Background Orthopaedic surgery training programs have lagged behind other surgical specialties in increasing their representation of women and people from under-represented minority (URM) groups. Comparative data between orthopaedic surgery and other specialties are needed to help identify solutions to closing the diversity gap. Questions/purposes (1) Which surgical specialties have the greatest representation of women residents and residents from URM groups? (2) How have the proportions of women residents and residents from URM groups changed across the surgical specialties during the past decade? Methods This was a retrospective evaluation of a large, longitudinally maintained survey database. Resident data by gender and ethnicity were retrieved from the Accreditation Council for Graduate Medical Education Data Resource Books for the 2011 to 2012 through 2019 to 2020 academic years. The Accreditation Council for Graduate Medical Education database is updated annually; thus, it is the most up-to-date and complete database available for gender and ethnicity data for all surgical residents. Data were obtained and analyzed for seven different surgical specialties: orthopaedic surgery, neurosurgery, ophthalmology, otolaryngology, plastic surgery, general surgery, and urology. No sampling was necessary, and thus descriptive statistics of the data were completed. Because the entire population of residents was included for the period of time in question, no statistical comparisons were made, and the reported differences represent absolute differences between the groups for these periods. Linear regression analyses were performed to estimate the annual growth rates of women residents and residents from URM groups in each specialty. Results Among the seven surgical specialties, representation of women residents increased from 28% (4640 of 16,854) of residents in 2012 to 33% (6879 of 20,788) in 2020. Orthopaedic surgery had the lowest representation of women residents every year, with women residents comprising 16% of residents (700 of 4342) in 2020. Among the seven surgical specialties, representation of residents from URM groups increased from 8.1% (1362 of 16,854) in 2012 to 9.7% (2013 of 20,788) in 2020. In 2020, the representation of residents from URM groups in orthopaedic surgery was 7.7% (333 of 4342). In 2020, general surgery had the highest representation of women residents (42%; 3696 of 8809) as well as residents from URM groups (12%; 1065 of 8809). Plastic surgery (1.46% per year) and general surgery (0.95% per year) had larger annual growth rates of women residents than the other specialties did. In each surgical specialty, the annual growth rate of residents from URM groups was insignificant. Conclusion During the past decade, there was only a small increase in the representation of women in orthopaedic surgery, while the representation of people from URM groups did not change. In contrast, by 2020, general surgery had become the most diverse among the seven surgical specialties. To increase diversity in our field, we need to evaluate and implement some of the effective interventions that have helped general surgery become the diverse surgical specialty that it is today. Clinical Relevance General surgery has substantially reduced gender and ethnic disparities that existed in the past, while those in orthopaedic surgery still persist. General surgery residencies have implemented a holistic review of resident applications and longitudinal mentoring programs to successfully address these disparities. Orthopaedic surgery programs should consider placing less emphasis on United States Medical Licensing Examination score thresholds and more weight on applicants’ non-academic attributes, and put more efforts into targeted longitudinal mentorship programs, some of which should be led by non-minority faculty.

Rationale: Diabetic hyperglycemia is associated with cardiac dysfunction and increased arrhythmia risk, and calcium/calmodulin-dependent protein kinase II (CaMKII) function has been implicated. CaMKII activity is promoted by both oxidation and O linked β-N-acetylglucosamine (O GlcNAc) of known CaMKII sites. Objective: To investigate which post-translational modifications occur in human diabetic hearts and how they alter electrophysiological and Ca 2+ handling properties in hyperglycemia. Methods and Results: We assessed echocardiography, electrophysiology, Ca 2+ -handling, and protein expression in site-specific CaMKII mutant mice (O GlcNAc-resistant S280A and oxidation-resistant MM281/2VV knock-ins, and global and cardiac-specific knockouts), in myocytes subjected to acute hyperglycemia and angiotensin II (Ang-II) and mice after streptozotocin injections (to induce diabetes). Human patients with diabetes exhibit elevated CaMKII O GlcNAcylation but not oxidation. In mice, acute hyperglycemia increased spontaneous diastolic Ca 2+ sparks and waves and arrhythmogenic action potential changes (prolongation, alternans and delayed afterdepolarizations), all of which required CaMKII-S280 O GlcNAcylation. Ang-II effects were dependent on NADPH oxidase 2 (NOX2)-mediated CaMKII MM281/2 oxidation. Diabetes led to much greater Ca 2+ leak, RyR2 S2814 phosphorylation, electrophysiological remodeling, and increased susceptibility to in vivo arrhythmias, requiring CaMKII activation, predominantly via S280 O GlcNAcylation and less via MM281/2 oxidation. These effects were present in myocytes at normal glucose, but were exacerbated with the in-vivo high circulating glucose. Phospholamban (PLB) O-GlcNAcylation was increased and coincided with reduced PLB S16 phosphorylation in diabetes. Dantrolene, that reverses CaMKII-dependent proarrhythmic RyR-mediated Ca 2+ leak, also prevented hyperglycemia-induced APD prolongation and delayed afterdepolarizations. Conclusions: We found that CaMKII-S280 O GlcNAcylation is required for increased arrhythmia susceptibility in diabetic hyperglycemia, which can be worsened by an additional angiotensin II-NOX2-CaMKII MM281/2 oxidation pathway. CaMKII-dependent RyR2 S2814 phosphorylation markedly increases proarrhythmic Ca 2+ leak and PLB O-GlcNAcylation may limit SR Ca 2+ reuptake, leading to impaired excitation-contraction coupling and arrhythmogenesis in diabetic hyperglycemia.

SUMMARY Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death can be triggered by defects in chromosome synapsis and recombination, which involve repair of DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocyte elimination in meiotic mutants require RNF212. RNF212 sensitizes oocytes to DSB-induced apoptosis within a narrow window as chromosomes desynapse and cells transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a “memory” of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.

Oocyte quality control culls eggs with defects in meiosis. In mouse, oocyte death is triggered by defects in chromosome synapsis and recombination, which involve repair of programmed DNA double-strand breaks (DSBs) between homologous chromosomes. We show that RNF212, a SUMO ligase required for crossing over, also mediates oocyte quality control. Both physiological apoptosis and wholesale oocytes elimination in meiotic mutants require RNF212.RNF212 sensitizes cells to DSB-induced apoptosis within a narrow window when chromosomes desynapse during the transition into quiescence. Analysis of DNA damage during this transition implies that RNF212 impedes DSB repair. Consistently, RNF212 is required for HORMAD1, a negative regulator of inter-sister recombination, to associate with desynapsing chromosomes. We infer that oocytes impede repair of residual DSBs to retain a "memory" of meiotic defects that enables quality control processes. These results define the logic of oocyte quality control and suggest RNF212 variants may influence transmission of defective genomes.