Modelling the impact of JNJ-1802, a first-in-class dengue inhibitor blocking the NS3-NS4B interaction, on in-vitro DENV-2 dynamics.

Dengue virus (DENV) is a public health challenge across the tropics and subtropics. Currently, there is no licensed prophylactic or antiviral treatment for dengue. The novel DENV inhibitor JNJ-1802 can significantly reduce viral load in mice and non-human primates. Here, using a mechanistic viral kinetic model calibrated against viral RNA data from experimental in-vitro infection studies, we assess the in-vitro inhibitory effect of JNJ-1802 by characterising infection dynamics of two DENV-2 strains in the absence and presence of different JNJ-1802 concentrations. Viral RNA suppression to below the limit of detection was achieved at concentrations of >1.6 nM, with a median concentration exhibiting 50% of maximal inhibitory effect (IC50) of 1.23x10-02 nM and 1.28x10-02 nM for the DENV-2/RL and DENV-2/16681 strains, respectively. This work provides important insight into the in-vitro inhibitory effect of JNJ-1802 and presents a first step towards a modelling framework to support characterization of viral kinetics and drug effect across different host systems.

Combined strategy of upfront CTCA and optimal treatment for stable chest pain: rationale and design of the CLEAR-CAD trial.

BACKGROUND: Patients with stable chest pain suspected of coronary artery disease (CAD) usually undergo multiple diagnostic tests to confirm or rule out obstructive CAD. Some tests may not effectively assess the presence of CAD, precluding optimal treatment. A diagnostic strategy of upfront computed tomography coronary angiography (CTCA) combined with optimal medical therapy (OMT) tailored to the extent of CAD may be superior to standard care in preventing major adverse cardiac events. STUDY DESIGN: The CLEAR-CAD trial is a prospective, open-label, multicentre, randomised, superiority trial of an upfront CTCA-guided strategy in 6444 patients presenting in an outpatient setting with suspected CAD compared with standard care, in approximately 30 participating centres in the Netherlands. The upfront CTCA-guided strategy consists of an initial CTCA which is assessed using the Coronary Artery Disease-Reporting and Data System (CAD-RADS 2.0). In patients without CAD (CAD-RADS 0) no specific cardiac medication is mandated. Patients with non-obstructive CAD (CAD-RADS 1-2) are treated with preventive OMT. Patients with obstructive CAD (CAD-RADS ≥ 3) are treated with preventive and anti-anginal OMT; in the presence of pharmacologically refractory symptoms patients undergo selective revascularisation after non-invasive functional imaging for myocardial ischaemia (≥ 10%). Patients with significant left main or proximal left anterior descending coronary artery stenosis on CTCA undergo direct invasive coronary angiography and subsequent revascularisation. The primary endpoint is the composite of all-cause death and myocardial infarction. CONCLUSION: The CLEAR-CAD trial is the first randomised study to investigate the efficacy of a combined upfront CTCA-guided medical and selective revascularisation strategy in an outpatient setting with suspected CAD compared with standard care.

Vitamin D supplementation and adverse skeletal and non-skeletal outcomes in individuals at increased cardiovascular risk: Results from the International Polycap Study (TIPS)-3 randomized controlled trial.

BACKGROUND AND AIMS: Vitamin D has mostly been tested in Western populations. We examined the effect of high dose vitamin D in a population drawn predominantly from outside of Western countries. METHODS AND RESULTS: This randomized trial tested vitamin D 60,000 IU monthly in 5670 participants without vascular disease but at increased CV risk. The primary outcome was fracture. The secondary outcome was the composite of CV death, myocardial infarction stroke, cancer, fracture or fall. Death was a pre-specified outcome. Mean age was 63.9 years, and 3005 (53.0%) were female. 3034 (53.5%) participants resided in South Asia, 1904 (33.6%) in South East Asia, 480 (8.5%) in South America, and 252 (4.4%) in other regions. Mean follow-up was 4.6 years. A fracture occurred in 20 participants (0.2 per 100 person years) assigned to vitamin D, and 19 (0.1 per 100 person years) assigned to placebo (HR 1.06, 95% CI 0.57-1.99, p-value = 0.86). The secondary outcome occurred in 222 participants (1.8 per 100 person years) assigned to vitamin D, and 198 (1.6 per 100 person years) assigned to placebo (HR 1.13, 95% CI 0.93-1.37, p = 0.22). 172 (1.3 per 100 person years) participants assigned to vitamin D died, compared with 135 (1.0 per 100 person years) assigned to placebo (HR 1.29, 95% CI 1.03-1.61, p = 0.03). CONCLUSION: In a population predominantly from South Asia, South East Asia and South America, high-dose vitamin D did not reduce adverse skeletal or non-skeletal outcomes. Higher mortality was observed in the vitamin D group. REGISTRATION NUMBER: NCT01646437.

