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2.
J Asthma ; : 1-8, 2019 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-31702415

RESUMO

Objective: The recruitment setting plays a key role in the evaluation of behavioral interventions. We evaluated a behavioral intervention for urban adolescents with asthma in three randomized trials conducted separately in three different settings over the course of 8 years. We hypothesized that characteristics of trial participants recruited from the ED and clinic settings would be significantly different from that of youth participating in the school-based trials. The intervention evaluated was Puff City, a web-based program that uses tailoring to improve asthma management behaviors.Methods: The present analysis includes youth aged 13-19 years who reported a physician diagnosis of asthma and symptoms at trial baseline. In the three trials, all participants were randomized post-baseline to a web-based, tailored intervention (treatment) or generic web-based asthma education (control).Results: Compared to school-based trial participants, ED participants had significantly more acute-care visits for asthma (p < 0.001) and more caregiver depression (p < 0.001). Clinic-based participants were more likely to have computer/ internet access than participants from the school-based trial (p < 0.001). Both ED and clinic participants were more likely to report controller medication (p's < 0.001) and higher teen emotional support (p's < 0.01) when compared to the schools, but were less likely to report Medicaid (p's < 0.014) and exposure to environmental tobacco smoke (p < 0.001).Conclusion: Compared to participants in the school-based trials, participants recruited from ED and clinic settings differed significantly in terms of healthcare use, as well as psychosocial and sociodemographic factors. These factors can inform intervention content, and may impact external validity of behavioral interventions for asthma.

4.
Nat Microbiol ; 4(11): 1851-1861, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31332384

RESUMO

Neonates at risk of childhood atopy and asthma exhibit perturbation of the gut microbiome, metabolic dysfunction and increased concentrations of 12,13-diHOME in their faeces. However, the mechanism, source and contribution of this lipid to allergic inflammation remain unknown. Here, we show that intra-abdominal treatment of mice with 12,13-diHOME increased pulmonary inflammation and decreased the number of regulatory T (Treg) cells in the lungs. Treatment of human dendritic cells with 12,13-diHOME altered expression of PPARγ-regulated genes and reduced anti-inflammatory cytokine secretion and the number of Treg cells in vitro. Shotgun metagenomic sequencing of neonatal faeces indicated that bacterial epoxide hydrolase (EH) genes are more abundant in the gut microbiome of neonates who develop atopy and/or asthma during childhood. Three of these bacterial EH genes (3EH) specifically produce 12,13-diHOME, and treatment of mice with bacterial strains expressing 3EH caused a decrease in the number of lung Treg cells in an allergen challenge model. In two small birth cohorts, an increase in the copy number of 3EH or the concentration of 12,13-diHOME in the faeces of neonates was found to be associated with an increased probability of developing atopy, eczema or asthma during childhood. Our data indicate that elevated 12,13-diHOME concentrations impede immune tolerance and may be produced by bacterial EHs in the neonatal gut, offering a mechanistic link between perturbation of the gut microbiome during early life and atopy and asthma during childhood.


Assuntos
Asma/imunologia , Bactérias/classificação , Epóxido Hidrolases/genética , Fezes/química , Ácidos Linoleicos/análise , Animais , Bactérias/enzimologia , Bactérias/genética , Fenômenos Fisiológicos Bacterianos , Proteínas de Bactérias/genética , Modelos Animais de Doenças , Feminino , Microbioma Gastrointestinal , Humanos , Tolerância Imunológica , Recém-Nascido , Masculino , Camundongos , Linfócitos T Reguladores/metabolismo
7.
J Asthma ; 56(8): 882-890, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29984589

