Invasive Mechanical Ventilation.

Invasive mechanical ventilation allows clinicians to support gas exchange and work of breathing in patients with respiratory failure. However, there is also potential for iatrogenesis. By understanding the benefits and limitations of different modes of ventilation and goals for gas exchange, clinicians can choose a strategy that provides appropriate support while minimizing harm. The ventilator can also provide crucial diagnostic information in the form of respiratory mechanics. These, and the mechanical ventilation strategy, should be regularly reassessed.

Mitochondrial One-Carbon Metabolism is Required for TGF-ß-Induced Glycine Synthesis and Collagen Protein Production.

A hallmark of Idiopathic Pulmonary Fibrosis is the TGF-ß-dependent activation of lung fibroblasts, leading to excessive deposition of collagen proteins and progressive scarring. We have previously shown that synthesis of collagen by lung fibroblasts requires de novo synthesis of glycine, the most abundant amino acid in collagen protein. TGF-ß upregulates the expression of the enzymes of the de novo serine/glycine synthesis pathway in lung fibroblasts through mTORC1 and ATF4-dependent transcriptional programs. SHMT2, the final enzyme of the de novo serine/glycine synthesis pathway, transfers a one-carbon unit from serine to tetrahydrofolate (THF), producing glycine and 5,10-methylene-THF (meTHF). meTHF is converted back to THF in the mitochondrial one-carbon (1C) pathway through the sequential actions of MTHFD2 (which converts meTHF to 10-formyl-THF), and either MTHFD1L, which produces formate, or ALDH1L2, which produces CO2. It is unknown how the mitochondrial 1C pathway contributes to glycine biosynthesis or collagen protein production in fibroblasts, or fibrosis in vivo. Here, we demonstrate that TGF-ß induces the expression of MTHFD2, MTHFD1L, and ALDH1L2 in human lung fibroblasts. MTHFD2 expression was required for TGF-ß-induced cellular glycine accumulation and collagen protein production. Combined knockdown of both MTHFD1L and ALDH1L2 also inhibited glycine accumulation and collagen protein production downstream of TGF-ß; however knockdown of either protein alone had no inhibitory effect, suggesting that lung fibroblasts can utilize either enzyme to regenerate THF. Pharmacologic inhibition of MTHFD2 recapitulated the effects of MTHFD2 knockdown in lung fibroblasts and ameliorated fibrotic responses after intratracheal bleomycin instillation in vivo. Our results provide insight into the metabolic requirements of lung fibroblasts and provide support for continued development of MTHFD2 inhibitors for the treatment of IPF and other fibrotic diseases.

Interprofessional Education Without Limits: A Video-Based Workshop.

Introduction: Interprofessional collaboration improves patient outcomes. Many institutions lack access to learners from other health care professions, limiting the feasibility of many published interprofessional curricula. We created a video-based workshop to fill the need for an introductory interactive interprofessional activity for third-year medical students (MS 3) in their internal medicine clerkship, in which other health care students and standardized patients were not readily accessible. Methods: This session introduced medical students to the interprofessional model of care through a video workshop. Learners engaged in reflective observation as a video presented a physician interviewing a patient. The training and roles of interprofessional providers were discussed with the aid of video demonstrations. Learners completed postworkshop and postmedicine clerkship surveys with responses indicated using a Likert scale (1 = strongly disagree, 5 = strongly agree). Results: Sixty-seven MS 3s participated in this workshop; postworkshop survey response rate was 82%. Of students who responded to the surveys, 87% agreed that the video increased their understanding of when it would be beneficial to consult interprofessional team members. Students' confidence in interacting with interprofessional team members improved from a mean of 3.0 before the workshop to 3.7 after the workshop. At the end of the medicine clerkship, 71% indicated that the video improved their ability to work with interprofessional team members at least moderately. Discussion: This video-based workshop improved students' self-rated understanding of interprofessional team members' roles and increased their confidence interacting with other members of the interprofessional health care team.