Footprint evidence of early hominin locomotor diversity at Laetoli, Tanzania.

Bipedal trackways discovered in 1978 at Laetoli site G, Tanzania and dated to 3.66 million years ago are widely accepted as the oldest unequivocal evidence of obligate bipedalism in the human lineage1-3. Another trackway discovered two years earlier at nearby site A was partially excavated and attributed to a hominin, but curious affinities with bears (ursids) marginalized its importance to the paleoanthropological community, and the location of these footprints fell into obscurity3-5. In 2019, we located, excavated and cleaned the site A trackway, producing a digital archive using 3D photogrammetry and laser scanning. Here we compare the footprints at this site with those of American black bears, chimpanzees and humans, and we show that they resemble those of hominins more than ursids. In fact, the narrow step width corroborates the original interpretation of a small, cross-stepping bipedal hominin. However, the inferred foot proportions, gait parameters and 3D morphologies of footprints at site A are readily distinguished from those at site G, indicating that a minimum of two hominin taxa with different feet and gaits coexisted at Laetoli.

Sex-Based Differences and Asymmetry in Hip Kinematics During Unilateral Extension From Deep Hip Flexion.

The purpose of this study was to identify side-to-side and sex-based differences in hip kinematics during a unilateral step-up from deep flexion. Twelve (eight men, four women) asymptomatic young adults performed a step ascent motion while synchronized biplane radiographs of the hip were collected at 50 images per second. Femur and pelvis position were determined using a validated volumetric model-based tracking technique that matched digitally reconstructed radiographs created from subject-specific computed tomography (CT) bone models to each pair of synchronized radiographs. Hip kinematics and side-to-side differences were calculated and a linear mixed effects model evaluated sex-based differences. Women were on average 10.2 deg more abducted and 0.2 mm more medially translated than men across the step up motion (p < 0.001). Asymmetry between hips was up to 14.1 ± 12.1 deg in internal rotation and 1.3 ± 1.4 mm in translation. This dataset demonstrates the inherent asymmetry during movements involving unilateral hip extension from deep flexion and may be used provide context for observed kinematics differences following surgery or rehabilitation. Previously reported kinematic differences between total hip arthroplasty and contralateral hips may be well within the natural side-to-side differences that exist in asymptomatic native hips.

Permanent Sterilization in Nulliparous Patients: Is Legislative Anxiety an Indication for Surgery?

AbstractThe Supreme Court's Dobbs v. Jackson Women's Health Organization decision, first leaked to the public on 2 May 2022 and officially released on 24 June 2022, overturned Roe v. Wade and thereby determined that abortion is no longer a federally protected right under the Constitution. Instead, the decision gives individual states the right to regulate abortion. Since the Dobbs decision first leaked, our institution has received numerous requests for permanent contraception from individuals stating that their motivation to pursue permanent contraception was influenced by the Dobbs decision and concerns about their reproductive autonomy. Discussions with patients seeking permanent contraception since the Supreme Court's leaked decision have led us to ask ourselves, is legislative anxiety an indication for surgery? This article presents a case series consisting of a convenience sample of 17 young, nulliparous individuals who sought out permanent contraception in the six months following the leak of the Dobbs decision. Healthcare professionals often feel discomfort in offering permanent contraception to young and nulliparous individuals. Accordingly, we discuss pertinent legal issues, review relevant ethical considerations, and offer a framework for these discussions intended to empower the consulting healthcare professional to center the bodily autonomy of every patient regardless of age, parity, or indication for permanent contraception.

Does Femoral Head Translation Vary by Sex and Side in Asymptomatic Hips During a Weightbearing Apprehension Test?

