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Aflatoxin B1 (AFB1) is the most common toxic mycotoxin that contaminates food. The treatment of its intoxication and the management of contaminations are a constant subject of health agendas worldwide. However, such efforts are not always enough to avoid population intoxication. Our objective was to investigate whether intermittent exposure to AFB1 would cause any impairment in biochemical and behavioral parameters, intending to simulate an irregular consumption. Male Wistar rats received four AFB1 administrations (250 µg/kg) by intragastric route separated by a 96-h interval. Toxicity was evaluated using behavioral tests (open field, object recognition, nest construction, marble burying, and splash test), biochemical markers of oxidative stress (cerebral cortex, hippocampus, liver, and kidneys), and plasma parameters of hepatic and renal functions. The intermittent exposure caused no modification in body weight gain as well as in organ weight. Both control and AFB1 groups presented similar profiles of behavior to all tests performed. Furthermore, AFB1 administrations alter neither antioxidant defenses nor markers of oxidation in all assayed tissues and in the plasma markers of hepatic and renal functions. Therefore, AFB1 intermittent administration did not cause its common damage from exposure to this toxicant, which must be avoided, and additional studies are required.

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Several studies demonstrated the toxicity of aspartame (ASP) and aflatoxin B1 (AFB1 ) in preclinical models. Although the majority of these reports assessed the toxic effects of each substance separately, their concomitant exposure and hazardous consequences are scarce. Importantly, the deleterious effects at the central nervous system caused by ASP and AFB1 co-exposure are rarely addressed. We evaluated if concomitant exposure to AFB1 and ASP would cause behavioral impairment and alteration in oxidative status of the brain in male rats. Animals received once a day for 14 days AFB1 (250 µg/kg, intragastric gavage [i.g.]), ASP (75 mg/kg, i.g.), or both substances (association). On day 14, they were subjected to behavioral evaluation, and biochemical and molecular parameters of oxidative status were measured in the cerebral cortex and hippocampus. In the open field test, AFB1 and combination treatments modified the motor, exploratory, and grooming behavior. In the splash test, all treatments caused a reduction in grooming time compared to the control group. An increase in thiobarbituric acid-reactive substances content induced by AFB1 and combination treatments was observed. The antioxidant defenses (vitamin C, nonprotein sulfhydryl, and ferric reducing antioxidant power) were impaired in all groups compared to control. Regarding molecular evaluation, mitochondrial superoxide dismutase-2 immunoreactivity decreased after AFB1 or ASP exposition in the hippocampus. Thus, co-exposure to ASP and AFB1 was potentially more toxic because it aggravated behavioral impairments and oxidative status disbalance in comparison to the groups that received only ASP or AFB1 . Therefore, our data suggest that those substances caused a disruption in brain homeostasis.

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The potential interactions among food additives/contaminants and the consequences to biological systems is a topic that is rarely addressed in scientific literature. Thus, the current study investigated if the combined administration of ASP and AFB1 would impair hepatic and renal oxidative status. Male Wistar rats received during 14 days once a day ASP (75 mg/Kg) and/or AFB1 (250 µg/Kg) through intragastric route. At the end of experimental protocol, samples of liver and kidneys were collected for assessing biochemical markers of oxidative status. In the hepatic tissue, the treatment with a single substance (ASP or AFB1) caused an increase in TBARS levels, and a reduction in non-enzymatic antioxidant defenses (Vit C and NPSH levels and FRAP test). In the kidneys, TBARS levels were increased only in the group that received ASP + AFB1. The association reduced NPSH content, while the treatment with AFB1 reduced the FRAP levels. GST and CAT activities were increased in all treatments. Overall, ASP and AFB1 association presented higher toxic effects to the tissues. To the best of our knowledge, this is the first study demonstrating that the associated use of both ASP and AFB1 induces more extensive injuries in comparison to the effects caused by each one alone. Therefore, these data demonstrated that concomitant exposure to ASP and AFB1 potentiated their oxidative damage in hepatic tissue, suggesting that this organ is particularly sensitive to the toxic action induced by these substances.

