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Social decision-making is omnipresent in everyday life, carrying the potential for both positive and negative consequences for the decision-maker and those closest to them. While evidence suggests that decision-makers use value-based heuristics to guide choice behavior, very little is known about how decision-makers' representations of other agents influence social choice behavior. We used multivariate pattern expression analyses on fMRI data to understand how value-based processes shape neural representations of those affected by one's social decisions and whether value-based encoding is associated with social decision preferences. We found that stronger value-based encoding of a given close other (e.g. parent) relative to a second close other (e.g. friend) was associated with a greater propensity to favor the former during subsequent social decision-making. These results are the first to our knowledge to explicitly show that value-based processes affect decision behavior via representations of close others.
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Toma de Decisiones , Conducta Social , Humanos , Amigos , Imagen por Resonancia MagnéticaRESUMEN
Exposure to early life adversity (ELA) is hypothesized to sensitize threat-responsive neural circuitry. This may lead individuals to overestimate threat in the face of ambiguity, a cognitive-behavioral phenotype linked to poor mental health. The tendency to process ambiguity as threatening may stem from difficulty distinguishing between ambiguous and threatening stimuli. However, it is unknown how exposure to ELA relates to neural representations of ambiguous and threatening stimuli, or how processing of ambiguity following ELA relates to psychosocial functioning. The current fMRI study examined multivariate representations of threatening and ambiguous social cues in 41 emerging adults (aged 18 to 19 years). Using representational similarity analysis, we assessed neural representations of ambiguous and threatening images within affective neural circuitry and tested whether similarity in these representations varied by ELA exposure. Greater exposure to ELA was associated with greater similarity in neural representations of ambiguous and threatening images. Moreover, individual differences in processing ambiguity related to global functioning, an association that varied as a function of ELA. By evidencing reduced neural differentiation between ambiguous and threatening cues in ELA-exposed emerging adults and linking behavioral responses to ambiguity to psychosocial wellbeing, these findings have important implications for future intervention work in at-risk, ELA-exposed populations.
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We tested the hypothesis that milk proteins, through microencapsulation, guarantee protection against bioactive substances in coffee silverskin extracts. Therefore, the aim of this study was to carry out technological, nutritional and physicochemical characterisation of a coffee silverskin extract microencapsulated using instant skim milk powder and whey protein concentrate as wall materials. The aqueous extract of coffee silverskin was spray-dried using 10% (w/v) skim milk powder and whey protein concentrate. The samples were characterised by determining the water content, water activity, particle size distribution, colour analysis and total phenolic compound content as well as antioxidant activity using 2,2-diphenyl-radical 1-picrylhydrazyl scavenging methods, nitric oxide radical inhibition and morphological analysis. The product showed water activity within a range that ensured greater stability, and the reduced degradation of the dried coffee silverskin extract with whey protein concentrate resulted in better rehydration ability. The luminosity parameter was higher and the browning index was lower for the encapsulated samples than for the pure coffee silverskin extract. The phenolic compound content (29.23 ± 8.39 and 34.00 ± 8.38 mg gallic acid equivalents/g for the coffee silverskin extract using skimmed milk powder and whey protein concentrate, respectively) and the antioxidant activity of the new product confirmed its potential as a natural source of antioxidant phenolic compounds. We conclude that the dairy matrices associated with spray drying preserved the bioactive and antioxidant activities of coffee silverskin extracts.
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Antioxidantes , Leche , Secado por Pulverización , Proteína de Suero de Leche , Proteína de Suero de Leche/química , Animales , Leche/química , Extractos Vegetales/química , Café/química , Manipulación de Alimentos/métodos , Proteínas de la Leche/análisis , Proteínas de la Leche/química , Fenoles/análisis , Tamaño de la Partícula , Polvos , Composición de Medicamentos/métodosRESUMEN
Hereditary amyloid transthyretin (ATTRv) amyloidosis is a fatal neurodegenerative disorder, first identified in Portugal. The most common transthyretin (TTR) mutation in ATTRv results from an exchange of a methionine for a valine at position 30 (V30M). ATTRv is characterized by the extracellular deposition of aggregates and fibrils of mutant forms of TTR, particularly in the nerves and ganglia of the peripheral nervous system (PNS). This phenotype is often accompanied by the lack of inflammatory infiltrates, despite the importance of macrophages in removal of TTR deposits in ATTRv patients. The mechanisms underlying this impairment of inflammatory responses in ATTRv patients are poorly understood. Here, we show a significant down-regulation in the expression of several chemokines by bone marrow-derived macrophages (BMDM) generated from V30M TTR mice upon stimulation with toll-like receptor 4 (TLR4) and TLR2 agonists. The phosphorylation of the MAP kinase p38, important for TLR4 and TLR2 signaling pathways, was also down-regulated in V30M macrophages, as compared with wild-type (WT) ones. The present study contributes with new insights to unravel the molecular mechanisms underlying the lack of inflammatory immune responses observed in ATTRv patients and may help in the development of new immune therapeutic strategies for the disease.
