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Bone morphogenetic protein 2 (BMP2) and BMP6 are key regulators of systemic iron homeostasis. All BMPs are generated as inactive precursor proteins that dimerize and are cleaved to generate the bioactive ligand and inactive prodomain fragments, but nothing is known about how BMP2 or BMP6 homodimeric or heterodimeric precursor proteins are proteolytically activated. Here, we conducted in vitro cleavage assays, which revealed that BMP2 is sequentially cleaved by furin at two sites, initially at a site upstream of the mature ligand, and then at a site adjacent to the ligand domain, while BMP6 is cleaved at a single furin motif. Cleavage of both sites of BMP2 is required to generate fully active BMP2 homodimers when expressed in Xenopus embryos or liver endothelial cells, and fully active BMP2/6 heterodimers in Xenopus . We analyzed BMP activity in Xenopus embryos expressing chimeric proteins consisting of the BMP2 prodomain and BMP6 ligand domain, or vice versa. We show that the prodomain of BMP2 is necessary and sufficient to generate active BMP6 homodimers and BMP2/6 heterodimers, whereas the BMP6 prodomain cannot generate active BMP2 homodimers or BMP2/6 heterodimers. We examined BMP2 and BMP6 homodimeric and heterodimeric ligands generated from native and chimeric precursor proteins expressed in Xenopus embryos. Whereas native BMP6 is not cleaved when expressed alone, it is cleaved to generate BMP2/6 heterodimers when co-expressed with BMP2. Furthermore, BMP2-6 chimeras are cleaved to generate BMP6 homodimers. Our findings reveal an important role for the BMP2 prodomain in dimerization and proteolytic activation of BMP6.
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OBJECTIVE: To describe the Bayley Scales of Infant Development 3rd Edition (Bayley-III) of infants discharged home receiving tube feeds. STUDY DESIGN: Retrospective review of infants discharged with nasogastric or gastrostomy tube feeds and completed a Bayley-III assessment at 2-3-years of age through a neonatal follow-up program. Results were reported using descriptive statistics. RESULTS: Of infants discharged with nasogastric feeds, median Bayley-III scores were in the low-average to average range, and full oral feeds were achieved in 75%. Of infants discharged with gastrostomy tube feeds, median Bayley-III scores were in the extremely low range, and full oral feeds were achieved in 36%. Our data set did not demonstrate a distinct patient demographic that correlated to the type of feeding tube at discharge. CONCLUSION: Neurodevelopmental outcome at 2-3 years does not appear to be negatively impacted by the decision to discharge an infant from the NICU with home NG feedings.
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ABSTRACT: Iron-mediated induction of bone morphogenetic protein (BMP)6 expression by liver endothelial cells is essential for iron homeostasis regulation. We used multiple dietary and genetic mouse cohorts to demonstrate a minor functional role for the metal-ion transporter ZIP8 in regulating BMP6 expression under high-iron conditions.