RESUMO

Introduction: People with low health literacy have poorer self-management of chronic diseases like asthma. Studies of parent health literacy and education level on the management of children's chronic illnesses reveal inconclusive results. We hypothesized a correlation between parent and adolescent health literacy in teens with asthma. Methods: Sociodemographic data were obtained; health literacy was assessed on adolescents and parents with three instruments: Rapid Estimate of Adolescent/Adult Literacy in Medicine (REALM), Single Item Literacy Screener (SILS) and Newest Vital Sign (NVS). Agreement between scores was examined by calculating weighted kappa statistics and performing Bowkers test of symmetry. Results: In all, 243 adolescents and 203 parents completed health literacy assessments yielding 198 paired observations. 9th-12th graders, 60.6% female, 72.7% African-American (AA), mean age: 15.3 years (±0.9). Parent education ranged from < high school (19.1%) to college graduate (24.0%). Agreement between adolescent and parent scores was poor: REALM (κw = 0.26), SILS (κw = 0.12), and NVS (κw = 0.29) and disagreement did not significantly differ by race. Positive correlations of moderate strength (overall and between racial groups) were found between reading scores and both REALM and NVS scores, and between REALM and NVS scores. Due to the inverse relationship of SILS scores with health literacy level, SILS scores (overall and between racial groups) were weakly and negatively correlated with reading scores, REALM and NVS. Conclusion: Correlation between education level and traditional literacy suggests that these are contributing factors to the health literacy of adolescents with asthma. Correlation between adolescent and caregiver health literacy was not supported.

8.
Artigo em Inglês | MEDLINE | ID: mdl-28649417

RESUMO

BACKGROUND: Low-income African-American adolescents use preventive medical services less frequently than their White counterparts, indicating a need for effective interventions targeting this group. Puff City is a Web-based, asthma management program for urban adolescents that has been evaluated in high school settings with promising results. The objective of this pilot was to assess the feasibility of initiating Puff City (treatment) in an emergency department setting, thereby informing the conduct of an individual randomized trial to evaluate its effectiveness compared to a generic, Web-based program (control) in preventing subsequent emergency department (ED) visits. METHODS: Teens aged 13-19 years presenting with acute asthma to two urban EDs within the study period were eligible. Subsequent ED visits were collected using the electronic medical record. A priori indication of a potential intervention effect was p < 0.20. RESULTS: Of the 121 teens randomized (65 treatment, 56 control), 86.0% were African-American and 44.6% male, with the mean age = 15.4 years. Computer ownership was reported by 76.8% of teens. Overall, 64.5% of teens completed >3 of 4 sessions and 90% completed the 12-month survey. At 12 months, the treatment group showed a trend toward fewer ED visits than controls (33.8 versus 46.4%), p = 0.15. CONCLUSIONS: Results indicate the feasibility of enrolling at-risk adolescents in ED settings and set the stage for a large, pragmatic trial using a technology-based intervention to reduce the burden of pediatric asthma. TRIAL REGISTRATION: ClinicalTrials.gov, NCT01695031.

10.
J Pediatr Gastroenterol Nutr ; 65(3): e60-e67, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28827481

RESUMO

BACKGROUND AND OBJECTIVES: Breast milk is a complex bioactive fluid that varies across numerous maternal and environmental conditions. Although breast-feeding is known to affect neonatal gut microbiome, the milk components responsible for this effect are not well-characterized. Given the wide range of immunological activity breast milk cytokines engage in, we investigated 3 essential breast milk cytokines and their association with early life gut microbiota. METHODS: A total of 52 maternal-child pairs were drawn from a racially diverse birth cohort based in Detroit, Michigan. Breast milk and neonatal stool specimens were collected at 1-month postpartum. Breast milk transforming growth factor (TGF)ß1, TGFß2, and IL-10 were assayed using enzyme-linked immunosorbent assays, whereas neonatal gut microbiome was profiled using 16S rRNA sequencing. RESULTS: Individually, immunomodulators TGFß1 and TGFß2 were significantly associated with neonatal gut microbial composition (R = 0.024, P = 0.041; R = 0.026, P = 0.012, respectively) and increased richness, evenness, and diversity, but IL-10 was not. The effects of TGFß1 and TGFß2, however, were not independent of one another, and the effect of TGFß2 was stronger than that of TGFß1. Higher levels of TGFß2 were associated with the increased relative abundance of several bacteria, including members of Streptococcaceae and Ruminococcaceae, and lower relative abundance of distinct Staphylococcaceae taxa. CONCLUSIONS: Breast milk TGFß concentration explains a portion of variability in gut bacterial microbiota composition among breast-fed neonates. Whether TGFß acts in isolation or jointly with other bioactive components to alter bacterial composition requires further investigation. These findings contribute to an increased understanding of how breast-feeding affects the gut microbiome-and potentially immune development-in early life.