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Zika virus (ZIKV) has been associated with serious health conditions, and an intense search to discover different ways to prevent and treat ZIKV infection is underway. Berberine and emodin possess several pharmacological properties and have been shown to be particularly effective against the entry and replication of several viruses. We show that emodin and berberine trigger a virucidal effect on ZIKV. When the virus was exposed to 160 µM of berberine, a reduction of 77.6% in the infectivity was observed; when emodin was used (40 µM), this reduction was approximately 83.3%. Dynamic light scattering data showed that both compounds significantly reduce the hydrodynamic radius of virus particle in solution. We report here that berberine and emodin, two natural compounds, have strong virucidal effect in Zika virus.

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In recent years, synthetic peptides have been considered promising targets for drug development that possess low side-effects, are cost-effective and are susceptible to rational design. Hecate was initially described as a potent bacterial inhibitor and subsequently as an anticancer drug with functions related to its lipid interaction property. Viruses, such as hepatitis C virus (HCV), have a lipid-dependent life cycle and could be affected by Hecate in many ways. Here, we assessed modifications on Hecate's N-terminus region and its effects on HCV and hepatotoxicity. Gallic acid-conjugated Hecate was the most efficient Hecate-derivative, presenting high potential as an antiviral and inhibiting between 50 to 99% of all major steps within the HCV infectious cycle. However, the most promising aspect was GA-Hecate's mechanism of action, which was associated with a balanced lipid interaction with the viral envelope and lipid droplets, as well as dsRNA intercalation, allowing for the possibility to affect other ssRNA viruses and those with a lipid-dependent cycle.

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PURPOSE: To verify indicators of cognitive development, receptive language skills and adaptive behavioral patterns in toddlers with Williams syndrome (WS). METHODS: The sample comprised 8 children of both sex, aged between 48 and 72 months with WS. Instruments of data collection were Denver Developmental Screening Test II; Peabody Picture Vocabulary Test; Vineland Adaptive Behavior Scale; Child Behavior Checklist for Ages 1½-5and 6 to 18; Columbia Mental Maturity Scale (CMMS), and Behavior Problems Inventory-01. RESULTS: The major developmental impairments were associated with fine motor skills and personal care abilities. Deficits in receptive language and communication skills were reported according to the PPVT and Denver II, respectively. The caregivers reported behavioral and emotional problems associated to anxiety and depression, and attention problems scales of CBCL. CONCLUSION: The toddlers demonstrated deficits in adaptive functioning and behavioral, motor and cognitive difficulties such as inattention and hyperactivity, stereotypies and aggressive behavior.

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ABSTRACT Purpose To verify indicators of cognitive development, receptive language skills and adaptive behavioral patterns in toddlers with Williams syndrome (WS). Methods The sample comprised 8 children of both sex, aged between 48 and 72 months with WS. Instruments of data collection were Denver Developmental Screening Test II; Peabody Picture Vocabulary Test; Vineland Adaptive Behavior Scale; Child Behavior Checklist for Ages 1½-5and 6 to 18; Columbia Mental Maturity Scale (CMMS), and Behavior Problems Inventory-01. Results The major developmental impairments were associated with fine motor skills and personal care abilities. Deficits in receptive language and communication skills were reported according to the PPVT and Denver II, respectively. The caregivers reported behavioral and emotional problems associated to anxiety and depression, and attention problems scales of CBCL. Conclusion The toddlers demonstrated deficits in adaptive functioning and behavioral, motor and cognitive difficulties such as inattention and hyperactivity, stereotypies and aggressive behavior.

