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Recent studies demonstrate that metabolic disturbance, such as augmented glycolysis, contributes to fibrosis. The molecular regulation of this metabolic perturbation in fibrosis, however, has been elusive. COUP-TFII (also known as NR2F2) is an important regulator of glucose and lipid metabolism. Its contribution to organ fibrosis is undefined. Here, we found increased COUP-TFII expression in myofibroblasts in human fibrotic kidneys, lungs, kidney organoids, and mouse kidneys after injury. Genetic ablation of COUP-TFII in mice resulted in attenuation of injury-induced kidney fibrosis. A non-biased proteomic study revealed the suppression of fatty acid oxidation and the enhancement of glycolysis pathways in COUP-TFII overexpressing fibroblasts. Overexpression of COUP-TFII in fibroblasts also induced production of alpha-smooth muscle actin (αSMA) and collagen 1. Knockout of COUP-TFII decreased glycolysis and collagen 1 levels in fibroblasts. Chip-qPCR revealed the binding of COUP-TFII on the promoter of PGC1α. Overexpression of COUP-TFII reduced the cellular level of PGC1α. Targeting COUP-TFII serves as a novel treatment approach for mitigating fibrosis in chronic kidney disease and potentially fibrosis in other organs.
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Fator II de Transcrição COUP , Receptores Nucleares Órfãos , Animais , Fator II de Transcrição COUP/genética , Fator II de Transcrição COUP/metabolismo , Fibrose , Glicólise/genética , Rim , Camundongos , Camundongos Knockout , Miofibroblastos , Receptores Nucleares Órfãos/metabolismo , ProteômicaRESUMO
It cannot be assumed that the experience of having an autistic child is the same across countries since demographic and systemic factors are as diverse as the manifestation of ASD symptomatology. This study explores the lived experiences of 20 Venezuelan parents after receiving an autism diagnosis for their child. Applied thematic analysis was used to analyze parental attitudes, challenges in identifying their child's delay, access to diagnostic services, beliefs towards autism, professional evaluations, family support, and perceptions toward health and educational services for autistic children. Venezuelan parents reported a generalized lack of autism awareness, an unsupportive school system, and judgment from their extended family. Despite the universal health coverage in the country, Venezuelan parents commented on the scarcity of services, as well as the lengthy and costly processes to receive an ASD diagnosis. The results support previous research findings showing that socioeconomic factors influence how parents experience the process of obtaining an autism diagnosis for their children. For most Venezuelan parents, it might imply a long journey in which limited resources and knowledge about autism will determine its route and length. For parents, cultural values and spiritual and religious beliefs will serve as both coping mechanisms and barriers to accessing services.
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Transtorno Autístico , Criança , Humanos , Transtorno Autístico/diagnóstico , Pais , Fatores Socioeconômicos , Instituições AcadêmicasRESUMO
LAY ABSTRACT: An earlier diagnosis of autism spectrum disorder might lead to earlier intervention. However, people living in Latin American and Caribbean countries do not have much knowledge about autism spectrum disorder symptoms. It has been suggested that the older a child is when diagnosed, the fewer opportunities he or she will have to receive services. We asked 2520 caregivers of autistic children in six different Latin America and Caribbean Countries, the child's age when they noticed some developmental delays and their child's age when they received their first autism spectrum disorder diagnosis. Results indicate that, on average, caregivers were concerned about their child's development by 22 months of age; however, the diagnosis was received when the child was 46 months of age. In addition, older children with better language abilities and public health coverage (opposed to private health coverage) were diagnosed later. On the contrary, children with other medical problems and more severe behaviors received an earlier diagnosis. In our study, children were diagnosed around the time they entered formal schooling, delaying the access to early intervention programs. In summary, the characteristics of the autistic person and the type of health coverage influence the age of diagnosis in children living in Latin America and Caribbean Countries.