BACKGROUND: Hip microinstability is an increasingly recognized source of pain and dysfunction but has no agreed upon diagnostic criteria and the pathophysiology remains unclear. It has been suggested that pain associated with microinstability is caused by excess translation of the femoral head. Recent research indicates that single-plane femoral head translation can be reliably measured using dynamic ultrasonography during a supine clinical examination; however, the overall accuracy of that technique has not been established, and the range of femoral head translation values that are found in individuals with no history of surgery or symptomatic pathology is unknown. QUESTIONS/PURPOSES: (1) How much femoral head translation is present in native, uninjured hips during a weightbearing apprehension position for females and males? (2) How large is the side-to-side difference in hip translation and rotation within the same individual in females and males with no history of surgery or pain during the weightbearing apprehension position? (3) What differences exist in femoral head translation and rotation when comparing females to males? METHODS: Twenty-two young adults (11 males, 11 females; mean age 22 ± 2 years; BMI 22 ± 5 kg/m2) with no history of hip pain, no known hip injury, and who never had hip surgery participated in this study. High-resolution CT images of the femur and pelvis were acquired for each participant, and the bone tissue was segmented from the CT volume. Synchronized biplane radiographs were collected during a neutral standing trial and during a static weightbearing apprehension position in which the participant extended, externally rotated, and abducted at their back hip while standing with their feet split in the AP direction. A validated volumetric model-based tracking technique was used to match the patient-specific bone models to the biplane radiographs with an accuracy of 0.3 mm for translation and 0.8° for rotation. Translation of the center of the femoral head relative to the center of the acetabulum and rotation of the femur relative to the pelvis from neutral to the weightbearing apprehension position were calculated. Sex-based differences in hip kinematics were assessed by bivariate linear regression. RESULTS: The median (range) translation during the weightbearing apprehension position in females was 0.9 mm (0.2 to 2.7 mm), which was less than in the 1.3 mm (0.2 to 2.6 mm) translation found in males (median difference of 0.5 mm; p = 0.04). The median absolute side-to-side difference in translation during the pivot was 1.4 mm (0.1 to 3.8 mm) in females and 1.3 mm (0.1 to 4.4 mm) in males. CONCLUSION: These findings demonstrate that the femoral head translates the same under bodyweight loading as previously observed during supine exam, showing the inherent stability of the hip with no history of surgery or symptomatic pathology. This study also provides normal values for comparison with individuals who have suspected microinstability. Future directions for research include directly comparing biplane radiography to alternative imaging techniques, such as dynamic ultrasound, for identifying hip microinstability and identifying threshold values for symptomatic hip microinstability. LEVEL OF EVIDENCE: Level III, prognostic study.

Increases in Load Carriage Magnitude and Forced Marching Change Lower-Extremity Coordination in Physically Active, Recruit-Aged Women.

The objective was to examine the interactive effects of load magnitude and locomotion pattern on lower-extremity joint angles and intralimb coordination in recruit-aged women. Twelve women walked, ran, and forced marched at body weight and with loads of +25%, and +45% of body weight on an instrumented treadmill with infrared cameras. Joint angles were assessed in the sagittal plane. Intralimb coordination of the thigh-shank and shank-foot couple was assessed with continuous relative phase. Mean absolute relative phase (entire stride) and deviation phase (stance phase) were calculated from continuous relative phase. At heel strike, forced marching exhibited greater (P < .001) hip flexion, knee extension, and ankle plantar flexion compared with running. At mid-stance, knee flexion (P = .007) and ankle dorsiflexion (P = .04) increased with increased load magnitude for all locomotion patterns. Forced marching (P = .009) demonstrated a "stiff-legged" locomotion pattern compared with running, evidenced by the more in-phase mean absolute relative phase values. Running (P = .03) and walking (P = .003) had greater deviation phase than forced marching. Deviation phase increased for running (P = .03) and walking (P < .001) with increased load magnitude but not for forced marching. With loads of >25% of body weight, forced marching may increase risk of injury due to inhibited energy attenuation up the kinetic chain and lack of variability to disperse force across different supportive structures.

Using Peer Health Educators to Conduct Community Level Surveillance of HPV Vaccination Status: Findings Among Women Who Live in Medically Underserved Areas of Chicago.