Comparative Study of Molecular Descriptors of Pent-Heptagonal Nanostructures Using Neighborhood M-Polynomial Approach.

In this article, a novel technique to evaluate and compare the neighborhood degree molecular descriptors of two variations of the carbon nanosheet C5C7(a,b) is presented. The conjugated molecules follow the graph spectral theory, in terms of bonding, non-bonding and antibonding Ruckel molecular orbitals. They are demonstrated to be immediately determinable from their topological characteristics. The effort of chemical and pharmaceutical researchers is significantly increased by the need to conduct numerous chemical experiments to ascertain the chemical characteristics of such a wide variety of novel chemicals. In order to generate novel cellular imaging techniques and to accomplish the regulation of certain cellular mechanisms, scientists have utilized the attributes of nanosheets such as their flexibility and simplicity of modification, out of which carbon nanosheets stand out for their remarkable strength, chemical stability, and electrical conductivity. With efficient tools like polynomials and functions that can forecast compound features, mathematical chemistry has a lot to offer. One such approach is the M-polynomial, a fundamental polynomial that can generate a significant number of degree-based topological indices. Among them, the neighborhood M-polynomial is useful in retrieving neighborhood degree sum-based topological indices that can help in carrying out physical, chemical, and biological experiments. This paper formulates the unique M-polynomial approach which is used to derive and compare a variety of neighborhood degree-based molecular descriptors and the corresponding entropy measures of two variations of pent-heptagonal carbon nanosheets. Furthermore, a regression analysis on these descriptors has also been carried out which can further help in the prediction of various properties of the molecule.

Kinesiophobia Is Related to Acute Musculoskeletal Injury Incidence Following Concussion.

CONTEXT: Athletes with a history of sport concussion (SC) have an increased risk of musculoskeletal injury (MSK); however, the underlying mechanisms have yet to be determined. The purpose of our study was to evaluate kinesiophobia in college athletes with or without a time-loss MSK within 180 days of unrestricted return to play following a SC. DESIGN: This was a retrospective cohort study within a sports medicine facility. METHODS: Participants were eligible if they were diagnosed with a SC, completed the Tampa Scale of Kinesiophobia (TSK), and completed an unrestricted return to play. Fifty-six college athletes (40 men and 16 women) with an average age of 19.5 (1.25) years, height of 183.5 (10.45) cm, and mass of 94.72 (24.65) kg, were included in the study. MSK participants were matched to non-MSK participants 1:1. Demographic and TSK outcome scores were compared using independent t tests. The proportion of participants in each group who scored above the clinical threshold (TSK ≥ 37) was compared using a chi-square analysis. Alpha was set at α = .05. RESULTS: The MSK group (31.2 [6.30]) reported similar TSK scores to the matched group (28.9 [3.34]; t54 = 1.70, P = .10, d = 0.45 [-0.08 to 0.97]). A greater proportion of athletes who were diagnosed with an MSK-reported scores above the cutoff (χ2[1] = 6.49, P = .01). CONCLUSIONS: Athletes diagnosed with SC had similar kinesiophobia values regardless of MSK status. However, a higher proportion of athletes with a time-loss MSK injury reported a TSK score greater than the clinical cutoff. Our results suggest that factors such as kinesiophobia should be considered following a SC.

Reevaluating clinical assessment outcomes after unrestricted return to play following sport-related concussion.

