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1.
J Clin Orthop Trauma ; 56: 102522, 2024 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-39286006

RESUMO

Background/aims: Racial and ethnic minorities are under-represented in orthopaedic surgery despite efforts to promote diversity and inclusion in the specialty. The purpose of this study was to determine the proportion of international medical graduates (IMGs) in the surgical workforce and future residency pipeline. We further analyze IMG applicant qualifications relative to their US-based counterparts to assess the viability of recruiting IMG candidates as one strategy to advance diversity and inclusion in orthopaedic surgery. Methods: Physician workforce data from the American Medical Association and residency match data from the National Resident Match Program were analyzed for Orthopaedic Surgery. Trends in the proportion of IMG applicants were compared with those from other specialties. Qualifications of applicants were compared including board exam scores, number of abstracts/publications, and additional graduate degrees. Results: In 2020, orthopaedic surgery had the lowest percentage of IMGs relative to otolaryngology (5.8 %, p < 0.001), neurosurgery (12.1 %, p < 0.001), obstetrics & gynecology (14.0 %, p < 0.001), and general surgery (19.1 %, p < 0.001). From 1986 to 2021, IMG Graduates who matched into orthopaedic surgery increased from 1 (0.3 %) to 8 (0.9 %). Compared to other surgical specialties, orthopaedic surgery had among the lowest annual rates of incoming IMG residents. In 2021, most respondents to the orthopaedic surgery residency program directors survey reported never selecting IMG applicants for interview (74 % for non-US IMG applicants and 53 % for US IMG applicants). From 2020 to 2021, non-US IMG applicants (17 %) and US IMG applicants (26 %) had lower match rates than DO Senior (74 %) and MD Senior (80 %) applicants (p < 0.001). In 2020, matched non-US IMGs had similar board scores as matched US MD Senior applicants, but more abstracts/publications. Conclusion: The recruitment of IMGs into orthopaedic surgery residency remains limited and lower than other surgical specialties. IMGs have similar board scores and more abstracts/publications, thus representing a potential pipeline for workforce diversity. More research is needed to understand the special needs of IMGs in the orthopaedic surgery match.

2.
Artigo em Inglês | MEDLINE | ID: mdl-39302098

RESUMO

PURPOSE: This study sought to quantify the tunnel widening associated with quadriceps tendon (QT) autograft after anterior cruciate ligament reconstruction (ACLR) and compare it to bone-patellar tendon-bone (BTB) autografts. METHODS: A retrospective review of each ACLR performed at a single academic institution from 2011 to 2021 were reviewed. Subjects with repeat ipsilateral knee magnetic resonance imaging (MRI) studies performed after ACLR were included. Two reviewers independently measured the maximum diameter of the femoral and tibial tunnels 1 cm from the aperture. Tunnel widening was calculated as the difference between the initial drilled diameter and the measured diameters. RESULTS: Seventy-five patients (38 BTB and 37 QT autografts) were identified including 42 females and 33 males. With respect to graft type (QT vs. BTB), there was no statistically significant difference in median patient age (19.0 (16.0-31.5) years vs. 20.0 (16.8-30.0) years respectively; p = n.s.) or median time to MRI (12.0 [9.0-19.5] months vs. 13.0 [7.0-43.3] months respectively, p = n.s.). Mean tunnel diameter changes or widening was statistically significantly greater for QT autografts than BTB autografts at the tibial tunnel: (0.4 [±0.6] mm] vs. -0.4 [±1.1 mm; p < 0.001). Similarly, the mean tunnel diameter change was also significantly greater at the femoral tunnel for QT compared to BTB. (0.2 [±0.6] mm vs. -0.4 [±0.8] mm; p < 0.001) However, no patients with QT grafts demonstrated tibial or femoral tunnel diameters >12 mm. CONCLUSION: Although QT autografts had a statistically significant greater amount of tunnel widening compared to BTB autografts; the mean tibial and femoral net widening of 0.4 mm and 0.2 mm, respectively, does not meet previously reported clinically significant values. Thus, the tunnel widening presented in this study is unlikely to affect clinical outcomes and should not preclude the use of either graft. LEVEL OF EVIDENCE: Level III (Retrospective comparative study).