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Neuropatías Amiloides Familiares , Prealbúmina , Ratones , Animales , Prealbúmina/genética , Prealbúmina/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 4/genética , Neuropatías Amiloides Familiares/genética , Neuropatías Amiloides Familiares/metabolismo , Macrófagos/metabolismoRESUMEN
Early caregiving adversity (ECA) is associated with elevated psychological symptomatology. While neurobehavioral ECA research has focused on socioemotional and cognitive development, ECA may also increase risk for "low-level" sensory processing challenges. However, no prior work has compared how diverse ECA exposures differentially relate to sensory processing, or, critically, how this might influence psychological outcomes. We examined sensory processing challenges in 183 8-17-year-old youth with and without histories of institutional (orphanage) or foster caregiving, with a particular focus on sensory over-responsivity (SOR), a pattern of intensified responses to sensory stimuli that may negatively impact mental health. We further tested whether sensory processing challenges are linked to elevated internalizing and externalizing symptoms common in ECA-exposed youth. Relative to nonadopted comparison youth, both groups of ECA-exposed youth had elevated sensory processing challenges, including SOR, and also had heightened internalizing and externalizing symptoms. Additionally, we found significant indirect effects of ECA on internalizing and externalizing symptoms through both general sensory processing challenges and SOR, covarying for age and sex assigned at birth. These findings suggest multiple forms of ECA confer risk for sensory processing challenges that may contribute to mental health outcomes, and motivate continuing examination of these symptoms, with possible long-term implications for screening and treatment following ECA.
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Cognición , Salud Mental , Adolescente , Recién Nacido , Humanos , PercepciónRESUMEN
Schistosoma mansoni eggs retained in host tissues induce innate cytokine release, contributing to the induction of Type-2 immune responses and granuloma formation, important to restrain cytotoxic antigens, but leading to fibrosis. Interleukin(IL)-33 participates in experimental models of inflammation and chemically induced fibrosis, but its role in S. mansoni-induced fibrosis is still unknown. To explore the role of the IL-33/suppressor of the tumorigenicity 2 (ST2) pathway, serum and liver cytokine levels, liver histopathology, and collagen deposition were comparatively evaluated in S. mansoni-infected wild-type (WT) and IL-33-receptor knockout (ST2-/-) BALB/c mice. Our data show similar egg counts and hydroxyproline in the livers of infected WT and ST2-/- mice; however, the extracellular matrix in ST2-/- granulomas was loose and disorganised. Pro-fibrotic cytokines, such as IL-13 and IL-17, and the tissue-repairing IL-22 were significantly lower in ST2-/- mice, especially in chronic schistosomiasis. ST2-/- mice also showed decreased α-smooth muscle actin (α-SMA) expression in granuloma cells, in addition to reduced Col III and Col VI mRNA levels and reticular fibres. Therefore, IL-33/ST2 signalling is essential for tissue repairing and myofibroblast activation during S. mansoni infection. Its disruption results in inappropriate granuloma organisation, partly due to the reduced type III and VI collagen and reticular fibre formation.
