A Public BCR Present in a Unique Dual-Receptor-Expressing Lymphocyte from Type 1 Diabetes Patients Encodes a Potent T Cell Autoantigen.

T and B cells are the two known lineages of adaptive immune cells. Here, we describe a previously unknown lymphocyte that is a dual expresser (DE) of TCR and BCR and key lineage markers of both B and T cells. In type 1 diabetes (T1D), DEs are predominated by one clonotype that encodes a potent CD4 T cell autoantigen in its antigen binding site. Molecular dynamics simulations revealed that this peptide has an optimal binding register for diabetogenic HLA-DQ8. In concordance, a synthetic version of the peptide forms stable DQ8 complexes and potently stimulates autoreactive CD4 T cells from T1D patients, but not healthy controls. Moreover, mAbs bearing this clonotype are autoreactive against CD4 T cells and inhibit insulin tetramer binding to CD4 T cells. Thus, compartmentalization of adaptive immune cells into T and B cells is not absolute, and violators of this paradigm are likely key drivers of autoimmune diseases.

A mutagenesis study of autoantigen optimization for potential T1D vaccine design.

A previously reported autoreactive antigen, termed the X-idiotype, isolated from a unique cell population in Type 1 diabetes (T1D) patients, was found to stimulate their CD4+ T cells. This antigen was previously determined to bind more favorably than insulin and its mimic (insulin superagonist) to HLA-DQ8, supporting its strong role in CD4+ T cell activation. In this work, we probed HLA-X-idiotype-TCR binding and designed enhanced-reactive pHLA-TCR antigens using an in silico mutagenesis approach which we functionally validated by cell proliferation assays and flow cytometry. From a combination of single, double, and swap mutations, we identified antigen-binding sites p4 and p6 as potential mutation sites for HLA binding affinity enhancement. Site p6 is revealed to favor smaller but more hydrophobic residues than the native tyrosine, such as valine (Y6V) and isoleucine (Y6I), indicating a steric mechanism in binding affinity improvement. Meanwhile, site p4 methionine mutation to hydrophobic residues isoleucine (M4I) or leucine (M4L) modestly increases HLA binding affinity. Select p6 mutations to cysteine (Y6C) or isoleucine (Y6I) exhibit favorable TCR binding affinities, while a swap p5-p6 tyrosine-valine double mutant (V5Y_Y6V) and a p6-p7 glutamine-glutamine double mutant (Y6Q_Y7Q) exhibit enhanced HLA binding affinity but weakened TCR affinity. This work holds relevance to potential T1D antigen-based vaccine design and optimization.

In silico design and validation of high-affinity RNA aptamers targeting epithelial cellular adhesion molecule dimers.

Nucleic acid aptamers hold great promise for therapeutic applications due to their favorable intrinsic properties, as well as high-throughput experimental selection techniques. Despite the utility of the systematic evolution of ligands by the exponential enrichment (SELEX) method for aptamer determination, complementary in silico aptamer design is highly sought after to facilitate virtual screening and increased understanding of important nucleic acid-protein interactions. Here, with a combined experimental and theoretical approach, we have developed two optimal epithelial cellular adhesion molecule (EpCAM) aptamers. Our structure-based in silico method first predicts their binding modes and then optimizes them for EpCAM with molecular dynamics simulations, docking, and free energy calculations. Our isothermal titration calorimetry experiments further confirm that the EpCAM aptamers indeed exhibit enhanced affinity over a previously patented nanomolar aptamer, EP23. Moreover, our study suggests that EP23 and the de novo designed aptamers primarily bind to EpCAM dimers (and not monomers, as hypothesized in previous published works), suggesting a paradigm for developing EpCAM-targeted therapies.

Impact of COVID-19 on the physical activity, quality of life and mental health of adolescent athletes: a 2-year evaluation of over 17 000 athletes.

