Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 91
Filtrar
Mais filtros

Base de dados
Tipo de documento
Intervalo de ano de publicação
1.
J Pharmacol Exp Ther ; 385(2): 95-105, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36849411

RESUMO

Leucine-rich repeat-containing G-protein-coupled receptor (LGR5) and LGR6 mark epithelial stem cells in normal tissues and tumors. They are expressed by stem cells in the ovarian surface and fallopian tube epithelia from which ovarian cancer arises. High-grade serous ovarian cancer is unique in expressing unusually high levels of LGR5 and LGR6 mRNA. R-spondins are the natural ligands for LGR5 and LGR6 to which they bind with nanomolar affinity. To target stem cells in ovarian cancer, we used the sortase reaction to site-specifically conjugate the potent cytotoxin monomethyl auristatin E (MMAE) via a protease sensitive linker to the two furin-like domains of RSPO1 (Fu1-Fu2) that mediate its binding to LGR5 and LGR6 and their co-receptors Zinc And Ring Finger 3 and Ring Finger Protein 43 via a protease-cleavable linker. An immunoglobulin Fc domain added to the N-terminal end served to dimerize the receptor-binding domains so that each molecule carries two MMAE. The resulting molecule, FcF2-MMAE, demonstrated: 1) selective LGR5-dependent low nanomolar cytotoxicity against ovarian cancer cells in vitro; 2) selectivity that was dependent on binding to both the LGR receptors and ubiquitin ligase co-receptors; 3) favorable stability and plasma pharmacokinetic properties when administered intravenously with an elimination half-life of 29.7 hours; 4) selective inhibition of LGR5-rich as opposed to isogenic LGR5-poor tumors in vivo; and, 5) therapeutic efficacy in three aggressive wild-type human ovarian cancer xenograft models. These results demonstrate the successful use of the Fu1-Fu2 domain of RSPO1 as a drug carrier and the ability of FcF2-MMAE to target cells in tumors that express stem cell markers. SIGNIFICANCE STATEMENT: FcF2-MMAE is a novel cancer therapeutic that exploits the high-affinity binding domains of RSPO1 to target monomethyl auristatin E to tumor stem cells that express LGR5. FcF2-MMAE has low nanomolar LGR5-dependent cytotoxicity in vitro, favorable pharmacokinetics, and differential efficacy in an isogenic LGR5-poor versus LGR5-rich ovarian cancer xenograft model when given on a weekly schedule.


Assuntos
Neoplasias Ovarianas , Receptores Acoplados a Proteínas G , Feminino , Humanos , Leucina , Neoplasias Ovarianas/tratamento farmacológico , Peptídeo Hidrolases , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo , Células-Tronco/metabolismo , Trombospondinas/metabolismo
2.
MMWR Morb Mortal Wkly Rep ; 71(24): 791-796, 2022 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-35709015

RESUMO

Approximately 27% of adults in the United States live with a disability,* some of whom qualify for Medicare benefits. Persons with disabilities are at increased risk for severe COVID-19-associated outcomes compared with the general population (1); however, existing studies have limited generalizability† or only pertain to a specific disability (e.g., intellectual) (2). Older age is also associated with COVID-19-associated hospitalization and death, but the extent to which age might contribute to increased risk for severe COVID-19-associated outcomes among persons with disabilities is unknown (3). To describe the impact of COVID-19 on persons with disabilities and whether and how age contributes to disease rates, CDC assessed COVID-19 cases and hospitalizations during January 2020-November 2021, among Centers for Medicare & Medicaid Services (CMS) Medicare beneficiaries aged ≥18 years who were either eligible because of a disability (disability-eligible§) or only eligible because of age ≥65 years (age-eligible). COVID-19 incidence and hospitalization rates were higher in the disability-eligible group (10,978 and 3,148 per 100,000 population, respectively) throughout the study period compared with the age-eligible group (8,102 and 2,129 per 100,000 population, respectively). Both COVID-19 incidence and hospitalization rates increased with age in both disability- and age-eligible beneficiaries. American Indian or Alaska Native (AI/AN) persons had the highest disability-eligible (4,962 per 100,000) and age-eligible (5,024 per 100,000) hospitalization rates. Among all other racial and ethnic groups, hospitalization rates were higher among disability-eligible than among age-eligible patients. COVID-19 incidence and hospitalization rates among disability-eligible Medicare beneficiaries were disproportionally higher than rates among age-eligible beneficiaries. Collection of disability status as a core demographic variable in public health surveillance data and identification, as well as the addition of disability questions in other existing data sources can guide research and development of interventions for persons with disabilities. Efforts to increase access to and use of COVID-19 prevention and treatment strategies, including activities that support equitable vaccine access regardless of the substantial challenges that older adults and persons with disability face, are critical to reducing severe COVID-19-associated outcomes among these groups.


