Functional profiling of CFTR-directed therapeutics offers the potential to provide significant benefits to young people with cystic fibrosis (CF). However, the development of 2D airway epithelial cell models for individual response tests in CF children remains a central task. The objective of this study was to determine the utility of EpiX TM technology for expansion of nasal epithelial cells for use in electrophysiological CFTR function measurements. An initial harvest of as few as 20,000 cells was sufficient to expand up to 50 million cells that were used to generate air-liquid interface (ALI) cultures for ion transport studies with the Ussing assay. CFTR function was assessed by measuring responses to forskolin and the CFTR potentiator VX-770 (ivacaftor) in ALI cultures generated from passage 3 and 4 cells. Short-circuit current (Isc) measurements of blocked CFTR currents (I CFTRinh) discriminated CFTR function between healthy control (wild type, WT) and patients with intermediate (F508del/R117H-7T: 56% WT) and severe (F508del/F508del: 12% WT) CF disease. For the mixed genotypes, CFTR activity for F508del/c.850dupA was 12% WT, R334W/406-1G>A was 24% WT, and CFTRdele2,3(21 kb)/CFTRdele2,3(21 kb) was 9% WT. The CFTR correctors VX-809 (lumacaftor) and VX-661 (tezacaftor) significantly increased CFTR currents for F508del/R117H to 73 and 67% WT, respectively. Cultures with the large deletion mutation CFTRdele2,3(21 kb) unexpectedly responded to VX-661 treatment (20% WT). Amiloride-sensitive sodium currents were robust and ranged between 20-80 µA/cm 2 depending on the subject. In addition to characterizing the electrophysiological profile of mutant CFTR activity in cultures for five genotypes, our study exemplifies the promising paradigm of bed-to-bench side cooperation and personalized medicine.
Lately, the premier ateliers of contemporary architecture -- such as Herzog & de Meuron, or the Office of Metropolitan Architecture -- are showing increasing interest in hospital design, once the realm of highly specialized architectural firms. This trend towards reevaluating hospital design and architecture is most opportune, as the COVID-19 pandemic urges us all to rethink the ways in which our healthcare institutions can be better designed. This commentary is a discussion on the emerging issues of contemporary hospital architecture, especially as reinforced by the pandemic. For instance, while hospital architecture today focuses on individualized care, providing each patient with hotel-like rooms, the pandemic has reminded us of the issue of capacity and inequality in these limited and costly spaces. To what extent should hospitals be centralized or decentralized? Specialized or despecialized? This commentary discusses how COVID-19 has provided insight into some of contemporary hospital architecture’s greatest problems; specifically, it argues that the hospital of the future must exist on a more decentralized platform, both physically and digitally, and be more flexible in function.
Lately, the premier ateliers of contemporary architecture -- such as Herzog & de Meuron, or the Office of Metropolitan Architecture -- are showing increasing interest in hospital design, once the realm of highly specialized architectural firms. This trend towards reevaluating hospital design and architecture is most opportune, as the COVID-19 pandemic urges us all to rethink the ways in which our healthcare institutions can be better designed. This commentary is a discussion on the emerging issues of contemporary hospital architecture, especially as reinforced by the pandemic. For instance, while hospital architecture today focuses on individualized care, providing each patient with hotel-like rooms, the pandemic has reminded us of the issue of capacity and inequality in these limited and costly spaces. To what extent should hospitals be centralized or decentralized? Specialized or despecialized? This commentary discusses how COVID-19 has provided insight into some of contemporary hospital architecture’s greatest problems; specifically, it argues that the hospital of the future must exist on a more decentralized platform, both physically and digitally, and be more flexible in function.
Road traffic injury (RTI) is a frequently overlooked issue in the literature of global health. This perspective examines the ways in which wealth inequality exacerbates RTI risk characterization in the specific model of Vietnam. The framework of the Equality-Sustainability Hypothesis, as suggested by Cushing et. al, is used, with a specific focus on three factors: political misrepresentation, discrepancy in consumption intensity, and lack of social cohesion. Policies regarding helmet coverage, healthcare infrastructure, road quality and social psychology are critically analyzed, with sources drawn primarily from epidemiological study designs. Such analyses provide the basis for various policy suggestions towards the end of the perspective that focus specifically on wealth inequality as the primary point of intervention. Overall, this perspective suggests that the Equality-Sustainability Hypothesis holds true in the example of RTIs in Vietnam, which is specifically referred to as a “Vehicle Gap”, and that this hypothesis be made more comprehensive by liberalizing its definition of environment to also include man-made infrastructure.
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