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Schistosoma mansoni , Esquistosomiasis mansoni , Ratones , Animales , Proteína 1 Similar al Receptor de Interleucina-1/genética , Interleucina-33/genética , Cirrosis Hepática/patología , Hígado/metabolismo , Fibrosis , Citocinas , Ratones Endogámicos BALB C , Colágeno/metabolismo , Granuloma/patologíaRESUMEN
Understanding adolescent decision-making is significant for informing basic models of neurodevelopment as well as for the domains of public health and criminal justice. System-based theories posit that adolescent decision-making is guided by activity amongst reward and control processes. While successful at explaining behavior, system-based theories have received inconsistent support at the neural level, perhaps because of methodological limitations. Here, we used two complementary approaches to overcome said limitations and rigorously evaluate system-based models. Using decision-level modeling of fMRI data from a risk-taking task in a sample of 2000+ decisions across 51 human adolescents (25 females, mean age = 15.00 years), we find support for system-based theories of decision-making. Neural activity in lateral prefrontal cortex and a multivariate pattern of cognitive control both predicted a reduced likelihood of risk-taking, whereas increased activity in the nucleus accumbens predicted a greater likelihood of risk-taking. Interactions between decision-level brain activity and age were not observed. These results garner support for system-based accounts of adolescent decision-making behavior.SIGNIFICANCE STATEMENT:Adolescent decision-making behavior is of great import for basic science, and carries equally consequential implications for public health and criminal justice. While dominant psychological theories seeking to explain adolescent decision-making have found empirical support, their neuroscientific implementations have received inconsistent support. This may be partly due to statistical approaches employed by prior neuroimaging studies of system-based theories. We used brain modeling-an approach that predicts behavior from brain activity-of univariate and multivariate neural activity metrics to better understand how neural components of psychological systems guide decision behavior in adolescents. We found broad support for system-based theories such that neural systems involved in cognitive control predicted a reduced likelihood to make risky decisions, whereas value-based systems predicted greater risk-taking propensity.
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The severity of chronic schistosomiasis has been mainly associated with the intensity and extension of the inflammatory response induced by egg-secreted antigens in the host tissue, especially in the liver and intestine. During acute schistosomiasis, eosinophils account for approximately 50% of the cells that compose the liver granulomas; however, the role of this cell-type in the pathology of schistosomiasis remains controversial. In the current study, we compared the parasite burden and liver immunopathological changes during experimental schistosomiasis in wild-type (WT) BALB/c mice and BALB/c mice selectively deficient for the differentiation of eosinophils (ΔdblGATA). Our data demonstrated that the absence of eosinophil differentiation did not alter the S. mansoni load or the liver retention of parasite eggs; however, there were significant changes in the liver immune response profile and tissue damage. S. mansoni infection in ΔdblGATA mice resulted in significantly lower liver concentrations of IL-5, IL-13, IL-33, IL-17, IL-10, and TGF-ß and higher concentrations of IFN-γ and TNF-α, as compared to WT mice. The changes in liver immune response observed in infected ΔdblGATA mice were accompanied by lower collagen deposition, but higher liver damage and larger granulomas. Moreover, the absence of eosinophils resulted in a higher mortality rate in mice infected with a high parasite load. Therefore, the data indicated that eosinophils participate in the establishment and/or amplification of liver Th-2 and regulatory response induced by S. mansoni, which is necessary for the balance between liver damage and fibrosis, which in turn is essential for modulating disease severity.
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Eosinófilos/inmunología , Inmunidad/inmunología , Hepatopatías/inmunología , Hígado/inmunología , Enfermedades Desatendidas/inmunología , Esquistosomiasis mansoni/inmunología , Animales , Citocinas/inmunología , Modelos Animales de Enfermedad , Eosinófilos/parasitología , Femenino , Fibrosis/inmunología , Fibrosis/parasitología , Granuloma/inmunología , Granuloma/parasitología , Intestinos/inmunología , Intestinos/parasitología , Hígado/parasitología , Hepatopatías/parasitología , Ratones , Ratones Endogámicos BALB C , Enfermedades Desatendidas/parasitologíaRESUMEN
The ability to regulate emotions is key to goal attainment and well-being. Although much has been discovered about neurodevelopment and the acquisition of emotion regulation, very little of this work has leveraged information encoded in whole-brain networks. Here we employed a network neuroscience framework to parse the neural underpinnings of emotion regulation skill acquisition, while accounting for age, in a sample of children and adolescents (N = 70, 34 female, aged 8-17 years). Focusing on three key network metrics-network differentiation, modularity, and community number differences between active regulation and a passive emotional baseline-we found that the control network, the default mode network, and limbic network were each related to emotion regulation ability while controlling for age. Greater network differentiation in the control and limbic networks was related to better emotion regulation ability. With regards to network community structure (modularity and community number), more communities and more crosstalk between modules (i.e., less modularity) in the control network were associated with better regulatory ability. By contrast, less crosstalk (i.e., greater modularity) between modules in the default mode network was associated with better regulatory ability. Together, these findings highlight whole-brain connectome features that support the acquisition of emotion regulation in youth.