Assuntos
COVID-19 , Pessoas com Deficiência , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/terapia , Hospitalização , Humanos , Medicare , Grupos Raciais , Estados Unidos/epidemiologia
3.
MMWR Morb Mortal Wkly Rep ; 71(12): 453-458, 2022 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-35324879

RESUMO

Developmental delays, disorders, or disabilities (DDs) manifest in infancy and childhood and can limit a person's function throughout life* (1-3). To guide strategies to optimize health for U.S. children with DDs, CDC analyzed data from 44,299 participants in the 2014-2018 National Health Interview Survey (NHIS). Parents reported on 10 DDs,† functional abilities, health needs, and use of services. Among the approximately one in six (17.3%) U.S. children and adolescents aged 3-17 years (hereafter children) with one or more DDs, 5.7% had limited ability to move or play, 4.7% needed help with personal care, 4.6% needed special equipment, and 2.4% received home health care, compared with ≤1% for each of these measures among children without DDs. Children with DDs were two to seven times as likely as those without DDs to have taken prescription medication for ≥3 months (41.6% versus 8.4%), seen a mental health professional (30.6% versus 4.5%), a medical specialist (26.0% versus 12.4%), or a special therapist, such as a physical, occupational, or speech therapist, (25.0% versus 4.5%) during the past year, and 18 times as likely to have received special education or early intervention services (EIS) (41.9% versus 2.4%). These percentages varied by type of disability and by sociodemographic subgroup. DDs are common, and children with DDs often need substantial health care and services. Policies and programs that promote early identification of children with developmental delays and facilitate increased access to intervention services can improve health and reduce the need for services later in life.§ Sociodemographic inequities merit further investigation to guide public health action and ensure early and equitable access to needed care and services.


Assuntos
Deficiências do Desenvolvimento , Aceitação pelo Paciente de Cuidados de Saúde/estatística & dados numéricos , Adolescente , Criança , Pré-Escolar , Atenção à Saúde/estatística & dados numéricos , Intervenção Educacional Precoce/estatística & dados numéricos , Educação Inclusiva/estatística & dados numéricos , Humanos , Fatores Socioeconômicos , Estados Unidos
4.
MMWR Morb Mortal Wkly Rep ; 70(39): 1365-1371, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34591826

RESUMO

Estimates from the 2019 American Community Survey (ACS) indicated that 15.2% of adults aged ≥18 years had at least one reported functional disability (1). Persons with disabilities are more likely than are those without disabilities to have chronic health conditions (2) and also face barriers to accessing health care (3). These and other health and social inequities have placed persons with disabilities at increased risk for COVID-19-related illness and death, yet they face unique barriers to receipt of vaccination (4,5). Although CDC encourages that considerations be made when expanding vaccine access to persons with disabilities,* few public health surveillance systems measure disability status. To describe COVID-19 vaccination status and intent, as well as perceived vaccine access among adults by disability status, data from the National Immunization Survey Adult COVID Module (NIS-ACM) were analyzed. Adults with a disability were less likely than were those without a disability to report having received ≥1 dose of COVID-19 vaccine (age-adjusted prevalence ratio [aPR] = 0.88; 95% confidence interval [CI] = 0.84-0.93) but more likely to report they would definitely get vaccinated (aPR = 1.86; 95% CI = 1.43-2.42). Among unvaccinated adults, those with a disability were more likely to report higher endorsement of vaccine as protection (aPR = 1.29; 95% CI = 1.16-1.44), yet more likely to report it would be or was difficult to get vaccinated than did adults without a disability (aPR = 2.69; 95% CI = 2.16-3.34). Reducing barriers to vaccine scheduling and making vaccination sites more accessible might improve vaccination rates among persons with disabilities.


