Impact of employer-covered planned oocyte cryopreservation on decision-making for medical training.

PURPOSE: To characterize how employer coverage of planned oocyte cryopreservation (POC) might impact medical career decision-making. METHODS: A cross-sectional survey was distributed to all medical students at two large academic programs in December 2022 to better understand attitudes towards childbearing, POC, and how employer coverage of POC might influence future career decisions. RESULTS: Of the 630/1933 (32.6%) medical students who participated, 71.8% identified as women and 28.1% as men. More women (89.2%) than men (75.1%, P < 0.001) felt pressure to delay childbearing. Regarding childbearing, women more than men were concerned about the physical demand of residency (76.5% vs. 50.8%, P < 0.001), stigma in residency hiring practices (41.2% vs. 9.0%, P < 0.001), and parental leave interfering with team dynamics (49.6% vs. 20.9%, P < 0.001). Respondents were more likely to pursue POC if it were covered by residency employer health insurance (60.0% vs. 11.6%, P < 0.001). Women were more likely than men to state that employer-sponsored POC would influence their residency ranking (46.0% vs. 23.7%, P < 0.001), pursuit of additional degrees (50.9% vs. 30.5%, P < 0.001), and pursuit of fellowship training (50.9% vs. 30.5%, P < 0.001). Additionally, 25.4% of women and 19.8% of men felt their choice in medical specialty would be impacted by employer-sponsored POC. CONCLUSIONS: Medical students, particularly women, feel pressure to delay childbearing during medical training and are concerned about future fertility. Both male and female students were interested in employer-sponsored POC and more likely to pursue it with financial coverage. Further research is needed to determine the full impact of employer-sponsored POC on medical career decision-making.

Disparities in access to fertility preservation among adolescents undergoing gonadotoxic therapies.

PURPOSE: Fertility preservation (FP) for adolescents prior to potentially gonadotoxic therapies is not accessible for all patients. Current literature acknowledges multiple barriers to FP, but research surrounding disparities for accessing these services is limited. We aimed to identify inequities in receiving FP services among adolescents undergoing gonadotoxic therapy. METHODS: A retrospective chart review was performed at a single academic medical center for patients aged 0-21 referred for FP counseling prior to gonadotoxic therapy. Exclusions included referral after treatment, prior to gender-affirming therapy, or for fertility discussion due to a genetic condition. Minority patients were defined as non-White race and/or Hispanic ethnicity. Non-minority patients were defined as White, non-Hispanic. Analyses to assess differences in receiving FP based on minority identity and insurance status were performed via logistic regression, with receiving desired care as the outcome variable. RESULTS: Our cohort included 136 patients-38 minority and 98 non-minority. Forty-six (33.8%) patients had Medicaid, which did not differ between minority and non-minority (42.1% vs. 38.8%, P = .73). Most patients (83.1%) had a cancer diagnosis. Similar proportions of minority and non-minority patients had gonadotoxic treatment starting urgently (52.6% vs. 55.1%, P = .80), while more minority than non-minority patients desired FP (89.5% vs .77.5%, P = .10). When controlling for insurance type and age, minority participants were 12.8% less likely to receive desired FP (marginal effect = - .128, P = .05). CONCLUSIONS: This study identified significant inequities for minority populations in accessing FP. Further research is needed to determine how to make FP services more accessible to all patients, regardless of minority status.

Assessment of Iron Status in Adolescents Presenting to the Emergency Department With Heavy Menstrual Bleeding.

OBJECTIVE: Iron deficiency is extremely common in adolescents with heavy menstrual bleeding (HMB) presenting to the emergency department; however, patients are rarely screened for this. The objective of this study was to evaluate screening for iron deficiency in adolescents presenting to the emergency department for HMB. METHODS: This is a secondary analysis of a single-center, cross-sectional observational study using retrospective chart review. The study subjects are adolescents ages 11 to 19 years with International Classification of Diseases, Ninth Revision, Clinical Modification/International Classification of Diseases, Tenth Revision, Clinical Modification, codes for HMB who presented to the emergency department at a national tertiary care hospital from 2006 to 2018. Pregnant adolescents with HMB were excluded. Chart abstraction for demographic data, symptoms, laboratory tests, treatments, and outcomes was performed. The main outcome measure was the number of adolescents who had an iron evaluation in the emergency department and were discharged on oral iron. RESULTS: Of the 258 nonpregnant adolescents who sought care for HMB in the emergency department, 225 (87.2%) were evaluated with serum hemoglobin testing. Ninety-four (41.7%) of those tested were anemic. Only 23 of the 258 patients (8.9%) had iron studies (serum ferritin) performed; 18 of 23 (78.3%) had iron deficiency and 21 of 23 (92.3%) were anemic. Subjects presenting with fatigue, headache, or palpitations were more likely to have iron studies performed than those without these symptoms (all P < 0.01). Thirty-two of the 258 subjects (12.4%) were discharged on oral iron therapy, which included only 15 of the 18 subjects (83.3%) with iron deficiency determined by ferritin testing. CONCLUSIONS: Adolescents presenting to the emergency department with HMB are at significant risk of iron deficiency but are not being screened or treated, which may have significant consequences.