Young women are key stakeholders in efforts to increase human papillomavirus (HPV) vaccination uptake. Community health workers who engage with young women can provide valuable information to inform intervention strategies to increase vaccine uptake. We aimed to determine HPV vaccination and sexually transmitted infection (STI) rates among urban women and to identify barriers to vaccination. A trained health educator collaborated with community-based organizations to host health education and STI testing sessions for women in Chicago, Illinois. Forty-nine sessions took place at 15 sites over two years. Each attendee met with the educator about sexual health and HPV vaccination, and completed a health survey. We used contingency tables and logistic regression to determine factors associated with HPV vaccination using the cross-sectional survey data. Of the 292 women who answered questions about history of HPV vaccination, the average age was 17 (SD 2.3) years old, 63% (n = 184) were African American, and 33% (n = 98) Hispanic. Only 13.4% (n = 39) previously received the vaccine, and 6.2% (n = 18) received two to three doses. After adjustment, prior HIV testing was associated with 4.6 times higher odds (95% CI 1.71, 12.53, p = 0.002) of being vaccinated compared to women without prior testing. Our study provides evidence that young African American and Hispanic women living in Chicago may have low HPV vaccination rates. Women who received prior STI testing (i.e., sought healthcare) were more likely to be vaccinated relative to their peers who did not, indicating that racial/ethnic or socioeconomic disparities may inhibit utilization of preventative services.

Comparison of Fontan Surgical Options for Patients with Apicocaval Juxtaposition.

Apicocaval juxtaposition (ACJ) is a rare form of viscerocardiac malpositions in association with single-ventricle congenital heart defects. The Fontan surgery is the common palliation, and possible surgical options include ipsilateral, contralateral, and intra-atrial conduits. Concerns include lower hemodynamic performances or risks of conduit compression by the cardiac mass. This study investigates the hemodynamics and clinical outcomes of ACJ patients and potential surgical improvements. Ten consecutive ACJ patients were included, along with a reference cohort of ten non-ACJ patients. Magnetic resonance images were acquired at 6 ± 0.6 year follow-up for anatomical analysis and hemodynamic assessments using computational fluid dynamics. Metrics of interest are deformation index (DI), indexed power loss (iPL), and hepatic flow distribution (HFDoff). A "virtual" surgery was performed to explore potential hemodynamic improvements using a straightened conduit. DI for ACJ patients fell within the DI range of non-ACJ patients. Contralateral conduits had insignificantly higher iPL (0.070 [0.032,0.137]) than ipsilateral conduits (0.041 [0.013,0.095]) and non-ACJ conduits (0.034 [0.011,0.061]). HFDoff was similar for the ipsilateral (21 [12,35]), contralateral (26 [7,41]), and non-ACJ Fontan conduits (17 [0,48]). Virtual surgery demonstrated that a straightened conduit reduced HFDoff and iPL for the contralateral and ipsilateral conduits, potentially leading to improved clinical outcomes. In this limited sample, the hemodynamic performance of ACJ patients was not significantly different from their non-ACJ counterparts. The use of a straightened conduit option could potentially improve patient outcomes. Additionally, the fear of significant compression of conduits for ACJ patients was unsupported.

The Cervical Dysplasia Worksheet: A Longitudinal Map of Cervical Dysplasia Cytology and Histology Tests and Procedures.

OBJECTIVE: Our objectives were to describe the Cervical Dysplasia Worksheet (CDW), provide evidence of its feasibility to view patient cervical dysplasia results over time, and evaluate patient attitudes toward the tool in the setting of abnormal result follow-up. MATERIALS AND METHODS: The CDW augments the ASCCP guidelines for managing abnormal cervical cancer screenings by visually depicting cervical cytological and histological history along a color gradient showing severity. We evaluated tool feasibility by graphing a retrospectively reviewed convenience sample of patient data. A cross-sectional evaluation of the tool was then performed to assess patient attitudes in the setting of either dysplasia or colposcopy clinic. Patients had their data graphed on the CDW and explained to them before their clinical encounter. They then gave general comments about the tool and filled out a short evaluation survey. RESULTS: The large majority of retrospective patient data (N = 167) fit well within the CDW with roughly 20% requiring space for additional comments. Among the 30 patients who participated in our evaluation, almost all agreed (n = 29, 96.7%) that the tool helped them understand their history and results and that they would use the tool in the future. CONCLUSIONS: The CDW is a novel tool to display a patient's cervical dysplasia history to visualize treatment and future care while enhancing patient-provider communication. Patient evaluation of the tool was largely positive, and suggestions will be taken into consideration for future modification. Further evaluation of the CDW among healthcare providers is needed to analyze its efficacy in the clinical setting.