Assuntos
Vacinas contra COVID-19/administração & dosagem , Pessoas com Deficiência/estatística & dados numéricos , Disparidades em Assistência à Saúde/estatística & dados numéricos , Vacinação/psicologia , Vacinação/estatística & dados numéricos , Adolescente , Adulto , Idoso , COVID-19/epidemiologia , COVID-19/prevenção & controle , Feminino , Pesquisas sobre Atenção à Saúde , Humanos , Intenção , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia , Adulto Jovem
5.
Soc Psychiatry Psychiatr Epidemiol ; 54(6): 693-701, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30850887

RESUMO

PURPOSE: The criteria for autism spectrum disorder (ASD) were revised in the fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM). The objective of this study was to compare the sensitivity and specificity of DSM-IV-Text Revision (DSM-IV-TR) and DSM-5 definitions of ASD in a community-based sample of preschool children. METHODS: Children between 2 and 5 years of age were enrolled in the Study to Explore Early Development-Phase 2 (SEED2) and received a comprehensive developmental evaluation. The clinician(s) who evaluated the child completed two diagnostic checklists that indicated the presence and severity of DSM-IV-TR and DSM-5 criteria. Definitions for DSM-5 ASD, DSM-IV-TR autistic disorder, and DSM-IV-TR Pervasive Developmental Disorder Not Otherwise Specified (PDD-NOS) were created from the diagnostic checklists. RESULTS: 773 children met SEED2 criteria for ASD and 288 met criteria for another developmental disorder (DD). Agreement between DSM-5 and DSM-IV-TR definitions of ASD were good for autistic disorder (0.78) and moderate for PDD-NOS (0.57 and 0.59). Children who met DSM-IV-TR autistic disorder but not DSM-5 ASD (n = 71) were more likely to have mild ASD symptoms, or symptoms accounted for by another disorder. Children who met PDD-NOS but not DSM-5 ASD (n = 66), or vice versa (n = 120) were less likely to have intellectual disability and more likely to be female. Sensitivity and specificity were best balanced with DSM-5 ASD criteria (0.95 and 0.78, respectively). CONCLUSIONS: The DSM-5 definition of ASD maximizes diagnostic sensitivity and specificity in the SEED2 sample. These findings support the DSM-5 conceptualization of ASD in preschool children.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Manual Diagnóstico e Estatístico de Transtornos Mentais , Lista de Checagem , Pré-Escolar , Feminino , Humanos , Deficiência Intelectual/diagnóstico , Masculino , Sensibilidade e Especificidade
6.
J Clin Child Adolesc Psychol ; 47(sup1): S176-S189, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-27588608

RESUMO

Exposure to community violence disproportionately impacts low-income, minority youth and is associated with posttraumatic stress symptoms and maladaptive adjustment. This study investigates whether posttraumatic stress mediates the relation between exposure to community violence and externalizing symptoms and the moderating role of family cohesion and daily family support in buffering these effects on later externalizing. Low-income, African American 7th-grade students (M age = 12.57 years; N = 254) from high-crime neighborhoods participated in a 2-year longitudinal study measuring the effects of community violence exposure. The students completed questionnaires administered by research staff over 5 consecutive days for each year of the study. Family cohesion and daily family support exhibited a significant buffering effect for several outcomes. Posttraumatic stress significantly mediated the effect of witnessing community violence on subsequent aggression. The strength of these indirect effects depended on level of family cohesion. The findings provide evidence in support of interventions provided at both individual and family levels. Mental health providers working with this population should be aware of the intertwined nature of exposure to community violence, posttraumatic stress, and subsequent maladaptive outcomes.

7.
Child Adolesc Ment Health ; 23(3): 206-213, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32677288

RESUMO

BACKGROUND: Widely recommended socioemotional developmental surveillance methods include monitoring and development screening techniques. Currently, very little research has compared the effectiveness of monitoring and screening together, and existing research primarily focuses on the relationship between surveillance techniques and referrals or receipt of early intervention (EI). This study investigates the relationship between monitoring and screening and mental health treatment receipt in 3-5 year olds. METHODS: The authors conducted logistic regression analyses on data from the National Surveys of Children's Health (NSCH; 2007) and NSCH (2011/2012) on the odds of mental health treatment receipt in children aged 3-5 years of age who either received (a) screening only, (b) monitoring only, (c) both monitoring and screening, or (d) no monitoring or screening. Sociodemographic control variables were also considered. RESULTS: In both 2007 and 2011/2012 datasets, monitoring and screening together was the best predictor of mental health treatment receipt. Neither screening alone nor monitoring alone was associated with mental health treatment receipt. CONCLUSIONS: Children who received monitoring and screening together had the greatest odds of treatment receipt compared with children receiving screening only, monitoring only, or no monitoring or screening.