3.
Physiol Rev ; 2024 Aug 15.
Artigo em Inglês | MEDLINE | ID: mdl-39146250

RESUMO

Parenting behavior comprises a variety of adult-infant and adult-adult interactions across multiple timescales that require an extensive reorganization of individual priorities and physiology. The state transition from non-parent to parent is facilitated by combinatorial hormone action on specific cell types that are integrated throughout interconnected and brain-wide neuronal circuits. In this review we take a comprehensive approach to integrate historical and current literature on each of these topics across multiple species, with a focus on rodents. New and emerging molecular, circuit based and computational technologies have recently been used to address outstanding gaps in our current framework of knowledge on infant-mediated behavior, mainly in murine models. This work is raising fundamental questions about the interplay between instinctive and learned components of parenting and the mutual regulation of parenting and anti-parenting behaviors in health and disease. Whenever possible, we point to how these technologies have helped gain novel insights, while opening new avenues of research into studies of parenting. We hope this review will serve as an introduction for those new to the field, a comprehensive resource for those already studying parenting, and a guidepost for designing future studies.

4.
Am J Sports Med ; 52(10): 2450-2455, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39097771

RESUMO

BACKGROUND: The ideal graft for anterior cruciate ligament (ACL) reconstruction (ACLR) in young athletes has a high return-to-sport (RTS) rate and a low reinjury rate. Quadriceps tendon autografts are being used with increasing frequency for ACLR in this population, despite a paucity of evidence to support their use. PURPOSE: To report the RTS rate, ipsilateral reinjury rate, and contralateral ACL injury rate in a young athletic population undergoing primary ACLR using an all-soft tissue quadriceps tendon (ASTQT) autograft. STUDY DESIGN: Cases series; Level of evidence, 4. METHODS: Patients aged 14 to 22 years who underwent primary ACLR using an ASTQT autograft by a single surgeon between January 1, 2005, and April 30, 2020, were identified via electronic medical records and contacted ≥24 months after ACLR to complete a survey regarding subsequent ipsilateral or contralateral ACL injuries and RTS. Patients who had undergone previous ACLR (ipsilateral or contralateral) were excluded. RESULTS: A total of 656 patients (330 male, 326 female; mean age, 17.9 years) were identified, and 395 patients completed the survey (60.2%; 174 male, 221 female; mean age, 17.8 years) with a mean follow-up of 73 ± 29 months (range, 24-139 months). The RTS rate was high (male: 87.7%; female: 82.8%; P = .19). Male and female patients had similar rates of revision ACLR (male: 12.6%; female: 10.0%; P = .40) and contralateral ACL injuries (male: 13.8%; female: 11.3%; P = .46). CONCLUSION: A high RTS rate and similar rates of ipsilateral and contralateral ACL injuries were found for male and female patients in a young athletic population undergoing primary ACLR using an ASTQT autograft. These results help one to better understand the utility of ASTQT grafts to support successful ACLR in young athletic populations, for which ASTQT grafts appear to yield favorable outcomes.


Assuntos
Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Autoenxertos , Músculo Quadríceps , Relesões , Volta ao Esporte , Tendões , Humanos , Reconstrução do Ligamento Cruzado Anterior/métodos , Masculino , Feminino , Adolescente , Lesões do Ligamento Cruzado Anterior/cirurgia , Adulto Jovem , Músculo Quadríceps/transplante , Fatores Sexuais , Tendões/transplante , Transplante Autólogo , Estudos Retrospectivos
5.
PM R ; 2024 Jul 18.
Artigo em Inglês | MEDLINE | ID: mdl-39022815

