Palliative Ventilator Withdrawal Practices in an Inpatient Hospice Unit.

BACKGROUND: Palliative ventilator withdrawal (PVW) involves removal of mechanical ventilation in patients not expected to survive to allow a peaceful death. This process traditionally occurs in Intensive Care Units (ICU) and recently has evolved to occur in Inpatient Hospice and Palliative Care Units (IPU). OBJECTIVES: To describe the process and response of patients undergoing PVW in an IPU setting. METHODS: This is a longitudinal observational cohort study of adult patients who underwent PVW in an IPU from January 2021 through March 2022. RESULTS: Among 25 enrolled subjects, median age was 68 (IQR 62.5-76.5) years and 14 (56%) were females. Median time from PVW to death was 16.8 (IQR 2.6-100) hours. A registered nurse and attending physician were present in all the cases, while a respiratory therapist was present in 20 (80%) and chaplain in 9 (36%) of the cases. Before PVW, opioids and benzodiazepines were administered to 24 (96%) patients. Post PVW, respiratory distress was noted among 16 (64%) patients and medication was given to 15 (60%) patients for respiratory distress. There was a significant association between the presence of respiratory distress and administration of medication within 30 minutes after PVW (P = .009). The rituals performed during PVW were reciting prayers for 11 (44%), playing music for 8 (32%), and observing silence for 6 (24%) of the patients. CONCLUSION: This study describes the PVW practices in an IPU setting where a multidisciplinary team was present during PVW for most of the cases and two-third of the patients undergoing PVW experienced respiratory distress immediately after PVW.

An assay for lateral line regeneration in adult zebrafish.

Due to the clinical importance of hearing and balance disorders in man, model organisms such as the zebrafish have been used to study lateral line development and regeneration. The zebrafish is particularly attractive for such studies because of its rapid development time and its high regenerative capacity. To date, zebrafish studies of lateral line regeneration have mainly utilized fish of the embryonic and larval stages because of the lower number of neuromasts at these stages. This has made quantitative analysis of lateral line regeneration/and or development easier in the earlier developmental stages. Because many zebrafish models of neurological and non-neurological diseases are studied in the adult fish and not in the embryo/larvae, we focused on developing a quantitative lateral line regenerative assay in adult zebrafish so that an assay was available that could be applied to current adult zebrafish disease models. Building on previous studies by Van Trump et al. that described procedures for ablation of hair cells in adult Mexican blind cave fish and zebrafish (Danio rerio), our assay was designed to allow quantitative comparison between control and experimental groups. This was accomplished by developing a regenerative neuromast standard curve based on the percent of neuromast reappearance over a 24 hr time period following gentamicin-induced necrosis of hair cells in a defined region of the lateral line. The assay was also designed to allow extension of the analysis to the individual hair cell level when a higher level of resolution is required.

Parp inhibition prevents ten-eleven translocase enzyme activation and hyperglycemia-induced DNA demethylation.

Studies from human cells, rats, and zebrafish have documented that hyperglycemia (HG) induces the demethylation of specific cytosines throughout the genome. We previously documented that a subset of these changes become permanent and may provide, in part, a mechanism for the persistence of complications referred to as the metabolic memory phenomenon. In this report, we present studies aimed at elucidating the molecular machinery that is responsible for the HG-induced DNA demethylation observed. To this end, RNA expression and enzymatic activity assays indicate that the ten-eleven translocation (Tet) family of enzymes are activated by HG. Furthermore, through the detection of intermediates generated via conversion of 5-methyl-cytosine back to the unmethylated form, the data were consistent with the use of the Tet-dependent iterative oxidation pathway. In addition, evidence is provided that the activity of the poly(ADP-ribose) polymerase (Parp) enzyme is required for activation of Tet activity because the use of a Parp inhibitor prevented demethylation of specific loci and the accumulation of Tet-induced intermediates. Remarkably, this inhibition was accompanied by a complete restoration of the tissue regeneration deficit that is also induced by HG. The ultimate goal of this work is to provide potential new avenues for therapeutic discovery.