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Encéfalo/anatomía & histología , Encéfalo/crecimiento & desarrollo , Regulación Emocional/fisiología , Red Nerviosa/anatomía & histología , Red Nerviosa/crecimiento & desarrollo , Adolescente , Desarrollo del Adolescente , Encéfalo/diagnóstico por imagen , Niño , Desarrollo Infantil , Conectoma , Red en Modo Predeterminado , Emociones/fisiología , Femenino , Humanos , Sistema Límbico/fisiología , Imagen por Resonancia Magnética , Masculino , Red Nerviosa/diagnóstico por imagenRESUMEN
Beginning college involves changes that can increase one's vulnerability to loneliness and associated negative outcomes. Parent and friend relationships are potential protective factors against loneliness given their positive association with adjustment. The present longitudinal study, with data collection at baseline, 1 month, and 2 months later, assessed the comparative effects of self-reported parent and friend relationship quality on loneliness in first-year college students (N = 101; 80 female, Mage = 18.36). At baseline, parent and friend relationship quality were negatively associated with loneliness. Longitudinal data revealed that friend relationship quality interacted with time, such that its effects on loneliness attenuated over the course of 2 months. By contrast, parent relationship quality continued to predict lower loneliness 2 months post-baseline. These results highlight the importance of close relationships and suggest that targeting relationship quality could be effective in helping youth transition to college.
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Over the past decade extensive research has examined the segregation of the human brain into large-scale functional networks. The resulting network maps, i.e. parcellations, are now commonly used for the a priori identification of functional networks. However, the use of these parcellations, particularly in developmental and clinical samples, hinges on four fundamental assumptions: (1) the various parcellations are equally able to recover the networks of interest; (2) adult-derived parcellations well represent the networks in children's brains; (3) network properties, such as within-network connectivity, are reliably measured across parcellations; and (4) parcellation selection does not impact the results with regard to individual differences in given network properties. In the present study we examined these assumptions using eight common parcellation schemes in two independent developmental samples. We found that the parcellations are equally able to capture networks of interest in both children and adults. However, networks bearing the same name across parcellations (e.g., default network) do not produce reliable within-network measures of functional connectivity. Critically, parcellation selection significantly impacted the magnitude of associations of functional connectivity with age, poverty, and cognitive ability, producing meaningful differences in interpretation of individual differences in functional connectivity based on parcellation choice. Our findings suggest that work employing parcellations may benefit from the use of multiple schemes to confirm the robustness and generalizability of results. Furthermore, researchers looking to gain insight into functional networks may benefit from employing more nuanced network identification approaches such as using densely-sampled data to produce individual-derived network parcellations. A transition towards precision neuroscience will provide new avenues in the characterization of functional brain organization across development and within clinical populations.