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Transtorno do Espectro Autista , Transtorno Autístico , Criança , Feminino , Humanos , Adolescente , Transtorno Autístico/diagnóstico , América Latina , Transtorno do Espectro Autista/diagnóstico , Região do CaribeRESUMO
Autistic youth often present with comorbid anxiety and depression yet there is a dearth of validated assessment tools. The Revised Children's Anxiety and Depression Scale (RCADS) assesses internalizing symptoms but there is little psychometric data in autistic youth. Treatment-seeking autistic youth with anxiety or obsessive-compulsive symptoms (N = 74; age 6-14 years), and caregivers, were administered the RCADS-Parent, RCADS-Child, and assessments of internalizing, externalizing symptoms and social impairment indicative of autism. RCADS-Parent and RCADS-Child total anxiety scores demonstrated excellent internal consistency, and the six subscales demonstrated acceptable-to-good internal consistency. The RCADS-Child and Parent total anxiety scores were weakly correlated, and neither child age nor gender altered the strength of this association. Convergent validity was supported by moderate-to-strong correlations with clinician and parent-reported anxiety symptoms. Support for divergent validity was mixed. Results provide support for the RCADS-Parent and RCADS-Child as reliable, valid measures of internalizing symptoms in autistic youth.
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Hydrogels are polymers of great importance due to their multiple applications, which have led to an exponential increase in their production. However, once they have fulfilled their function, they become waste and their ecotoxicological effects are unknown. The aim of the present study was to evaluate the acute toxicity and total antioxidant capacity of the earthworm (Eisenia fetida) exposed to a terpolymeric hydrogel (acrylic acid, acrylamide, and 2-acrylamido-2-methyl-1-propane-sulfonic acid) crosslinked with modified kraft lignin. Four different amounts of hydrogel per unit area were evaluated (0.0924, 0.1848, 0.9242, and 1.848 mg hydrogel/cm2) plus a control, and three replicates were performed for each group. Starting from the amount of 0.1848 mg hydrogel/cm2, the earthworms showed physiological and behavioral alterations; at higher amounts, 0.9242 and 1.848 mg hydrogel/cm2, more acute signs were observed with mortality rates of 51.7% and 100%, respectively. On the other hand, the antioxidant activity assay showed that the higher the hydrogel exposure amount, the higher the oxidative stress, as evidenced by lower antioxidant activity (67.09% inhibition of the ABTSâ+ radical). Therefore, we concluded that the lignin-modified hydrogel generated oxidative stress and acute lethal toxic effects in Eisenia fetida.
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Background: The COVID-19 pandemic brought an increased incidence of disease and mortality in the world at large, making it a particularly salient and stressful life event. For those individuals residing in Latin America, the pandemic was met with fragmented healthcare systems, economic downturn, and sociopolitical crisis which puts autistic individuals at risk for more detrimental outcomes. Behavioral and emotional challenges experienced by autistic individuals at the beginning of the pandemic could later develop into more severe symptomatology as the pandemic progresses. The present study aimed to explore changes in dysregulated (overt and internalizing) behaviors and preoccupation with getting sick during the COVID-19 pandemic among autistic children in 7 Latin American countries. Method: Sample consisted of 1,743 caregivers, residing in: Argentina (n = 677, 38.8%) Brazil (n = 156, 9%), Chile (n = 251, 14.4%), Dominican Republic (n = 171, 9.8%), Mexico (n = 126, 7.2%), Uruguay (n = 259, 14.9%) and Venezuela (n = 103, 5.9%). The majority of caregivers who completed the questionnaire were mothers (85.1%), and most had a male autistic child (81.6%). A series of independent sample t-tests were conducted to assess country differences in dysregulated behaviors and preoccupation with getting sick. Linear regressions were conducted to identify which demographic characteristics and micro-level contextual factors predicted dysregulated overt behaviors and psychological changes. Results: Contextual factors, such as country of residence, were related to preoccupation with getting sick and dysregulated behavior. Particularly, residing in Mexico and Brazil were related to changes in preoccupation with getting sick and mental health concerns. Coexistence predicted dysregulated internalizing behaviors, while being older significantly predicted preoccupation with getting sick. Increased screen time only predicted anxiety. Conclusion: Our findings highlight differences and predictions of behavioral challenges and psychological changes based on certain contextual factors and individual characteristics while experiencing severe life stressors such as a worldwide pandemic. This knowledge could help inform policies and decrees aimed at protecting those most vulnerable due to their increased difficulty adapting to change.