RESUMO

BACKGROUND: The recruitment of high-quality applicants is critical to the vitality of the sports medicine physician workforce. OBJECTIVE: To analyze changes in the total number of available training positions, applicants, and unfilled training positions in the Sports Medicine Match from 2012 to 2022. DESIGN: This was a retrospective cohort study of sports medicine fellowship applicants. SETTING: Accreditation Council for Graduate Medical Education-accredited sports medicine fellowship training programs. PARTICIPANTS: A total of 3763 individuals applying for sports medicine fellowship training from 2012 to 2022. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Annual number of applicants, training positions, and number of unfilled training positions. RESULTS: From 2012 to 2022, the annual number of training positions in sports medicine increased from 177 to 353 (99% increase, p < .001) while the annual number of applicants increased from 256 to 428 (67% increase, p < .001). The annual applicant-to-training position ratio decreased (1.4 to 1.2, p < .001). Annual match rates increased for both U.S. MD graduates (64% to 86%, p < .001) and non-U.S. MD graduates (64% to 77%, p < .001). U.S. MD graduates had higher match rates than non-U.S. MD graduates in 2021 (79% vs 70%, p < .05) and 2022 (86% vs 77%, p < .05). The percentage of applicants who matched at their first (36%-36%, p > .05), second (14%-15%, p > .05), and third (9%-8%, p > .05) ranked programs did not change. The percentage of applicants who did not match decreased (33%-19%, p < .001). The percentage of available fellowship training positions that went unfilled decreased (8%-2%, p < .001). CONCLUSIONS: Interest in sports medicine fellowship training is increasing as evidenced by an increasing number of applications and decreasing rate of unfilled training positions. Continued monitoring of future match cycles is important given projected shortages in the physician workforce.

6.
JBJS Case Connect ; 14(3)2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-39028832

RESUMO

CASE: A 14-year-old adolescent girl and 18-year-old man underwent right anterior cruciate ligament (ACL) reconstruction using quadriceps tendon (QT) autografts via partial-thickness harvest. While both patients initially recovered well, later they experienced a painful snapping in their knee localized to the lateral QT, just proximal to the patella. Surgical completion of the previous partial-thickness defect with imbrication provided resolution of symptoms at 4 and 9 months postoperatively, respectively. CONCLUSION: We present a snapping QT as a rare complication of partial-thickness QT harvest for ACL reconstruction. Surgical completion of the partial-thickness defect with imbrication resolved the snapping sensation in these two cases.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Humanos , Adolescente , Reconstrução do Ligamento Cruzado Anterior/efeitos adversos , Masculino , Feminino , Tendões/transplante , Tendões/cirurgia , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/cirurgia , Autoenxertos , Lesões do Ligamento Cruzado Anterior/cirurgia , Músculo Quadríceps , Transplante Autólogo
7.
Knee Surg Sports Traumatol Arthrosc ; 32(7): 1672-1681, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38651565

RESUMO

PURPOSE: Extensor mechanism injuries, which comprise patella fractures, patella tendon tears and quadriceps tendon tears, are severely debilitating injuries and a common cause of traumatic knee pathology that requires surgical intervention. Risk factors for short-term surgical complications and venous thromboembolism (VTE) in this population have not been well characterised. The aim of this study was to identify perioperative risk factors associated with these short-term complications. METHODS: The National Surgical Quality Improvement Program database was used to identify patients who underwent an isolated, primary extensor mechanism repair from 2015 to 2020. Patients were stratified by injury type. Demographic data were collected and compared. A multivariate logistic regression was used to control for demographic and comorbid factors while assessing risk factors for developing short-term complications. RESULTS: A total of 8355 patients were identified for inclusion in this study. Overall, 3% of patients sustained short-term surgical complications and 1% were diagnosed with VTE within 30 days of surgery. Patella fracture fixation had a nearly twofold higher risk for surgical complications compared to quadriceps tendon repair (p = 0.004). Patella tendon repair had a twofold higher risk for VTE (p = 0.045), specifically deep vein thrombosis (p = 0.020), compared to patella fracture fixation. Increasing age, smoking and American Society of Anesthesiologists Classifications 3 and 4 were also found to be risk factors for surgical complications (p = 0.012, p = 0.004, p = 0.011 and p = 0.032, respectively). CONCLUSION: This study used a nationally representative, widely validated, peer-reviewed database to provide valuable insights into risk factors for short-term postoperative complications associated with extensor mechanism repair procedures, revealing notable differences in risk profiles among distinct surgical procedures. The results of this study will inform surgeons and patients in enhancing risk assessment, guiding procedure-specific decision-making, optimising preoperative care, improving postoperative monitoring and contributing to future research of extensor mechanism injuries. LEVEL OF EVIDENCE: Level III.