Accuracy of conventional motion capture in measuring hip joint center location and hip rotations during gait, squat, and step-up activities.

Accurate measurements of hip joint kinematics are essential for improving our understanding of the effects of injury, disease, and surgical intervention on long-term hip joint health. This study assessed the accuracy of conventional motion capture (MoCap) for measuring hip joint center (HJC) location and hip joint angles during gait, squat, and step-up activities while using dynamic biplane radiography (DBR) as the reference standard. Twenty-four young adults performed six trials of treadmill walking, six body-weight squats, and six step-ups within a biplane radiography system. Synchronized biplane radiographs were collected at 50 images per second and MoCap was collected simultaneously at 100 images per second. Bone motion during each activity was determined by matching digitally reconstructed radiographs, created from subject-specific CT-based bone models, to the biplane radiographs using a validated registration process. Errors in estimating HJC location and hip angles using MoCap were quantified by the root mean squared error (RMSE) across all frames of available data. The MoCap error in estimating HJC location was larger during step-up (up to 89.3 mm) than during gait (up to 16.6 mm) or squat (up to 31.4 mm) in all three anatomic directions (all p < 0.001). RMSE in hip joint flexion (7.2°) and abduction (4.3°) during gait was less than during squat (23.8° and 8.9°) and step-up (20.1° and 10.6°) (all p < 0.01). Clinical analysis and computational models that rely on skin-mounted markers to estimate hip kinematics should be interpreted with caution, especially during activities that involve deeper hip flexion.

Improved joint function when reaching behind the back is associated with patient reported outcomes in individuals with rotator cuff tears following exercise therapy.

BACKGROUND: Reaching behind the back is painful for individuals with rotator cuff tears. The objectives of the study were to determine changes in glenohumeral kinematics when reaching behind the back, passive range of motion (RoM), patient reported outcomes and the relationships between kinematics and patient reported outcomes following exercise therapy. METHODS: Eighty-four individuals with symptomatic isolated supraspinatus tears were recruited for this prospective observational study. Glenohumeral kinematics were measured using biplane radiography during a reaching behind the back movement. Passive glenohumeral internal rotation and patient reported outcome measures were collected. Depending on data normality, appropriate tests were utilized to determine changes in variables. Spearman's correlations were utilized for associations, and Stuart-Maxwell tests for changes in distributions. FINDINGS: Maximum active glenohumeral internal rotation increased by 3.2° (P = 0.001), contact path length decreased by 5.5% glenoid size (P = 0.022), passive glenohumeral internal rotation RoM increased by 4.9° (P = 0.001), and Western Ontario Rotator Cuff Index and American Shoulder and Elbow Surgeons scores increased by 29.8 and 21.1 (P = 0.001), respectively. Changes in Western Ontario Rotator Cuff Index scores positively associated with changes in maximum active glenohumeral internal rotation and negatively associated with changes in contact path lengths (P = 0.008 and P = 0.006, respectively). INTERPRETATION: The reaching behind the back movement was useful in elucidating in-vivo mechanistic changes associated with patient reported outcomes. Glenohumeral joint function and patient reported outcomes improved, where changes in Western Ontario Rotator Cuff Index scores were associated with kinematics. These findings inform clinicians of functional changes following exercise therapy and new targetable treatment factors.

Comparing the effects of various ß-blockers on cardiovascular mortality in breast cancer patients.