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Mental healthcare professionals often have limited awareness of different obsessive-compulsive disorder (OCD) symptom presentations, which may contribute to years between OCD symptom onset and treatment initiation. While research has identified high rates of OCD misdiagnosis among clinicians from the United States and Canada, research on OCD symptom awareness among healthcare providers in Latin American (LATAM) regions is limited. In this study, LATAM mental healthcare providers (N = 83) provided diagnostic impressions based on five OCD vignettes: three with symptoms centered on taboo thoughts (sexual, harming others, and religion/scrupulosity) and two about contamination or symmetry obsessions. Rates of incorrect (non-OCD) diagnoses were significantly higher for the taboo thoughts vignettes (sexual, 52.7%; harm/aggression, 42.0%; and religious, 34.7%) vs. contamination obsessions (11.0%) and symmetry obsessions (6.9%). The OCD vignette depicting sexual obsessions was often attributed to a paraphilic disorder (36.5%). Bachelor's level clinicians had significantly lower odds of accurately identifying all three vignettes related to taboo thoughts compared to respondents with a graduate degree. Accurate identification of the three taboo vignettes was also associated with first-line psychological treatment recommendations (i.e., cognitive-behavioral therapy) even when controlling for respondents' theoretical orientation. Exposure was rarely mentioned when clinicians were prompted to provide treatment recommendations for each vignette (8-9% of the time for symmetry and contamination vignettes, 5-7% for taboo though vignettes). Like clinicians in the United States and Canada, mental health professionals in LATAM may misidentify OCD symptom presentations, particularly sexual obsessions, highlighting a need for education and training.
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This trial examined stepped-care cognitive-behavioral treatment (CBT) among 96 autistic youth with co-occurring anxiety. Step 1 included an open trial of parent-led, therapist-guided bibliotherapy. Step 2 was family-based CBT for those who did not respond to Step 1 or maintenance for those who did. Eighteen participants (28%) who completed Step 1 responded. Responders reported significantly lower pre-treatment anxiety, internalizing symptoms, and functional impairment than non-responders. After Steps 1 and 2, 80% of completers (55% intent-to-treat) were responders. Anxiety, impairment, and ASD-related impairments significantly improved. Youth in maintenance experienced faster improvement through post-treatment, though there were no group differences at 3-month-follow-up. A stepped approach may help some individuals in Step 1, particularly those who are less anxious.
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The COVID-19 pandemic has had an emotional impact on healthcare professionals at different levels of care, and it is important to understand the levels of anxiety of hospital personnel (HP) compared to those of primary care personnel (PCP). The objectives herein were to assess the differences in anxiety levels between these populations and to detect factors that may influence them. The anxiety levels (measured using the Hospital Anxiety and Depression (HAD) scale) of the HP and PCP groups were compared using data collected from a cross-sectional study. The secondary variables included demographic and health data, confinement factors, contact with COVID-19 patients, having suffered from COVID-19, perceptions of protection, caregiver overload, threat, and satisfaction with management. We found anxiety "case" (35.6%) and "at-risk" (21%), with statistically significant differences in the group "at risk", and higher scores in the PCP group. The factors associated with the perception of threat and protection were significant determinants of an increase in anxiety, with all of them showing statistically significant differences. There were greater symptoms of anxiety in the PCP group than the HP group (32% vs. 18%). The factors associated with the prevalence of anxiety symptoms were the perceptions of threat, protection, management, caregiver overload, and perceived degree of threat associated with COVID-19.
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COVID-19 , Pandemias , Ansiedade/epidemiologia , Estudos Transversais , Atenção à Saúde , Depressão/epidemiologia , Pessoal de Saúde , Hospitais , Humanos , Atenção Primária à Saúde , SARS-CoV-2RESUMO
In the case of Tenebrionidae family insects, studies focus on larval stage, leaving a lack of information regarding other stages. Therefore, this study was performed in order to understand the differences between the nutritional composition and the bioactivity of two species of this family in their adult stage, fed with a specific diet. Adult beetles of both species were defatted, lyophilized and protein extracted with buffer. Proximal and phytochemical analysis of the extracts of each insect were performed, along with protein extract and hydrolysis analysis by Tris-Tricine and Tris Glycine SDS PAGE. This analysis showed that T. molitor contained more protein and fat than U. dermestoides but contained less crude fiber. The protein extraction was made with PBS, where 130 and 45 kDa bands showed predominant for U. dermestoides, and less protein was present for T. molitor. Antioxidant and antimicrobial activities of the enzymatic protein hydrolysates and protein crude extracts were determined. Presence of protein associated with the antioxidant activity were found in both insects. Nonetheless U. dermestoides had a higher antioxidant activity with the protein extract in contrast with the higher antioxidant activity shown by U. dermestoides once the extracts were digested. After proteolysis, protein extracts showed an increasing antioxidant activity, plus, the ability to inhibit microbial growth of Proteus, Shigella and Bacillus. Insect protein hydrolysates with protease open the possibility for the use of these beetles as new sources of encrypted peptides for microbiological control once characterized.