Assuntos
Complicações Pós-Operatórias , Tromboembolia Venosa , Humanos , Masculino , Tromboembolia Venosa/etiologia , Tromboembolia Venosa/epidemiologia , Feminino , Fatores de Risco , Complicações Pós-Operatórias/epidemiologia , Complicações Pós-Operatórias/etiologia , Pessoa de Meia-Idade , Adulto , Traumatismos dos Tendões/cirurgia , Traumatismos dos Tendões/etiologia , Patela/lesões , Patela/cirurgia , Ligamento Patelar/lesões , Fraturas Ósseas/cirurgia , Idoso , Estudos Retrospectivos
8.
Arthroscopy ; 2024 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-38537725

RESUMO

PURPOSE: To evaluate and synthesize the available literature related to platelet-rich plasma (PRP) treatment of knee pathologies and to provide recommendations to inform future research in the field. METHODS: PubMed, CINAHL, and Scopus databases were queried on October 6, 2023. All identified citations were collated and uploaded into Covidence for screening and data extraction. Studies were included if they were human studies published in English with adult cohorts that received PRP as a procedural injection or surgical augmentation for knee pathologies with patient-reported outcome measures (PROMs) and level of evidence Levels I-IV. RESULTS: Our search yielded 2,615 studies, of which 155 studies from 2006 to 2023 met the inclusion criteria. Median follow-up was 9 months (±11.2 months). Most studies (75.5%) characterized the leukocyte content of PRP, although most studies (86%) did not use a comprehensive classification scheme. In addition, most studies were from Asia (50%) and Europe (32%) and were from a single center (96%). In terms of treatment, 74% of studies examined PRP as a procedural injection, whereas 26% examined PRP as an augmentation. Most studies (68%) examined treatment of knee osteoarthritis. Many studies (83%) documented significant improvements in PROMs, including 93% of Level III/IV evidence studies and 72% of Level I/II evidence studies, although most studies (70%) failed to include minimal clinically important difference values. The visual analog scale was the most-used PROM (58% of studies), whereas the Short Form Health Survey 36-item was the least-used PROM (5% of studies). CONCLUSIONS: Most published investigations of knee PRP are performed in Asia, investigate procedural injection for osteoarthritis, and show significant outcome improvements. In addition, this review highlights the need for better classification of PRP formulations. LEVEL OF EVIDENCE: Level IV, scoping Review of level I-IV studies.

9.
bioRxiv ; 2024 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-38328205

RESUMO

Mammalian behavior and physiology undergo dramatic changes in early life. Young animals rely on conspecifics to meet their homeostatic needs, until weaning and puberty initiate nutritional independence and sex-specific social interactions, respectively. How neuronal populations regulating homeostatic functions and social behaviors develop and mature during these transitions remains unclear. We used paired transcriptomic and chromatin accessibility profiling to examine the developmental trajectories of neuronal populations in the hypothalamic preoptic region, where cell types with key roles in physiological and behavioral control have been identified1-6. These data reveal a remarkable diversity of developmental trajectories shaped by the sex of the animal, and the location and behavioral or physiological function of the corresponding cell types. We identify key stages of preoptic development, including the perinatal emergence of sex differences, postnatal maturation and subsequent refinement of signaling networks, and nonlinear transcriptional changes accelerating at the time of weaning and puberty. We assessed preoptic development in various sensory mutants and find a major role for vomeronasal sensing in the timing of preoptic cell type maturation. These results provide novel insights into the development of neurons controlling homeostatic functions and social behaviors and lay ground for examining the dynamics of these functions in early life.

10.
Phys Rev Lett ; 132(4): 043802, 2024 Jan 26.
Artigo em Inglês | MEDLINE | ID: mdl-38335343

RESUMO

We suggest the use of broadband frequency modulation to construct a novel type of optical interferometer. This interferometer is insensitive to optical phase and allows measurement of the group velocity and group velocity dispersion without the need for short pulse apparatus.

