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1.
Pediatr Clin North Am ; 67(4): 725-733, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32650869

RESUMO

Retinopathy of prematurity (ROP) is the leading cause of childhood blindness in very-low-birthweight and very preterm infants in the United States. With improved survival of smaller babies, more infants are at risk for ROP, yet there is an increasing shortage of providers to screen and treat ROP. Through a literature review of new and emerging technologies, screening criteria, and analysis of a national survey of pediatric ophthalmologists and retinal specialists, the authors found the shortage of ophthalmology workforce for ROP a serious and growing concern. When used appropriately, emerging technologies have the potential to mitigate gaps in the ROP workforce.


Assuntos
Inteligência Artificial , Oftalmologistas/provisão & distribuição , Retinopatia da Prematuridade/diagnóstico , Retinopatia da Prematuridade/terapia , Telemedicina , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Unidades de Terapia Intensiva Neonatal , Triagem Neonatal , Inquéritos e Questionários , Estados Unidos
2.
J Mol Biol ; 358(2): 509-22, 2006 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-16527308

RESUMO

The p21-activated kinases (PAKs) are important effector proteins of the small GTPases Cdc42 and Rac and control cytoskeletal rearrangements and cell proliferation. The direct interaction of PAKs with guanine nucleotide exchange factors from the PIX/Cool family, which is responsible for the localization of PAK kinases to focal complexes in the cell, is mediated by a 24-residue peptide segment in PAKs and an N-terminal src homology 3 (SH3) domain in PIX/Cool. The SH3-binding segment of PAK contains the atypical consensus-binding motif PxxxPR, which is required for unusually high affinity binding. In order to understand the structural basis for the high affinity and specificity of the PIX-PAK interaction, we solved crystal structures for the N-terminal SH3 domain of betaPIX and for the complex of the atypical binding segment of PAK2 with the N-terminal SH3 domain of betaPIX at 0.92 A and 1.3A resolution, respectively. The asymmetric unit of the crystal contains two SH3 domains and two peptide ligands. The bound peptide adopts a conformation that allows for intimate contacts with three grooves on the surface of the SH3 domain that lie between the n-Src and RT-loops. Most notably, the arginine residue of the PxxxPR motif forms a salt-bridge and is tightly coordinated by a number of residues in the SH3 domain. This arginine-specific interaction appears to be the key determinant for the high affinity binding of PAK peptides. Furthermore, C-terminal residues of the peptide engage in additional interactions with the surface of the RT-loop, which significantly increases binding specificity. Compared to a recent NMR structure of a similar complex, our crystal structure reveals an alternate binding mode. Finally, we compare our crystal structure with the recently published betaPIX/Cbl-b complex structure, and suggest the existence of a molecular switch.


Assuntos
Proteínas de Ciclo Celular/química , Fatores de Troca do Nucleotídeo Guanina/química , Proteínas Serina-Treonina Quinases/química , Domínios de Homologia de src , Sequência de Aminoácidos , Animais , Proteínas de Ciclo Celular/genética , Proteínas de Ciclo Celular/metabolismo , Cristalização , Cristalografia por Raios X , Fatores de Troca do Nucleotídeo Guanina/genética , Fatores de Troca do Nucleotídeo Guanina/metabolismo , Modelos Moleculares , Dados de Sequência Molecular , Conformação Proteica , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Fatores de Troca de Nucleotídeo Guanina Rho , Homologia de Sequência de Aminoácidos , Quinases Ativadas por p21
3.
Acad Pediatr ; 15(4): 430-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26142069

RESUMO

OBJECTIVE: To explore existing barriers and challenges to Early Intervention (EI) referral, enrollment, and service provision for very low birth weight (VLBW; <1500 g) infants. METHODS: We conducted 10 focus groups with parents of VLBW children (n = 44) and 32 interviews with key informants from EI (n = 7), neonatal intensive care units (n = 17), and outpatient clinics (n = 8) at 6 sites in 2 states. We used grounded theory to identify themes about gaps in services. RESULTS: Both parents and providers found EI helpful. However, they also identified gaps in the current EI system at the levels of eligibility, referral, family receptivity, and service provision and coordination with medical care. Inadequate funding and variable procedures for evaluation may affect children's eligibility. Referrals can be missed as a result of simple oversight or communication failure among hospitals, EI, and families; referral outcomes often are not formally tracked. Families may not be receptive to services as a result of wariness of home visits, social stressors, denial about potential developmental delays, or lack of understanding of the benefits of EI. Once a child is deemed eligible, services may be delayed or terminated early, and EI providers may have little specialized training. Communication and coordination with the child's medical care team is often limited. CONCLUSIONS: Systemic barriers, including funding and staffing issues, state and federal regulations, and communication with families and medical providers, have led to gaps in the EI system. The chronic care model may serve as a framework for integrating community-based interventions like EI with medical care for VLBW children and other vulnerable populations.


Assuntos
Deficiências do Desenvolvimento/terapia , Intervenção Educacional Precoce , Acessibilidade aos Serviços de Saúde , Doenças do Prematuro/terapia , Adulto , Deficiências do Desenvolvimento/psicologia , Feminino , Grupos Focais , Humanos , Lactente , Recém-Nascido , Recém-Nascido Prematuro , Doenças do Prematuro/psicologia , Recém-Nascido de muito Baixo Peso , Masculino , Massachusetts , Pessoa de Meia-Idade , Pais , South Carolina , Adulto Jovem
4.
J Hum Lact ; 29(3): 381-9, 2013 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-23764482

RESUMO

BACKGROUND: Pasteurized human donor milk (DM) is recommended by the World Health Organization and American Academy of Pediatrics for preterm infants when mother's own milk is unavailable, yet the extent and predictors of use and criteria for use in US neonatal intensive care units (NICUs) are unknown. OBJECTIVE: This study aimed to evaluate current DM use in US level 3 NICUs and predictors and criteria of use. METHODS: We sent mail surveys to 302 US level 3 NICU directors. We used multivariable logistic regression to analyze predictors of DM use. RESULTS: Survey response rate was 60%, and 76 of 182 (42%) directors reported DM use. Among DM users, 30% have used DM < 2 years and 55% for 2 to 5 years. Among nonusers, 63% were uncertain of turnaround time when ordering DM, 36% were unclear what guidelines milk banks followed, and 31% were unsure of parent receptiveness. In multivariate analyses, > 800 annual admissions (odds ratio [OR], 4.11; 95% confidence interval [CI], 1.43-11.82; reference ≤ 400 admissions) and location in the Midwest (OR, 3.02; 95% CI, 1.17-7.76) and West (OR, 6.33; 95% CI, 2.28-15.57; reference Northeast) were positively associated with DM use; safety-net hospitals (> 75% Medicaid insurance) were negatively associated (OR, 0.35; 95% CI, 0.14-0.89). CONCLUSION: Pasteurized human donor milk use is rapidly emerging among US level 3 NICUs. Larger NICUs and those in the West and Midwest were more likely to use DM, while safety-net hospitals were less likely to use DM. Lack of knowledge by medical directors of accessibility, safety, and parental receptiveness may be barriers to DM use.


Assuntos
Unidades de Terapia Intensiva Neonatal/estatística & dados numéricos , Terapia Intensiva Neonatal/métodos , Bancos de Leite Humano/estatística & dados numéricos , Leite Humano , Pasteurização , Atitude do Pessoal de Saúde , Pesquisas sobre Atenção à Saúde , Humanos , Recém-Nascido , Recém-Nascido Prematuro , Terapia Intensiva Neonatal/estatística & dados numéricos , Modelos Logísticos , Análise Multivariada , Estados Unidos
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