8.
Child Adolesc Ment Health ; 23(3): 217-219, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32677300

RESUMO

In this response, we build on insights from Dr. David Foreman's commentary on our recent article "Socio-emotional Surveillance in Preschoolers: Monitoring and Screening Best Identify Children Who Need Mental Health Treatment." In particular, we build on Foreman's insights that underidentification is likely related to clinician error, measurement error, and population properties by also including the role of community systems within which children are identified. We also provide frameworks for considering screening tools and developmental monitoring processes to help direct future research on this important topic.

9.
J Pediatr ; 174: 232-239.e2, 2016 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-27157446

RESUMO

OBJECTIVE: To characterize wandering, or elopement, among children with autism spectrum disorder (ASD) and intellectual disability. STUDY DESIGN: Questions on wandering in the previous year were asked of parents of children with ASD with and without intellectual disability and children with intellectual disability without ASD as part of the 2011 Survey of Pathways to Diagnosis and Services. The Pathways study sample was drawn from the much larger National Survey of Children with Special Health Care Needs conducted in 2009-2010. RESULTS: For children with special healthcare needs diagnosed with either ASD, intellectual disability, or both, wandering or becoming lost during the previous year was reported for more than 1 in 4 children. Wandering was highest among children with ASD with intellectual disability (37.7%) followed by children with ASD without intellectual disability (32.7%), and then children with intellectual disability without ASD (23.7%), though the differences between these groups were not statistically significant. CONCLUSIONS: This study affirms that wandering among children with ASD, regardless of intellectual disability status, is relatively common. However, wandering or becoming lost in the past year was also reported for many children with intellectual disability, indicating the need to broaden our understanding of this safety issue to other developmental disabilities.


Assuntos
Transtorno do Espectro Autista/psicologia , Deficiência Intelectual/psicologia , Comportamento Errante/psicologia , Adolescente , Estudos de Casos e Controles , Criança , Estudos Transversais , Feminino , Humanos , Masculino , Avaliação das Necessidades , Fatores Socioeconômicos , Inquéritos e Questionários
10.
Nature ; 467(7314): 460-4, 2010 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-20827270

RESUMO

Combined analyses of gene networks and DNA sequence variation can provide new insights into the aetiology of common diseases that may not be apparent from genome-wide association studies alone. Recent advances in rat genomics are facilitating systems-genetics approaches. Here we report the use of integrated genome-wide approaches across seven rat tissues to identify gene networks and the loci underlying their regulation. We defined an interferon regulatory factor 7 (IRF7)-driven inflammatory network (IDIN) enriched for viral response genes, which represents a molecular biomarker for macrophages and which was regulated in multiple tissues by a locus on rat chromosome 15q25. We show that Epstein-Barr virus induced gene 2 (Ebi2, also known as Gpr183), which lies at this locus and controls B lymphocyte migration, is expressed in macrophages and regulates the IDIN. The human orthologous locus on chromosome 13q32 controlled the human equivalent of the IDIN, which was conserved in monocytes. IDIN genes were more likely to associate with susceptibility to type 1 diabetes (T1D)-a macrophage-associated autoimmune disease-than randomly selected immune response genes (P = 8.85 × 10(-6)). The human locus controlling the IDIN was associated with the risk of T1D at single nucleotide polymorphism rs9585056 (P = 7.0 × 10(-10); odds ratio, 1.15), which was one of five single nucleotide polymorphisms in this region associated with EBI2 (GPR183) expression. These data implicate IRF7 network genes and their regulatory locus in the pathogenesis of T1D.