Assuntos
Aleitamento Materno , Microbioma Gastrointestinal , Interleucina-10/imunologia , Leite Humano/imunologia , Fator de Crescimento Transformador beta1/imunologia , Fator de Crescimento Transformador beta2/imunologia , Adulto , Biomarcadores/metabolismo , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Lactente , Recém-Nascido , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Leite Humano/metabolismo , Estudos Prospectivos , Análise de Regressão , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta2/metabolismo
11.
Curr Allergy Asthma Rep ; 17(6): 37, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28484946

RESUMO

PURPOSE OF REVIEW: Asthma is the most common chronic illness of children and adolescents in the USA. While asthma has been understood to disproportionately affect urban dwellers, recent investigations have revealed rural pediatric asthma prevalence to be very similar to urban and to be more closely correlated with socioeconomic and environmental factors than geographic location or population density. RECENT FINDINGS: Rural children experience factors unique to location that impact asthma development and outcomes, including housing quality, cigarette smoke exposure, and small/large-scale farming. Additionally, there are challenging barriers to appropriate asthma care that frequently are more severe for those living in rural areas, including insurance status, lack of primary care providers and pulmonary specialists, knowledge deficits (both patient and provider), and a lack of culturally tailored asthma interventions. Interventions designed to address rural pediatric asthma disparities are more likely to be successful when targeted to specific challenges, such as the use of school-based services or telemedicine to mitigate asthma care access issues. Continued research on understanding the complex interaction of specific rural environmental factors with host factors can inform future interventions designed to mitigate asthma disparities.


Assuntos
Asma/epidemiologia , População Rural/estatística & dados numéricos , Adolescente , Asma/prevenção & controle , Asma/terapia , Criança , Humanos , Prevalência
12.
Transl Res ; 179: 60-70, 2017 01.
Artigo em Inglês | MEDLINE | ID: mdl-27469270

RESUMO

Among the many areas being revolutionized by the recent introduction of culture-independent microbial identification techniques is investigation of the relationship between close contact with large animals, antibiotics, breast feeding, mode of birth, and other exposures during infancy as related to a reduced risk of asthma and allergic disease. These exposures were originally clustered under the "Hygiene Hypothesis" which has evolved into the "Microbiota Hypothesis". This review begins by summarizing epidemiologic studies suggesting that the common feature of these allergy risk-related exposures is their influence on the founding and early development of a child's gut microbiota. Next, studies using culture-independent techniques are presented showing that children who have experienced the exposures of interest have altered gut microbiota. Finally, selected mouse and human studies are presented which begin to corroborate the protective exposures identified in epidemiologic studies by elucidating mechanisms through which microbes can alter immune development and function. These microbially driven immune alterations demonstrate that microbial exposures in many cases could alter the risk of subsequent allergic disease and asthma. Hopefully, a better understanding of how microbes influence allergic disease will lead to safe and effective methods for reducing the prevalence of all forms of allergic disease.


Assuntos
Asma/etiologia , Asma/microbiologia , Bactérias/metabolismo , Microbioma Gastrointestinal , Hipersensibilidade/etiologia , Hipersensibilidade/microbiologia , Animais , Asma/epidemiologia , Asma/imunologia , Bactérias/imunologia , Criança , Humanos , Hipótese da Higiene , Hipersensibilidade/epidemiologia , Hipersensibilidade/imunologia , Imunidade , Lactente , Fatores de Risco
14.
Nat Med ; 22(10): 1187-1191, 2016 10.
Artigo em Inglês | MEDLINE | ID: mdl-27618652