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Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Adolescente , Niño , Cognición , Conectoma , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Individualidad , Masculino , Vías Nerviosas/diagnóstico por imagen , NeuroimagenRESUMEN
Gas fermentation is a promising way to convert CO-rich gases to chemicals. We studied the use of synthetic cocultures composed of carboxydotrophic and propionigenic bacteria to convert CO to propionate. So far, isolated carboxydotrophs cannot directly ferment CO to propionate, and therefore, this cocultivation approach was investigated. Four distinct synthetic cocultures were constructed, consisting of Acetobacterium wieringae (DSM 1911T) and Pelobacter propionicus (DSM 2379T), Ac. wieringae (DSM 1911T) and Anaerotignum neopropionicum (DSM 3847T), Ac. wieringae strain JM and P. propionicus (DSM 2379T), and Ac. wieringae strain JM and An. neopropionicum (DSM 3847T). Propionate was produced by all the cocultures, with the highest titer (â¼24 mM) being measured in the coculture composed of Ac. wieringae strain JM and An. neopropionicum, which also produced isovalerate (â¼4 mM), butyrate (â¼1 mM), and isobutyrate (0.3 mM). This coculture was further studied using proteogenomics. As expected, enzymes involved in the Wood-Ljungdahl pathway in Ac. wieringae strain JM, which are responsible for the conversion of CO to ethanol and acetate, were detected; the proteome of An. neopropionicum confirmed the conversion of ethanol to propionate via the acrylate pathway. In addition, proteins related to amino acid metabolism and stress response were highly abundant during cocultivation, which raises the hypothesis that amino acids are exchanged by the two microorganisms, accompanied by isovalerate and isobutyrate production. This highlights the importance of explicitly looking at fortuitous microbial interactions during cocultivation to fully understand coculture behavior. IMPORTANCE Syngas fermentation has great potential for the sustainable production of chemicals from wastes (via prior gasification) and flue gases containing CO/CO2. Research efforts need to be directed toward expanding the product portfolio of gas fermentation, which is currently limited to mainly acetate and ethanol. This study provides the basis for a microbial process to produce propionate from CO using synthetic cocultures composed of acetogenic and propionigenic bacteria and elucidates the metabolic pathways involved. Furthermore, based on proteomics results, we hypothesize that the two bacterial species engage in an interaction that results in amino acid exchange, which subsequently promotes isovalerate and isobutyrate production. These findings provide a new understanding of gas fermentation and a coculturing strategy for expanding the product spectrum of microbial conversion of CO/CO2.
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Acetobacterium/metabolismo , Monóxido de Carbono/metabolismo , Deltaproteobacteria/metabolismo , Propionatos/metabolismo , Acetobacterium/efectos de los fármacos , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Técnicas de Cocultivo , Deltaproteobacteria/efectos de los fármacos , Fermentación , Proteoma/metabolismo , Acetato de Sodio/farmacologíaRESUMEN
Leachate generation contains a variety of toxic compounds, and is a major problem for municipal solid waste (MSW). Microbial profile knowledge is essential to new alternatives and improvements in current treatments of these effluents. In this respect, the microbial community in the leachate from the sanitary landfill of the city of Foz do Iguaçu was analyzed. The 16S rDNA metabarcoding suggested the dominance of fermenting bacteria belonging to Firmicutes phylum, followed by Proteobacteria, Bacteroidetes, and Synergistetes. The most abundant genera were Sedimentibacter, Vulcanibacillus, and Anaerovorax. However, 60% of amplicon sequence variants (ASVs) were not classified taxonomically. In addition, an expressive abundance was attributed to the superphylum known as PVC group, little studied and with unknown scientific potential. The leachate acidogenic phase was masked in the chemical and physical analyzes. Nevertheless, it was evidenced in the metabarcoding methodology. No specifically methanogenic group was detected in significant abundance. Therefore, from bacterial community identification, a bioremediation process can be designed. Enriched culture media can be developed and targeted to the recovery of specific groups which may be involved in leachate biodegradation. What is more, the results expand the knowledge of bacterial diversity, especially from the presence of unknown genera in this habitat.
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Microbiota , Contaminantes Químicos del Agua , Biodegradación Ambiental , Código de Barras del ADN Taxonómico , Microbiota/genética , Residuos Sólidos/análisis , Instalaciones de Eliminación de Residuos , Contaminantes Químicos del Agua/análisisRESUMEN
Multiple studies about tumor biology have revealed the determinant role of the tumor microenvironment in cancer progression, resulting from the dynamic interactions between tumor cells and surrounding stromal cells within the extracellular matrix. This malignant microenvironment highly impacts the efficacy of anticancer nanoparticles by displaying drug resistance mechanisms, as well as intrinsic physical and biochemical barriers, which hamper their intratumoral accumulation and biological activity.Currently, two-dimensional cell cultures are used as the initial screening method in vitro for testing cytotoxic nanocarriers. However, this fails to mimic the tumor heterogeneity, as well as the three-dimensional tumor architecture and pathophysiological barriers, leading to an inaccurate pharmacological evaluation.Biomimetic 3D in vitro tumor models, on the other hand, are emerging as promising tools for more accurately assessing nanoparticle activity, owing to their ability to recapitulate certain features of the tumor microenvironment and thus provide mechanistic insights into nanocarrier intratumoral penetration and diffusion rates.Notwithstanding, in vivo validation of nanomedicines remains irreplaceable at the preclinical stage, and a vast variety of more advanced in vivo tumor models is currently available. Such complex animal models (e.g., genetically engineered mice and patient-derived xenografts) are capable of better predicting nanocarrier clinical efficiency, as they closely resemble the heterogeneity of the human tumor microenvironment.Herein, the development of physiologically more relevant in vitro and in vivo tumor models for the preclinical evaluation of anticancer nanoparticles will be discussed, as well as the current limitations and future challenges in clinical translation.