BACKGROUND: Cardiovascular (CV) disease is a leading cause of death in breast cancer (BC) patients due to the increased age and treatments. While individual ß-blockers have been investigated to manage CV complications, various ß-blockers have not been compared for their effects on CV death in this population. We aimed to compare CV mortality in older BC patients taking one of the commonly used ß-blockers. METHODS: This retrospective cohort study was conducted using the Surveillance, Epidemiology and End Results (SEER) - Medicare data (2010-2015). Patients of age 66 years or older at BC diagnosis receiving metoprolol, atenolol, or carvedilol monotherapy were included. The competing risk regression model was used to determine the risk of CV mortality in the three ß-blocker groups. The multivariable model was adjusted for demographic and clinical covariates. The adjusted hazard ratio (HR) and 95% confidence intervals (CI) were reported for the risk of CV mortality. RESULTS: The study cohort included 6,540 patients of which 55% were metoprolol users, 30% were atenolol users, and 15% were carvedilol users. Metoprolol was associated with a 37% reduced risk of CV mortality (P = 0.03) compared to carvedilol after adjusting for the covariates (HR = 0.63; 95% CI 0.41-0.96). No significant difference in the risk of CV mortality between atenolol and carvedilol users was observed (HR = 0.74; 95% CI 0.44-1.22). CONCLUSIONS: Our findings suggest that metoprolol is associated with a reduced risk of CV mortality in BC patients. Future studies are needed to confirm these findings and understand the mechanism of action.

Load carriage changes tibiofemoral arthrokinematics during ambulatory tasks in recruit-aged women.

The introduction of women into U.S. military ground close combat roles requires research into sex-specific effects of military training and operational activities. Knee osteoarthritis is prevalent among military service members; its progression has been linked to occupational tasks such as load carriage. Analyzing tibiofemoral arthrokinematics during load carriage is important to understand potentially injurious motion and osteoarthritis progression. The study purpose was to identify effects of load carriage on knee arthrokinematics during walking and running in recruit-aged women. Twelve healthy recruit-aged women walked and ran while unloaded (bodyweight [BW]) and carrying additional + 25%BW and + 45%BW. Using dynamic biplane radiography and subject-specific bone models, tibiofemoral arthrokinematics, subchondral joint space and center of closest contact location between subchondral bone surfaces were analyzed over 0-30% stance (separate one-way repeated measures analysis of variance, load by locomotion). While walking, medial compartment contact location was 5% (~ 1.6 mm) more medial for BW than + 45%BW at foot strike (p = 0.03). While running, medial compartment contact location was 4% (~ 1.3 mm) more lateral during BW than + 25%BW at 30% stance (p = 0.04). Internal rotation was greater at + 45%BW compared to + 25%BW (p < 0.01) at 30% stance. Carried load affects tibiofemoral arthrokinematics in recruit-aged women. Prolonged load carriage could increase the risk of degenerative joint injury in physically active women.

Duration of Induction of Labor for Second-Trimester Medication Abortion and Adverse Outcomes.

OBJECTIVE: To evaluate the relationship between duration of labor during second-trimester medication abortion and adverse outcomes. METHODS: We conducted a retrospective cohort study including all individuals with a singleton gestation undergoing second-trimester medication abortion without evidence of advanced cervical dilation, rupture of membranes, or preterm labor at four centers. The primary exposure was duration of labor (ie, hours spent from receiving misoprostol to fetal expulsion). The primary outcome was composite morbidity , defined as uterine rupture, need for blood transfusion, clinical chorioamnionitis, intensive care unit admission, or need for readmission. We performed bivariate and multivariate negative binomial analyses. A post hoc subgroup analysis was performed to assess for the risk of the primary outcome by gestational age. We performed tests of homogeneity based on history of uterine scarring and parity. RESULTS: Six hundred eighty-one individuals were included. The median duration of labor was 11 hours (interquartile range 8-17 hours). One hundred thirty-one (19.2%) experienced the primary outcome. When duration of labor was evaluated continuously, a longer duration of labor was associated with an increased frequency of morbidity (adjusted ß=0.68, 95% CI, 0.32-1.04). When duration of labor was evaluated categorically, those experiencing the highest quartile of duration (ie, 17 hours or more) had a statistically higher risk for experiencing morbidity compared with individuals in all other quartiles (adjusted relative risk 1.99, 95% CI, 1.34-2.96). When we focused on components of the composite outcome, clinical chorioamnionitis was significantly different between those experiencing a longer duration and those experiencing a shorter duration of labor (26.2% vs 10.6%, P <.001). On subgroup analysis, gestational age was not associated with the risk of composite morbidity. Tests of homogeneity demonstrated no significant difference in the risk for morbidity among individuals with a history of uterine scarring or based on parity. CONCLUSION: Duration of labor was independently associated with risks for adverse maternal outcomes during second-trimester medication abortion, specifically clinical chorioamnionitis.