RESUMO

Gut microbiota bacterial depletions and altered metabolic activity at 3 months are implicated in childhood atopy and asthma. We hypothesized that compositionally distinct human neonatal gut microbiota (NGM) exist, and are differentially related to relative risk (RR) of childhood atopy and asthma. Using stool samples (n = 298; aged 1-11 months) from a US birth cohort and 16S rRNA sequencing, neonates (median age, 35 d) were divisible into three microbiota composition states (NGM1-3). Each incurred a substantially different RR for multisensitized atopy at age 2 years and doctor-diagnosed asthma at age 4 years. The highest risk group, labeled NGM3, showed lower relative abundance of certain bacteria (for example, Bifidobacterium, Akkermansia and Faecalibacterium), higher relative abundance of particular fungi (Candida and Rhodotorula) and a distinct fecal metabolome enriched for pro-inflammatory metabolites. Ex vivo culture of human adult peripheral T cells with sterile fecal water from NGM3 subjects increased the proportion of CD4+ cells producing interleukin (IL)-4 and reduced the relative abundance of CD4+CD25+FOXP3+ cells. 12,13-DiHOME, enriched in NGM3 versus lower-risk NGM states, recapitulated the effect of NGM3 fecal water on relative CD4+CD25+FOXP3+ cell abundance. These findings suggest that neonatal gut microbiome dysbiosis might promote CD4+ T cell dysfunction associated with childhood atopy.


Assuntos
Asma/epidemiologia , Linfócitos T CD4-Positivos/imunologia , Microbioma Gastrointestinal/genética , Hipersensibilidade/epidemiologia , RNA Ribossômico 16S/genética , Asma/imunologia , Bifidobacterium/genética , Linfócitos T CD4-Positivos/metabolismo , Candida/genética , Diferenciação Celular/imunologia , Pré-Escolar , Faecalibacterium/genética , Fezes/química , Feminino , Fatores de Transcrição Forkhead/metabolismo , Microbioma Gastrointestinal/imunologia , Humanos , Hipersensibilidade/imunologia , Lactente , Recém-Nascido , Subunidade alfa de Receptor de Interleucina-2/metabolismo , Interleucina-4/imunologia , Masculino , Razão de Chances , Rhodotorula/genética , Análise de Sequência de RNA , Linfócitos T/imunologia
15.
Sci Rep ; 6: 31775, 2016 08 25.
Artigo em Inglês | MEDLINE | ID: mdl-27558272

RESUMO

The joint impact of pregnancy, environmental, and sociocultural exposures on early life gut microbiome is not yet well-characterized, especially in racially and socioeconomically diverse populations. Gut microbiota of 298 children from a Detroit-based birth cohort were profiled using 16S rRNA sequencing: 130 neonates (median age = 1.2 months) and 168 infants (median age = 6.6 months). Multiple factors were associated with neonatal gut microbiome composition in both single- and multi-factor models, with independent contributions of maternal race-ethnicity, breastfeeding, mode of delivery, marital status, exposure to environmental tobacco smoke, and indoor pets. These findings were consistent in the infants, and networks demonstrating the shared impact of factors on gut microbial composition also showed notable topological similarity between neonates and infants. Further, latent groups defined by these factors explained additional variation, highlighting the importance of combinatorial effects. Our findings also have implications for studies investigating the impact of the early life gut microbiota on disease.


Assuntos
Microbioma Gastrointestinal , Intestinos/microbiologia , Microbiota , Adulto , Algoritmos , Animais , Aleitamento Materno , Características Culturais , Meio Ambiente , Fezes , Feminino , Humanos , Lactente , Recém-Nascido , Estilo de Vida , Pessoa de Meia-Idade , Mães , Animais de Estimação , Filogenia , Gravidez , Complicações na Gravidez , RNA Ribossômico 16S/genética , Fumar/efeitos adversos , Classe Social , Adulto Jovem
16.
Ethn Dis ; 26(1): 61-8, 2016 01 21.
Artigo em Inglês | MEDLINE | ID: mdl-26843797