11.
Cell Rep Methods ; 4(2): 100711, 2024 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-38382523

RESUMO

In vivo 2-photon calcium imaging has led to fundamental advances in our understanding of sensory circuits in mammalian species. In contrast, few studies have exploited this methodology in birds, with investigators primarily relying on histological and electrophysiological techniques. Here, we report the development of in vivo 2-photon calcium imaging in awake pigeons. We show that the genetically encoded calcium indicator GCaMP6s, delivered by the adeno-associated virus rAAV2/7, allows high-quality, stable, and long-term imaging of neuronal populations at single-cell and single-dendrite resolution in the pigeon forebrain. We demonstrate the utility of our setup by investigating the processing of colors in the visual Wulst, the avian homolog of the visual cortex. We report that neurons in the Wulst are color selective and display diverse response profiles to light of different wavelengths. This technology provides a powerful tool to decipher the operating principles that underlie sensory encoding in birds.


Assuntos
Cálcio , Columbidae , Animais , Neurônios/fisiologia , Diagnóstico por Imagem , Cálcio da Dieta , Mamíferos
12.
Placenta ; 152: 72-85, 2024 07.
Artigo em Inglês | MEDLINE | ID: mdl-38245404

RESUMO

INTRODUCTION: Cultured mouse trophoblast stem cells (mTSC) maintain proliferation/normal stemness (NS) under FGF4, which when removed, causes normal differentiation (ND). Hypoxic, or hyperosmotic stress forces trophoblast giant cells (TGC) differentiate. Hypoxic, hyperosmotic, and genotoxic benzo(a)pyrene (BaP), which is found in tobacco smoke, force down-regulation of inhibitor of differentiation (Id)2, enabling TGC differentiation. Hypoxic and hyperosmotic stress induce TGC by SAPK-dependent HAND1 increase. Here we test whether BaP forces mTSC-to-TGC while inducing SAPK and HAND1. METHODS: Hand1 and SAPK activity were assayed by immunoblot, mTSC-to-TGC growth and differentiation were assayed at Tfinal after 72hr exposure of BaP, NS, ND, Retinoic acid (RA), or sorbitol. Nuclear-stained cells were micrographed automatically by a live imager, and assayed by ImageJ/FIJI, Biotek Gen 5, AIVIA proprietary artificial intelligence (AI) software or open source, CellPose artificial intelligence/AI software. RESULTS: BaP (0.05-1µM) activated SAPK and HAND1 without diminishing growth. TSC-to-TGC differentiation was assayed with increasingly accuracy for 2-4 N cycling nuclei and >4 N differentiating TGC nuclei, using ImageJ/FIJI, Gen 5, AIVIA, or CellPose AI software. The AIVIA and Cellpose AI software matches human accuracy. The lowest BaP effects on SAPK activation/HAND1 increase are >10-fold more sensitive than similar effects for mESC. RA induces 44-47% 1st lineage TGC differentiation, but the same RA dose induces only 1% 1st lineage mESC differentiation. DISCUSSION: First, these pilot data suggest that mTSC can be used in high throughput screens (HTS) to predict toxicant exposures that force TGC differentiation. Second, mTSC differentiated more cells than mESC for similar stress exposures, Third, open source AI can replace human micrograph quantitation and enable a miscarriage-predicting HTS.


Assuntos
Fatores de Transcrição Hélice-Alça-Hélice Básicos , Benzo(a)pireno , Diferenciação Celular , Trofoblastos , Benzo(a)pireno/toxicidade , Benzo(a)pireno/farmacologia , Trofoblastos/efeitos dos fármacos , Trofoblastos/metabolismo , Animais , Camundongos , Diferenciação Celular/efeitos dos fármacos , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Células Gigantes/efeitos dos fármacos , Células Gigantes/metabolismo , Células Gigantes/citologia , Ensaios de Triagem em Larga Escala/métodos , Células-Tronco/efeitos dos fármacos , Células-Tronco/metabolismo , Feminino , Células Cultivadas , Gravidez
13.
Arthroscopy ; 40(1): 136-145, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-37355187