PURPOSE: To evaluate the changes in mental health, quality of life (QOL) and physical activity (PA) among adolescent athletes during the COVID-19 pandemic as organised sports resumed. METHODS: Adolescent athletes completed surveys including demographic and sport participation information, 7-item Generalized Anxiety Disorder, 9-item Patient Health Questionnaire, Pediatric Quality of Life Inventory and the Hospital for Special Surgery Pediatric Functional Activity Brief Scale in May 2020 following COVID-19-related sport cancellations (Spring20) and after returning to sports in May 2021 (Spring21). The groups were balanced by inverse propensity score weighting and compared using analysis of variance models and ordinal regression models. RESULTS: 17 421 participants were included (Spring20=13 002; Spring21=4419; 16.2±1.2 years; 53% female). Anxiety was significantly lower (better) in Spring21 (Spring20=7.0, 95% CI 6.9 to 7.1; Spring21=4.9, 95% CI 4.8 to 5.0, p<0.001), as was the prevalence of moderate to severe anxiety (Spring20=29.4%, Spring21=17.1%, p<0.001). Depression was significantly improved in Spring21 (Spring20=7.6, 95% CI 7.5 to 7.7; Spring21=4.6, 95% CI 4.5 to 4.8, p<0.001), as was the prevalence of moderate to severe depression (Spring20=32.2%, Spring21=15.4%, p<0.001). Athletes in Spring21 reported higher QOL (Spring20=79.6, 95% CI 79.3 to 79.9; Spring21=84.7, 95% CI 84.4 to 85.0, p<0.001) and increased levels of PA (Spring20=13.8, 95% CI 13.6 to 13.9; Spring21=22.7, 95% CI 22.6 to 22.9, p<0.001). CONCLUSION: Early COVID-19 sports restrictions were associated with worsening mental health in adolescents. In 2021, after returning to sports, athletes reported significant improvements in mental health, QOL and PA, although mental health adversities remain an important priority.

Secondary School Athletic Trainers' Strategies and Barriers to Overuse Injury Treatment in Adolescent Athletes.

CONTEXT: Studies have illustrated that overuse injuries occur in adolescent athletes more often than previously reported. The general purpose of this study was to provide a thorough report of secondary school athletic trainers encounters, practices, and perceptions of overuse injury in adolescent athletes. DESIGN: Cross-sectional. METHODS: An anonymous online questionnaire was distributed via email to athletic trainers in the secondary school setting. The questionnaire was sent to participants during the summer of 2021 and 430 participants (highest educational degree earned: master's degree = 66%) completed the survey. Various survey methods were used to evaluate athletic trainers (1) demographics, (2) estimations about what percentage of injuries evaluated and treated were classified as overuse, (3) methods for treating overuse injuries, (4) confidence in treating overuse injuries and the complete implementation of their treatment plan, (5) perceptions of various barriers to treating overuse injuries, and (6) perception as to why patients did not want to reduce activity to treat their overuse injuries. RESULTS: Participants reported that about half of all evaluations and treatments in a year were overuse injuries and they were "fairly" or "completely" confident (90%) in their ability to treat these injuries. The most common treatments cited were stretching (91%) and reducing activity (90%). Only 61% of participants were "fairly" or "completely" confident in the complete implementation of their treatment plan. Participants believed that patients' reluctance to reduce sport activities (82% "moderate" or "extreme" barrier) was the most significant barrier to treatment. Participants cited athletes' avoidance of missing games as the most common reason athletes were reluctant to reduce sporting activity. CONCLUSIONS: Participants felt confident in treating overuse injuries yet faced significant barriers in treating these injuries. Clinicians should be prepared to have conversations about the importance of reducing sporting activity to allow proper healing for overuse injuries in adolescent athletes.

Toward Guided Mutagenesis: Gaussian Process Regression Predicts MHC Class II Antigen Mutant Binding.

Antigen-specific immunotherapies (ASI) require successful loading and presentation of antigen peptides into the major histocompatibility complex (MHC) binding cleft. One route of ASI design is to mutate native antigens for either stronger or weaker binding interaction to MHC. Exploring all possible mutations is costly both experimentally and computationally. To reduce experimental and computational expense, here we investigate the minimal amount of prior data required to accurately predict the relative binding affinity of point mutations for peptide-MHC class II (pMHCII) binding. Using data from different residue subsets, we interpolate pMHCII mutant binding affinities by Gaussian process (GP) regression of residue volume and hydrophobicity. We apply GP regression to an experimental data set from the Immune Epitope Database, and theoretical data sets from NetMHCIIpan and Free Energy Perturbation calculations. We find that GP regression can predict binding affinities of nine neutral residues from a six-residue subset with an average R2 coefficient of determination value of 0.62 ± 0.04 (±95% CI), average error of 0.09 ± 0.01 kcal/mol (±95% CI), and with an receiver operating characteristic (ROC) AUC value of 0.92 for binary classification of enhanced or diminished binding affinity. Similarly, metrics increase to an R2 value of 0.69 ± 0.04, average error of 0.07 ± 0.01 kcal/mol, and an ROC AUC value of 0.94 for predicting seven neutral residues from an eight-residue subset. Our work finds that prediction is most accurate for neutral residues at anchor residue sites without register shift. This work holds relevance to predicting pMHCII binding and accelerating ASI design.