Auditory Outcomes Following Cochlear Implantation in Children with Unilateral Hearing Loss.

OBJECTIVE: Unilateral hearing loss (UHL) in children is associated with speech and language delays. Cochlear implantation (CI) is currently the only rehabilitative option that restores binaural hearing. This study aims to describe auditory outcomes in children who underwent CI for UHL and to determine the association between duration of hearing loss and auditory outcomes. STUDY DESIGN: Retrospective case series. SETTING: Three tertiary-level, academic institutions. PATIENTS: Children <18 years with UHL who underwent CI between 2018 and 2021. INTERVENTION: Cochlear implantation. MAIN OUTCOME MEASURES: Speech perception and Speech, Spatial and Qualities of Hearing Scale (SSQ) were assessed postimplantation. Scores >50% on speech perception and SSQ scores >8 points were considered satisfactory. Associations between duration of UHL and implantation age and outcomes were assessed using Spearman's rank correlation. RESULTS: Of the 38 children included, mean age at CI was 7.9 ± 3.2 years and mean UHL duration was 5.0 ± 2.8 years. Mean datalogging was 8.1 ± 3.1 hours/day. Mean auditory testing scores were SSQ, 7.9 ± 1.2; BABY BIO, 68.1 ± 30.2%; CNC, 38.4 ± 28.4%; WIPI, 52.5 ± 23.1%. Scores >50% on CNC testing were achieved by 40% of patients. SSQ scores >8 points were reported by 78% (7/9) of patients. There were no significant correlations between UHL duration and auditory outcomes. CONCLUSION: Overall, children with UHL who undergo CI can achieve satisfactory speech perception scores and SSQ scores. There were no associations between duration of hearing loss and age at implantation with auditory outcomes. Multiple variables may impact auditory outcomes, including motivation, family support, access to technology, and consistent isolated auditory training postactivation and should be taken into consideration in addition to age at implantation and duration of UHL in determination of CI candidacy.

Performance After Cochlear Reimplantation Using a Different Manufacturer.

OBJECTIVE: To better understand cochlear implant (CI) performance after reimplantation with a different device manufacturer. STUDY DESIGN: Multisite retrospective review. SETTING: Tertiary referral centers. PATIENTS: Patients older than 4 years who received a CI and subsequently underwent CI reimplantation with a different manufacturer over a 20-year period. INTERVENTION: Reimplantation. MAIN OUTCOME MEASURE: The primary outcome was difference in the best CNC score obtained with the primary CI, compared with the most recent CNC score obtained after reimplantation. RESULTS: Twenty-nine patients met the criteria at three centers. The best average CNC score achieved by adult patients after primary cochlear implantation was 46.2% (n = 16), measured an average of 14 months (range: 3-36 mo) postoperatively. When looking at the most recent CNC score of adult patients before undergoing reimplantation, the average CNC score dropped to 19.2% (n = 17). After reimplantation, the average 3- to 6-month CNC score was 48.3% (n = 12), with most recent average CNC score being 44.4% (n = 17) measured an average of 19 months (range: 3-46 mo) postoperatively. There was no statistically significant difference (p = 0.321; t11 = 0.48) identified in performance between the best CNC score achieved by adult patients after primary cochlear implantation, and the most recent score achieved after reimplantation (n = 12). Analysis of prerevision and postrevision speech performance was not possible in pediatric patients (<18 yr old) because of differences in tests administered. CONCLUSION: Patients undergoing reimplantation with a different manufacturer achieved CNC score performance comparable to their best performance with their original device.