Assuntos
Diabetes Mellitus Tipo 1/genética , Loci Gênicos/genética , Predisposição Genética para Doença/genética , Imunidade Inata/genética , Vírus/imunologia , Animais , Sequência de Bases , Cromossomos Humanos Par 13/genética , Cromossomos de Mamíferos/genética , Diabetes Mellitus Tipo 1/imunologia , Redes Reguladoras de Genes/genética , Estudo de Associação Genômica Ampla , Humanos , Inflamação/genética , Inflamação/imunologia , Fator Regulador 7 de Interferon/imunologia , Macrófagos/imunologia , Macrófagos/metabolismo , Especificidade de Órgãos , Polimorfismo de Nucleotídeo Único/genética , Locos de Características Quantitativas/genética , Ratos , Receptores Acoplados a Proteínas G/genética , Receptores Acoplados a Proteínas G/metabolismo
11.
Am J Public Health ; 105(5): 963-71, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25790396

RESUMO

OBJECTIVES: We assessed the association between assisted reproductive technology (ART) and diagnosed autistic disorder in a population-based sample of California births. METHODS: We performed an observational cohort study using linked records from the California Birth Master Files for 1997 through 2007, the California Department of Developmental Services autism caseload for 1997 through 2011, and the Centers for Disease Control and Prevention's National ART Surveillance System for live births in 1997 through 2007. Participants were all 5 926 251 live births, including 48 865 ART-originated infants and 32 922 cases of autism diagnosed by the Department of Developmental Services. We compared births originated using ART with births originated without ART for incidence of autism. RESULTS: In the full population, the incidence of diagnosed autism was twice as high for ART as non-ART births. The association was diminished by excluding mothers unlikely to use ART; adjustment for demographic and adverse prenatal and perinatal outcomes reduced the association substantially, although statistical significance persisted for mothers aged 20 to 34 years. CONCLUSIONS: The association between ART and autism is primarily explained by adverse prenatal and perinatal outcomes and multiple births.


Assuntos
Transtorno Autístico/epidemiologia , Técnicas de Reprodução Assistida/estatística & dados numéricos , Adulto , Fatores Etários , California/epidemiologia , Feminino , Idade Gestacional , Humanos , Incidência , Prole de Múltiplos Nascimentos , Gravidez , Resultado da Gravidez/epidemiologia , Fatores Socioeconômicos , Estados Unidos
12.
Matern Child Health J ; 19(8): 1687-97, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25701197

RESUMO

We examined prevalence of diagnosed autism spectrum disorder (ASD) and age at diagnosis according to child's race/ethnicity and primary household language. From the 2009-2010 National Survey of Children with Special Health Care Needs, we identified 2729 3-17-year-old US children whose parent reported a current ASD diagnosis. We compared ASD prevalence, mean diagnosis age, and percentage with later diagnoses (≥5 years) across racial/ethnic/primary household language groups: non-Hispanic-white, any language (NHW); non-Hispanic-black, any language (NHB); Hispanic-any-race, English (Hispanic-English); and Hispanic-any-race, other language (Hispanic-Other). We assessed findings by parent-reported ASD severity level and adjusted for family sociodemographics. ASD prevalence estimates were 15.3 (NHW), 10.4 (NHB), 14.1 (Hispanic-English), and 5.2 (Hispanic-Other) per 1000 children. Mean diagnosis age was comparable across racial/ethnic/language groups for 3-4-year-olds. For 5-17-year-olds, diagnosis age varied by race/ethnicity/language and also by ASD severity. In this group, NHW children with mild/moderate ASD had a significantly higher proportion (50.8 %) of later diagnoses than NHB (33.5 %) or Hispanic-Other children (18.0 %). However, NHW children with severe ASD had a comparable or lower (albeit non-significant) proportion (16.4 %) of later diagnoses than NHB (37.8 %), Hispanic-English (30.8 %), and Hispanic-Other children (12.0 %). While NHW children have comparable ASD prevalence and diagnosis age distributions as Hispanic-English children, they have both higher prevalence and proportion of later diagnoses than NHB and Hispanic-Other children. The diagnosis age findings were limited to mild/moderate cases only. Thus, the prevalence disparity might be primarily driven by under-representation (potentially under-identification) of older children with mild/moderate ASD in the two minority groups.


