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1.
Artigo em Inglês | MEDLINE | ID: mdl-33092990

RESUMO

INTRODUCTION: Academic medical centers (AMCs) and community physicians seeking to establish a clinically integrated network (CIN) may benefit from a road map to navigate the opportunities and challenges of such an organizational structure. Creating and participating in a CIN requires careful consideration, investment of time, financial resources, alignment of a new quality infrastructure, shared governance, and vision. POTENTIAL BENEFITS, CHALLENGES, AND REGULATORY CONSIDERATIONS: Potential AMC benefits include geographic clinical expansion, the ability to provide care for a broader population of patients, a mechanism to collaborate with regional physician graduates, and an expansion of available teaching sites for trainees. Potential benefits to community practices include propagation of high-value care, enhanced access to evidence-based protocols and priority measures, preparation for value-based reimbursement structures, and connection to an institution that produces future health care practitioners. Challenges to CIN creation include goal alignment, trust between AMC and community partners, acceptance of common quality measures and benchmarks, access to shared data, and local adoption of quality improvement activities. QUALITY AND INFORMATION TECHNOLOGY CONSIDERATIONS: At inception the mission was to create an innovative academic-community alliance delivering high-quality, high-value, personalized care. Defining the clinical quality goals, measurement, governance, and improvement strategy, as well as information technology structure and decision making, are described. FUTURE DIRECTIONS: The network continues to grow and now includes more than 350 physicians, in 16 different specialties across 50 different independent medical practices throughout Southern California. We believe this builds a firm foundation for value-based health care.

2.
Bioorg Med Chem Lett ; 30(8): 127014, 2020 04 15.
Artigo em Inglês | MEDLINE | ID: mdl-32081448

RESUMO

Robust transport of therapeutic peptides and other medicinal molecules across tight epithelial barriers would overcome the major obstacle to oral delivery. We have already demonstrated that peptides conjugated to gangliosides (GM1 and GM3) having non-native short N-acyl groups hijack the endogenous process of intracellular lipid sorting resulting in transcytosis and delivery across epithelial barriers in vitro and in vivo. Here, we report synthetic methodologies to covalently conjugate peptides directly to short-acyl-chain C6-ceramides. We found that the short-acyl-chain ceramide domain is solely responsible for transcytosis in vitro. This clarifies and expands the platform of short-acyl-chain sphingolipids for conjugated peptide delivery across tight mucosal cell barriers from gangliosides to just the ceramide itself.


Assuntos
Ceramidas/metabolismo , Células Epiteliais/metabolismo , Mucosa Intestinal/metabolismo , Peptídeos/metabolismo , Transporte Biológico Ativo , Células Cultivadas , Ceramidas/química , Relação Dose-Resposta a Droga , Células Epiteliais/química , Humanos , Mucosa Intestinal/química , Mucosa Intestinal/citologia , Estrutura Molecular , Peptídeos/química , Relação Estrutura-Atividade
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