unbaited CDC-like light traps at various sites within each study area and were identified to species-level by taxonomists with expertise in Amazonian fauna. A total of 4,646 records are reported: 1,428 from the Suruwaha and 3,218 from the Wajãpi. These records will contribute to a better understanding of ACL transmission dynamics, as well as the distribution of insect vectors, in these areas.
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An 8-week feeding trial was conducted to investigate the effects of high-starch diets and the supplementation of an olive extract (OE) on the growth performance, liver health and lipid metabolism of largemouth bass (Micropterus salmoides). Four isonitrogenous and isolipidic diets were prepared: two basal diets containing low (9.0%) and high (14.4%) levels of starch (named as LS and HS), and 0.125% OE was supplemented to each basal diet (named LSOE and HSOE). The results show that high-starch diets had significant negative effects on growth performance, with lower FR, SGR and higher FCR, whereas OE significantly lowered FCR, determined by two-way ANOVA analysis. High-starch diets induced oxidative stress, inflammatory response and liver function injury, with significant increases in the content of plasmatic AKP, AST, ALT, hepatic SOD and MDA, and up-regulation of hepatic TNFα, IL1ß, and TGFß1 gene expression. In addition, a high-starch diet decreased the phosphorylation of AMPK and upregulated the expression of SREBP, together with higher hepatic liver lipid and HSI. The oxidative stress and lipid metabolism disorders indicate metabolic liver disease (MLD) of largemouth bass fed high-starch diets. Feeding on OE-supplemented diets increased the hepatic antioxidant capacity by decreasing the content of MDA and SOD. Fish fed the HSOE diet had an activated phosphorylation of JNK and decreased expression of pro-inflammatory IL1ß compared with those fed the HS diet, which strongly indicated that the degree of inflammatory responses was reduced after OE supplementation. Interestingly, this study demonstrated that OE regulates hepatic lipid metabolism in fish by inhibiting the expression of hepatic lipogenesis genes (ACC1 and FASN) and promoting lipolysis (ATGL) and ß-oxidation (CPT1α) to prevent TG accumulation. In conclusion, high-starch feed induced oxidative stress and lipid metabolic disorder of largemouth bass, while supplementation with OE improved its antioxidant capacity, anti-inflammatory responses and lipid metabolism. However, hepatic histopathological results suggested that OE supplementation could not completely repair the MLD caused by the high level of starch in largemouth bass.
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Endoplasmic reticulum (ER) stress and mitochondrial dysfunction, which are key events in the initiation and/or progression of several diseases, are correlated with alterations at ER-mitochondria contact sites, the so-called "Mitochondria-Associated Membranes" (MAMs). These intracellular structures are also implicated in NLRP3 inflammasome activation which is an important driver of sterile inflammation, however, the underlying molecular basis remains unclear. This work aimed to investigate the role of ER-mitochondria communication during ER stress-induced NLRP3 inflammasome activation in both peripheral and central innate immune systems, by using THP-1 human monocytes and BV2 microglia cells, respectively, as in vitro models. Markers of ER stress, mitochondrial dynamics and mass, as well as NLRP3 inflammasome activation were evaluated by Western Blot, IL-1ß secretion was measured by ELISA, and ER-mitochondria contacts were quantified by transmission electron microscopy. Mitochondrial Ca2+ uptake and polarization were analyzed with fluorescent probes, and measurement of aconitase and SOD2 activities monitored mitochondrial ROS accumulation. ER stress was demonstrated to activate the NLRP3 inflammasome in both peripheral and central immune cells. Studies in monocytes indicate that ER stress-induced NLRP3 inflammasome activation occurs by a Ca2+-dependent and ROS-independent mechanism, which is coupled with upregulation of MAMs-resident chaperones, closer ER-mitochondria contacts, as well as mitochondrial depolarization and impaired dynamics. Moreover, enhanced ER stress-induced NLRP3 inflammasome activation in the immune system was found associated with pathological conditions since it was observed in monocytes derived from bipolar disorder (BD) patients, supporting a pro-inflammatory status in BD. In conclusion, by demonstrating that ER-mitochondria communication plays a key role in the response of the innate immune cells to ER stress, this work contributes to elucidate the molecular mechanisms underlying NLRP3 inflammasome activation under stress conditions, and to disclose novel potential therapeutic targets for diseases associated with sterile inflammation.