RESUMO Objetivo Verificar indicadores de desenvolvimento cognitivo, habilidades de linguagem receptiva e padrões comportamentais adaptativos em pré-escolares com Síndrome de Williams (SW). Método A amostra foi composta por 8 crianças de ambos os sexos, com idade entre 48 e 72 meses com SW. Os instrumentos de coleta de dados utilizados foram Denver Developmental Screening Test II; Peabody Picture Vocabulary Test; Escala de comportamento adaptativo Vineland; Child Behavior Checklist (CBCL) para as idades 1½-5 e 6 a 18; Inventário de Problemas de Comportamento (BPI-01) e Escala de Maturidade Mental Columbia. Resultados Os principais prejuízos de desenvolvimento foram associados a habilidades motoras finas e habilidades de cuidados pessoais. Os déficits em linguagem receptiva e habilidades de comunicação foram relatados de acordo com o PPVT e Denver II, respectivamente. Os cuidadores relataram problemas comportamentais e emocionais associados às escalas de ansiedade e depressão e de problemas de atenção do CBCL. Conclusão Os pré-escolares demonstraram déficits no funcionamento adaptativo e dificuldades comportamentais, motoras e cognitivas, como desatenção e hiperatividade, estereotipias e comportamento agressivo.

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Hepatitis C is a disease caused by the hepatitis C virus (HCV), and an estimated 3% of the world population is infected with the virus. During replication, HCV interacts with several cellular proteins. Studies have shown that several heat shock proteins (HSPs) have an altered expression profile in the presence of the virus, and some HSPs interact directly with HCV proteins. In the present study, we evaluated the expression levels of heat shock proteins in vitro in the presence and absence of HCV. The differential expression of 84 HSPs and chaperones was observed using a qPCR array, comparing HCV uninfected and infected Huh7.5 cells. To validate qPCR array, the differentially expressed genes were tested by real-time PCR in three different HCV models: subgenomic HCV replicon cells (SGR-JFH-1), JFH-1 infected cells (both genotype 2a) and subgenomic S52 cells (genotype 3). The HSPB8 gene showed increased expression in all three viral models. We silenced HSPB8 expression and observed an increase in viral replication. In contrast, when we increased the expression of HSPB8, a decrease in the HCV replication rate was observed. The same procedure was adopted for DNAJC5B, and HCV showed a similar replication pattern as that observed for HSPB8. These results suggest that HSPB8 may act as an intracellular factor against hepatitis C virus replication and that DNAJC5B has the same function, with more relevant results for genotype 3. We also evaluated the direct interactions between HCV and HSP proteins, and the IP experiments showed that the HCV NS4B protein interacts with HSPB8. These results contribute to a better understanding of the mechanisms involved in HCV replication.

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OBJECTIVE: To assess the diagnostic status, the sociodemographic and health profiles for students with special educational needs (SEN) in a public educational system, and to map their use of educational/social services. METHODS: The sample comprised 1,202 SEN students from a total of 59,344 students. RESULTS: Only 792 students of the 1,202 had an established diagnosis. The most prevalent SEN condition was intellectual disability. There was a low percentage (29.4%) of use of specialized educational services or support. It was found that, for some neurodevelopmental disorders, prevalence data suggest an under-reporting in the school system. CONCLUSION: Results suggest that there is a mismatch between the diagnostic reports and the SEN condition legally recognized according to Brazilian law, in addition to the under-reporting and under specialized service use of students with disabilities.

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ABSTRACT Objective To assess the diagnostic status, the sociodemographic and health profiles for students with special educational needs (SEN) in a public educational system, and to map their use of educational/social services. Methods The sample comprised 1,202 SEN students from a total of 59,344 students. Results Only 792 students of the 1,202 had an established diagnosis. The most prevalent SEN condition was intellectual disability. There was a low percentage (29.4%) of use of specialized educational services or support. It was found that, for some neurodevelopmental disorders, prevalence data suggest an under-reporting in the school system. Conclusion Results suggest that there is a mismatch between the diagnostic reports and the SEN condition legally recognized according to Brazilian law, in addition to the under-reporting and under specialized service use of students with disabilities.