Structural architecture of the CARMA1/Bcl10/MALT1 signalosome: nucleation-induced filamentous assembly.

The CARMA1/Bcl10/MALT1 (CBM) signalosome mediates antigen receptor-induced NF-κB signaling to regulate multiple lymphocyte functions. While CARMA1 and Bcl10 contain caspase recruitment domains (CARDs), MALT1 is a paracaspase with structural similarity to caspases. Here we show that the reconstituted CBM signalosome is a helical filamentous assembly in which substoichiometric CARMA1 nucleates Bcl10 filaments. Bcl10 filament formation is a highly cooperative process whose threshold is sensitized by oligomerized CARMA1 upon receptor activation. In cells, both cotransfected CARMA1/Bcl10 complex and the endogenous CBM signalosome are filamentous morphologically. Combining crystallography, nuclear magnetic resonance, and electron microscopy, we reveal the structure of the Bcl10 CARD filament and the mode of interaction between CARMA1 and Bcl10. Structure-guided mutagenesis confirmed the observed interfaces in Bcl10 filament assembly and MALT1 activation in vitro and NF-κB activation in cells. These data support a paradigm of nucleation-induced signal transduction with threshold response due to cooperativity and signal amplification by polymerization.

The H3K27me3 demethylase UTX is a gender-specific tumor suppressor in T-cell acute lymphoblastic leukemia.

T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive form of leukemia that is mainly diagnosed in children and shows a skewed gender distribution toward males. In this study, we report somatic loss-of-function mutations in the X-linked histone H3K27me3 demethylase ubiquitously transcribed X (UTX) chromosome, in human T-ALL. Interestingly, UTX mutations were exclusively present in male T-ALL patients and allelic expression analysis revealed that UTX escapes X-inactivation in female T-ALL lymphoblasts and normal T cells. Notably, we demonstrate in vitro and in vivo that the H3K27me3 demethylase UTX functions as a bona fide tumor suppressor in T-ALL. Moreover, T-ALL driven by UTX inactivation exhibits collateral sensitivity to pharmacologic H3K27me3 inhibition. All together, our results show how a gender-specific and therapeutically relevant defect in balancing H3K27 methylation contributes to T-cell leukemogenesis.

All in the first glance: first fixation predicts individual differences in valence bias.

Surprised expressions are interpreted as negative by some people, and as positive by others. When compared to fearful expressions, which are consistently rated as negative, surprise and fear share similar morphological structures (e.g. widened eyes), but these similarities are primarily in the upper part of the face (eyes). We hypothesised, then, that individuals would be more likely to interpret surprise positively when fixating faster to the lower part of the face (mouth). Participants rated surprised and fearful faces as either positive or negative while eye movements were recorded. Positive ratings of surprise were associated with longer fixation on the mouth than negative ratings. There were also individual differences in fixation patterns, with individuals who fixated the mouth earlier exhibiting increased positive ratings. These findings suggest that there are meaningful individual differences in how people process faces.

Biomechanical evaluation contribution of the acetabular labrum to hip stability.

PURPOSE: Knowledge of the effect of hip pathologies on hip biomechanics is important to the understanding of the development of osteoarthritis, and the contribution of the labrum to hip joint stability has had limited study. The purpose of this study was to evaluate the effect of labral injury to stability of the femoral head in the acetabular socket. METHODS: Ten cadaver hip specimens were tested using a robotic system under four different loading conditions: axial loading (80 N) along the femoral axis and axial loading (80 N) combined with either anterior, posterior or lateral loading (60 N). The hip states were examined were intact, with a 1.5 cm capsulotomy and with a 1 cm resection of the anterosuperior labrum. RESULTS: At 30° of flexion, under axial load, the displacement of the hip with capsulotomy and labral resection (9.6 ± 2.5 mm) was significantly larger then the hip with capsulotomy alone (5.6 ± 4.1 mm, p = 0.005) and the intact hip (5.2 ± 3.8 mm, p = 0.005). Also, at 30° of flexion, the displacement under combined axial and anterior/posterior load was increased with capsulotomy and labral resection. CONCLUSION: The acetabular labrum provides stability to the hip joint in response to a distraction force and combined distraction and translation forces. One centimetre of labral resection caused significant displacement ("wobbling" effect) of the femoral head within the acetabulum with normal range of motion. Successful labral repair could be crucial for restoration of the hip biomechanics and prevention of coxarthrosis.

