Blaine T. Bafus

Fertilization typically involves membrane fusion between sperm and eggs. In Drosophila, however, sperm enter eggs with membranes intact. Consequently, sperm plasma membrane breakdown (PMBD) and subsequent events of sperm activation occur in the egg cytoplasm. We previously proposed that mutations in the sneaky (snky) gene result in male sterility due to failure in PMBD. Here we support this proposal by demonstrating persistence of a plasma membrane protein around the head of snky sperm after entry into the egg. We further show that snky is expressed in testes and encodes a predicted integral membrane protein with multiple transmembrane domains, a DC-STAMP-like domain, and a variant RING finger. Using a transgene that expresses an active Snky-Green fluorescent protein fusion (Snky-GFP), we show that the protein is localized to the acrosome, a membrane-bound vesicle located at the apical tip of sperm. Snky-GFP also allowed us to follow the fate of the protein and the acrosome during fertilization. In many animals, the acrosome is a secretory vesicle with exocytosis essential for sperm penetration through the egg coats. Surprisingly, we find that the Drosophila acrosome is a paternally inherited structure. We provide evidence that the acrosome induces changes in sperm plasma membrane, exclusive of exocytosis and through the action of the acrosomal membrane protein Snky. Existence of testis-expressed Snky-like genes in many animals, including humans, suggests conserved protein function. We relate the characteristics of Drosophila Snky, acrosome function and sperm PMBD to membrane fusion events that occur in other systems.

Importance: Distal radius fractures (DRFs) are common injuries among older adults and can result in substantial disability. Current evidence regarding long-term outcomes in older adults is scarce. Objective: To compare outcomes across treatment groups at 24 months among adults with DRFs who participated in the WRIST trial. Design, Setting, and Participants: The Wrist and Radius Injury Surgical Trial (WRIST) randomized, international, multicenter trial was conducted from April 1, 2012, through December 31, 2016. Participants were adults aged 60 years or older with isolated, unstable DRFs at 24 health systems in the US, Canada, and Singapore. Data analysis was performed from March 2019 to March 2021. Interventions: Participants were randomized to open reduction and volar locking plate system (VLPS), external fixation with or without supplementary pinning (EFP), and percutaneous pinning (CRPP). The remaining participants chose closed reduction and casting. Main Outcomes and Measures: The primary outcome was the 24-month Michigan Hand Outcomes Questionnaire (MHQ) summary score. Secondary outcomes were scores on the MHQ subdomains hand strength and wrist motion. Results: A total of 304 adults were recruited for the study, and 187 were randomized to undergo surgery, 65 to VLPS, 64 to EFP, and 58 to CRPP; 117 participants opted for closed reduction and casting. Assessments were completed at 24 months for 182 participants (160 women [87.9%]; mean [SD] age, 70.1 [8.5] years). Mean MHQ summary scores at 24 months were 88 (95% CI, 83-92) for VLPS, 83 (95% CI, 78-88) for EFP, 85 (95% CI, 79-90) for CRPP, and 85 (95% CI, 79-90) for casting, with no clinically meaningful difference across groups after adjusting for covariates (χ23 = 1.44; P = .70). Pain scores also did not differ across groups at 24 months (χ23 = 2.64; P = .45). MHQ summary scores changed from 82 (95% CI, 80-85) to 85 (95% CI, 83-88) (P = .12) between 12 and 24 months across groups. The rate of malunion was higher in the casting group (26 participants [59.1%]) than in the other groups (4 participants [8.0%] for VLPS, 8 participants [17.0%] for EFP, and 4 participants [9.8%] for CRPP; χ23 = 43.6; P < .001), but malunion was not associated with the 24-month outcome difference across groups. Conclusions and Relevance: The study did not find clinically meaningful patient-reported outcome differences 24 months after injury across treatment groups, with little change between 12 and 24 months. These findings suggest that long-term outcomes need not necessarily be considered in deciding between treatment options. Patient needs and recovery goals that fit to relative risks and benefits of each treatment type will be more valuable in treatment decision-making. Trial Registration: ClinicalTrials.gov Identifier: NCT01589692.

BACKGROUND: The purpose of this study was to identify the utilization rate and most common reasons for presentation to the emergency department (ED) after elective outpatient hand surgery and to determine preoperative risk factors for these ED visits. METHODS: Patients who underwent elective hand surgery at an ambulatory surgery center between 2014 and 2015 were retrospectively evaluated using the New York and Florida State Databases. The primary outcome was all-cause 7- and 30-day ED utilization rates. Reasons for presentation to the ED were recorded and manually stratified. Bivariate and multivariate analyses were performed to identify independent predictors of ED utilization. RESULTS: From 2014 to 2015, 212,506 procedures were identified; the 7- and 30-day ED visit rates were 1.8% and 4.4%, respectively. Postoperative pain was the most common cause of an ED visit after outpatient hand surgery at 7 days (25.4%) and 30 days (16.1%) postoperatively. Overall, 98% of patients presenting to the ED for postoperative pain were subsequently discharged home. After controlling for confounding, comorbid congestive heart failure, chronic lung disease, diabetes, renal failure, schizophrenia, and depression were independent risk factors for an ED visit at up to 30 days postoperatively. Those with Medicare insurance were 94% more likely to present to the ED within 30 days than those with private health insurance, whereas those with Medicaid were more than three times as likely to present to the ED as those with private insurance. DISCUSSION: ED utilization after outpatient hand surgery is low, with postoperative pain being the most common cause of an ED visit at all time points. Nearly 98% of patients presenting to the ED for postoperative pain are subsequently discharged home. LEVEL OF EVIDENCE: Level III, Retrospective Cohort.