PRIMARY OBJECTIVE: The objective of this study was to examine neurocognition, postural control, and symptomology at multiple timepoints following concussion. We hypothesized that collegiate athletes would perform similar to or better than their baseline in terms of each outcome at both timepoints. RESEARCH DESIGN: This was a retrospective study of 71 collegiate athletes (18.3 ± 0.89 years old; 182.2 ± 10.05 cm; 84.2 ± 20.07 kg) to observe changes in outcomes from a previously established clinical protocol. METHODS AND PROCEDURES: Participants were administered ImPACT™, the Sensory Organization Test (SOT), and the revised head injury scale (HIS-r) prior to their seasons (baseline); upon reporting symptom-free following concussion (post-injury); and approximately 8-months after return-to-play to establish a new baseline. MAIN OUTCOMES AND RESULTS: There were no changes in ImPACT scores or HIS-r reporting over time. ImPACT total symptom score (TSS) decreased over time (p = .002, ηp2 = 0.08). Significant main effects occurred for the SOT equilibrium score (p < .01, ηp2 = 0.34) and Vestibular sensory ratio (p < .001, ηp2 = 0.22). CONCLUSIONS: Our data suggest no decline in neurocognition, balance, or symptom burden approximately eight months post-injury. As clinicians continue to explore "best practices" for concussion management and potential long-term implications of these injuries it is important to monitor outcome measures longitudinally.

Increasing impact of COVID-19 on young adults: evidence from hospitalisations in Brazil.

OBJECTIVES: Concerns about the increasing impact of severe COVID-19 in younger individuals in Brazil came after a recent synchronised country-wide wave of cases in Brazil. This communication analyses how hospitalisations due to COVID-19 changed in the age groups 18-49 years and ≥70 years. STUDY DESIGN: Longitudinal study based on secondary data. METHODS: Data from SIVEP-Gripe, a public and open-access database of Severe Acute Respiratory Illness records (including COVID-19 notifications), were used in this study. Statistical control charts examined changes in the magnitude and variation of younger (18-49 years) and older (≥70 years) adults who were hospitalised between 15th March 2020 and 19th June 2021. RESULTS: During the few first weeks of the pandemic in Brazil, the number of COVID-19 hospitalisations increased in older adults but decreased in younger adults. Subsequently, hospitalisations reached statistical control zones in epidemiological weeks (EW) 19-48 of 2020 (EW 19-48/2020) and EW 03-05/2021 (18-49 y, mean = 26.1%; ≥70 y, mean = 32.8%). Between EW 49/2020 and EW 02/2021, the number of hospitalisations of younger adults dropped to levels below the lower control limit. In contrast, the number of hospitalisations of older adults surpassed the upper limit of the corresponding statistical control zones. However, from EW 06/2021, numbers of hospitalisations changed from statistical control zones, with hospitalisations of younger adults increasing and reaching 44.9% in EW 24/2021 and hospitalisations of older adults decreasing until EW 19/2021 (14.1%) and reaching 17.3% in EW 24/2021. CONCLUSIONS: An increasing number of COVID-19 hospitalisations were observed in younger adults from EW 06/2021. This could be a result of the successful vaccination programme in older adults, who were initially prioritised, and possibly an increased exposure to highly transmissible variants of COVID-19 in younger adults who had to go to work in the absence of social protection (i.e. government financial support). Potential consequences of COVID-19 hospitalisations in younger adults could include a reduced life expectancy of the population and an increased number of people unable to perform daily activities due to post-COVID-19 conditions.

Contribution of Complex I NADH Dehydrogenase to Respiratory Energy Coupling in Glucose-Grown Cultures of Ogataea parapolymorpha.