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Proteína Morfogenética Óssea 6 , Proteínas de Transporte de Cátions , Ferro , Animais , Proteína Morfogenética Óssea 6/metabolismo , Proteína Morfogenética Óssea 6/genética , Camundongos , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Ferro/metabolismo , Células Endoteliais/metabolismo , Camundongos Knockout , Regulação da Expressão Gênica , Fígado/metabolismo , Camundongos Endogâmicos C57BL , HomeostaseRESUMO
BACKGROUND: Little has been reported regarding the prevalence and severity of exercise-induced pulmonary hemorrhage (EIPH) in 2-year-old Thoroughbred racehorses. OBJECTIVES: Evaluate EIPH prevalence and severity and its association with performance, speed index, furosemide administration, race distance, and track surface. ANIMALS: A total of 830 2-year-old Thoroughbreds. METHODS: Prospective blinded observational study. Videoendoscopy was performed 30 to 60 minutes postrace at 15 American racetracks. Three blinded observers independently assigned an EIPH grade (0-4) to each video, and prevalence and severity of EIPH were determined. Relationships of EIPH grade to performance, speed index, race distance, track surface, and prerace administration of furosemide were evaluated using Pearson's chi-squared test for categorical variables and analysis of variance (ANOVA) for numerical variables. Multivariable logistic regression assessed relationships between EIPH prevalence and severity, respectively, and the aforementioned independent variables. A P < .05 was considered significant. RESULTS: A total of 1071 tracheoendoscopies were recorded. The EIPH prevalence was 74% and for EIPH grade ≥3 was 8%. Speed index (P = .02) and finishing place (P = .004) were lower with EIPH ≥3. The EIPH prevalence and severity were lower at 2 tracks where postrace tracheoendoscopy was mandatory rather than voluntary (P < .001). Probability of observing EIPH was negatively associated with speed index (P = .01) at tracks where postrace tracheoendoscopy was mandatory. Prerace furosemide administration decreased the probability of EIPH occurrence (P = .007) and severity (P = .01) where study participation was voluntary. CONCLUSIONS AND CLINICAL IMPORTANCE: Prevalence and severity of EIPH in 2-year-old racehorses were consistent with that of older racehorses. An EIPH grade ≥3 was associated with decreased performance. Prerace furosemide administration was associated with a decreased likelihood, but not severity, of EIPH at most tracks.
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Doenças dos Cavalos , Pneumopatias , Condicionamento Físico Animal , Animais , Furosemida/uso terapêutico , Hemorragia/epidemiologia , Hemorragia/etiologia , Hemorragia/veterinária , Doenças dos Cavalos/epidemiologia , Doenças dos Cavalos/etiologia , Cavalos , Pneumopatias/epidemiologia , Pneumopatias/etiologia , Pneumopatias/veterinária , Condicionamento Físico Animal/efeitos adversos , Prevalência , Estudos ProspectivosRESUMO
BACKGROUND: Black families of children with autism spectrum disorder have less access to high quality, culturally responsive care for their children. METHOD: We assessed satisfaction and service utilization among fifty (29%) Black caregivers and 124 (71%) White caregivers of children with autism spectrum disorder. We also examined whether race moderated the association between satisfaction and service utilization. RESULTS: We did not identify racial differences in satisfaction or service utilization. Race moderated the association between satisfaction and total service use, F(170) = 5.29, p =.02, therapy service use, F(163) = 3.59, p =.046, and community service use, F(169) = 4.76, p =.046. For Black families, there was a positive association between satisfaction and service use. There was no association between satisfaction and service use among White families. DISCUSSION: Satisfaction may be particularly important among Black families, who have been mistreated by the healthcare system and frequently face discrimination. Our results suggest the importance of culturally responsive care for Black families.
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Purpose: Pediatric brain tumor survivors (PBTS) commonly experience mental health challenges, which can be exacerbated during adolescence and emerging adulthood (AEA). We examined survivors and caregivers' perceived need for mental health services and barriers to receiving mental health care. Methods: Families completed surveys to assess perceived need for mental health services, socioemotional impairment, and barriers to mental health services. Survivors were between 13 and 25 years of age and were at least 5 years from diagnosis. Results: Sixty-nine caregiver-PBTS dyads participated, as well as 18 survivors and 20 caregivers who participated individually. Approximately half of survivors were male (n = 57, 52.3%), 85% (n = 93) were White, and their average age was 19.31. Most caregivers (n = 63, 70.8%) and survivors (n = 55, 63.2%) endorsed need for services for the survivors. Adolescents endorsed more barriers related to perceived helpfulness, t(18) = 2.3, p = 0.03, d = 0.54, and effects of services, t(18) = 3.8, p < 0.001, d = 0.88, than their caregivers. Emerging adults, t(34) = 2.4, p = 0.02, d = 0.41, endorsed more content barriers than their caregivers.. Discussion: Both survivors and their caregivers reported obstacles to accessing mental health services such as perceived lack of need, concerns regarding the effectiveness and usefulness of services, and limited knowledge about the content of services. Psychoeducation and psychosocial screening can support families in understanding survivors' need for mental health services.