RESUMO Objetivo Avaliar a situação diagnóstica, o perfil sociodemográfico e de saúde dos alunos com necessidades educacionais especiais (NEE) de uma rede municipal de educação, assim como mapear o uso de serviços educacionais e sociais. Métodos A amostra foi composta por 1202 alunos com NEE de um total de 59344 alunos. Resultados Dos 1202 alunos somente 792 tinha diagnóstico estabelecido. A condição de NEE mais prevalente foi a deficiência intelectual. Verificou-se um baixo percentual (29,4%) de uso de serviços educacionais especializados ou de apoio. Foi constatado que, para alguns transtornos do neurodesenvolvimento, os dados de prevalência parecem indicar uma subnotificação. Conclusão Os resultados sugerem um descompasso entre os registros diagnósticos e a condição de necessidade educacional especial segundo a legislação brasileira, além disso verificou-se uma subnotificação diagnóstica e baixo uso de serviços especializados entre estudantes com deficiências.

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Hepatitis C (HCV) is a viral disease affecting millions of people worldwide, and persistent HCV infection can lead to progressive liver disease with the development of liver cirrhosis and hepatocellular carcinoma. During treatment for hepatitis C, the occurrence of viral resistance is common. To reduce the occurrence of resistance, new viral treatments should target both viral and cellular factors. Many interactions occur between viral and host proteins during the HCV replication cycle and might be used for the development of new therapies against hepatitis C. Heat shock protein 90 (Hsp90) plays a role in the folding of cellular and viral proteins and also interacts with HCV proteins. In the present study, we knocked down the expression of the Hsp90 gene and inhibited viral replication using siRNA molecules. Reducing the expression of Hsp90 successfully decreased HCV replication. All siRNA molecules specific to the viral genome showed the efficient inhibition of viral replication, particularly siRNA targeted to the 5'UTR region. The combination of siRNAs targeting the viral genome and Hsp90 mRNA also successfully reduced HCV replication and reduced the occurrence of viral resistance. Moreover, these results suggest that an approach based on the combination of cellular and viral siRNAs can be used as an effective alternative for hepatitis C viral suppression.

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Fumonisin B1 (FB1) is a Fusarium spp. mycotoxin which constitutes a major public health issue because of its worldwide distribution and diversity of toxic effects.While the liver and kidney are considered the major target organs of FB1 toxicity in several species, evidence indicates that FB1 may be toxic to the brain. To further investigate the effects of FB1 on the central nervous system the present study aimed to test the hypothesis that acute FB1 exposure causes brain hyperexcitability and the potential underlying mechanisms. For these purposes, adult male C57BL/6 mice were injected with FB1 (8 mg/kg, i.p.) or its vehicle and 30 min thereafter received with a low dose of the classical convulsant pentylenetetrazol (PTZ, 30 mg/kg, i.p.) or its vehicle. After behavioral evaluation the cerebral cortex and the hippocampus were collected for analysis of Na(+),K(+)-ATPase activity, mitochondrial membrane potential (ΔΨm) and mitochondrial complex I and II activities. We found that FB1 reduced the latency for PTZ-induced myoclonic jerks and increased the number of these events. After exposure to FB1 total and α1 Na(+),K(+)-ATPase activities increased in cerebral cortex, whereas the same enzyme activities decreased in the hippocampus. Although no changes in mitochondrial complex I and II activities were found, acute exposure to FB1 increased ΔΨm in the cerebral cortex. Altogether, present results indicate that FB1 causes brain hyperexcitability in vivo, and that mitochondrial dysfunction may represent a potential underlying mechanism.

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Os bifenilos policlorados (PCBs) estão entre os poluentes mais tóxicos presentes no meio ambiente, apresentando os alimentos como principal fonte de exposição humana. Com base nisso, este trabalho teve como objetivo determinar os sete PCBs indicadores de contaminação ambiental em 22 amostras de arroz e 18 de feijão do estado do Rio Grande do Sul, Brasil. Além disso, objetivou-se calcular a ingestão diária estimada de resíduos, a partir da contaminação existente no arroz e feijão, assim como determinar o teor de gordura das amostras para correlacioná-lo com os níveis de PCBs. A extração e purificação dos compostos foram realizadas pelo método QuEChERS, seguido de identificação e quantificação por CG-EM. Os PCBs 153 e 101 apresentaram as maiores concentrações médias nas amostras de arroz e feijão, respectivamente. Considerando o somatório dos PCBs, este foi de 4,39ng g-1 para o arroz e de 4,17ng g-1 para o feijão. Quanto à ingestão diária estimada, esta foi de 7,82ng kg-1 e de 3,14ng kg-1 de peso corporal por dia, para o arroz e o feijão, respectivamente. Em relação ao percentual de gordura, o arroz e o feijão apresentaram teores de gordura de 0,32% e de 1,1%, respectivamente. No entanto, a correlação com os níveis de PCBs não foi significativa. Os resultados demonstram que o estado do RS apresenta fontes importantes de contaminação desses resíduos químicos persistentes.