RESUMO

PURPOSE: To investigate the biomechanical effects of tape-reinforced graft suturing and graft retensioning for all-soft tissue quadriceps tendon (ASTQT) anterior cruciate ligament reconstruction (ACLR) in a full-construct human cadaveric model. METHODS: Harvested cadaveric ASTQT grafts were assigned to either (1) double-suspensory adjustable-loop cortical button device (ALD) fixation in which both graft ends were fixed with a suspensory fixation device with (n = 5) or without (n = 5) tape-reinforced suturing or (2) single-suspensory distal tendon fixation in which only the patellar end was fixed with an ALD (n = 5) or fixed-loop cortical button device (FLD) (n = 5). All specimens were prepared using a No. 2 whipstitch technique, and tape-reinforced specimens had an integrated braided tape implant. Graft preparation time was recorded for double-suspensory constructs. Samples were tested on an electromechanical testing machine using a previously published protocol simulating rehabilitative kinematics and loading. RESULTS: Tape-reinforced graft suturing resulted in greater graft load retention after cycling (11.9% difference, P = .021), less total elongation (mean [95% confidence interval (CI)], 5.57 mm [3.50-7.65 mm] vs 32.14 mm [25.38-38.90 mm]; P < .001), greater ultimate failure stiffness (mean [95% CI], 171.9 N/mm [158.8-185.0 N/mm] vs 119.4 N/mm [108.7-130.0 N/mm]; P < .001), and less graft preparation time (36.4% difference, P < .001) when compared with unreinforced specimens. Retensioned ALD constructs had less cyclic elongation compared with FLD constructs (mean total elongation [95% CI], 7.04 mm [5.47-8.61 mm] vs 12.96 mm [8.67-17.26 mm]; P = .004). CONCLUSIONS: Tape-reinforced graft suturing improves time-zero ASTQT ACLR construct biomechanics in a cadaveric model with 83% less total elongation, 44% greater stiffness, and reduced preparation time compared with a whipstitched graft without tape reinforcement. ALD fixation improves construct mechanics when compared with FLD fixation as evidenced by 46% less total elongation. CLINICAL RELEVANCE: Tape-reinforced implants and graft retensioning using ALDs improve time-zero ACLR graft construct biomechanics in a time-zero biomechanical model. Clinical studies will be necessary to determine whether these implants improve clinical outcomes including knee laxity and the incidence of graft rupture.


Assuntos
Reconstrução do Ligamento Cruzado Anterior , Ligamento Cruzado Anterior , Humanos , Ligamento Cruzado Anterior/cirurgia , Fenômenos Biomecânicos , Autoenxertos , Tendões/cirurgia , Reconstrução do Ligamento Cruzado Anterior/métodos , Cadáver
14.
Knee Surg Sports Traumatol Arthrosc ; 31(12): 5463-5476, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37804345

RESUMO

PURPOSE: Research regarding revision anterior cruciate ligament reconstruction (RACLR) with quadriceps tendon (QT) autografts is lacking. The purpose of this study was to perform a systematic review and meta-analysis of RACLR with QT and compare its patient outcomes to RACLR with hamstring tendon (HT) and bone-patellar tendon-bone (BTB) autografts. METHODS: Adhering to PRISMA guidelines, a search for studies using QT in RACLR was performed within PubMed, Scopus, and CINAHL from database date of inception through December 26, 2022. Primary outcomes sought included: failure rate, Lysholm scores, International Knee Documentation Committee (IKDC) scores, IKDC grades, arthrometric knee side-to-side differences (STSD), pivot shift grade, donor site morbidity, return to sport, visual analog scale (VAS) pain scores. RESULTS: Nine studies were included consisting of 606 RACLR: 349 QT, 169 HT, and 88 BTB. Overall failure rates were 7.6% QT, 13.3% HT, and 8.7% BTB. Mean weighted Lysholm scores were 85.8 ± 3.8 QT, 82.5 ± 3.8 HT and 86.6 ± 4.5 BTB. IKDC average scores were 82.3 ± 1.6 QT, 80.1 ± 1.7 HT, and 81.7 ± 5.5BTB. Combined rates of IKDC A/B grades were 88.4% and 80.0% for QT and HT, respectively. VAS average scores were 0.9 ± 1.1 QT, 1.4 ± 0.2 HT, and 0.7 ± 0.8 for BTB. Side-to-side difference was reported for QT and HT with average values of 1.7 ± 0.6 mm and 2.1 ± 0.5 mm, respectively. Grade 0 or 1 pivot shifts were reported in 96.2% of QT patients and 91.3% of HT. Donor site morbidity, only reported for QT and HT, was 14.6 ± 9.7% and 23.6 ± 14.1%, respectively. QT resulted in a mean Tegner score of 5.9 ± 1.5 versus HT 5.7 ± 1.5. Rate of return to pivoting sports was 38.0% QT, 48.6% HT, and 76.9% BTB. Across all outcomes, there was no significant difference when comparing QT to HT, QT to BTB, and QT compared to HT and BTB combined. CONCLUSIONS: RACLR with QT yields satisfactory patient reported outcomes, satisfactory improvement in knee laxity, expected return to sport rates, and has an overall 7.6% failure rate. Outcomes are comparative to those of HT and BTB making it an acceptable graft choice for RACLR. Surgeons should consider using QT autograft for RACLR, especially when other autografts are unavailable. LEVEL OF EVIDENCE: IV.