Recruit-aged adults may preferentially weight task goals over deleterious cost functions during short duration loaded and imposed gait tasks.

Optimal motor control that is stable and adaptable to perturbation is reflected in the temporal arrangement and regulation of gait variability. Load carriage and forced-marching are common military relevant perturbations to gait that have been implicated in the high incidence of musculoskeletal injuries in military populations. We investigated the interactive effects of load magnitude and locomotion pattern on motor variability, stride regulation and spatiotemporal complexity during gait in recruit-aged adults. We further investigated the influences of sex and task duration. Healthy adults executed trials of running and forced-marching with and without loads at 10% above their gait transition velocity. Spatiotemporal parameters were analyzed using a goal equivalent manifold approach. With load and forced-marching, individuals used a greater array of motor solutions to execute the task goal (maintain velocity). Stride-to-stride regulation became stricter as the task progressed. Participants exhibited optimal spatiotemporal complexity with significant but not meaningful differences between sexes. With the introduction of load carriage and forced-marching, individuals relied on a strategy that maximizes and regulates motor solutions that achieve the task goal of velocity specifically but compete with other task functions. The appended cost penalties may have deleterious effects during prolonged execution, potentially increasing the risk of musculoskeletal injuries.

Improving access to pre-exposure prophylaxis for HIV prescribing in a primary care setting.

Although emtricitabine-tenofovir was approved for HIV pre-exposure prophylaxis (PrEP) in 2012, use by persons at risk of acquiring HIV has been limited. Because many primary care providers lacked familiarity and comfort prescribing PrEP, at our institution PrEP prescribing was concentrated among the infectious disease specialists, effectively limiting access. This project sought to increase the number of patients receiving new prescriptions for PrEP. The interventions targeted primary care providers (including internal medicine and family medicine), and were designed to increase the number of unique providers offering PrEP to their patients. The overall strategy was to expand the clinical scope of practice for primary care providers through education and provision of detailed care templates in the electronic health record. These initiatives were implemented through a series of informal Plan-Do-Study-Act cycles, then generalised throughout the medical system. To evaluate the success of the project, we queried the electronic medical record for all new prescriptions for PrEP, with provider name and specialty, for all outpatients 18 years of age and older from 2012 through 2020. In 2015, prior to the intervention, only 78 patients received new prescriptions for PrEP at our institution, and only 38% (30 of 78) of these were from primary care clinicians. After the intervention, the number of patients receiving PrEP increased to 190 in 2019, with 85% (162 of 190) prescribed by primary care providers. In addition, the number of primary care providers making a new prescription for PrEP increased from 20 in 2015 to 73 in 2019. We conclude that targeted clinical education, combined with electronic health record templates, was associated with a significant increase in PrEP prescribing.

Hip kinematics in healthy adults during gait and squatting: Sex differences and asymmetry revealed through dynamic biplane radiography.

There is a lack of data unaffected by soft tissue artifact describing bilateral symmetry and sex differences in hip kinematics in asymptomatic individuals during activities of daily living. This study aimed to identify sex-based differences and to quantify bilateral symmetry in continuous hip kinematics during walking and bodyweight squatting using biplane radiography. Twenty-four asymptomatic young adults (13 women, 11 men; age: 21.9 ± 2.2 years) performed treadmill walking and squatting while synchronized biplane radiographs of the hip were collected at 50 frames/s. Pelvis and proximal femur bone tissue were segmented from CT images and reconstructed into subject-specific 3D bone models. Femoroacetabular kinematics were determined using a validated volumetric model-based tracking technique that matched digitally reconstructed radiographs generated from the CT-based bone models to the biplane radiographs. Symmetry was calculated as the average absolute side-to-side difference (SSD) in kinematic waveforms for each participant. Sex-based and phase-based (eccentric vs. concentric squatting) kinematic variations were assessed using linear mixed model analysis. Women were 0.2 mm more anteriorly translated and 0.1 mm more inferiorly translated than men across the gait cycle (both p < 0.04), but no sex-based or phase-based kinematic differences during squatting were identified. The maximum SSD across all movements was up to 18.6° (internal-external rotation) and 1.0 mm (superior-inferior translation), respectively. Asymmetry in internal rotation, superior translation, and medial translation was greater during squatting than during walking (all p < 0.002). This study provides a reference dataset of healthy young adults for evaluating hip kinematics and symmetry in symptomatic cohorts or in individuals undergoing surgery or rehabilitation.

