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1.
Arthroscopy ; 39(10): 2211-2227, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37116550

RESUMO

PURPOSE: To assess differences in postoperative outcomes between male and female patients following hip arthroscopy. METHODS: A systematic review was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. Medline, Embase, Cochrane, and PubMed databases were searched. Key words included "hip," "arthroscopy," "outcome," "gender difference," "sex difference," "gender," and "patient-reported outcome." Studies were included that reported sex-specific analysis of outcomes following primary hip arthroscopy with minimum 2-year follow-up. Methodological Index for Non-Randomized Studies criteria were applied to each study. Data collected included patient-reported outcome measures (PROMs), complications, rates of revision arthroscopy (RA), and conversion to total hip arthroplasty (THA). Forest plots were generated for the most frequently reported PROMs, RA, and THA rates. RESULTS: In total, 38 studies met the inclusion criteria, with 40,194 (57% female) hips included. The most common indications for hip arthroscopy were femoroacetabular impingement and labral tears. Eighteen studies reported PROMs, with no clear trend towards sex differences. Eleven studies reported on RA rates, with 4 showing a significantly greater rate of RA in female patients. Seventeen studies reported on conversion to THA, with an overall conversion rate of 9.64%. There were no clear sex differences in conversion to THA. CONCLUSIONS: There was no difference between sexes for postoperative PROM scores. Male patients were less likely to reach the MCID for the HOS-SSS than female patients in the majority of studies, and there were no sex differences for PASS rates. There were no significant differences between sexes in revision arthroscopy rates and conversion to total hip arthroplasty. LEVEL OF EVIDENCE: Level IV, systematic review of Level II, III and IV studies.


Assuntos
Artroplastia de Quadril , Impacto Femoroacetabular , Humanos , Masculino , Feminino , Articulação do Quadril/cirurgia , Artroscopia/efeitos adversos , Impacto Femoroacetabular/cirurgia , Artroplastia de Quadril/efeitos adversos , Quadril/cirurgia , Medidas de Resultados Relatados pelo Paciente , Resultado do Tratamento , Seguimentos , Estudos Retrospectivos
2.
J Am Chem Soc ; 144(2): 832-844, 2022 01 19.
Artigo em Inglês | MEDLINE | ID: mdl-34985906

RESUMO

Owing to its roles in human health and disease, the modification of nuclear, cytoplasmic, and mitochondrial proteins with O-linked N-acetylglucosamine residues (O-GlcNAc) has emerged as a topic of great interest. Despite the presence of O-GlcNAc on hundreds of proteins within cells, only two enzymes regulate this modification. One of these enzymes is O-GlcNAcase (OGA), a dimeric glycoside hydrolase that has a deep active site cleft in which diverse substrates are accommodated. Chemical tools to control OGA are emerging as essential resources for helping to decode the biochemical and cellular functions of the O-GlcNAc pathway. Here we describe rationally designed bicyclic thiazolidine inhibitors that exhibit superb selectivity and picomolar inhibition of human OGA. Structures of these inhibitors in complex with human OGA reveal the basis for their exceptional potency and show that they extend out of the enzyme active site cleft. Leveraging this structure, we create a high affinity chemoproteomic probe that enables simple one-step purification of endogenous OGA from brain and targeted proteomic mapping of its post-translational modifications. These data uncover a range of new modifications, including some that are less-known, such as O-ubiquitination and N-formylation. We expect that these inhibitors and chemoproteomics probes will prove useful as fundamental tools to decipher the mechanisms by which OGA is regulated and directed to its diverse cellular substrates. Moreover, the inhibitors and structures described here lay out a blueprint that will enable the creation of chemical probes and tools to interrogate OGA and other carbohydrate active enzymes.


Assuntos
Antígenos de Neoplasias/metabolismo , Compostos Bicíclicos com Pontes/química , Inibidores Enzimáticos/química , Histona Acetiltransferases/metabolismo , Hialuronoglucosaminidase/metabolismo , Sequência de Aminoácidos , Encéfalo/metabolismo , Compostos Bicíclicos com Pontes/metabolismo , Domínio Catalítico , Cromatografia Líquida de Alta Pressão , Inibidores Enzimáticos/metabolismo , Histona Acetiltransferases/antagonistas & inibidores , Humanos , Hialuronoglucosaminidase/antagonistas & inibidores , Espectrometria de Massas , Peptídeos/análise , Peptídeos/química , Processamento de Proteína Pós-Traducional , Proteômica/métodos , Relação Estrutura-Atividade , Tiazolidinas/química , Tiazolidinas/metabolismo , Cadeia alfa da beta-Hexosaminidase/antagonistas & inibidores , Cadeia alfa da beta-Hexosaminidase/metabolismo
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