Assuntos
Lesões do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Ligamento Patelar , Humanos , Tendões dos Músculos Isquiotibiais/transplante , Autoenxertos/cirurgia , Ligamento Patelar/cirurgia , Lesões do Ligamento Cruzado Anterior/cirurgia , Tendões/transplante , Transplante Autólogo , Enxerto Osso-Tendão Patelar-Osso
15.
Cancer Res ; 83(19): 3252-3263, 2023 10 02.
Artigo em Inglês | MEDLINE | ID: mdl-37339176

RESUMO

Outcomes for patients with recurrent/metastatic (R/M) head and neck squamous cell carcinoma (HNSCC) are poor, with median overall survival (OS) ranging from 6 to 18 months. For those who progress on standard-of-care (chemo)immunotherapy, treatment options are limited, necessitating the development of rational therapeutic strategies. Toward this end, we targeted the key HNSCC drivers PI3K-mTOR and HRAS via the combination of tipifarnib, a farnesyltransferase (FTase) inhibitor, and alpelisib, a PI3Kα inhibitor, in multiple molecularly defined subsets of HNSCC. Tipifarnib synergized with alpelisib at the level of mTOR in PI3Kα- or HRAS-dependent HNSCCs, leading to marked cytotoxicity in vitro and tumor regression in vivo. On the basis of these findings, the KURRENT-HN trial was launched to evaluate the effectiveness of this combination in PIK3CA-mutant/amplified and/or HRAS-overexpressing R/M HNSCC. Preliminary evidence supports the clinical activity of this molecular biomarker-driven combination therapy. Combined alpelisib and tipifarnib has potential to benefit >45% of patients with R/M HNSCC. By blocking feedback reactivation of mTORC1, tipifarnib may prevent adaptive resistance to additional targeted therapies, enhancing their clinical utility. SIGNIFICANCE: The mechanistically designed, biomarker-matched strategy of combining alpelisib and tipifarnib is efficacious in PIK3CA- and HRAS-dysregulated head and neck squamous carcinoma and could improve outcomes for many patients with recurrent, metastatic disease. See related commentary by Lee et al., p. 3162.


Assuntos
Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Humanos , Carcinoma de Células Escamosas de Cabeça e Pescoço/tratamento farmacológico , Carcinoma de Células Escamosas/tratamento farmacológico , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/patologia , Recidiva Local de Neoplasia/tratamento farmacológico , Serina-Treonina Quinases TOR/metabolismo , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Neoplasias de Cabeça e Pescoço/genética , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Biomarcadores , Proteínas Proto-Oncogênicas p21(ras)/genética
16.
Birth Defects Res ; 115(12): 1109-1119, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37243321

RESUMO

BACKGROUND: A survey of laboratories in North American and Europe that routinely conduct fetal skeletal examinations was performed with the purpose of (1) understanding current terminology used for classifying skeletal findings in developmental toxicity (DT) studies and (2) understanding the criteria used to identify relatively common findings that sufficiently deviate from normal. The goal was to promote terminology harmonization and improve interlaboratory consistency in the criteria used to identify developmental anomalies. METHODS: The survey, designed based on terminology for developmental anomalies recommended by an international collaboration (Makris et al., Congenital Anomalies, 2009;49(3):123-246), was conducted by a subgroup (authors of this publication) of the Royal Society of Biology's International Register of Fetal Morphologists (IRFM). RESULTS: Individual and summarized anonymized responses are provided here. The authors, who are expert fetal morphologists with experience performing fetal examinations, reviewed the responses and generated recommendations on preferred terminology and criteria for determining when morphological variations deviate from normal and warrant recording of the findings for skeletal observations in Sprague Dawley (SD) fetal rats. The objective of these recommendations is to complement Makris et al. (Congenital Anomalies, 2009;49(3):123-246). CONCLUSION: The broad application will improve interlaboratory harmonization of recording fetal skeleton findings in developmental toxicity studies intended for regulatory submissions, including SEND (Standard for Exchange of Nonclinical Data).


