Assuntos
Anemia Falciforme/genética , Anemia Falciforme/metabolismo , Células Precursoras Eritroides/metabolismo , Hemoglobina Fetal/biossíntese , Hemoglobina Fetal/genética , Domínios e Motivos de Interação entre Proteínas , Dedos de Zinco , Anemia Falciforme/sangue , Animais , Regulação da Expressão Gênica , Humanos , Camundongos , Ligação Proteica , gama-Globinas/biossíntese , gama-Globinas/genéticaRESUMO
BACKGROUND: Reverse total shoulder arthroplasty (RTSA) is a procedure growing in prevalence among younger populations. Consequently, its use in revision arthroplasty is growing in this demographic. However, studies examining the functional outcomes of revision RTSA in younger populations compared with older populations are lacking. The primary purpose of this study is to evaluate the functional outcomes of revision RTSA in patients 65 years old and younger compared with older patients who underwent revision RTSA. We hypothesized that younger patients would have similar outcomes to older patients and both groups would demonstrate improvement in outcomes. METHODS: A retrospective review was conducted on a prospectively collected research database at a single tertiary referral center of all patients who underwent RTSA between 2007 and 2018. Patients 65 years old or younger who underwent a revision RTSA and had minimum 2-year follow-up were evaluated. A control group of patients ≥70 years old who underwent revision RTSA were also evaluated. Demographics, surgical factors, active range of motion (ROM), and patient-reported outcomes (PROMs) were compared. The ROM parameters measured were forward elevation, abduction, external rotation, and level of internal rotation. The PROMs collected included American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, University of California-Los Angeles score, Constant score, normalized Constant, and Shoulder Pain and Disability Index 130. The differences in outcomes were compared against the minimal clinically important difference and substantial clinical benefit reported for primary reverse shoulder arthroplasty. RESULTS: A total of 81 patients undergoing revision RTSA were evaluated at a mean follow-up of 4.5 years with 42 patients in the study group and 39 patients in the control group. Both groups demonstrated similar demographics and rates of prior surgeries. Preoperative outcome scores were lower in the study group (≤65 years old) than those in the older control group with American Shoulder and Elbow Surgeons score, Simple Shoulder Test score, and Shoulder Pain and Disability Index 130 remaining worse postoperatively. Both groups experienced statistically significant improvements in ROM from before operation to after operation, with slightly higher improvements in overhead motion in the younger cohort. Both the study group and the control group demonstrated statistically significant improvements in all PROMs with improvement above the substantial clinical benefit for the Constant and Simple Shoulder Test scores. Despite lower functional outcomes reported in the study group postoperatively, the improvement from before operation to after operation in all PROMs was similar between groups. CONCLUSION: Revision RTSA is a viable option for patients ≤65 years old with a poorly functioning shoulder arthroplasty. ROM and outcome improvements are similar compared with older patients undergoing revision RTSA, but the preoperative and postoperative functional outcomes are worse in the younger patients.
RESUMO
BACKGROUND: Many studies have been done on the strength and mobility of the shoulder and hip in baseball players, but fewer studies have examined these metrics in softball players. PURPOSE: The purpose of this study was to observe and analyze changes in range of motion (ROM) and strength at the hip and shoulder that occur over the course of a competitive season, to describe preseason ROM and strength at the hip and shoulder in healthy college softball players through side-to-side comparison, and to compare measurements between pitchers and position players. STUDY DESIGN: Descriptive Cohort Study. METHODS: Data was collected over the course of six seasons, and a total of fifty-four healthy softball athletes (including pitchers and postiion players) who completed at least one set of preseason and postseason measurements were included. Subjects underwent passive ROM (External rotation [ER], internal rotation [IR], total arc of motion [TAM]) and strength (ER/IR at the shoulder, abduction/extension at the hip) measurements at preseason and postseason timepoints. RESULTS: Over a season, position players demonstrated an increase in all ROM metrics in both shoulders, except dominant IR, and a decrease in ER strength at the shoulder bilaterally (p<0.05). They also showed decreased ROM in all metrics across both hips (p<0.05). Pitchers had increased IR and TAM ROM in the dominant shoulder, decreased strength in both shoulders (ER throwing; ER and IR non-throwing), decreased ROM in both hips, and decreased abduction strength in the non-dominant hip (p<0.05). Position players showed less preseason IR in the dominant shoulder compared to non-dominant IR (Dominant: 31.7 ± 1.6°, Non-dominant: 37.0 ± 2.3°; p<0.05). CONCLUSION: Softball pitchers and position players both show increased ROM at the shoulder and decreased ROM at the hip over the course of a season. Position players demonstrated side-to-side discrepancies and seasonal changes at the throwing shoulder similar to those seen in baseball players. The preseason mobility of the dominant shoulder of pitchers increased over the season while strength of hip abduction in the non-dominant side was reduced. LEVEL OF EVIDENCE: 3.
RESUMO
The organization of the five ß-type globin genes on chromosome 11 reflects the timing of expression during erythroid cell development, with the embryonic ε-globin gene being located at the 5' end, followed by the two fetal γ-globin genes, and with the adult ß- and δ-globin genes being located at the 3' end. Here, we functionally characterized a DNase I-hypersensitive site (HS) located 4 kb upstream of the Gγ-globin gene (HBG-4kb HS). This site is occupied by transcription factors USF1, USF2, EGR1, MafK, and NF-E2 in the human erythroleukemia cell line K562 and exhibits histone modifications typical for enhancers. We generated a synthetic zinc finger (ZF) DNA-binding domain targeting the HBG-4kb HS (HBG-4kb ZF). The HBG-4kb ZF interacted with the target site in vitro and in the context of cells with a high affinity and specificity. Direct delivery of the HBG-4kb ZF to K562 and primary human erythroid cells caused a reduction in γ-globin gene expression which was associated with decreased binding of transcription factors and active histone marks at and downstream of the HS. The data demonstrate that the HBG-4kb HS is important for fetal globin production and suggest that it may act by opening chromatin in a directional manner.