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Neoplasias Encefálicas , Sobreviventes de Câncer , Serviços de Saúde Mental , Humanos , Adolescente , Masculino , Feminino , Adulto Jovem , Neoplasias Encefálicas/psicologia , Neoplasias Encefálicas/terapia , Adulto , Sobreviventes de Câncer/psicologia , Cuidadores/psicologia , Necessidades e Demandas de Serviços de Saúde , Acessibilidade aos Serviços de Saúde , CriançaRESUMO
BACKGROUND: Preterm birth is associated with adverse mental health outcomes, including internalizing problems, social difficulties and inattention. Interventions are needed beyond infancy and toddlerhood to support children and their families. We examined the feasibility and acceptability of the I-InTERACT Preterm pilot study, an online parenting intervention for preterm children ages 3-8. METHOD: Families participated in a weekly intervention comprised of seven sessions with online modules followed by videoconference coaching sessions with a therapist. Following completion of the study, caregivers completed a survey to assess their satisfaction and were asked to participate in a voluntary semi-structured interview to provide feedback. We anticipated greater than a 50% participation rate (enrollment feasibility) and 75% completion rate (adherence feasibility). We also hypothesized that at least 80% of participants would be satisfied with the intervention (acceptability). RESULTS: Nineteen of 32 families (59%) enrolled in the study, suggesting adequate enrollment feasibility. Feasibility of programme completion (adherence) was lower than anticipated (59%). Regarding satisfaction, all caregivers agreed that the programme's information was relevant to them and their family. Nearly all participants (92%) indicated that they had a better understanding of the effects of preterm birth on behaviour, that they enjoyed the programme, that it met their expectations and that they recommend the programme to others. In qualitative interviews, caregivers expressed satisfaction with the content, skills they learned, and receiving direct coaching. Caregivers suggested improvements to increase intervention feasibility and skill implementation, including offering biweekly sessions and more hands-on coaching. CONCLUSION: Our largely satisfactory acceptability rates suggest the value of and need for a parenting intervention for children born preterm past the initial period of early development. Future directions include modifying the intervention in response to caregiver feedback to improve recruitment, engagement and adherence.
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Poder Familiar , Nascimento Prematuro , Recém-Nascido , Criança , Feminino , Pré-Escolar , Humanos , Poder Familiar/psicologia , Pais/psicologia , Estudos de Viabilidade , Projetos Piloto , Lactente Extremamente PrematuroRESUMO
Hepcidin is the master hormone governing systemic iron homeostasis. Iron regulates hepcidin by activating bone morphogenetic protein (BMP)6 expression in liver endothelial cells (LECs), but the mechanisms are incompletely understood. To address this, we performed proteomics and RNA-sequencing on LECs from iron-adequate and iron-loaded mice. Gene set enrichment analysis identified transcription factors activated by high iron, including Nrf-2, which was previously reported to contribute to BMP6 regulation, and c-Jun. Jun (encoding c-Jun) knockdown blocked Bmp6 but not Nrf-2 pathway induction by iron in LEC cultures. Chromatin immunoprecipitation of mouse livers showed iron-dependent c-Jun binding to predicted sites in Bmp6 regulatory regions. Finally, c-Jun inhibitor blunted induction of Bmp6 and hepcidin, but not Nrf-2 activity, in iron-loaded mice. However, Bmp6 and iron parameters were unchanged in endothelial Jun knockout mice. Our data suggest that c-Jun participates in iron-mediated BMP6 regulation independent of Nrf-2, though the mechanisms may be redundant and/or multifactorial.