Impact of in-season injury on quality of life and sleep duration in female youth volleyball athletes: a prospective study of 2073 players.

OBJECTIVES: The psychological impacts of injuries in youth athletes remain poorly defined. The purpose of this study was to evaluate the influence of injury on quality of life (QOL) and sleep in female high school volleyball athletes. METHODS: 2073 female high school volleyball players (15.6±1.1 years) completed the Pediatric Quality of Life survey (total QOL, physical, social, school, emotional and psychosocial function) and reported average sleep duration at the start and end of the season. Injury data were collected by school athletic trainers. Mixed effects linear regression models were used to compare changes in QOL and sleep duration during the season between (1) injured and uninjured athletes and (2) injured athletes who did or did not suffer a season-ending injury. RESULTS: Time-loss injuries were reported in 187 athletes with complete preseason and postseason data. During the season, injured athletes demonstrated a greater decrease in total QOL (ß=-1.3±0.5, p=0.012), as well as physical function (ß=-1.6±0.6, p=0.012), school function (ß=-2.0±0.76, p=0.01) and psychosocial function domains (ß=-1.2±0.6, p=0.039) compared with uninjured athletes. Athletes who sustained a season-ending injury had a significantly greater decrease in total QOL (ß=-6.8±2.0, p=0.006) and physical function (ß=-17±2.9, p<0.001) compared with injured athletes who were able to return to play during the season. CONCLUSION: In-season injuries are associated with significant decreases in total QOL as well as physical and psychosocial function. Healthcare providers should consider the impacts of injuries on QOL and sleep in youth athletes in order to optimise management and improve overall health.

Parents' Awareness and Perceptions of Sport Specialization and Injury Prevention Recommendations.

OBJECTIVE: To conduct a survey of parents to determine their knowledge of sport volume recommendations and examine their perceptions toward sport specialization. DESIGN: Cross-sectional survey. SETTING: Youth sport athletic tournaments, competitions, and practices. PATIENTS OR OTHER PARTICIPANTS: Parents (n = 1000, 614 women, age: 44.5 ± 6.7 years) of youth athletes completed the survey. Parents had to have a child between 10 and 18 years of age who participated in organized sport in the previous 12 months. INTERVENTIONS: The survey was anonymous and consisted of yes/no and Likert-scale questions and consisted of background of parent and child and perceptions and knowledge of safe sport recommendations. An expert panel validated the survey. MAIN OUTCOME MEASURES: Data were summarized by frequencies, proportions (%), and mean values and SDs, when appropriate. Chi-square analyses were used to determine if parent sex influenced distributions. RESULTS: Over 80% of parents had no knowledge of sport volume recommendations regarding h/wk (84.5%), mo/yr (82.2%), or simultaneous participation in multiple leagues (89.9%). Twenty-four percent of parents considered it appropriate to participate in multiple leagues in the same sport, whereas 60.5% considered it appropriate to participate in multiple leagues of a different sport. Thirty-four percent of parents indicated that they were concerned about the risk of injury in youth sports. Although 55% of parents considered sport specialization a problem in youth sports, only 43.3% thought that year-round sport participation increased the chances of sustaining an overuse injury. Female parents were more likely to be concerned about injury and believe that year-round sport participation results in overuse injury compared with men. CONCLUSIONS: Recommendations associated with youth sport participation are not well known. However, parents are concerned about the risk of injury and consider sport specialization a problem.

Knowledge, Attitudes, and Beliefs of Youth Sports Coaches Regarding Sport Volume Recommendations and Sport Specialization.