The thermotolerant yeast Ogataea parapolymorpha (formerly Hansenula polymorpha) is an industrially relevant production host that exhibits a fully respiratory sugar metabolism in aerobic batch cultures. NADH-derived electrons can enter its mitochondrial respiratory chain either via a proton-translocating complex I NADH-dehydrogenase or via three putative alternative NADH dehydrogenases. This respiratory entry point affects the amount of ATP produced per NADH/O2 consumed and therefore impacts the maximum yield of biomass and/or cellular products from a given amount of substrate. To investigate the physiological importance of complex I, a wild-type O. parapolymorpha strain and a congenic complex I-deficient mutant were grown on glucose in aerobic batch, chemostat, and retentostat cultures in bioreactors. In batch cultures, the two strains exhibited a fully respiratory metabolism and showed the same growth rates and biomass yields, indicating that, under these conditions, the contribution of NADH oxidation via complex I was negligible. Both strains also exhibited a respiratory metabolism in glucose-limited chemostat cultures, but the complex I-deficient mutant showed considerably reduced biomass yields on substrate and oxygen, consistent with a lower efficiency of respiratory energy coupling. In glucose-limited retentostat cultures at specific growth rates down to ∼0.001 h-1, both O. parapolymorpha strains showed high viability. Maintenance energy requirements at these extremely low growth rates were approximately 3-fold lower than estimated from faster-growing chemostat cultures, indicating a stringent-response-like behavior. Quantitative transcriptome and proteome analyses indicated condition-dependent expression patterns of complex I subunits and of alternative NADH dehydrogenases that were consistent with physiological observations.IMPORTANCE Since popular microbial cell factories have typically not been selected for efficient respiratory energy coupling, their ATP yields from sugar catabolism are often suboptimal. In aerobic industrial processes, suboptimal energy coupling results in reduced product yields on sugar, increased process costs for oxygen transfer, and volumetric productivity limitations due to limitations in gas transfer and cooling. This study provides insights into the contribution of mechanisms of respiratory energy coupling in the yeast cell factory Ogataea parapolymorpha under different growth conditions and provides a basis for rational improvement of energy coupling in yeast cell factories. Analysis of energy metabolism of O. parapolymorpha at extremely low specific growth rates indicated that this yeast reduces its energy requirements for cellular maintenance under extreme energy limitation. Exploration of the mechanisms for this increased energetic efficiency may contribute to an optimization of the performance of industrial processes with slow-growing eukaryotic cell factories.

Healing Effect of Controlled Anti-Electromigration on Conventional and High-Tc Superconducting Nanowires.

The electromigration process has the potential capability to move atoms one by one when properly controlled. It is therefore an appealing tool to tune the cross section of monoatomic compounds with ultimate resolution or, in the case of polyatomic compounds, to change the stoichiometry with the same atomic precision. As demonstrated here, a combination of electromigration and anti-electromigration can be used to reversibly displace atoms with a high degree of control. This enables a fine adjustment of the superconducting properties of Al weak links, whereas in Nb the diffusion of atoms leads to a more irreversible process. In a superconductor with a complex unit cell (La2-x Cex CuO4 ), the electromigration process acts selectively on the oxygen atoms with no apparent modification of the structure. This allows to adjust the doping of this compound and switch from a superconducting to an insulating state in a nearly reversible fashion. In addition, the conditions needed to replace feedback controlled electromigration by a simpler technique of electropulsing are discussed. These findings have a direct practical application as a method to explore the dependence of the characteristic parameters on the exact oxygen content and pave the way for a reversible control of local properties of nanowires.

Novel patient-derived xenograft and cell line models for therapeutic testing of pediatric liver cancer.

BACKGROUND & AIMS: Pediatric liver cancer is a rare but serious disease whose incidence is rising, and for which the therapeutic options are limited. Development of more targeted, less toxic therapies is hindered by the lack of an experimental animal model that captures the heterogeneity and metastatic capability of these tumors. METHODS: Here we established an orthotopic engraftment technique to model a series of patient-derived tumor xenograft (PDTX) from pediatric liver cancers of all major histologic subtypes: hepatoblastoma, hepatocellular cancer and hepatocellular malignant neoplasm. We utilized standard (immuno) staining methods for histological characterization, RNA sequencing for gene expression profiling and genome sequencing for identification of druggable targets. We also adapted stem cell culturing techniques to derive two new pediatric cancer cell lines from the xenografted mice. RESULTS: The patient-derived tumor xenografts recapitulated the histologic, genetic, and biological characteristics-including the metastatic behavior-of the corresponding primary tumors. Furthermore, the gene expression profiles of the two new liver cancer cell lines closely resemble those of the primary tumors. Targeted therapy of PDTX from an aggressive hepatocellular malignant neoplasm with the MEK1 inhibitor trametinib and pan-class I PI3 kinase inhibitor NVP-BKM120 resulted in significant growth inhibition, thus confirming this PDTX model as a valuable tool to study tumor biology and patient-specific therapeutic responses. CONCLUSIONS: The novel metastatic xenograft model and the isogenic xenograft-derived cell lines described in this study provide reliable tools for developing mutation- and patient-specific therapies for pediatric liver cancer. LAY SUMMARY: Pediatric liver cancer is a rare but serious disease and no experimental animal model currently captures the complexity and metastatic capability of these tumors. We have established a novel animal model using human tumor tissue that recapitulates the genetic and biological characteristics of this cancer. We demonstrate that our patient-derived animal model, as well as two new cell lines, are useful tools for experimental therapies.