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Antineoplásicos , Nanopartículas , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Nanomedicina , Esferoides Celulares , Microambiente TumoralRESUMEN
Early adversity, including institutional orphanage care, is associated with the development of internalizing disorders. Previous research suggests that institutionalization can disrupt emotion regulation processes, which contribute to internalizing symptoms. However, no prior work has investigated how early orphanage care shapes emotion regulation strategy usage (e.g., cognitive reappraisal, expressive suppression) and whether the said strategy usage contributes to internalizing symptoms. This study probed emotion regulation strategy usage and internalizing symptoms in a sample of 36 previously institutionalized and 58 comparison youth. As hypothesized, previously institutionalized youth exhibited higher rates of internalizing symptoms than comparison youth, and more frequent use of suppression partially accounted for the relationship between early institutional care and elevated internalizing symptoms. Contrary to our initial hypotheses, reappraisal use did not buffer previously institutionalized or comparison youth against internalizing symptoms. Our findings highlight the potential utility of targeting emotion regulation strategy usage in adversity-exposed youth in future intervention work.
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Regulación Emocional , Adolescente , HumanosRESUMEN
INTRODUCTION: This longitudinal study designed and tested the validity of a new measure of prosocial risk taking - risks that individuals take in order to help others. METHODS: The sample was racially and ethnically diverse adolescents in the rural Southeastern United States (N = 867; Mage = 12.82 years, 10-14 years at Wave 1; 50% Girls, 33% White non-Latinx, 27% Latinx, 20% Black, 20% Mixed/Other race/ethnicity). Adolescents completed self-report measures of the new prosocial risk-taking scale at baseline and one- and two-year follow-ups. RESULTS: Confirmatory factor analysis demonstrated excellent model fit with a 6-item single factor score. Further, the scale demonstrated good test-retest reliability at one and two-year follow ups. The scale also demonstrated convergent validity, such that prosocial risk taking was positively correlated with prosocial tendencies, empathy, and sensation seeking, and negatively correlated with negative risk-taking behavior and risk tolerance. Finally, we found significant differences by race/ethnicity (but not by gender) in prosocial risk taking, which were not attributable to measurement invariance, and should be interpreted in the context of ongoing societal inequalities between youth. CONCLUSIONS: The new Prosocial Risk-Taking Scale yielded reliable scores in our sample. It may be used in future research to investigate individual differences in adolescents' prosocial risk taking, developmental change in prosocial risk taking, and the significance of prosocial risk taking for adolescents' emotional and social adaptation.
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Asunción de Riesgos , Adolescente , Humanos , Estudios Longitudinales , Reproducibilidad de los Resultados , Sudeste de Estados UnidosRESUMEN
Prior research described three stable patterns of organized behavior employed by infants to manage stressful interactive situations with their mothers in the Face-to-Face Still-Face paradigm (FFSF) at 3 and 9 months postpartum. The current longitudinal study expands this research by examining the extent to which these patterns predict infants' later attachment quality. For that purpose, 108 full-term infants and their mothers participated in the FFSF at 3 and 9 months, and in the Strange Situation at 12 months. Cross-tabulation analyses indicated a significant association between (1) the Social-positive oriented pattern and secure attachment, (2) the Distressed-inconsolable pattern and insecure-ambivalent attachment, and (3) the Self-comfort oriented pattern and insecure-avoidant attachment. Our results contribute to a growing body of studies suggesting that patterns of infants' regulatory behavior assessed during the FFSF during the first year, may be early developmental precursors of attachment patterns at 12 months.