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Background: Pediatric brain tumor survivors (PBTS) are at risk of worse quality of life (QOL) due to the impact of neurotoxic treatments on the developing nervous system. Parenting factors such as protectiveness have been linked to worse QOL in childhood cancer survivors generally, but have yet to be explored for PBTS. We examined whether parenting behaviors moderated the association between neurotoxic treatment and QOL for PBTS. Methods: PBTS (nâ =â 40; ages 10-25) and their caregivers (nâ =â 47) completed measures of parenting behaviors including warmth (support/connectedness) and psychological control (protectiveness) and QOL. We divided the sample into moderate/high and low neurotoxicity groups based on chart review using the Pediatric Neuro-Oncology Rating of Treatment Intensity and examined moderator effects. Results: Survivor-reported primary caregiver warmth moderated the relationship between neurotoxicity and caregiver-reported QOL. Moderate/high neurotoxicity was associated with lower caregiver-reported QOL only when survivor-reported primary caregiver warmth was low, Pâ =â .02. Similar results were found for survivor-reported QOL. Caregiver-reported psychological control moderated the association between neurotoxicity and caregiver-reported QOL such that neurotoxicity only affected QOL at high levels of psychological control, Pâ =â .01. Conclusions: Heightened associations between parenting and QOL in the context of neurotoxic treatments underscore the need to better support PBTS. Findings are consistent with research suggesting that family factors may be particularly important for children with other neurological insults. Limitations include cross-sectional design and a small/heterogeneous clinical sample with low ethnic/racial diversity. Prospective studies are needed to refine evidence-based screening and develop psychosocial intervention strategies to optimize QOL for PBTS and their families.
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Hepcidin is the master regulator of systemic iron homeostasis. The bone morphogenetic protein (BMP) signaling pathway is a critical regulator of hepcidin expression in response to iron and erythropoietic drive. Although endothelial-derived BMP6 and BMP2 ligands have key functional roles as endogenous hepcidin regulators, both iron and erythropoietic drives still regulate hepcidin in mice lacking either or both ligands. Here, we used mice with an inactivating Bmp5 mutation (Bmp5se), either alone or together with a global or endothelial Bmp6 knockout, to investigate the functional role of BMP5 in hepcidin and systemic iron homeostasis regulation. We showed that Bmp5se-mutant mice exhibit hepcidin deficiency at age 10 days, blunted hepcidin induction in response to oral iron gavage, and mild liver iron loading when fed on a low- or high-iron diet. Loss of 1 or 2 functional Bmp5 alleles also leads to increased iron loading in Bmp6-heterozygous mice and more profound hemochromatosis in global or endothelial Bmp6-knockout mice. Moreover, double Bmp5- and Bmp6-mutant mice fail to induce hepcidin in response to long-term dietary iron loading. Finally, erythroferrone binds directly to BMP5 and inhibits BMP5 induction of hepcidin in vitro. Although erythropoietin suppresses hepcidin in Bmp5se-mutant mice, it fails to suppress hepcidin in double Bmp5- and Bmp6-mutant males. Together, these data demonstrate that BMP5 plays a functional role in hepcidin and iron homeostasis regulation, particularly under conditions in which BMP6 is limited.
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Hemocromatose , Hepcidinas , Animais , Masculino , Camundongos , Proteína Morfogenética Óssea 6/metabolismo , Hemocromatose/genética , Hepcidinas/genética , Hepcidinas/metabolismo , Homeostase , Ferro/metabolismo , Fígado/metabolismo , Camundongos KnockoutRESUMO
Pregnancy entails a large negative balance of iron, an essential micronutrient. During pregnancy, iron requirements increase substantially to support both maternal red blood cell expansion and the development of the placenta and fetus. As insufficient iron has long been linked to adverse pregnancy outcomes, universal iron supplementation is common practice before and during pregnancy. However, in high-resource countries with iron fortification of staple foods and increased red meat consumption, the effects of too much iron supplementation during pregnancy have become a concern because iron excess has also been linked to adverse pregnancy outcomes. In this review, we address physiologic iron homeostasis of the mother, placenta, and fetus and discuss perturbations in iron homeostasis that result in pathological pregnancy. As many mechanistic regulatory systems have been deduced from animal models, we also discuss the principles learned from these models and how these may apply to human pregnancy.