Screening of GPCR drugs for repurposing in breast cancer.

Drug repurposing can overcome both substantial costs and the lengthy process of new drug discovery and development in cancer treatment. Some Food and Drug Administration (FDA)-approved drugs have been found to have the potential to be repurposed as anti-cancer drugs. However, the progress is slow due to only a handful of strategies employed to identify drugs with repurposing potential. In this study, we evaluated GPCR-targeting drugs by high throughput screening (HTS) for their repurposing potential in triple-negative breast cancer (TNBC) and drug-resistant human epidermal growth factor receptor-2-positive (HER2+) breast cancer (BC), due to the dire need to discover novel targets and drugs in these subtypes. We assessed the efficacy and potency of drugs/compounds targeting different GPCRs for the growth rate inhibition in the following models: two TNBC cell lines (MDA-MB-231 and MDA-MB-468) and two HER2+ BC cell lines (BT474 and SKBR3), sensitive or resistant to lapatinib + trastuzumab, an effective combination of HER2-targeting therapies. We identified six drugs/compounds as potential hits, of which 4 were FDA-approved drugs. We focused on ß-adrenergic receptor-targeting nebivolol as a candidate, primarily because of the potential role of these receptors in BC and its excellent long-term safety profile. The effects of nebivolol were validated in an independent assay in all the cell line models. The effects of nebivolol were independent of its activation of ß3 receptors and nitric oxide production. Nebivolol reduced invasion and migration potentials which also suggests its inhibitory role in metastasis. Analysis of the Surveillance, Epidemiology and End Results (SEER)-Medicare dataset found numerically but not statistically significant reduced risk of all-cause mortality in the nebivolol group. In-depth future analyses, including detailed in vivo studies and real-world data analysis with more patients, are needed to further investigate the potential of nebivolol as a repurposed therapy for BC.

Cognitive correlates of autism spectrum disorder symptoms.

Due to the diverse behavioral presentation of autism spectrum disorder (ASD), identifying ASD subtypes using patterns of cognitive abilities has become an important point of research. Some previous studies on cognitive profiles in ASD suggest that the discrepancy between verbal intelligence quotient (VIQ) and performance IQ (PIQ) is associated with ASD symptoms, while others have pointed to VIQ as the critical predictor. Given that VIQ is a component of the VIQ-PIQ discrepancy, it was unclear which was most driving these associations. This study tested whether VIQ, PIQ, or the VIQ-PIQ discrepancy was most associated with ASD symptoms in children and adults with ASD (N = 527). Using data from the Autism Brain Imaging Data Exchange (ABIDE), we tested the independent contribution of each IQ index and their discrepancy to ASD symptom severity using multiple linear regressions predicting ASD symptoms. VIQ was most associated with lower symptom severity as measured by the Autism Diagnostic Observation Schedule (ADOS) total score, and when VIQ was included in models predicting ASD symptoms, associations with PIQ and IQ discrepancy were not significant. An association between VIQ and ASD communication symptoms drove the association with ASD symptom severity. These results suggest that associations between ASD communication symptoms and IQ discrepancy or PIQ reported in prior studies likely resulted from variance shared with VIQ. Subtyping ASD on the basis of VIQ should be a point of future research, as it may allow for the development of more personalized approaches to intervention. LAY SUMMARY: Previous research on links between autism severity and verbal and nonverbal intelligence has produced mixed results. Our study examined whether verbal intelligence, nonverbal intelligence, or the discrepancy between the two was most related to autism symptoms. We found that higher verbal intelligence was most associated with less severe autism communication symptoms. Given the relevance of verbal intelligence in predicting autism symptom severity, subtyping autism on the basis of verbal intelligence could lead to more personalized treatments.