A prospective study on the precision of height data from electronic medical records in tidal volume calculation for lung-protective ventilation.

Lung-protective ventilation is now the norm for all patients, regardless of the presence of acute respiratory distress syndrome (ARDS), owing to the mortality associated with higher tidal volumes (TV). Clinicians calculate TV using recorded height from medical records and predicted body weight (PBW); however, the accuracy remains uncertain. Our study aimed to validate accurate TV settings for lung-protective ventilation by examining the correlation between the charted height and bedside measurements. In a single-center study, we compared PBW-based TV calculated from recorded height to PBW-based TV from measured height and identified factors causing height overestimation during charting. Our team measured patient height within 24 hours of admission using metal tape. TV calculated from recorded height (6-8 mL/kg PBW) was significantly larger (391.55 ±â€…65.98 to 522.07 ±â€…87.97) than measured height-based TV (162.62 ±â€…12.62 to 470.28 ±â€…89.64) (P < .01). In the height overestimated group, 57.7% were prescribed TV by healthcare provider, which was more than TV of 8 mL/kg of PBW, as determined by measured height. Negative predictors for height overestimation were male sex (OR: 0.45 [95% CI: 0.25-0.82]; P = .008) and presence of driver's license information (OR: 0.45 [95% CI: 0.25-0.80]; P = .007), whereas Asian ethnicity was a positive predictor (OR: 4.34 [95% CI: 1.09-17.27]; P = .04). The height overestimation group had a higher in-patient mortality rate (38.5%) than the matched/underestimation group (20%) (P < .01). In stadiometer-limited hospitals, the PBW-based TV is overestimated using the recorded height instead of the measured height. In the group where heights were overestimated, over half of the patients received TV prescriptions from healthcare providers that surpassed the TV of calculated 8 mL/kg PBW based on their measured height. The risk factors for height overestimation include female sex, Asian ethnicity, and missing driver's license data. Alternative height measurement methods should be explored to ensure precise ventilation settings and patient safety.

VCP suppresses proteopathic seeding in neurons.

BACKGROUND: Neuronal uptake and subsequent spread of proteopathic seeds, such as αS (alpha-synuclein), Tau, and TDP-43, contribute to neurodegeneration. The cellular machinery participating in this process is poorly understood. One proteinopathy called multisystem proteinopathy (MSP) is associated with dominant mutations in Valosin Containing Protein (VCP). MSP patients have muscle and neuronal degeneration characterized by aggregate pathology that can include αS, Tau and TDP-43. METHODS: We performed a fluorescent cell sorting based genome-wide CRISPR-Cas9 screen in αS biosensors. αS and TDP-43 seeding activity under varied conditions was assessed using FRET/Flow biosensor cells or immunofluorescence for phosphorylated αS or TDP-43 in primary cultured neurons. We analyzed in vivo seeding activity by immunostaining for phosphorylated αS following intrastriatal injection of αS seeds in control or VCP disease mutation carrying mice. RESULTS: One hundred fifty-four genes were identified as suppressors of αS seeding. One suppressor, VCP when chemically or genetically inhibited increased αS seeding in cells and neurons. This was not due to an increase in αS uptake or αS protein levels. MSP-VCP mutation expression increased αS seeding in cells and neurons. Intrastriatal injection of αS preformed fibrils (PFF) into VCP-MSP mutation carrying mice increased phospho αS expression as compared to control mice. Cells stably expressing fluorescently tagged TDP-43 C-terminal fragment FRET pairs (TDP-43 biosensors) generate FRET when seeded with TDP-43 PFF but not monomeric TDP-43. VCP inhibition or MSP-VCP mutant expression increases TDP-43 seeding in TDP-43 biosensors. Similarly, treatment of neurons with TDP-43 PFFs generates high molecular weight insoluble phosphorylated TDP-43 after 5 days. This TDP-43 seed dependent increase in phosphorlyated TDP-43 is further augmented in MSP-VCP mutant expressing neurons. CONCLUSION: Using an unbiased screen, we identified the multifunctional AAA ATPase VCP as a suppressor of αS and TDP-43 aggregate seeding in cells and neurons. VCP facilitates the clearance of damaged lysosomes via lysophagy. We propose that VCP's surveillance of permeabilized endosomes may protect against the proteopathic spread of pathogenic protein aggregates. The spread of distinct aggregate species may dictate the pleiotropic phenotypes and pathologies in VCP associated MSP.

Phthalate Plasticizers in Children's Products and Estimation of Exposure: Importance of Migration Rate.

Plasticizers are added to diverse consumer products including children's products. Owing to their potential for endocrine disruption, the use of phthalate plasticizers is restricted in many children's products. In this study, exposure to five phthalate esters (dibutylphthalate, di(2-ethylhexyl) phthalate (DEHP), diethyl phthalate, di-isobutyl phthalate, and diisononyl phthalate (DINP)) and an alternative (di-ethylhexyl adipate) was assessed by the use of children's products based on chemical analysis of 3345 products purchased during 2017 and 2019 in Korea. Plasticizers were found above the detection limits in 387 products, and DEHP and DINP were the two most predominantly detected plasticizers. Deterministic and probabilistic estimation of the margin of exposure at a screening level revealed that the use of children's products might be an important risk factor. However, it is also highly likely that the exposure could be overestimated, because the migration rate was estimated based solely on the content of plasticizers in children's products. Chemical migration is a key process determining the absorption of plasticizers from products; thus, further refinements in experimental determination or model estimation of the migration rate are required.