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1.
Am J Public Health ; 113(12): 1254-1257, 2023 12.
Artigo em Inglês | MEDLINE | ID: mdl-37824811

RESUMO

We used a collective impact model to form a statewide diabetes quality improvement collaborative to improve diabetes outcomes and advance diabetes health equity. Between 2020 and 2022, in collaboration with the Ohio Department of Medicaid, Medicaid Managed Care Plans, and Ohio's seven medical schools, we recruited 20 primary care practices across the state. The percentage of patients with hemoglobin A1c greater than 9% improved from 25% to 20% over two years. Applying our model more broadly could accelerate improvement in diabetes outcomes. (Am J Public Health. 2023;113(12):1254-1257. https://doi.org/10.2105/AJPH.2023.307410).


Assuntos
Diabetes Mellitus , Medicaid , Estados Unidos , Humanos , Ohio , Melhoria de Qualidade , Diabetes Mellitus/epidemiologia , Diabetes Mellitus/terapia
2.
Pediatr Transplant ; 24(1): e13601, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31657119

RESUMO

Cell-mediated immunity to CMV, if known, could improve antiviral drug therapy in at-risk children and young adults with LT and IT. Host immunity has been measured with CMV-specific T cells, which express IFNγ, but not those which express CD154, a possible substitute for IFNγ. CMV-specific CD154+ T cells and their subsets were measured with flow cytometry after stimulating PBL from recipient blood samples with an overlapping peptide mix of CMV-pp65 antigen for up to 6 hours. CMV-specific CD154+ T cells co-expressed IFNγ in PBL from three healthy adults and averaged 3.8% (95% CI 3.2%-4.4%) in 40 healthy adults. CMV-specific T cells were significantly lower in 19 CMV DNAemic LT or IT recipients, compared with 126 non-DNAemic recipients, 1.3% (95% CI 0.8-1.7) vs 4.1 (95% CI 3.6-4.6, P < .001). All T-cell subsets demonstrated similar between-group differences. In logistic regression analysis of 46 training set samples, 12 with DNAemia, all obtained between days 0 and 60 from transplant, CMV-specific T-cell frequencies ≥1.7% predicted freedom from DNAemia with NPV of 93%. Sensitivity, specificity, and PPV were 83%, 74%, and 53%, respectively. Test performance was replicated in 99 validation samples. In 32 of 46 training set samples, all from seronegative recipients, one of 19 recipients with CMV-specific T-cell frequencies ≥1.7% experienced DNAemia, compared with 8 of 13 recipients with frequencies <1.7% (P = .001). CMV-specific CD154+ T cells are associated with freedom from DNAemia after LT and IT. Among seronegative recipients, CMV-specific T cells may protect against the development of CMV DNAemia.


Assuntos
Ligante de CD40/sangue , Citomegalovirus/imunologia , Intestinos/transplante , Transplante de Fígado , Complicações Pós-Operatórias/imunologia , Linfócitos T/virologia , Viremia/imunologia , Adolescente , Adulto , Biomarcadores/sangue , Criança , Pré-Escolar , DNA Viral/sangue , Feminino , Citometria de Fluxo , Voluntários Saudáveis , Humanos , Imunidade Celular , Lactente , Modelos Logísticos , Masculino , Complicações Pós-Operatórias/virologia , Fatores de Proteção , Valores de Referência , Fatores de Risco , Sensibilidade e Especificidade , Linfócitos T/imunologia , Linfócitos T/metabolismo , Viremia/etiologia , Adulto Jovem
3.
Diabetes Care ; 2024 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-39388337