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Relaciones Madre-Hijo , Madres , Femenino , Humanos , Lactante , Conducta del Lactante , Estudios Longitudinales , Apego a ObjetosRESUMEN
Human co-infection by helminth species is frequent, but their consequences are mostly unknown. Here, we investigate the impact of Strongyloides venezuelensis co-infection on the immune response, schistosome burden, and the associated pathology of schistosomiasis in mice. Co-infection did not alter the schistosome parasite burden, but reduced the IL-4/IL-10 ratio during acute schistosomiasis, indicating induction of modulatory mechanisms. Simultaneous infection with S. venezuelensis and S. mansoni increased the liver concentration of IFN-γ and altered the Th2/Th1 balance, leading to great infiltration of neutrophils and macrophages, which resulted in larger liver inflammation and increased serum transaminase activity in comparison with mono-infected mice. Mice infected with S. venezuelensis at two and four weeks after S. mansoni infection showed significant increase of Th1/Th2/Th17/Treg cytokines and strong cellular infiltration in the liver in comparison with mono-infected mice. However, only in mice co-infected after two weeks of schistosomiasis, the liver immune response leads to more intense Th2 polarization, increased liver inflammation, and transaminase serum activity. S. venezuelensis co-infection during chronic schistosomiasis did not significantly alter liver inflammation. Therefore, S. venezuelensis co-infection affects the host immune responses and morbidity of schistosomiasis, but the effects largely depend on the stage of the S. mansoni infection.
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Coinfección/inmunología , Citocinas/inmunología , Inflamación/inmunología , Hígado/inmunología , Esquistosomiasis mansoni/inmunología , Estrongiloidiasis/inmunología , Animales , Coinfección/metabolismo , Coinfección/parasitología , Citocinas/sangre , Citocinas/metabolismo , Femenino , Interacciones Huésped-Parásitos/inmunología , Inflamación/metabolismo , Hígado/metabolismo , Hígado/patología , Ratones , Schistosoma mansoni/inmunología , Schistosoma mansoni/fisiología , Esquistosomiasis mansoni/metabolismo , Esquistosomiasis mansoni/parasitología , Strongyloides/inmunología , Strongyloides/fisiología , Estrongiloidiasis/metabolismo , Estrongiloidiasis/parasitología , Células TH1/inmunología , Células TH1/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Células Th2/inmunología , Células Th2/metabolismoRESUMEN
Quality-by-design (QbD) approach has been applied to optimize lipid-based nanosystems formulations, including solid lipid nanoparticles (SLN), nanostructured lipid carriers (NLC) and nanoemulsions, besides being increasingly requested by regulatory authorities. Different mathematical models and statistical tests have been used, with similar conclusions regarding the parameters that influence the physical features of the resulting nanosystems. These include, variations in composition (e.g. lipid(s) and/or emulsifier(s)) and manufacturing parameters (e.g. emulsification rate and/or time, sonication amplitude and/or time, and homogenization pressure and/or cycles). These are critical parameters that influence nanoparticle/globule mean size, polydispersity index, zeta potential, drug encapsulation efficiency and in vitro drug release. This review addresses the concepts and applications of QbD for the development of lipid-based nanosystems, reporting successful examples published in the last 2 years. Although, some limitations have been identified, it is expected that in the upcoming years the application of QbD in pharmaceutical development will be an established approach.
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Lípidos/química , Nanopartículas/química , Animales , Composición de Medicamentos , Emulsiones/química , HumanosRESUMEN
We investigated daily associations between helping behaviors and emotional well-being during late adolescence, examining whether these links depend on the recipient of help (i.e., friend vs. roommate), type of help (i.e., instrumental vs. emotional), and individual differences in the helper (i.e., gender and empathy). First-year college students (N = 411, 63.5% women, Mage = 18.62 years) completed diary checklists for eight days, reporting whether they provided instrumental and emotional support to a friend or roommate, and positive and negative emotions. On days that adolescents provided instrumental assistance to friends they felt more positive affect, but men also felt more negative affect. Providing instrumental and emotional support to roommates and providing emotional support to friends did not predict daily emotions.