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Placenta , Resultado da Gravidez , Animais , Gravidez , Feminino , Humanos , Feto , Ferro , HomeostaseRESUMO
The data provided here are related to the article "Resolving the Deep Phylogeny: Implications for Early Adaptive Radiation, Cryptic, and Present-day Ecological Diversity of Papuan Microhylid Frogs" [1]. The dataset is based on 233 tissue samples of the subfamily Asteroprhyinae, with representatives from all recognized genera, in addition to three outgroup taxa. The sequence dataset contains over 2400 characters per sample for five genes: three nuclear (Seventh in Absentia (SIA), Brain Derived Neurotrophic Factor (BDNF), Sodium Calcium Exchange subunit-1 (NXC-1)), and two mitochondrial loci (Cytochrome oxidase b (CYTB), and NADH dehydrogenase subunit 4 (ND4)); and is 99% complete. New primers were designed for all loci and accession numbers for the raw sequence data are provided. The sequences are used with geological time calibrations to produce time-calibrated Bayesian inference (BI) and Maximum Likelihood (ML) phylogenetic reconstructions using BEAST2 and IQ-TREE. Lifestyle data (arboreal, scansorial, terrestrial, fossorial, semi-aquatic) were collected from the literature and field notes and used to infer ancestral character states for each lineage. Collection location and elevation data were used to verify sites where multiple species or candidate species co-occur. All sequence data, alignments, and associated metadata (voucher specimen number, species identification, type locality status, global positioning system [GPS] coordinates, elevation, site with species list, and lifestyle) as well as the code to produce all analyses and figures are provided.
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BACKGROUND: The role of vaccine hesitancy on influenza vaccination is not clearly understood. Low influenza vaccination coverage in U.S. adults suggests that a multitude of factors may be responsible for under-vaccination or non-vaccination including vaccine hesitancy. Understanding the role of influenza vaccination hesitancy is important for targeted messaging and intervention to increase influenza vaccine confidence and uptake. The objective of this study was to quantify the prevalence of adult influenza vaccination hesitancy (IVH) and examine association of IVH beliefs with sociodemographic factors and early-season influenza vaccination. METHODS: A four-question validated IVH module was included in the 2018 National Internet Flu Survey. Weighted proportions and multivariable logistic regression models were used to identify correlates of IVH beliefs. RESULTS: Overall, 36.9% of adults were hesitant to receive an influenza vaccination; 18.6% expressed concerns about vaccination side effects; 14.8% personally knew someone with serious side effects; and 35.6% reported that their healthcare provider was not the most trusted source of information about influenza vaccinations. Influenza vaccination ranged from 15.3 to 45.2 percentage points lower among adults self-reporting any of the four IVH beliefs. Being female, age 18-49 years, non-Hispanic Black, having high school or lower education, being employed, and not having primary care medical home were associated with hesitancy. CONCLUSIONS: Among the four IVH beliefs studied, being hesitant to receiving influenza vaccination followed by mistrust of healthcare providers were identified as the most influential hesitancy beliefs. Two in five adults in the United States were hesitant to receive an influenza vaccination, and hesitancy was negatively associated with vaccination. This information may assist with targeted interventions, personalized to the individual, to reduce hesitancy and thus improve influenza vaccination acceptance.