RESUMO

OBJECTIVE: To evaluate the Ohio Diabetes Quality Improvement Project (QIP) equity aim to reduce the percentage of Non-Hispanic Black (NHB) and Hispanic patients with A1C >9% by ≥20% over 2 years. RESEARCH DESIGN AND METHODS: The Ohio Department of Medicaid, Ohio Colleges of Medicine Government Resource Center, Ohio Medicaid managed care plans, and seven medical schools in Ohio formed the Diabetes QIP collaborative using the collective impact model to improve diabetes outcomes and equity in 20 practices across 11 health systems. The quality improvement (QI) strategies included data audit and feedback, peer-to-peer learning, QI coaching/practice facilitation, and subject matter expert consultation through coaching calls, monthly webinars, and annual virtual learning sessions. Electronic health record data were collected for preintervention (2019-2020) and intervention (2020-2022) periods. Assessments of improvements in A1C were based on prevalence of A1C >9% from preintervention, year 1, and year 2 with stratification by race and ethnicity. RESULTS: The Diabetes QIP included 7,689 (54% female) sociodemographically diverse patients, self-identifying as non-Hispanic White (NHW) (42%), NHB (43%), Hispanic (8%), non-Hispanic Asian (4%), or other (3%). In year 2 compared with baseline, there were decreases in the proportion of patients with A1C >9% among NHW, NHB, and Hispanic patients (NHW from 19% to 12% [37% reduction], NHB 23% to 18% [22% reduction], and Hispanic 29% to 23% [20% reduction]). CONCLUSIONS: The Ohio Diabetes QIP, focused on multisector collaborative approaches, reduced the percentage of patients with A1C >9% by ≥20% among NHW, NHB, and Hispanic populations. Given the persistence of disparities, further equity-focused refinements are warranted to address disparities in diabetes control.

4.
J Healthc Qual ; 45(6): 324-331, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37788440

RESUMO

ABSTRACT: Symptoms of urgent maternal warning signs (UMWS) may occur during pregnancy or after delivery and may have lasting effects or indicate a life-threatening situation if left untreated. The state department of health sponsored a quality improvement project (QIP) to broaden the reach of UMWS education beyond traditional clinical settings, to public health settings where prenatal and postpartum women are seen. Specifically, the QIP implemented process changes to provide education (written and verbal) and resources to individuals receiving services from Women, Infants, and Children clinics during pregnancy and up to 12 weeks postpartum. Clinics submitted participant-level data although the Research Electronic Data Capture secure data portal. The key results indicated an increase in both written and verbal education. In addition, the project monitored referrals made specific to conditions identified through project-specific data collection and the provision of UMWS education.


Assuntos
Saúde Materna , Feminino , Humanos , Lactente , Gravidez
5.
J Biol Chem ; 286(49): 42099-42104, 2011 Dec 09.
Artigo em Inglês | MEDLINE | ID: mdl-22033927

RESUMO

Chromatin remodelers are ATP-dependent machines that dynamically alter the chromatin packaging of eukaryotic genomes by assembling, sliding, and displacing nucleosomes. The Chd1 chromatin remodeler possesses a C-terminal DNA-binding domain that is required for efficient nucleosome sliding and believed to be essential for sensing the length of DNA flanking the nucleosome core. The structure of the Chd1 DNA-binding domain was recently shown to consist of a SANT and SLIDE domain, analogous to the DNA-binding domain of the ISWI family, yet the details of how Chd1 recognized DNA were not known. Here we present the crystal structure of the Saccharomyces cerevisiae Chd1 DNA-binding domain in complex with a DNA duplex. The bound DNA duplex is straight, consistent with the preference exhibited by the Chd1 DNA-binding domain for extranucleosomal DNA. Comparison of this structure with the recently solved ISW1a DNA-binding domain bound to DNA reveals that DNA lays across each protein at a distinct angle, yet contacts similar surfaces on the SANT and SLIDE domains. In contrast to the minor groove binding seen for Isw1 and predicted for Chd1, the SLIDE domain of the Chd1 DNA-binding domain contacts the DNA major groove. The majority of direct contacts with the phosphate backbone occur only on one DNA strand, suggesting that Chd1 may not strongly discriminate between major and minor grooves.