Maintenance-energy requirements and robustness of Saccharomyces cerevisiae at aerobic near-zero specific growth rates.

BACKGROUND: Saccharomyces cerevisiae is an established microbial platform for production of native and non-native compounds. When product pathways compete with growth for precursors and energy, uncoupling of growth and product formation could increase product yields and decrease formation of biomass as a by-product. Studying non-growing, metabolically active yeast cultures is a first step towards developing S. cerevisiae as a robust, non-growing cell factory. Microbial physiology at near-zero growth rates can be studied in retentostats, which are continuous-cultivation systems with full biomass retention. Hitherto, retentostat studies on S. cerevisiae have focused on anaerobic conditions, which bear limited relevance for aerobic industrial processes. The present study uses aerobic, glucose-limited retentostats to explore the physiology of non-dividing, respiring S. cerevisiae cultures, with a focus on industrially relevant features. RESULTS: Retentostat feeding regimes for smooth transition from exponential growth in glucose-limited chemostat cultures to near-zero growth rates were obtained by model-aided experimental design. During 20 days of retentostats cultivation, the specific growth rate gradually decreased from 0.025 h(-1) to below 0.001 h(-1), while culture viability remained above 80 %. The maintenance requirement for ATP (mATP) was estimated at 0.63 ± 0.04 mmol ATP (g biomass)(-1) h(-1), which is ca. 35 % lower than previously estimated for anaerobic retentostats. Concomitant with decreasing growth rate in aerobic retentostats, transcriptional down-regulation of genes involved in biosynthesis and up-regulation of stress-responsive genes resembled transcriptional regulation patterns observed for anaerobic retentostats. The heat-shock tolerance in aerobic retentostats far exceeded previously reported levels in stationary-phase batch cultures. While in situ metabolic fluxes in retentostats were intentionally low due to extreme caloric restriction, off-line measurements revealed that cultures retained a high metabolic capacity. CONCLUSIONS: This study provides the most accurate estimation yet of the maintenance-energy coefficient in aerobic cultures of S. cerevisiae, which is a key parameter for modelling of industrial aerobic, glucose-limited fed-batch processes. The observed extreme heat-shock tolerance and high metabolic capacity at near-zero growth rates demonstrate the intrinsic potential of S. cerevisiae as a robust, non-dividing microbial cell factory for energy-intensive products.

Environmental filtering determines metacommunity structure in wetland microcrustaceans.

Metacommunity approaches are becoming popular when analyzing factors driving species distribution at the regional scale. However, until the popularization of the variation partitioning technique it was difficult to assess the main drivers of the observed patterns (spatial or environmental). Here we propose a new framework linking the emergence of different metacommunity structures (e.g., nested, Gleasonian, Clementsian) to spatial and environmental filters. This is a novel approach that provides a more profound analysis of how both drivers could lead to similar metacommunity structures. We tested this framework on 110 sites covering a strong environmental gradient (i.e., microcrustacean assemblages organized along a salinity gradient, from freshwater to brackish water wetlands). First we identified the metacommunity structure that better fitted these microcrustacean assemblages. Then, we used hierarchical variation partitioning to quantify the relative influences of environmental filters and the distance among wetlands on the identified structure. Our results showed that under strong environmental filtering metacommunity structures were non-random. We also noted that even passive dispersers, that are supposed to be poorly spatially filtered, showed spatial signals at a large geographical scale. However, some difficulties arose when inferring biotic interactions at finer-scale spatial signals. Overall, our study shows the potential of elements of metacommunity structure combined with variation partition techniques to detect environmental drivers and broadscale patterns of metacommunity structure, and that some caution is needed when interpreting finer-scale spatial signals.