RESUMO

OBJECTIVE: African American children are at higher risk of obesity than White children and African American women are more likely to undergo caesarean-section (CS) delivery than White women. CS is associated with childhood obesity; however, little is known whether this relationship varies by race. We examined if the association of CS with obesity at age 2 years varied by race. DESIGN: Longitudinal birth cohort. SETTING: Birth cohort conducted in a health care system in metropolitan Detroit, Michigan with follow-up at age 2 years. PARTICIPANTS: 639 birth cohort participants; 367 children (57.4%) were born to African American mothers and 230 (36.0%) children were born via CS. MAIN OUTCOME MEASURES: Obesity defined as body mass index ≥95th percentile at age 2 years. RESULTS: Slightly more children of African American (n=37; 10.1%) than non-African American mothers (n=18; 6.6%) were obese (P=.12). There was evidence of effect modification between race and delivery mode with obesity at age 2 years (interaction P=.020). In children of African American mothers, CS compared to vaginal birth was associated with a significantly higher odds of obesity (aOR=2.35 (95% CI: 1.16, 4.77), P=.017). In contrast, delivery mode was not associated with obesity at age 2 years in children of non-African American mothers (aOR=.47 (95% CI: .13, 1.71), P=.25). CONCLUSIONS: There is evidence for a race-specific effect of CS on obesity at age 2 years; potential underlying mechanisms may be racial differences in the developing gut microbiome or in epigenetic programming. Future research is needed to determine if this racial difference persists into later childhood.


Assuntos
Índice de Massa Corporal , Cesárea , Obesidade Pediátrica , Adulto , Afro-Americanos , Tamanho Corporal , Criança , Pré-Escolar , Grupo com Ancestrais do Continente Europeu , Feminino , Humanos , Michigan , Mães , Gravidez , Fatores de Risco
17.
Ann Allergy Asthma Immunol ; 116(3): 219-224.e1, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26837607

RESUMO

BACKGROUND: Suspected food allergies are the cause of more than 200,000 visits to the emergency department annually. Racial differences in the prevalence of food allergy have also been reported, but the evidence is less conclusive. Researchers continue to struggle with the identification of food allergy for epidemiologic studies. OBJECTIVE: To explore racial differences in IgE-mediated food allergy (IgE-FA) in a birth cohort. METHODS: We used a panel of board-certified allergists to systematically identify IgE-FA to egg, milk, or peanut in a multiethnic birth cohort in which patient medical history, patient symptoms, and clinical data were available through 36 months of age. RESULTS: Of the 590 infants analyzed, 52.9% were male and 65.8% African American. Sensitization (serum specific IgE >0.35 IU/mL) to the food allergens was significantly higher for African American children compared with non-African American children as has been previously reported. No statistically significant racial/ethnic differences in IgE-FA were observed; however, a higher proportion of African American children were designated as having peanut allergy, and the percentage of African American children with an IgE level greater than 95% predictive decision points for peanut was 1.7% vs 0.5% for non-African American children. With the use of logistic regression, race/ethnicity was not significantly associated with IgE-FA (adjusted odds ratio, 1.12; 95% confidence interval, 0.58-2.17; P = .75) but was associated with sensitization to more than 1 of the food allergens (adjusted odds ratio, 1.80; 95% confidence interval, 1.22-2.65; P = .003). CONCLUSION: We did not observe an elevated risk of IgE-FA for African American children, although established differences in sensitization were observed. Racial/ethnic differences in sensitization must be taken into consideration when investigating disparities in asthma and allergy.


Assuntos
Grupos Étnicos , Hipersensibilidade Alimentar/epidemiologia , Hipersensibilidade Alimentar/imunologia , Imunoglobulina E/imunologia , Alérgenos/classificação , Alérgenos/imunologia , Animais , Pré-Escolar , Estudos de Coortes , Feminino , Humanos , Imunoglobulina E/sangue , Lactente , Recém-Nascido , Masculino , Razão de Chances , Prevalência , Testes Cutâneos
18.
Expert Rev Clin Immunol ; 12(4): 379-88, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26776722

RESUMO

Our global hypothesis is that atopic conditions and asthma develop because an individual's immune system is not able to appropriately resolve inflammation resulting from allergen exposures. We propose that the failure to appropriately down-regulate inflammation and produce a toleragenic state results primarily from less robust immune homeostatic processes rather than from a tendency to over-respond to allergenic stimuli. An individual with lower immune homeostatic capacity is unable to rapidly and completely terminate, on average over time, immune responses to innocuous allergens, increasing risk of allergic disease. A lack of robust homeostasis also increases the risk of other inflammatory conditions, such as prolonged respiratory viral infections and obesity, leading to the common co-occurrence of these conditions. Further, we posit that the development of vigorous immune homeostatic mechanisms is an evolutionary adaptation strongly influenced by both 1) exposure to a diverse maternal microbiota through the prenatal period, labor and delivery, and, 2) an orderly assemblage process of the infant's gut microbiota ecosystem shaped by breastfeeding and early exposure to a wide variety of ingested foods and environmental microbes. This early succession of microbial communities together with early allergen exposures orchestrate the development of an immune system with a robust ability to optimally control inflammatory responses and a lowered risk for atopic disorders.