Assuntos
Transtorno do Espectro Autista/diagnóstico , Etnicidade/estatística & dados numéricos , Características da Família , Idioma , Adolescente , Negro ou Afro-Americano/estatística & dados numéricos , Transtorno do Espectro Autista/etnologia , População Negra/estatística & dados numéricos , Criança , Pré-Escolar , Feminino , Inquéritos Epidemiológicos , Hispânico ou Latino/estatística & dados numéricos , Humanos , Masculino , Vigilância da População , Prevalência , Grupos Raciais , Índice de Gravidade de Doença , Fatores Socioeconômicos , Estados Unidos/epidemiologia , População Branca/estatística & dados numéricos
13.
Hum Mol Genet ; 21(12): 2815-24, 2012 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-22403184

RESUMO

One mechanism by which disease-associated DNA variation can alter disease risk is altering gene expression. However, linkage disequilibrium (LD) between variants, mostly single-nucleotide polymorphisms (SNPs), means it is not sufficient to show that a particular variant associates with both disease and expression, as there could be two distinct causal variants in LD. Here, we describe a formal statistical test of colocalization and apply it to type 1 diabetes (T1D)-associated regions identified mostly through genome-wide association studies and expression quantitative trait loci (eQTLs) discovered in a recently determined large monocyte expression data set from the Gutenberg Health Study (1370 individuals), with confirmation sought in an additional data set from the Cardiogenics Transcriptome Study (558 individuals). We excluded 39 out of 60 overlapping eQTLs in 49 T1D regions from possible colocalization and identified 21 coincident eQTLs, representing 21 genes in 14 distinct T1D regions. Our results reflect the importance of monocyte (and their derivatives, macrophage and dendritic cell) gene expression in human T1D and support the candidacy of several genes as causal factors in autoimmune pancreatic beta-cell destruction, including AFF3, CD226, CLECL1, DEXI, FKRP, PRKD2, RNLS, SMARCE1 and SUOX, in addition to the recently described GPR183 (EBI2) gene.


Assuntos
Diabetes Mellitus Tipo 1/genética , Predisposição Genética para Doença/genética , Monócitos/metabolismo , Polimorfismo de Nucleotídeo Único , Transcriptoma , Adulto , Idoso , Algoritmos , Feminino , Estudo de Associação Genômica Ampla , Genótipo , Humanos , Desequilíbrio de Ligação , Masculino , Pessoa de Meia-Idade , Modelos Genéticos , Locos de Características Quantitativas/genética , Fatores de Risco
14.
Hum Mol Genet ; 21(2): 322-33, 2012 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-21989056

RESUMO

The chromosome 16p13 region has been associated with several autoimmune diseases, including type 1 diabetes (T1D) and multiple sclerosis (MS). CLEC16A has been reported as the most likely candidate gene in the region, since it contains the most disease-associated single-nucleotide polymorphisms (SNPs), as well as an imunoreceptor tyrosine-based activation motif. However, here we report that intron 19 of CLEC16A, containing the most autoimmune disease-associated SNPs, appears to behave as a regulatory sequence, affecting the expression of a neighbouring gene, DEXI. The CLEC16A alleles that are protective from T1D and MS are associated with increased expression of DEXI, and no other genes in the region, in two independent monocyte gene expression data sets. Critically, using chromosome conformation capture (3C), we identified physical proximity between the DEXI promoter region and intron 19 of CLEC16A, separated by a loop of >150 kb. In reciprocal experiments, a 20 kb fragment of intron 19 of CLEC16A, containing SNPs associated with T1D and MS, as well as with DEXI expression, interacted with the promotor region of DEXI but not with candidate DNA fragments containing other potential causal genes in the region, including CLEC16A. Intron 19 of CLEC16A is highly enriched for transcription-factor-binding events and markers associated with enhancer activity. Taken together, these data indicate that although the causal variants in the 16p13 region lie within CLEC16A, DEXI is an unappreciated autoimmune disease candidate gene, and illustrate the power of the 3C approach in progressing from genome-wide association studies results to candidate causal genes.


Assuntos
Doenças Autoimunes/genética , Proteínas de Ligação a DNA/genética , DNA/genética , Proteínas de Membrana/genética , Cromossomos Humanos Par 16 , Humanos , Monócitos/metabolismo , Reação em Cadeia da Polimerase , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas
15.
Disabil Health J ; 17(2): 101556, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38001004