Post, EG, Trigsted, SM, Schaefer, DA, Cadmus-Bertram, LA, Watson, AM, McGuine, TA, Brooks, MA, and Bell, DR. Knowledge, attitudes, and beliefs of youth sports coaches regarding sport volume recommendations and sport specialization. J Strength Cond Res 34(10): 2911-2919, 2020-Overuse injuries in youth athletes are becoming increasingly common, which may be a result of the prevalence of year-round specialized sport participation. Previous research has identified sport volume recommendations related to months per year, hours per week, and simultaneous participation in multiple sports leagues. Coaches are a primary influence on a youth athlete's decision to specialize in a single sport. Therefore, identifying coaches' baseline beliefs and perceptions is important for developing strategies to educate coaches about safe sport participation. A total of 253 youth sport coaches (207 males) completed an anonymous online questionnaire regarding knowledge of sport volume recommendations and attitudes and beliefs regarding sport specialization. Eligible participants were required to serve as a head or assistant coach of a youth sport team in the past 12 months whose members were between the ages of 12 and 18 years. Most coaches were unaware of recommendations regarding the maximum number of months per year (79.4%), hours per week in 1 sport (79.3%), or number of simultaneous leagues for an athlete to participate in to reduce injury (77.6%). Fewer than half (43.2%) of all coaches were "very" or "extremely" concerned about the risk of injury in youth sports. A majority (60.1%) believed that sport specialization was either "quite a bit" or "a great deal" of a problem. Two-thirds (67.2%) responded that year-round participation in a single sport was either "very" or "extremely" likely to increase an athlete's risk of injury. Although the responses to this survey were predominantly from coaches from 1 state, our results suggest that coaches are unaware of sport volume recommendations but are concerned about specialization. Future efforts are needed to communicate these recommendations to coaches to reduce the risk of overuse injury in youth sports.

Different Perceptions of Parents and Children on Factors Influencing Sport Specialization.

CONTEXT: Sport specialization among youth athletes has been associated with increased risk of overuse injuries. Previous research demonstrates that children perceive specialization to be beneficial in making their high school team and receiving athletic college scholarships. Previous research demonstrates that parents play a significant role in their child's sport experience. However, it is unknown if parents and children answer questions related to specialization factors in a similar manner. OBJECTIVE: To evaluate the beliefs of youth athletes and parents on factors related to sport specialization and evaluate the level of agreement between dyads on sports specialization. DESIGN: Cross-sectional. SETTING: Online and paper surveys. PATIENTS OR OTHER PARTICIPANTS: Aim 1: 1998 participants (993 children and 1005 parents). Aim 2: 77 paired parent-child dyads. INTERVENTIONS: Self-administered survey. MAIN OUTCOME MEASURES: The responses were summarized via frequency and proportions (%). Chi-squares were calculated between parent and child responses. Kappa coefficients were calculated for dyads to determine level of agreement. Sport specialization was classified using a common 3-point scale. RESULTS: The parents were more concerned about risk of injury in sports compared with children (P < .001, χ2 = 231.4; parent: extremely: 7.1%; child: extremely: 3.7%). However, children were more likely to believe that specialization was associated with their chances of obtaining an athletic college scholarship compared with parents (P < .001, χ2 = 201.6; parent: very/extremely likely: 13.7%; child: very/extremely likely: 15.8%). Dyad subanalysis indicated a moderate level of agreement for "quitting other sports to focus on one sport" (κ = .50) and a low level of agreement for "identifying a primary sport" (κ = .30) and "training >8 months per year in primary sport" (κ = .32). CONCLUSIONS: Parents and youth athletes had differing beliefs on the factors related to sport specialization. Dyad analysis shows that parents and children answer sport specialization classification questions differently. Health care providers should be aware of these differences, and messaging should be individualized to the audience.

Exploration of HIV-1 fusion peptide-antibody VRC34.01 binding reveals fundamental neutralization sites.

Antibody binding to a vulnerable site of HIV envelope glycoprotein (Env), the eight N-terminal residues of the gp41 fusion peptide, renders robust HIV neutralization. Here, we theoretically investigate HIV-1 fusion peptide binding to the neutralizing antibody N123-VRC34.01. We explore numerous fusion peptide mutations using all-atom molecular dynamics simulation with explicit-solvent models. Simulation results show that the hydrophobic interaction between Ile515 in the HIV-1 fusion peptide and the antibody VRC34.01 Fab plays an important role in antibody binding. Furthermore, we verify by free energy perturbation (FEP) calculations that two point mutations of Ile515Thr or Ile515Ala can dramatically weaken the binding affinity. Our findings provide new insights into fusion peptide-VRC34.01 binding, which can ultimately be utilized to design effective HIV vaccines.

Exploring the binding mechanism between human profilin (PFN1) and polyproline-10 through binding mode screening.