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Vacinas contra Influenza , Influenza Humana , Adulto , Humanos , Feminino , Estados Unidos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Masculino , Influenza Humana/prevenção & controle , Influenza Humana/epidemiologia , Hesitação Vacinal , Prevalência , Vacinação , Conhecimentos, Atitudes e Prática em SaúdeRESUMO
This paper is devoted to investigating the impact of vaccination on mitigating COVID-19 outbreaks. In this work, we propose a compartmental epidemic ordinary differential equation model, which extends the previous so-called SEIRD model [1,2,3,4] by incorporating the birth and death of the population, disease-induced mortality and waning immunity, and adding a vaccinated compartment to account for vaccination. Firstly, we perform a mathematical analysis for this model in a special case where the disease transmission is homogeneous and vaccination program is periodic in time. In particular, we define the basic reproduction number $ \mathcal{R}_0 $ for this system and establish a threshold type of result on the global dynamics in terms of $ \mathcal{R}_0 $. Secondly, we fit our model into multiple COVID-19 waves in four locations including Hong Kong, Singapore, Japan, and South Korea and then forecast the trend of COVID-19 by the end of 2022. Finally, we study the effects of vaccination again the ongoing pandemic by numerically computing the basic reproduction number $ \mathcal{R}_0 $ under different vaccination programs. Our findings indicate that the fourth dose among the high-risk group is likely needed by the end of the year.
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COVID-19 , Humanos , COVID-19/epidemiologia , COVID-19/prevenção & controle , Surtos de Doenças/prevenção & controle , Modelos Teóricos , Vacinação , Pandemias/prevenção & controleRESUMO
Many forms of anemia are caused or complicated by pathologic restriction of iron (Fe). Chronic inflammation and certain genetic mutations decrease the activity of ferroportin, the only Fe-exporter protein, so that endogenously recycled or nutritionally absorbed Fe cannot be exported to the extracellular Fe carrier protein transferrin for delivery to the bone marrow. Diminished ferroportin activity renders anemia correction challenging as Fe administered intravenously or through nutritional supplementation is trafficked through the ferroportin-transferrin axis. Utilizing judicious application of coordination chemistry principles, we designed an Fe complex (Fe-BBG) with solution thermodynamics and Fe dissociation kinetics optimized to replenish the transferrin-Fe pool rapidly, directly, and with precision. Fe-BBG is unreactive under conditions designed to force redox cycling and production of reactive oxygen species. The BBG ligand has a low affinity for divalent metal ions and does not compete for binding of other endogenously present ions including Cu and Zn. Treatment with Fe-BBG confers anemia correction in a mouse model of iron-refractory iron-deficiency anemia. Repeated exposure to Fe-BBG did not cause adverse clinical chemistry changes or trigger the expression of genes related to oxidative stress or inflammation. Fe-BBG represents the first entry in a promising new class of transferrin-targeted Fe replacement drugs.
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Anemia Ferropriva , Anemia , Animais , Camundongos , Ferro/metabolismo , Transferrina , InflamaçãoRESUMO
Highly strained cage hydrocarbons have long stood as fundamental molecules to explore the limits of chemical stability and reactivity, probe physical properties, and more recently as bioactive molecules and in materials discovery. Interestingly, the nitrogenous congeners have attracted much less attention. Previously absent from the literature, azahomocubanes, offer an opportunity to investigate the effects of a nitrogen atom when incorporated into a highly constrained polycyclic environment. Herein disclosed is the synthesis of 1-azahomocubane, accompanied by comprehensive structural characterization, physical property analysis and chemical reactivity. These data support the conclusion that nitrogen is remarkably well tolerated in a highly strained environment.
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For young children with autism spectrum disorder (ASD), early intensive intervention is imperative. The Bridge Skill Development Program is a parent-mediated intervention designed to "bridge the gap" during the period after a diagnosis of ASD while children wait for intensive intervention. This program introduces applied behavior analysis (ABA) teaching techniques, including the use of parent-mediated discrete trial teaching (DTT), to promote skill acquisition of target behaviors. Significant improvements were observed across four target behaviors taught to all participants. The program also aims to connect participants to intensive ABA programming.