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Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.
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Transtorno do Espectro Autista , Transtorno Autístico , Adolescente , Adulto , Ansiedade/terapia , Transtornos de Ansiedade/terapia , Cognição , Humanos , Pais , Resultado do TratamentoRESUMO
Social behavior is critical for relationship formation and is influenced by myriad environmental and individual factors. Basic and preclinical research typically relies on rodent models to identify the mechanisms that underlie behavior; however, it is important to use non-rodent models as well. A major objective of the present study was to test the hypothesis that biological sex and social experience modulate the expression of social behavior in the adult gray short-tailed opossum (Monodelphis domestica), a non-traditional model. We also investigated the non-associative learning abilities of these animals. Following a period of social isolation, animals of both sexes were paired with a non-familiar, same-sex partner for 10â¯min on three different occasions, with 24-hour inter-trial intervals. We are the first research group to find significant sex differences in submissive and nonsocial behaviors in Monodelphis. Females displayed significantly higher durations of nonsocial behavior that increased over trials. Males were more aggressive; their latencies to the first attack and submissive behavior decreased over trials whereas these latencies increased for females; males' duration of submissive behavior increased over trials whereas it decreased for females. A different group of subjects habituated in response to repeated presentations to neutral odors and dishabituated in response to novel odors. In addition, both males and females demonstrated the ability to form social memories in a standard individual (social) recognition test. Our results contribute to the characterization of this marsupial species, an important first step in developing it as a model of complex social behaviors.
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Comportamento Animal/fisiologia , Aprendizagem/fisiologia , Reconhecimento Psicológico/fisiologia , Caracteres Sexuais , Comportamento Social , Agressão/fisiologia , Animais , Feminino , Masculino , Monodelphis , Fatores SexuaisRESUMO
Abstract Introduction The COVID-19 lockdown has posed new challenges for individuals with autism spectrum disorder (ASD), including service suspension and reductions in support. Objective To explore the perspectives of caregivers on the impact of the COVID-19 lockdown on people with ASD in Mexico. Method 126 caregivers from Mexico completed a survey on the impact of lockdown on people with ASD. Results Suspension of at least one service was reported for 38.9% of subjects, with no significant association being found between symptom worsening and service administration modality. Discussion and conclusion Service suspension for people with ASD in Mexico has been a side effect of the pandemic, negatively impacting their behavior. Results indicate that certain services could be remotely maintained and provided to individuals with ASD in underserved areas.
Resumen Introducción El confinamiento debido a la pandemia por COVID-19 ha implicado nuevos desafíos para las personas con trastorno del espectro autista (TEA), incluyendo la suspensión de algunos servicios, y la disminución de los apoyos. Objetivo Explorar las perspectivas de los cuidadores acerca de las repercusiones del confinamiento por COVID-19 en las personas con TEA en México. Método 126 cuidadores residentes de México completaron una encuesta acerca del impacto del confinamiento en personas con TEA. Resultados Aunque el 38.9% de los participantes reportó la suspensión de al menos un servicio de salud tras el confinamiento, no hubo asociaciones significativas entre retroceso y modalidad de administración de los servicios. Discusión y conclusión La suspensión de servicios a las personas con TEA en México es uno de los efectos secundarios de la pandemia, y afecta negativamente su comportamiento. Los resultados indican que algunos tratamientos pudieran ser mantenidos remotamente y brindar servicios a personas con TEA en zonas de difícil acceso.
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Anxiety disorders affect up to 50% of individuals with autism spectrum disorder (ASD) and are significantly impairing to the person affected, as well as to their loved ones. Cognitive-behavioral therapy (CBT) has been established as the gold-standard treatment for anxiety disorders among typically developing youth and adults, and demonstrates similar efficacy among youth with high-functioning autism (HFA). Many CBT interventions utilize a "full-package" treatment approach to treat co-occurring anxiety in youth with ASD. However, these service delivery systems are often therapist-intensive, costly, and impractical, thereby compromising full engagement and treatment adherence. This paper describes the design, rationale, and methodology of a study examining stepped-care CBT for youth with HFA and co-occurring anxiety - a clinical trial examining the efficacy of low-intensity, parent-led CBT as the first line of treatment and utilizing a more intensive, therapist-led intervention for nonresponders. The study will evaluate the potential benefits of stepped-care and parent-led therapist-assisted interventions, predictors of treatment response, and the economic value of using a stepped-care model. Implications for practice will be discussed.