Polychlorinated biphenyls (PCBs) are among the most toxic pollutants in the environment showing foods as the main source of human exposure. Based on this, this study aimed to determine 7 PCBs indicators of environmental contamination in 22 samples of rice and 18 samples of beans in Rio Grande do Sul state, Brazil. Furthermore, this study aimed to calculate the waste estimated daily intake, starting from the existing contamination in rice and beans, as well as wanted to determine the samples fat content to correlate with levels of PCBs. The extraction and purification of the compounds were performed via QuEChERS method followed by identification and quantification by GC-MS. PCBs 153 and 101 showed the highest mean concentration in the samples of rice and bean, respectively. Considering the sum of PCBs in the samples, this was 4.39ng g-1 for the rice and 4.17ng g-1 for the beans. In estimated daily intake, this was 7.82ng kg-1 and 3.14ng kg-1 of body weight per day, for the rice and beans, respectively. Regarding the percentage of fat the rice and beans samples had fat contents of 0.32% and 1.1%, respectively. However, the correlation with the PCBs levels was not significant. The results demonstrate that the State of RS has important sources of these persistent chemical waste contaminations.

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Os bifenilos policlorados (PCBs) estão entre os poluentes mais tóxicos presentes no meio ambiente, apresentando os alimentos como principal fonte de exposição humana. Com base nisso, este trabalho teve como objetivo determinar os sete PCBs indicadores de contaminação ambiental em 22 amostras de arroz e 18 de feijão do estado do Rio Grande do Sul, Brasil. Além disso, objetivou-se calcular a ingestão diária estimada de resíduos, a partir da contaminação existente no arroz e feijão, assim como determinar o teor de gordura das amostras para correlacioná-lo com os níveis de PCBs. A extração e purificação dos compostos foram realizadas pelo método QuEChERS, seguido de identificação e quantificação por CG-EM. Os PCBs 153 e 101 apresentaram as maiores concentrações médias nas amostras de arroz e feijão, respectivamente. Considerando o somatório dos PCBs, este foi de 4,39ng g-1 para o arroz e de 4,17ng g-1 para o feijão. Quanto à ingestão diária estimada, esta foi de 7,82ng kg-1 e de 3,14ng kg-1 de peso corporal por dia, para o arroz e o feijão, respectivamente. Em relação ao percentual de gordura, o arroz e o feijão apresentaram teores de gordura de 0,32% e de 1,1%, respectivamente. No entanto, a correlação com os níveis de PCBs não foi significativa. Os resultados demonstram que o estado do RS apresenta fontes importantes de contaminação desses resíduos químicos persistentes.(AU)

Polychlorinated biphenyls (PCBs) are among the most toxic pollutants in the environment showing foods as the main source of human exposure. Based on this, this study aimed to determine 7 PCBs indicators of environmental contamination in 22 samples of rice and 18 samples of beans in Rio Grande do Sul state, Brazil. Furthermore, this study aimed to calculate the waste estimated daily intake, starting from the existing contamination in rice and beans, as well as wanted to determine the samples fat content to correlate with levels of PCBs. The extraction and purification of the compounds were performed via QuEChERS method followed by identification and quantification by GC-MS. PCBs 153 and 101 showed the highest mean concentration in the samples of rice and bean, respectively. Considering the sum of PCBs in the samples, this was 4.39ng g-1 for the rice and 4.17ng g-1 for the beans. In estimated daily intake, this was 7.82ng kg-1 and 3.14ng kg-1 of body weight per day, for the rice and beans, respectively. Regarding the percentage of fat the rice and beans samples had fat contents of 0.32% and 1.1%, respectively. However, the correlation with the PCBs levels was not significant. The results demonstrate that the State of RS has important sources of these persistent chemical waste contaminations.(AU)