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Transferrin receptor 1 (TfR1) performs a critical role in cellular iron uptake. Hepatocyte TfR1 is also proposed to influence systemic iron homeostasis by interacting with the hemochromatosis protein HFE to regulate hepcidin production. Here, we generated hepatocyte Tfrc knockout mice (Tfrcfl/fl;Alb-Cre+), either alone or together with Hfe knockout or ß-thalassemia, to investigate the extent to which hepatocyte TfR1 function depends on HFE, whether hepatocyte TfR1 impacts hepcidin regulation by serum iron and erythropoietic signals, and its contribution to hepcidin suppression and iron overload in ß-thalassemia. Compared with Tfrcfl/fl;Alb-Cre- controls, Tfrcfl/fl;Alb-Cre+ mice displayed reduced serum and liver iron; mildly reduced hematocrit, mean cell hemoglobin, and mean cell volume; increased erythropoietin and erythroferrone; and unchanged hepcidin levels that were inappropriately high relative to serum iron, liver iron, and erythroferrone levels. However, ablation of hepatocyte Tfrc had no impact on iron phenotype in Hfe knockout mice. Tfrcfl/fl;Alb-Cre+ mice also displayed a greater induction of hepcidin by serum iron compared with Tfrcfl/fl;Alb-Cre- controls. Finally, although acute erythropoietin injection similarly reduced hepcidin in Tfrcfl/fl;Alb-Cre+ and Tfrcfl/fl;Alb-Cre- mice, ablation of hepatocyte Tfrc in a mouse model of ß-thalassemia intermedia ameliorated hepcidin deficiency and liver iron loading. Together, our data suggest that the major nonredundant function of hepatocyte TfR1 in iron homeostasis is to interact with HFE to regulate hepcidin. This regulatory pathway is modulated by serum iron and contributes to hepcidin suppression and iron overload in murine ß-thalassemia.
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Proteína da Hemocromatose , Ferro , Receptores da Transferrina , Talassemia beta , Animais , Camundongos , Talassemia beta/genética , Talassemia beta/metabolismo , Eritropoetina/metabolismo , Proteína da Hemocromatose/genética , Proteína da Hemocromatose/metabolismo , Hepatócitos/metabolismo , Hepcidinas/genética , Hepcidinas/metabolismo , Homeostase , Ferro/metabolismo , Sobrecarga de Ferro/genética , Sobrecarga de Ferro/metabolismo , Camundongos Knockout , Receptores da Transferrina/genética , Receptores da Transferrina/metabolismoRESUMO
LAY ABSTRACT: Children of color are diagnosed with autism later than White children. Caregivers of color are also more likely than White caregivers to report that their child's healthcare providers do not treat them as a partner, spend enough time with them, or respect their culture and values. We wanted to better understand the experiences of caregivers of color with the diagnostic process of autism spectrum disorder, from the time they discuss developmental concerns with their child's primary care provider to when the diagnosis is shared with them. We systematically reviewed the literature and found 15 articles that explored the experiences of caregivers of color. Caregivers of color described that they faced large-scale barriers, such as the cost of appointments, transportation, and long wait lists. They also reported negative experiences with providers, including providers not taking their concerns seriously, making assumptions about caregivers, and delaying referrals for an evaluation. Caregivers stated that their own lack of knowledge of autism spectrum disorder, stigma, their family's thoughts and opinions, and cultural differences between providers and caregivers served as barriers during the diagnostic process. Communication challenges were discussed and included use of medical and technical jargon, a lack of follow-up, language barriers, and difficulty obtaining high-quality interpreters. Some families described providers, other individuals, community networks, and self-advocacy as helpful during the diagnostic process. Large-scale changes are needed, such as increases in the number of providers who are trained in diagnosing Autism. Provider-level changes (e.g. implicit bias training) are also important for improving caregivers' experiences.