Evaluation of the semitendinosus tendon graft shift in the bone tunnel: an experimental study.

PURPOSE: The purpose of this study was to measure the semitendinosus tendon graft shift at the tunnel aperture with graft bending using a simulated femoral bone tunnel. METHODS: Eight semitendinosus tendon grafts were used in this study. The median age of the specimen was 53 years (range 46-63). After stripping excess soft tissue, the semitendinosus tendon was doubled over the loop of the EndoButton CL (Smith and Nephew Inc.). The diameter of the graft was measured using a graft-sizing tube (Smith and Nephew Inc.) and verified to be 7.0 mm. A custom-made aluminium fixture, the size was 40.0 mm(3), with 7.0-mm-diameter hole was used as a simulated femoral bone tunnel. The graft was inserted to the tunnel, and EndoButton was positioned to the outside of the tunnel on the fixture. The distal end of the graft was tensioned with 30 N at an angle of 15°, 30°, 45°, 60°, 75° that reproduced the graft bending angle during knee range of motion. The photograph of the tunnel aperture was taken at each graft bending angle using a digital camera, and the graft shift amount in the simulated tunnel was analysed using the computer software (ImageJ). RESULTS: The amount of the graft shift significantly increased when the graft bending angle was increased (P < 0.05). The biggest shift was observed when the graft bending angle was 75° in all specimens, and the value was 1.10 mm ± 0.12. CONCLUSION: The present study suggests that even if the femoral tunnel was created in the centre of the ACL insertion site, the graft shifted within the tunnel in the direction of the tension applied to the graft during knee range of motion. Surgeons may have to consider the graft shift within the bone tunnel as well as the tunnel position in the restoration of the native ACL anatomy.

Effect of fixation angle and graft tension in double-bundle anterior cruciate ligament reconstruction on knee biomechanics.

PURPOSE: To compare the effect of graft fixation angle and tension in double-bundle anterior cruciate ligament (ACL) reconstruction on knee biomechanics. METHODS: Fourteen cadaver knees were tested using a robotic system under two loadings: (1) an 89-N anterior tibial load (ATL) at full extension (FE), 15°, 30°, 45°, 60°, and 90°, and (2) combined 7 N m valgus and 5 N m internal tibial torques (simulated pivot-shift test) at FE, 15° and 30°. Four graft fixation angles and tensions were used for the anteromedial (AM) and posterolateral (PL) bundles, respectively: (Recon 1) 30°/20N and FE/20N, (Recon 2) 30°/30N and FE/10N, (Recon 3) 45°/20N and 15°/20N, and (Recon 4) 45°/30N and 15°/10N. RESULTS: All fixation protocols closely restored the intact knee kinematics under ATL and simulated pivot-shift loading. For the AM bundle under ATL, the in situ force (ISF) with Recon 3 at the FE was significantly lower than that of the intact knee. For the PL bundle under ATL, the ISF with Recon 3 at the FE, 15° and 30° was significantly higher than that of the intact knee. In PL bundle under simulated pivot-shift loading, the ISF with Recon 1 and Recon 2 at FE was lower and the ISF of the PL bundle with Recon 3 at the 15° was higher than that of the intact knee. CONCLUSION: The AM-45°/30N and PL-15°/10N fixation most closely matched intact knee kinematics; however, stabilizing the knee during anterior tibial translation may risk an imbalance of the AM and the PL bundle loading. The results indicate that ACL bundle forces may not be restored even if the clinical assessment shows good results with the Lachman test and pivot-shift test. This may alter the loading on other structures of the knee.

Effect of graft fixation sequence on knee joint biomechanics in double-bundle anterior cruciate ligament reconstruction.

PURPOSE: To investigate the effect of graft fixation sequence in double-bundle anterior cruciate ligament (ACL) reconstruction on knee biomechanics. METHODS: Twelve mature porcine knees underwent double-bundle ACL reconstruction with a randomized fixation order of the two graft bundles. The knees were subjected to external loadings of (1) an 89 N anterior tibial load at 30°, 60° and 90° of knee flexion and (2) 4 N-m internal and external tibial torques at 30° and 60° of knee flexion for ACL intact, deficient and reconstructed states. Knee kinematics and in situ graft forces were measured under the applied loads. RESULTS: The anterior tibial translation of the two reconstructions was not different from each other but was significantly different from the intact ACL. There was no difference in internal and external rotations between the intact knees and the reconstructions. At lower flexion angles, the graft that was fixed last (whether anteromedial or posterolateral) tended to carry significantly higher in situ load under anterior tibial loading and tibial torques. CONCLUSION: While a difference in knee kinematics may not be observable with different graft fixation sequences, fixation sequence can alter the in situ forces that the grafts bear under knee loading.