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Conjugate compounds constitute a new class of molecules of important biological interest mainly for the treatment of diseases such as cancer. The N-terminus region of cationic peptides has been described as important for their biological activity. The aim of this study was to evaluate the lytic peptide Hecate (FALALKALKKALKKLKKALKKAL) and the effect of conjugating this macromolecule with gallic acid (C7H6O5) in terms of structure, anti-cancer activity, and toxicity. An N-terminus GA-Hecate peptide conjugate was synthesized to provide information regarding the relationship between the amino-terminal region and its charge and the secondary structure and biological activity of the peptide; and the effects of gallic acid on these parameters. Peptide secondary structure was confirmed using circular dichroism (CD). The CD measurements showed that the peptide has a high incidence of α-helical structures in the presence of SDS and LPC, while GA-Hecate presented lower incidence of α-helical structures in the same chemical environment. An evaluation of the anti-cancer activity in HeLa cancer cells indicated that both peptides are active, but that coupling gallic acid at the N-terminus decreased the activity of the free peptide. GA-Hecate showed lower activity in non-tumor keratinocyte cells but higher hemolytic activity. Our findings suggest that the N-terminus of Hecate plays an important role in its activity against cervical cancer by affecting it secondary structure, toxicity, and hemolytic activity. This study highlights the importance of the N-terminus in antitumor activity and could provide an important tool for developing new anti-cancer drugs.

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Hepatitis C is considered the major cause of cirrhosis and hepatocellular carcinoma. Conventional treatment is not effective against some hepatitis C virus (HCV) genotypes; therefore, new treatments are needed. Coffee and, more recently, caffeine, have been found to have a beneficial effect in several disorders of the liver, including those manifesting abnormal liver biochemistry, cirrhosis and hepatocellular carcinoma. Caffeine acts directly by delaying fibrosis, thereby improving the function of liver cellular pathways and interfering with pathways used by the HCV replication cycle. In the current study, the direct relationship between caffeine and viral replication was evaluated. The Huh-7.5 cell line was used for transient infections with FL-J6/JFH-5'C19Rluc2AUbi and to establish a cell line stably expressing SGR-Feo JFH-1. Caffeine efficiently inhibited HCV replication in a dose-dependent manner at non-cytotoxic concentrations and demonstrated an IC50 value of 0.7263 mM after 48 h of incubation. These data demonstrate that caffeine may be an important new agent for anti-HCV therapies due to its efficient inhibition of HCV replication at non-toxic concentrations.

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UNLABELLED: Individuals with Down syndrome (DS) tend to have impaired verbal short-term memory (STM), which persists even when visual support is provided for carrying out verbal tasks. OBJECTIVE: The current study aims to investigate whether visuospatial support, rather than just visual, can compensate for verbal STM deficits in these individuals. The performance of 25 children and adolescents with DS (mean age=12.5, SD=3.8) on five word span tasks was compared with that of two groups of typically developing children, matched for mental age (N=25; mean age=6.0, SD=.2) and for receptive vocabulary (N=25; mean age=4.0, SD=.8). Four of the five tasks varied in terms of input and output--verbal and/or visual--and the fifth task included a spatial component in addition to visual input and output. DS individuals performed equally bad in the pure verbal task and in those with visual components; however, there was a significant improvement when the spatial component was included in the task. The mental age matched group outperformed DS individuals in all tasks except for that with the spatial component; the receptive vocabulary matched group, outperformed DS individuals only in the pure verbal task. We found that visuospatial support improves verbal STM in individuals with DS. This result may have implications for intervention purposes.

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