Frequencies of allele groups HLA-A, HLA-B and HLA-DRB1 in a population from the northwestern region of São Paulo State, Brazil.

The aim of this study was to estimate the HLA-A, HLA-B and HLA-DRB1 allele groups frequencies in a population of 1559 volunteer bone marrow donors from the northwestern region of São Paulo State grouped according to ethnicity. An additional objective was to compare the allele frequencies of the current study with data published for other Brazilian populations. The allele groups were characterized by the PCR-rSSO method using Luminex(®) technology. Twenty HLA-A, 32 HLA-B and 13 HLA-DRB1 allele groups were identified. The most common allele groups in European descent and mixed African and European descent samples were HLA-A*02, HLA-B*35 and HLA-DRB1*13, while HLA-A*02, HLA-B*35 and HLA-DRB1*11 were more common in African descent samples. The HLA-A*23, HLA-A*36, HLA-B*58 and HLA-B*81 allele groups were more common in sample from African descent than European descent, and the HLA-DRB1*08 was more common in mixed African and European descent than in European descent. Allele group frequencies were compared with samples from other Brazilian regions. The HLA-A*30 and HLA-A*23 were more common in this study than in the populations of Rio Grande do Sul and Paraná; and the HLA-A*01, HLA-B*18, HLA-B*57 and HLA-DRB1*11 were more common in this study than in the population of Piauí. The least frequent allele groups were HLA-A*31, HLA-B*15, HLA-B*40 and HLA-DRB1*08 for the population of Piauí, HLA-A*01 and HLA-A*11 for Parana, HLA-A*02 and -A*03 for Rio Grande do Sul and HLA-DRB1*04 for Paraná, Rio Grande do Sul and Piauí. These data provide an overview on the knowledge on HLA diversity in the population of the northwestern region of São Paulo State and show that the genes of this system are useful to distinguish different ethnic groups.

Prediction of properties of boron [Formula: see text]-icosahedral nanosheet by bond-addictive [Formula: see text]-polynomial.

Nanosheets with boron elements have excellent characteristics which makes the boron polymorphs unique and super hard. A boron [Formula: see text]-icosahedral nanosheet in crystalline form has superconductivity and thermal electronic properties. In theoretical chemistry and QSPR/QSAR study, a topological descriptor is an important analytical tool. It helps to analyse the structure and its properties and also correlates the with numerical expressions. The valence-based M-polynomial provides quantitative measures of molecular properties based on their geometric, electrostatic, and quantum chemical characteristics. In this article, the QSPR/QSAR analysis is performed for this nanosheet and the analytical expressions are validated with original synthesized data, and received excellent correlation values of 0.9835 and 0.9932. The mathematical expression of the structure is analysed and the indices are compared graphically and numerically.

Associations Between Race & Socioeconomic Status, Lower Extremity Strength, and Patient Reported Outcomes Following Anterior Cruciate Ligament Reconstruction.

CONTEXT: There are significant disparities in access to health care, but there are limited data about the impact of race and socioeconomic status (SES) on postoperative outcomes following anterior cruciate ligament (ACL) reconstruction (ACLR) surgery. OBJECTIVE: To identify associations between area deprivation index (ADI), strength measures and patient-reported outcomes (PROs) following ACLR as well as to examine differences in outcomes between race, sex, and race. DESIGN: Case control study in a single hospital setting. SETTING: Database secondary analysis. PATIENTS OR OTHER PARTICIPANTS: Data was collected from 340 patients who underwent primary, isolated, unilateral ACLR. MAIN OUTCOME MEASURES: Strength measures and PROs were obtained at patients' postoperative assessments at approximately six months post-surgery. Area Deprivation Index values were calculated on each patient's census tract, determined through medical records review. Correlations were conducted to determine the relationship between ADI and KOOS measures, IKDC, and limb symmetry on strength measurements. The racial composition of the sample was heavily skewed and was excluded from statistical analyses. RESULTS: ADI was weakly correlated with IKDC (ρ=0.11, p=0.04) outcomes, with more disadvantaged patients reporting better quality of life and knee function. ADI was not correlated with other outcomes of interest. The median ADI value of the sample was 32 (range 1-86 [IQR 19-47]). CONCLUSIONS: Our study revealed a weak correlation between higher levels of socioeconomic disadvantage as measured by ADI and improved subjective assessment of knee function and quality of life as measured by IKDC. These findings are contrary to what other studies on this subject have found and highlight the importance of further research into the impact of SES and other social determinants of health on post ACLR outcomes.