Assuntos
Asma/imunologia , Disbiose/imunologia , Hipersensibilidade/imunologia , Intestinos/microbiologia , Alérgenos/efeitos adversos , Alérgenos/imunologia , Animais , Asma/microbiologia , Evolução Biológica , Exposição Ambiental/efeitos adversos , Homeostase , Humanos , Hipersensibilidade/microbiologia , Tolerância Imunológica , Lactente , Intestinos/imunologia
19.
Clin Res Regul Aff ; 33(2-4): 25-32, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-28479846

RESUMO

CONTEXT: Modernized approaches to multisite randomized controlled trials (RCT) include the use of electronic medical records (EMR) for recruitment, remote data capture (RDC) for multisite data collection, and strategies to reduce the need for research infrastructure. These features facilitate the conduct of pragmatic trials, or trials conducted in "real life" settings. OBJECTIVE: We describe the recruitment experience of an RCT to evaluate a clinic-based intervention targeting urban youth with asthma. MATERIALS AND METHODS: Using encounter and prescription databases, a list of potentially-eligible patients was linked to the Epic appointment scheduling system. Patients were enrolled during a scheduled visit and then electronically randomized to a tailored versus generic online intervention. RESULTS AND DISCUSSION: 1146 appointments for 580 eligible patients visiting 5 clinics were identified, of which 45.9% (266/580) were randomized to reach targeted enrollment (n=250). RDC facilitated multisite enrollment. Intervention content was further personalized through real- time entry of asthma medications prescribed at the clinic visit. EMR monitoring helped with recruitment trouble-shooting. Systemic challenges included a system-wide EMR transition and a system-wide reorganization of clinic staffing. CONCLUSIONS: Modernized RCTs can accelerate translation of research findings. Electronic initiatives facilitated implementation of this RCT; however, adaptations to recruitment strategies resulted in a more "explanatory" framework. .

20.
Biol Trace Elem Res ; 171(1): 41-7, 2016 May.
Artigo em Inglês | MEDLINE | ID: mdl-26358768

RESUMO

Rates of childhood obesity have risen at the same time rates of high blood lead levels (BLLs) have fallen. Recent studies suggest that higher BLL is inversely associated with body size in older children (ages 3-19 years). No contemporaneous studies have examined if having a detectable BLL is associated with body size in very early childhood. We examined if detectable BLL is associated with body size in early childhood. A total of 299 birth cohort participants completed a study visit at ages 2-3 years with weight and height measurements; prior to this clinic visit, a BLL was drawn as part of routine clinical care. Body mass index (BMI) percentile and Z-score were calculated; children with BMI ≥85th percentile were considered overweight/obese at age of 2 years. Detectable BLL was defined as BLL ≥1 µg/dL. A total of 131 (43.8 %) children had a detectable BLL measured at mean aged 15.4 ± 5.5 months. Mean age at body size assessment was 2.2 ± 0.3 years (53.2 % male, 68.6 % African-American). After adjusting for race, sex, and birth weight, children with a detectable BLL had a 43 % lower risk of BMI ≥85th percentile (P = 0.041) and a 0.35-unit lower BMI Z-score (P = 0.008) compared to children without a detectable BLL. Neither race nor sex modified this association (all interactions P > 0.21). Consistent with recent studies in older children, having a detectable BLL was associated with smaller body size at ages 2-3 years. Additional research on the mechanism of this association is needed but may include mechanisms of appetite suppression via lead.


Assuntos
Tamanho Corporal , Chumbo/sangue , Adolescente , Adulto , Índice de Massa Corporal , Criança , Pré-Escolar , Humanos , Pessoa de Meia-Idade , Adulto Jovem
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