Assuntos
Feto , Cuidado Pré-Natal , Ratos , Animais , Humanos , Gravidez , Feminino , Ratos Sprague-Dawley , Feto/anormalidades , Europa (Continente)
17.
Hastings Cent Rep ; 53(1): 33-45, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36840335

RESUMO

This ethnographic study introduces the term "distressed work" to describe the emergence of chronic frictions between moral imperatives for health care workers to keep working and the dramatic increase in distress during the Covid-19 pandemic. Interviews and observant participation conducted in a hospital intensive care unit during the Covid-19 pandemic reveal how health care workers connected job duties with extraordinary emotional, physical, and moral burdens. We explore tensions between perceived obligations of health care professionals and the structural contexts of work. Key findings cluster around the moral imperatives of health care work and the distress that work engendered as work spaces, senses of vocation, patient and family interactions, and end-of-life care shifted. While the danger of working beyond limits has long been an ordinary feature of health care work, it has now become a chronic crisis. Assessing this problem in terms of distressed work and its structural contexts can better address effective, worker-informed responses to current health care labor dilemmas.


Assuntos
COVID-19 , Estresse Psicológico , Humanos , Estresse Psicológico/psicologia , Pandemias , Emoções , Cuidados Críticos , Princípios Morais
19.
Nat Ecol Evol ; 7(1): 92-101, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36471120

RESUMO

There have been recent renewed commitments to increase the extent of protected areas to combat the growing biodiversity crisis but the underpinning evidence for their effectiveness is mixed and causal connections are rarely evaluated. We used data gathered by three large-scale citizen science programmes in the UK to provide the most comprehensive assessment to date of whether national (Sites of Special Scientific Interest) and European (Special Protection Areas/Special Areas of Conservation) designated areas are associated with improved state (occurrence, abundance), change (rates of colonization, persistence and trend in abundance), community structure and, uniquely, demography (productivity) on a national avifauna, while controlling for differences in land cover, elevation and climate. We found positive associations with state that suggest these areas are well targeted and that the greatest benefit accrued to the most conservation-dependent species since positive associations with change were largely restricted to rare and declining species and habitat specialists. We suggest that increased productivity provides a plausible demographic mechanism for positive effects of designation.


Assuntos
Biodiversidade , Conservação dos Recursos Naturais , Animais , Ecossistema , Aves , Reino Unido
20.
Nat Commun ; 13(1): 6328, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36319621

RESUMO

Seagrass conservation is critical for mitigating climate change due to the large stocks of carbon they sequester in the seafloor. However, effective conservation and its potential to provide nature-based solutions to climate change is hindered by major uncertainties regarding seagrass extent and distribution. Here, we describe the characterization of the world's largest seagrass ecosystem, located in The Bahamas. We integrate existing spatial estimates with an updated empirical remote sensing product and perform extensive ground-truthing of seafloor with 2,542 diver surveys across remote sensing tiles. We also leverage seafloor assessments and movement data obtained from instrument-equipped tiger sharks, which have strong fidelity to seagrass ecosystems, to augment and further validate predictions. We report a consensus area of at least 66,000 km2 and up to 92,000 km2 of seagrass habitat across The Bahamas Banks. Sediment core analysis of stored organic carbon further confirmed the global relevance of the blue carbon stock in this ecosystem. Data from tiger sharks proved important in supporting mapping and ground-truthing remote sensing estimates. This work provides evidence of major knowledge gaps in the ocean ecosystem, the benefits in partnering with marine animals to address these gaps, and underscores support for rapid protection of oceanic carbon sinks.


Assuntos
Ecossistema , Tubarões , Animais , Sequestro de Carbono , Mudança Climática , Carbono
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