RESUMO
Cellular esterases catalyze many essential biological functions by performing hydrolysis reactions on diverse substrates. The promiscuity of esterases complicates assignment of their substrate preferences and biological functions. To identify universal factors controlling esterase substrate recognition, we designed a 32-member structure-activity relationship (SAR) library of fluorogenic ester substrates and used this library to systematically interrogate esterase preference for chain length, branching patterns, and polarity to differentiate common classes of esterase substrates. Two structurally homologous bacterial esterases were screened against this library, refining their previously broad overlapping substrate specificity. Vibrio cholerae esterase ybfF displayed a preference for γ-position thioethers and ethers, whereas Rv0045c from Mycobacterium tuberculosis displayed a preference for branched substrates with and without thioethers. We determined that this substrate differentiation was partially controlled by individual substrate selectivity residues Tyr-119 in ybfF and His-187 in Rv0045c; reciprocal substitution of these residues shifted each esterase's substrate preference. This work demonstrates that the selectivity of esterases is tuned based on transition state stabilization, identifies thioethers as an underutilized functional group for esterase substrates, and provides a rapid method for differentiating structural isozymes. This SAR library could have multifaceted future applications, including in vivo imaging, biocatalyst screening, molecular fingerprinting, and inhibitor design.
Assuntos
Proteínas de Bactérias/genética , Esterases/química , Mycobacterium tuberculosis/enzimologia , Bibliotecas de Moléculas Pequenas/química , Vibrio cholerae/enzimologia , Ésteres/química , Corantes Fluorescentes/química , Relação Estrutura-Atividade , Especificidade por Substrato , SulfetosRESUMO
This study explored changes in bibliometric variables over the last 30 years for four major musculoskeletal science journals (BONE®), Calcified Tissue International® (CTI®), Journal of Bone and Mineral Research® (JBMR®), and Journal of Orthopaedic Research® (JOR®), with a specific focus on author gender. Bibliometric data were collected for all manuscripts in 1985 (BONE®, CTI®, JOR®), 1986 (JBMR®), 1995, 2005, and 2015; 2776 manuscripts met inclusion criteria. Manuscripts from Europe were more often published in BONE® or CTI®, while those from North America in JBMR® or JOR®. All journals demonstrated an increase over time in the number of authors (3.67-7.3), number of countries (1.1-1.4), number of institutions (1.4-3.1), and number of references (25.1-45.4). The number of manuscript pages increased (6.6-8.9) except for JOR® which showed a decline. CTI® had the lowest number of authors (4.9 vs. 5.6-6.8). There was a change in the corresponding author position from first to last for all journals; this change was highest for CTI® (35%) and lowest for BONE® (14.0%). All journals demonstrated an increase over time in female authors; however, CTI® was the highest amongst these four journals. The percentage of female first authors rose from 24.6 to 44.3% (CTI® 29.1-52.3%). The percentage of corresponding female authors rose from 17.5 to 33.6% (CTI® 22.9-40.0%). The proportion of female authors is increasing, likely reflecting the increasing number of women obtaining doctorates in science, medicine, and engineering.