Assuntos
Proteínas de Ligação a DNA/genética , Proteínas de Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Cromatina/química , Montagem e Desmontagem da Cromatina , Cristalografia por Raios X/métodos , DNA/química , DNA Fúngico/química , Proteínas de Ligação a DNA/química , Proteínas de Ligação a DNA/metabolismo , Modelos Moleculares , Conformação Molecular , Ácidos Nucleicos/química , Nucleossomos/metabolismo , Ligação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Proteínas de Saccharomyces cerevisiae/metabolismo
6.
Sci Transl Med ; 12(545)2020 05 27.
Artigo em Inglês | MEDLINE | ID: mdl-32461332

RESUMO

Effective delivery of protein therapeutics to the central nervous system (CNS) has been greatly restricted by the blood-brain barrier (BBB). We describe the development of a BBB transport vehicle (TV) comprising an engineered Fc fragment that exploits receptor-mediated transcytosis for CNS delivery of biotherapeutics by binding a highly expressed brain endothelial cell target. TVs were engineered using directed evolution to bind the apical domain of the human transferrin receptor (hTfR) without the use of amino acid insertions, deletions, or unnatural appendages. A crystal structure of the TV-TfR complex revealed the TV binding site to be away from transferrin and FcRn binding sites, which was further confirmed experimentally in vitro and in vivo. Recombinant expression of TVs fused to anti-ß-secretase (BACE1) Fabs yielded antibody transport vehicle (ATV) molecules with native immunoglobulin G (IgG) structure and stability. Peripheral administration of anti-BACE1 ATVs to hTfR-engineered mice and cynomolgus monkeys resulted in substantially improved CNS uptake and sustained pharmacodynamic responses. The TV platform readily accommodates numerous additional configurations, including bispecific antibodies and protein fusions, yielding a highly modular CNS delivery platform.


Assuntos
Secretases da Proteína Precursora do Amiloide , Barreira Hematoencefálica , Secretases da Proteína Precursora do Amiloide/metabolismo , Animais , Ácido Aspártico Endopeptidases/metabolismo , Barreira Hematoencefálica/metabolismo , Encéfalo/metabolismo , Haplorrinos/metabolismo , Fragmentos Fc das Imunoglobulinas , Camundongos , Receptores da Transferrina/metabolismo
7.
Mol Cell Biol ; 31(23): 4746-59, 2011 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-21969605

RESUMO

Chd1- and ISWI-type chromatin remodelers can sense extranucleosomal DNA and preferentially shift nucleosomes toward longer stretches of available DNA. The DNA-binding domains of these chromatin remodelers are believed to be responsible for sensing extranucleosomal DNA and are needed for robust sliding, but it is unclear how these domains contribute to directional movement of nucleosomes. Here, we show that the DNA-binding domain of Chd1 is not essential for nucleosome sliding but is critical for centering mononucleosomes on short DNA fragments. Remarkably, nucleosome centering was achieved by replacing the native DNA-binding domain of Chd1 with foreign DNA-binding domains of Escherichia coli AraC or Drosophila melanogaster engrailed. Introducing target DNA sequences recognized by the foreign domains enabled the remodelers to rapidly shift nucleosomes toward these binding sites, demonstrating that these foreign DNA-binding domains dictated the direction of sliding. Sequence-directed sliding occluded the target DNA sequences on the nucleosome enough to promote release of the remodeler. Target DNA sequences were highly stimulatory at multiple positions flanking the nucleosome and had the strongest influence when separated from the nucleosome by 23 or fewer base pairs. These results suggest that the DNA-binding domain's affinity for extranucleosomal DNA is the key determinant for the direction that Chd1 shifts the nucleosome.


Assuntos
Montagem e Desmontagem da Cromatina , Proteínas de Ligação a DNA/química , Nucleossomos/química , Proteínas de Saccharomyces cerevisiae/química , Saccharomyces cerevisiae , Trifosfato de Adenosina/química , Fator de Transcrição AraC/química , Fator de Transcrição AraC/genética , Sequência de Bases , Sítios de Ligação , Proteínas de Ligação a DNA/genética , Ensaio de Desvio de Mobilidade Eletroforética , Ensaios Enzimáticos , Proteínas de Escherichia coli/química , Proteínas de Escherichia coli/genética , Fluorometria , Ligação Proteica , Engenharia de Proteínas , Estrutura Terciária de Proteína , Proteínas Recombinantes de Fusão/química , Proteínas Recombinantes de Fusão/genética , Proteínas de Saccharomyces cerevisiae/genética , Deleção de Sequência
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