Transference of outdoor gait-training to treadmill running biomechanics and strength measures: A randomized controlled trial.

Outdoor gait-training has been successful in improving pain and reducing contact time during outdoor running for runners with exercise-related lower leg pain (ERLLP). However, it is unclear if these adaptations translate to gold standard treadmill running and clinical strength assessments. The study purpose was to assess the influence of a 4-week outdoor gait-training intervention with home exercises (FBHE) on treadmill running biomechanics and lower extremity strength compared to home exercises alone (HE) among runners with ERLLP. Seventeen runners with ERLLP were randomly allocated to FBHE and HE groups (FBHE: 3 M, 6F, 23 ± 4 years, 22.0 ± 4.6 kg/m2; HE: 3 M, 5F, 25 ± 5 years, 24.0 ± 4.0 kg/m2). Both groups completed eight sessions of home exercises over 4 weeks. The FBHE group received gait-training through wearable sensors to reduce contact time. Treadmill running gait and clinical strength assessments were conducted at baseline and 4-weeks. Multivariate repeated measures analyses of variance were used to assess the influence of group and timepoint for all outcomes. The FBHE group demonstrated significantly decreased contact time at 4-weeks compared to baseline and the HE group (Mean Difference [MD] range: -42 ms - -39 ms; p-range: <0.001-0.02). The FBHE group had significantly increased cadence (MD: +21 steps/min; p = 0.003) and decreased loading impulse (MD: -51, p < 0.001) during treadmill running at 4-weeks compared to the HE group. Strength did not significantly differ adjusting for multiple comparisons (p > 0.007). The outdoor FBHE intervention transferred to favorable changes in treadmill running biomechanics. Clinicians treating runners with ERLLP patients should implement data-driven outdoor gait-training to maximize patient benefits across running locations.

The effect of factors from different time points on psychological readiness following ACL reconstruction.

OBJECTIVE: The purpose of this study was to examine factors correlated with psychological readiness to return to activity after ACLR. DESIGN: cross sectional study. SETTING: controlled laboratory. PARTICIPANTS: 164 patients (82 M/82 F, 22.5 ± 8.9yr, 171.6 ± 11.0 cm, 77.4 ± 18.6 kg, 8.6 ± 3.4 months post-ACLR) participated in this study after a primary, isolated, and uncomplicated ACLR. MAIN OUTCOME MEASURES: ACL Return to Sport Index (ACL-RSI). RESULTS: ACL-RSI scores demonstrated a weak positive correlation with activity level at the time of injury and a fair positive correlation with activity level at the time of post-operative testing (p-values: 0.004, <0.001). ACL-RSI scores showed a statistically significant fair negative correlation with pain and a moderate negative correlation with kinesiophobia during rehabilitation (p-values: <0.001, <0.001). There was no statistical significance between ACL-RSI and the surgical variables (p-value range: 0.10-0.61). CONCLUSIONS: Outcomes from testing during postoperative rehabilitation were most correlated with psychological readiness to return to activity after ACLR. Increased pain and kinesiophobia were associated with a decreased psychological readiness. Increased activity level prior to injury and activity level at the time of testing during rehabilitation were both correlated with increased psychological readiness. Psychological readiness to return to activity may need to be customized based on potentially modifiable patient-specific factors during the post-operative rehabilitation.

Analysis of Limb Loading and Lower Extremity Strength Recovery Across Time After Anterior Cruciate Ligament Reconstruction.

