Multiple poloxamers increase plasma membrane repair capacity in muscle and nonmuscle cells.

Various previous studies established that the amphiphilic tri-block copolymer known as poloxamer 188 (P188) or Pluronic-F68 can stabilize the plasma membrane following a variety of injuries to multiple mammalian cell types. This characteristic led to proposals for the use of P188 as a therapeutic treatment for various disease states, including muscular dystrophy. Previous studies suggest that P188 increases plasma membrane integrity by resealing plasma membrane disruptions through its affinity for the hydrophobic lipid chains on the lipid bilayer. P188 is one of a large family of copolymers that share the same basic tri-block structure consisting of a middle hydrophobic propylene oxide segment flanked by two hydrophilic ethylene oxide moieties [poly(ethylene oxide)80-poly(propylene oxide)27-poly(ethylene oxide)80]. Despite the similarities of P188 to the other poloxamers in this chemical family, there has been little investigation into the membrane-resealing properties of these other poloxamers. In this study we assessed the resealing properties of poloxamers P181, P124, P182, P234, P108, P407, and P338 on human embryonic kidney 293 (HEK293) cells and isolated muscle from the mdx mouse model of Duchenne muscular dystrophy. Cell membrane injuries from glass bead wounding and multiphoton laser injury show that the majority of poloxamers in our panel improved the plasma membrane resealing of both HEK293 cells and dystrophic muscle fibers. These findings indicate that many tri-block copolymers share characteristics that can increase plasma membrane resealing and that identification of these shared characteristics could help guide design of future therapeutic approaches.

Proteomic Analysis of Surgery-induced Stress Post-Tracheal Transplantation Highlights Changes in Matrisome.

OBJECTIVE: Investigate the impact of Surgery-induced stress (SIS) on the normal airway repair process after airway reconstruction using a mouse microsurgery model, mass spectrometry (MS), and bioinformatic analysis. METHODS: Tracheal tissue from non-surgical (N = 3) and syngeneic tracheal grafts at 3 months post-replacement (N = 3) were assessed using mass spectrometry. Statistical analysis was done using MASCOT via Proteome Discoverer™. Proteins were categorized into total, dysregulated, suppressed, and evoked proteins in response to SIS. Dysregulated proteins were identified using cut-off values of -1 1 and t-test (p value <0.05). Enriched pathways were determined using STRING and Metascape. RESULTS: At the three-month post-operation mark, we noted a significant increase in submucosal cellular infiltration (14343 ± 1286 cells/mm2, p = 0.0003), despite reduced overall thickness (30 ± 3 µm, p = 0.01), compared to Native (4578 ± 723 cells/mm2; 42 ± 6 µm). Matrisome composition remained preserved, with proteomic analysis identifying 193 commonly abundant proteins, encompassing 7.2% collagens, 34.2% Extracellular matrix (ECM) glycoproteins, 6.2% proteoglycans, 33.2% ECM regulators, 14.5% Extracellular matrix-affiliated, and 4.7% secreted factors. Additionally, our analysis unveiled a unique proteomic signature of 217 "Surgery-evoked proteins" associated with SIS, revealing intricate connections among neutrophils, ECM remodeling, and vascularization through matrix metalloproteinase-9 interaction. CONCLUSIONS: Our study demonstrated the impact of SIS on the extracellular matrix, particularly MMP9, after airway reconstruction. The novel identification of MMP9 prompts further investigation into its potential role in repair. LEVEL OF EVIDENCE: NA Laryngoscope, 134:4052-4059, 2024.

Why Do Cochlear Implant Candidates Defer Surgery? A Retrospective Case-Control Study.

OBJECTIVE(S): Despite undergoing thorough cochlear implant (CI) candidacy evaluation and counseling, some patients ultimately elect against implantation. This study sought to identify patient-related and socioeconomic factors predicting CI deferral. METHODS: A retrospective study of adult (≥18 years old) CI candidates presenting between 2007 and 2021 at a tertiary academic CI center was performed. The primary outcome was device implantation. Data collected included age, gender, hearing status, race, zip code of residence, median family income (MFI), distance traveled from the CI center, marital status, employment status, and insurance status. Multivariable binary logistic regression was performed to identify predictors of implantation. RESULTS: A total of 200 patients qualifying for CI were included, encompassing 77 adults deferring surgery (CI-deferred) and 123 consecutive adults electing for surgery (CI-pursued). Age, gender, hearing status, insurance type, employment status, distance from the implant center, and MFI were comparable between the groups (p > 0.05). Compared to CI-pursued patients, CI-deferred patients were more likely to be non-Caucasian (24.7% vs. 9.8%, p = 0.015) and unmarried (55.8% vs. 38.2%, p = 0.015). On multivariable logistic regression, older age (OR 0.981, 0.964-0.998, p = 0.027), African American race (OR 0.227, 0.071-0.726, p = 0.012), and unmarried status (OR 0.505, 0.273-0.935, p = 0.030) were independent predictors of implant deferral. CONCLUSION: This study demonstrates that increasing age at evaluation, African American race, and unmarried status are predictors for deferring CI surgery despite being implant candidates. These patients may benefit from increased outreach in the form of counseling, education, and social support prior to undergoing CI surgery. LEVEL OF EVIDENCE: 3 - retrospective study with internal control group Laryngoscope, 134:2857-2863, 2024.

Evaluating Listening Effort in Unilateral, Bimodal, and Bilateral Cochlear Implant Users.

OBJECTIVE: Evaluate listening effort (LE) in unilateral, bilateral, and bimodal cochlear implant (CI) users. Establish an easy-to-implement task of LE that could be useful for clinical decision making. STUDY DESIGN: Prospective cohort study. SETTING: Tertiary neurotology center. METHODS: The Sentence Final Word Identification and Recall Task, an established measure of LE, was modified to include challenging listening conditions (multitalker babble, gender, and emotional variation; test), in addition to single-talker sentences (control). Participants listened to lists of sentences in each condition and recalled the last word of each sentence. LE was quantified by percentage of words correctly recalled and was compared across conditions, across CI groups, and within subjects (best aided vs monaural). RESULTS: A total of 24 adults between the ages of 37 and 82 years enrolled, including 4 unilateral CI users (CI), 10 bilateral CI users (CICI), and 10 bimodal CI users (CIHA). Task condition impacted LE (P < .001), but hearing configuration and listener group did not (P = .90). Working memory capacity and contralateral hearing contributed to individual performance. CONCLUSION: This study adds to the growing body of literature on LE in challenging listening conditions for CI users and demonstrates feasibility of a simple behavioral task that could be implemented clinically to assess LE. This study also highlights the potential benefits of bimodal hearing and individual hearing and cognitive factors in understanding individual differences in performance, which will be evaluated through further research.