RESUMO

BACKGROUND: The term "developmental disability" (DD) is inconsistently defined and applied depending on purpose and across sources, including in legislation. OBJECTIVE: This project aimed to identify existing definitions of disability and DD and to determine the extent to which each definition could be operationalized to produce prevalence estimates using data from U.S. national surveys. METHODS: Using data among children <18 years from the 2016-2018 National Health Interview Survey (NHIS) and National Survey of Children's Health (NSCH), we estimated the prevalence of two definitions of disability (Washington Group Short Set on Functioning, American Community Survey) and seven definitions of DD [Health and Human Services (ever/current), Developmental Disabilities Assistance and Bill of Rights Act of 2000 (1+, 2+, or 3+ components), and Diagnostic and Statistical Manual of Mental Disorders, 5th ed (ever/current)]. Complex sample design variables and weights were used to calculate nationally representative prevalence. RESULTS: Disability (NHIS: 5.2-6.3%; NSCH: 9.2-11.9%) and DD prevalence (NHIS: 0.6-18.0% and NSCH: 0.2-22.2%) varied depending on the definition and data source. For the same definition, NSCH prevalence estimates tended to be higher than NHIS estimates. CONCLUSIONS: The substantial variability in estimated prevalence of disability and DD among children in the United States may be in part due to the surveys not representing all components of each definition. Different or additional questions in national surveys may better capture existing definitions of disability and DD. Considering the data collection goals may help determine the optimal definition to provide useful information for public health action.


Assuntos
Deficiências do Desenvolvimento , Pessoas com Deficiência , Criança , Humanos , Adolescente , Estados Unidos , Deficiências do Desenvolvimento/epidemiologia , Saúde Pública , Inquéritos e Questionários , Prevalência , Inquéritos Epidemiológicos
16.
Vaccine ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38267333

RESUMO

This manuscript is being submitted as a Commentary; Abstract not applicable.

17.
J Epidemiol Glob Health ; 14(1): 223-233, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38498114

RESUMO

INTRODUCTION: Lesotho has the second-highest prevalence of HIV. Despite progress in achieving HIV epidemic control targets, inequities persist among certain groups, particularly associations between disability, HIV, and violence. We assessed the prevalence of disability and examined associations between disability and HIV and violence using data from the 2018 Lesotho Violence Against Children and Youth Survey (VACS). METHODS: Lesotho VACS was a nationally representative survey of females and males ages 13-24. We assessed the associations between disability status and HIV, sexual risk behaviours, and violence using logistic regression, incorporating survey weights. RESULTS: Weighted functional disability prevalence was 14.1% for females (95% confidence interval [CI] 12.7-15.4) and 7.3% for males (5.3-9.2). Compared with females with no disabilities, females with disabilities had higher odds of being HIV positive (adjusted odds ratio [aOR] 1.92, 1.34-2.76), having transactional sex (aOR 1.79, 1.09-2.95), and experiencing any lifetime violence (aOR 2.20, 1.82-2.65), sexual violence (aOR 1.77, 1.36-2.31), emotional violence (2.02. 1.61-2.53), physical violence (aOR 1.85, 1.54-2.24), witnessing interparental violence (aOR 1.71, 1.46-2.01), and witnessing community violence (aOR 1.52, 1.26-1.84). Males with disabilities had higher odds of having transactional sex (aOR 4.30, 1.35-13.73), having recent multiple sex partners (aOR 2.31, 1.13-4.75), experiencing emotional violence (aOR 2.85, 1.39-5.82), and witnessing interparental violence (aOR 1.78, 1.12-2.84). HIV models for males did not converge due to low numbers. CONCLUSION: Findings emphasize the importance of inclusion and accessibility for adolescents and young adults with disabilities in prevention and services for violence and HIV. Ending HIV in Lesotho depends on addressing the vulnerabilities that lead to potential infection including violence and ensuring equitable services for all.


Assuntos
Pessoas com Deficiência , Infecções por HIV , Violência , Humanos , Masculino , Adolescente , Feminino , Lesoto/epidemiologia , Pessoas com Deficiência/estatística & dados numéricos , Adulto Jovem , Prevalência , Infecções por HIV/epidemiologia , Violência/estatística & dados numéricos
18.
J Nurs Scholarsh ; 45(1): 69-78, 2013 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-23368711

