RESUMEN
Recent calls for the expansion of postgraduate residencies in nursing have led to an increase in advanced practice nursing residencies and fellowships concentrating on the adult population, whereas pediatric advanced practice nursing fellowships remain limited. The development and implementation of a postgraduate pediatric primary care advanced practice nursing fellowship and the positive impact on a children's health system are described.
Asunto(s)
Enfermería de Práctica Avanzada , Becas , Adulto , Niño , Humanos , Atención Primaria de SaludRESUMEN
Thalidomide-dependent degradation of the embryonic transcription factor SALL4 by the CRL4CRBN E3 ubiquitin ligase is a plausible major driver of thalidomide teratogenicity. The structure of the second zinc finger of SALL4 in complex with pomalidomide, cereblon and DDB1 reveals the molecular details of recruitment. Sequence differences and a shifted binding position relative to Ikaros offer a path to the rational design of cereblon-binding drugs with reduced teratogenic risk.
Asunto(s)
Proteínas Adaptadoras Transductoras de Señales/química , Proteínas de Unión al ADN/ultraestructura , Complejos Multiproteicos/ultraestructura , Factores de Transcripción/ultraestructura , Proteínas Adaptadoras Transductoras de Señales/genética , Cristalografía por Rayos X , Proteínas de Unión al ADN/química , Proteínas de Unión al ADN/genética , Humanos , Complejos Multiproteicos/química , Complejos Multiproteicos/genética , Unión Proteica , Conformación Proteica , Proteolisis/efectos de los fármacos , Especificidad por Sustrato , Talidomida/análogos & derivados , Talidomida/química , Talidomida/farmacología , Factores de Transcripción/química , Factores de Transcripción/genética , Ubiquitina-Proteína Ligasas/química , Ubiquitina-Proteína Ligasas/ultraestructura , Ubiquitinación/genéticaRESUMEN
The institution of pediatric quality in health care has grown in the past decade but continues to evolve. Children's health care emphasizes the importance of maintenance of health and prevention of illness, which can be measured based on immunization rates, routine or scheduled well care, and early intervention. Pediatric quality measures and indicators have become the basis for payment of services and a true goal to value. Designing processes such as pay-for-performance models, volume-based care, and coordination of care assist in assuring that children receive high-quality health care.
Asunto(s)
Salud Infantil/normas , Pediatría/normas , Indicadores de Calidad de la Atención de Salud/economía , Niño , HumanosRESUMEN
Targeted protein degradation via small-molecule modulation of cereblon offers vast potential for the development of new therapeutics. Cereblon-binding therapeutics carry the safety risks of thalidomide, which caused an epidemic of severe birth defects characterized by forelimb shortening or phocomelia. Here we show that thalidomide is not teratogenic in transgenic mice expressing human cereblon, indicating that binding to cereblon is not sufficient to cause birth defects. Instead, we identify SALL4 as a thalidomide-dependent cereblon neosubstrate. Human mutations in SALL4 cause Duane-radial ray, IVIC, and acro-renal-ocular syndromes with overlapping clinical presentations to thalidomide embryopathy, including phocomelia. SALL4 is degraded in rabbits but not in resistant organisms such as mice because of SALL4 sequence variations. This work expands the scope of cereblon neosubstrate activity within the formerly 'undruggable' C2H2 zinc finger family and offers a path toward safer therapeutics through an improved understanding of the molecular basis of thalidomide-induced teratogenicity.