BACKGROUND: Evidence as to how patient thigh muscle strength and limb loading (LL) during a squatting task recovers throughout rehabilitation after anterior cruciate ligament reconstruction (ACLR) is lacking. HYPOTHESIS: Patients will improve LL and strength throughout rehabilitation. Changes in LL and strength over time will be positively correlated. STUDY DESIGN: Prospective cohort study. LEVEL OF EVIDENCE: Level 3. METHODS: A total of 60 participants (28 male/32 female; age, 22.5 ± 9.35 years) participated in 2 visits post-ACLR, assessing LL and strength. Using an instrumented pressure mat, patients completed 3 sets of 3 repetitions of bodyweight squats. Peak force (N), unilateral cumulative load (%), and quadriceps and hamstring isokinetic peak torque (N·m) were calculated and recorded bilaterally. LL and peak torque were compared over time and between limbs. RESULTS: A significant limb-by-time interaction was observed for LL peak force (N), where patients underloaded the ACLR limb at visit 1 compared with the contralateral limb (P < 0.01). Patients increased their ACLR LL across visits (P = 0.04). A limb-by-time interaction for quadriceps peak torque (N·m) was observed where the ACLR limb increased peak torque across visits (P < 0.01); however, strength deficits persisted at visit 2 (P < 0.01) when compared with the nonoperative limb. Weak correlations were observed between all change scores metrics (r, 0.20-0.25). CONCLUSION: Patients recovering from ACLR exhibited more symmetric loading during a squatting task and improved their lower extremity strength over time. Changes in strength were not related to changes in LL during a squatting task over time. CLINICAL RELEVANCE: Squatting tasks are safe and easily implemented throughout ACLR recovery. As changes in functional LL and strength recovery are not related, both should be considered in serial postoperative testing for more comprehensive function and strength assessments.

Comparison of Limb Loading Characteristics and Subjective Functional Outcomes Between Sexes Following ACLR.

CONTEXT: ACL reconstruction (ACLR) patients commonly adopt poor movement patterns that potentially place them at an increased risk for reinjury if untreated. Limb loading characteristics during functional tasks can highlight movement compensations. OBJECTIVE: Examine loading symmetry during a bilateral bodyweight squatting task between sexes, compare loading metrics between limbs and sexes, and describe the relationship between loading metrics and patient reported outcomes (PROs) following ACLR. DESIGN: Cross-Sectional Study. SETTING: Laboratory. PATIENTS OR OTHER PARTICIPANTS: 142 patients (71M/71F, 24.4±11.10yrs) with a primary, unilateral, uncomplicated ACLR completed a squatting assessment and PROs at approximately 5.2 months post-ACLR. MAIN OUTCOME MEASURE(S): Normalized limb loading peak force (N/kg) and unilateral cumulative load (%) were collected bilaterally during the squatting task. Limb symmetry index (%) was calculated for normalized peak force. Our first objective compared limb loading symmetry (%) between sexes using independent samples t-test. Our second objective assessed differences in limb loading metrics between limbs and sexes were analyzed via an analysis of covariance. Our third objective was assessed using Spearman Rho correlations to determine the relationship between limb loading metrics and PROs. RESULTS: The majority of individuals (91/142, 64.1%) offloaded their ACLR limb (ACLR: 6.6±1.56 N/kg; contralateral: 7.3±1.61 N/kg, p<0.001). Females significantly offloaded their ACLR limb (ACLR: 6.3±1.38 N/kg; contralateral: 7.2±1.62 N/kg, p<0.001) where males did not significantly offload their ACLR limb (ACLR 6.98±1.65 N/kg; contralateral: 7.4±1.60, p=0.07). Weak relationships were observed (ρ-value range: -0.23 to 0.19) across limb loading metrics and PROs. CONCLUSION: Individuals approximately five months following ACLR, on average, offloaded their ACLR limb compared to the contralateral limb. Patients' tendency to offload their weight during a squat was influenced by sex. Relationships between limb loading metrics and PROs indicate patients who load their limbs disproportionately have a lower perception in their capability to complete activities of daily living and lower subjective knee function.