RESUMO

PURPOSE: To present the current state of the evidence regarding translation of genetics (the study of single genes) and genomics (the study of all genes and gene-gene or gene-environment interactions) into health care of children with autism spectrum disorder (ASD). METHODS: This article presents an overview of ASD as an international health challenge, the emerging science related to broad diagnostic criteria, and the role of the nurse in research, education, and practice. FINDINGS: Much progress is being made in the understanding of genetics and genomics of ASD. Environmental factors are thought to contribute to the risk of developing ASD by interacting with a number of genes in different ways, thus suggesting causal heterogeneity. The rising identified prevalence of ASD, the changing diagnostic criteria for ASD, and the complexity of the core and associated features have made it difficult to define the ASD phenotype (observable behaviors that result from gene-environment interaction). Because early identification improves opportunities for intervention, researchers are looking for a useful biomarker to detect ASD. This search is complicated by the likelihood that there are multiple causes for multiple expressions that are defined as the autism spectrum. CONCLUSIONS: To date, genetic and genomic research on ASD have underscored the complexity of the causes of ASD indicating that there are very complex genetic processes involved that are still not well understood. CLINICAL RELEVANCE: Nurses will benefit from new knowledge related to early identification, diagnosis, and implications for the family to promote early intervention. Families who have a child with ASD will require nursing support for advocacy for optimal health outcomes.


Assuntos
Transtornos Globais do Desenvolvimento Infantil/genética , Transtornos Globais do Desenvolvimento Infantil/enfermagem , Interação Gene-Ambiente , Genoma Humano , Genômica , Pesquisa Biomédica , Criança , Testes Genéticos , Humanos , Papel do Profissional de Enfermagem , Educação de Pacientes como Assunto , Fatores de Risco
19.
J Autism Dev Disord ; 53(5): 1739-1754, 2023 May.
Artigo em Inglês | MEDLINE | ID: mdl-35212866

RESUMO

The study examined timing of autism spectrum disorder (ASD) identification in education versus health settings for 8-year-old children with ASD identified through records-based surveillance. The study also examined type of ASD symptoms noted within special education evaluations. Results indicated that children with records from only education sources had a median time to identification of ASD over a year later than children with records from health sources. Black children were more likely than White children to have records from only education sources. Restricted and repetitive behaviors were less frequently documented in educational evaluations resulting in developmental delay eligibility compared to specific ASD eligibility among children with ASD. Future research could explore strategies reduce age of identification in educational settings and increase equitable access to health evaluations.


Assuntos
Transtorno do Espectro Autista , Transtornos Globais do Desenvolvimento Infantil , Humanos , Criança , Transtorno do Espectro Autista/diagnóstico , Transtorno do Espectro Autista/epidemiologia , Vigilância da População/métodos , Prevalência , Transtornos Globais do Desenvolvimento Infantil/diagnóstico , Educação Inclusiva
20.
Disabil Health J ; 16(4): 101509, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37558552

RESUMO

BACKGROUND: Some people with disabilities are likely at increased risk of health impacts from coronavirus disease 2019 (COVID-19). OBJECTIVE: To describe parent-reported COVID-19 vaccination status of adolescents (aged 13-17 years) and parental intent to get their child vaccinated, among adolescents with versus without disability. METHODS: National Immunization Survey-Child COVID Module data from interviews conducted July 22, 2021-February 26, 2022, were analyzed to assess disability status and type and COVID-19 vaccination status for adolescents (n = 12,445). Prevalence estimates with 95% confidence intervals were calculated; T-tests were conducted. RESULTS: A lower percentage of adolescents with disability received ≥1 dose of COVID-19 vaccine compared to adolescents without disability (52.5% vs. 58.6%), [those with cognition (50.8%) or not performing errands independently (49.5%) disabilities were significantly lower]; and a higher percentage of parents reported intent to definitely vaccinate (9.9% vs. 6.5%) and definitely not vaccinate (14.9% vs. 11.8%) their adolescent. Among the unvaccinated adolescents, parents of those with disability were more likely to report difficulty getting their child vaccinated (19.1% vs. 12.9%), inconvenient vaccination-site operating hours (7.6% vs. 3.9%), difficulty knowing where to get their child vaccinated (7.2% vs. 2.7%), and difficulty getting to vaccination sites (6.0% vs. 3.0%), than parents of those without disability. CONCLUSIONS: Adolescents with disability had lower vaccination coverage compared to adolescents without disability. Parents of adolescents with disability reported higher intent to get their adolescents vaccinated, but among unvaccinated adolescents with disability, parents reported greater difficulty in accessing COVID-19 vaccines. Findings highlight the need for prioritized outreach to increase COVID-19 vaccination for this population.


Assuntos
COVID-19 , Pessoas com Deficiência , Adolescente , Humanos , Vacinas contra COVID-19 , Cobertura Vacinal , COVID-19/prevenção & controle , Vacinação , Imunização , Pais
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA