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1.
Cancer Control ; 25(1): 1073274818806900, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30375235

RESUMO

Despite guidelines recommending annual low-dose computed tomography (LDCT) screening for lung cancer, uptake remains low due to the perceived complexity of initiating and maintaining a clinical program-problems that likely magnify in underserved populations. We conducted a survey of community providers at Federally Qualified Health Centers (FQHCs) in Santa Clara County, California, to evaluate provider-related factors that affect adherence. We then compared these findings to academic providers' (APs) LDCT screening knowledge, behaviors, and attitudes at an academic referral center in the same county. The 4 FQHCs enrolled care for 80 000 patients largely of minority descent and insured by Medi-Cal. Of the 75 FQHC providers (FQHCPs), 36 (48%) completed the survey. Of the 36 providers, 8 (22%) knew screening criteria. Fifteen (42%) FQHCPs discussed LDCT screening with patients. Compared to 36 APs, FQHCPs were more concerned about harms, false positives, discussion time, patient apathy, insurance coverage, and a lack of expertise for screening and follow-up. Yet, more FQHCPs thought screening was effective (27 [75%] of 36) compared to APs ( P = .0003). In conclusion, provider knowledge gaps are greater and barriers are different for community clinics caring for underserved populations compared to their academic counterparts, but practical and scalable solutions exist to enhance adoption.


Assuntos
Centros Médicos Acadêmicos/estatística & dados numéricos , Competência Clínica , Centros Comunitários de Saúde/estatística & dados numéricos , Detecção Precoce de Câncer/normas , Neoplasias Pulmonares/diagnóstico por imagem , Padrões de Prática Médica/estatística & dados numéricos , California , Detecção Precoce de Câncer/efeitos adversos , Detecção Precoce de Câncer/estatística & dados numéricos , Reações Falso-Positivas , Feminino , Fidelidade a Diretrizes/estatística & dados numéricos , Humanos , Pulmão/diagnóstico por imagem , Pulmão/efeitos da radiação , Masculino , Guias de Prática Clínica como Assunto , Padrões de Prática Médica/normas , Inquéritos e Questionários/estatística & dados numéricos , Tomografia Computadorizada por Raios X/efeitos adversos , Tomografia Computadorizada por Raios X/normas , Tomografia Computadorizada por Raios X/estatística & dados numéricos
2.
G3 (Bethesda) ; 8(5): 1497-1512, 2018 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-29540444

RESUMO

Endocytosis is a fundamental process for internalizing material from the plasma membrane, including many transmembrane proteins that are selectively internalized depending on environmental conditions. In most cells, the main route of entry is clathrin-mediated endocytosis (CME), a process that involves the coordinated activity of over 60 proteins; however, there are likely as-yet unidentified proteins involved in cargo selection and/or regulation of endocytosis. We performed a mutagenic screen to identify novel endocytic genes in Saccharomyces cerevisiae expressing the methionine permease Mup1 tagged with pHluorin (pHl), a pH-sensitive GFP variant whose fluorescence is quenched upon delivery to the acidic vacuole lumen. We used fluorescence-activated cell sorting to isolate mutagenized cells with elevated fluorescence, resulting from failure to traffic Mup1-pHl cargo to the vacuole, and further assessed subcellular localization of Mup1-pHl to characterize the endocytic defects in 256 mutants. A subset of mutant strains was classified as having general endocytic defects based on mislocalization of additional cargo proteins. Within this group, we identified mutations in four genes encoding proteins with known roles in endocytosis: the endocytic coat components SLA2, SLA1, and EDE1, and the ARP3 gene, whose product is involved in nucleating actin filaments to form branched networks. All four mutants demonstrated aberrant dynamics of the endocytic machinery at sites of CME; moreover, the arp3R346H mutation showed reduced actin nucleation activity in vitro Finally, whole genome sequencing of two general endocytic mutants identified mutations in conserved genes not previously implicated in endocytosis, KRE33 and IQG1, demonstrating that our screening approach can be used to identify new components involved in endocytosis.


Assuntos
Endocitose , Citometria de Fluxo/métodos , Saccharomyces cerevisiae/citologia , Saccharomyces cerevisiae/genética , Sequência de Aminoácidos , Membrana Celular/metabolismo , Proteínas de Fluorescência Verde/metabolismo , Mutagênese/genética , Mutação de Sentido Incorreto/genética , Fenótipo , Mutação Puntual/genética , Proteínas de Saccharomyces cerevisiae/química , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo
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