Assuntos
Autoria , Bibliometria , Comportamento Cooperativo , Ortopedia , Publicações Periódicas como Assunto , Autoria/história , Bibliometria/história , Feminino , História do Século XX , História do Século XXI , Humanos , Cooperação Internacional/história , Masculino , Fenômenos Fisiológicos Musculoesqueléticos , Ortopedia/história , Ortopedia/organização & administração , Ortopedia/estatística & dados numéricos , Ortopedia/tendências , Publicações Periódicas como Assunto/história , Publicações Periódicas como Assunto/normas , Publicações Periódicas como Assunto/estatística & dados numéricos , Publicações Periódicas como Assunto/tendências , Editoração/história , Editoração/estatística & dados numéricos , Editoração/tendências , Fatores SexuaisRESUMO
PURPOSE: One of the most common surgical procedures for gender affirmation surgery of the chest is mastectomy. The aims of this article are to review the outcomes of a single surgeon's experience with a drainless technique, which we named "masculoplasty" and compare morbidity in this group to previously published outcomes where drains were used. METHODS: A retrospective chart review was undertaken of all patients presenting to a single surgeon for gender-affirming chest surgery. A literature review was completed, compiling data from previously published studies of mastectomy with free nipple graft for the transgender patient. Outcomes of this drain-free group were compared with historical data, where drains were known to have been used. RESULTS: One hundred fifty-three patients underwent 306 masculoplasties in a university teaching hospital. The mean age of patients was 30 years (17-66 years). Sixty-five (42%) had 1 or more chronic medical comorbidities with 17 diabetic patients (11%). The mean body mass index was 32 kg/m (18-57 kg/m), and 83 (54%) were obese. Forty-two (27%) of the patients had a history of smoking. Mean operative time was 136 minutes (74-266 minutes).Hematoma occurred in 1 patient (0.3%). Infections occurred in 7 masculoplasties (2%) with wound dehiscence in 3 (1%). Two masculoplasties (0.7%) had partial nipple necrosis. Two patients (0.7%) developed a symptomatic pneumothorax. There were 0 seromas, and no procedures were performed to drain fluid. Eight masculoplasties (3%) underwent secondary corrections. Median follow-up was 9 months.Outcomes from this drain-free technique were compared with previously published outcomes of mastectomy where drains were known to be used. When compared with previously published series (n = 1334), the drain-free group had statistically significantly lower rates of hematoma (1/306 vs 39/1334, P = 0.0036) and acute reoperation (1/306 vs 42/1334, P = 0.0024). There was a shorter length of hospital stay in the drain-free group with a statistically significantly lower revision rate (8/306 vs 116/1334, P = 0.0001). CONCLUSIONS: Gender affirmation chest surgery can be safely offered using a drain-free or "masculoplasty" technique. Compared with historical data, the use of progressive tension sutures decreases the incidence of hematoma, the need for acute reoperation, and other complications.
Assuntos
Mastectomia/métodos , Músculos Peitorais/cirurgia , Procedimentos de Cirurgia Plástica/métodos , Complicações Pós-Operatórias/fisiopatologia , Melhoria de Qualidade , Procedimentos de Readequação Sexual/métodos , Adolescente , Adulto , Estudos de Coortes , Drenagem , Estética , Feminino , Hospitais Universitários , Humanos , Masculino , Pessoa de Meia-Idade , Duração da Cirurgia , Satisfação do Paciente , Complicações Pós-Operatórias/epidemiologia , Estudos Retrospectivos , Parede Torácica/cirurgia , Pessoas Transgênero , Resultado do Tratamento , Cicatrização/fisiologia , Adulto JovemRESUMO
OBJECTIVES: In the scientific and medical field, authorship has become increasingly important for tenure and career advancement in addition to improvement in medical care. It was the purpose of this study to investigate changes in bibliometric variables, authorship, and collaboration trends in the Journal of Orthopaedic Trauma (JOT) and Injury over a 30-year period. METHODS: A bibliometric analysis was completed for all manuscripts meeting the inclusion criteria and published throughout 1 representative year of each decade over the past 30 years. A total of 444 and 1105 manuscripts for JOT and Injury, respectively, met the inclusion criteria. Standard statistical analyses were performed with nonparametric methods for continuous variables and Pearson χ and Cochran linear trend tests for categorical variables. A P < 0.05 was considered statistically significant. RESULTS: There were significant increases over time in all bibliometric variables for both journals, except in the number of countries and pages in JOT. For JOT, the overall percentage of female first authors increased 2.3 times from 1987 to 2015 (P = 0.021). The overall percentage of female corresponding authors was 7.3%. For Injury, the overall percentage of female first authors increased 1.5 times (P = 0.007). The overall percentage of female corresponding authors was 13.1%. CONCLUSIONS: Understanding changes in publishing characteristics over time and by region is critical with the rising demands of publishing in academic medicine. JOT and Injury have showed an increase in most variables analyzed. However, female authorship in JOT is climbing at a higher rate than Injury.