The large magnitude of protein-protein interaction (PPI) pairs within the human interactome necessitates the development of predictive models and screening tools to better understand this fundamental molecular communication. However, despite enormous efforts from various groups to develop predictive techniques in the last decade, PPI complex structures are in general still very challenging to predict due to the large number of degrees of freedom. In this study, we use the binding complex of human profilin (PFN1) and polyproline-10 (P10) as a model system to examine various approaches, with the aim of going beyond normal protein docking for PPI prediction and evaluation. The potential of mean force (PMF) was first obtained from the time-consuming umbrella sampling, which confirmed that the most stable binding structure identified by the maximal PMF difference is indeed the crystallographic binding structure. Moreover, crucial residues previously identified in experimental studies, W3, H133, and S137 of PFN1, were found to form favorable hydrogen bonds with P10, suggesting a zipping process during the binding between PFN1 and P10. We then explored both regular molecular dynamics (MD) and steered molecular dynamics (SMD) simulations, seeking for better criteria of ranking the PPI prediction. Despite valuable information obtained from conventional MD simulations, neither the commonly used interaction energy between the two binding parties nor the long-term root mean square displacement correlates well with the PMF results. On the other hand, with a sizable collection of trajectories, we demonstrated that the average and minimal rupture works calculated from SMD simulations correlate fairly well with the PMFs (R 2 = 0.67), making this a promising PPI screening method.

Greater fear of reinjury is related to stiffened jump-landing biomechanics and muscle activation in women after ACL reconstruction.

PURPOSE: Fear of reinjury is an important factor in determining who returns to sport following anterior cruciate ligament reconstruction (ACLR). Evidence from other musculoskeletal injuries indicates fear of reinjury may be related to stiffened movement patterns observed in individuals following ACLR. The relationship between fear of reinjury and performance on dynamic tasks, however, has not been investigated. Therefore, the purpose of this study was to investigate the relationship between fear of reinjury and jump-landing biomechanics. METHODS: Thirty-six females (height = 168.7 ± 6.5 cm, body mass = 67.2 ± 10.0 kg, age = 18.9 ± 1.5 years) with a history of ACLR (time from surgery = 26.1 ± 13.3 months) participated in the study. Each participant performed five trials of a standard jump-landing task. 3D motion capture and surface electromyography was used to record peak kinematics and lower extremity muscle activation on the injured limb during the jump landings. Spearman's rank correlations established the relationship between TSK-11 scores and each biomechanical variable of interest. RESULTS: There was a significant, negative relationship between fear of reinjury (TSK-11: 19.9 ± 4.5) and knee (p = 0.006), hip (p = 0.003), and trunk flexion (p = 0.013). There was also a significant, positive relationship between hip adduction (p = 0.007), and gluteus maximus preparatory activation (p = 0.001). CONCLUSIONS: The results of this study indicate that higher fear of reinjury is associated with stiffened movement patterns that are associated with increased risk of a second ACL injury. Similar movement patterns have been observed in patients with low back pain. Clinicians should evaluate psychological and emotional consequences of injury in addition to the physical consequences as they appear to be related. LEVEL OF EVIDENCE: III.

Correction to: Estrogen and muscle stiffness have a negative relationship in females.

In the original publication the name of the fourth reviewer was incorrectly published.

LNA Thymidine Monomer Enables Differentiation of the Four Single-Nucleotide Variants by Melting Temperature.

High-resolution melting (HRM) analysis of DNA is a closed-tube single-nucleotide polymorphism (SNP) detection method that has shown many advantages in point-of-care diagnostics and personalized medicine. While recently developed melting probes have demonstrated significantly improved discrimination of mismatched (mutant) alleles from matched (wild-type) alleles, no effort has been made to design a simple melting probe that can reliably distinguish all four SNP alleles in a single experiment. Such a new probe could facilitate the discovery of rare genetic mutations at lower cost. Here we demonstrate that a melting probe embedded with a single locked thymidine monomer (tL) can reliably differentiate the four SNP alleles by four distinct melting temperatures (termed the "4Tm probe"). This enhanced discriminatory power comes from the decreased melting temperature of the tL·C mismatched hybrid as compared to that of the t·C mismatched hybrid, while the melting temperatures of the tL-A, tL·G and tL·T hybrids are increased or remain unchanged as compared to those of their canonical counterparts. This phenomenon is observed not only in the HRM experiments but also in the molecular dynamics simulations.

Impact of graphyne on structural and dynamical properties of calmodulin.

Carbon-based nanomaterials such as graphyne, graphene, and carbon nanotubes have attracted considerable attention for their applications, but questions remain regarding their biosafety through potential adverse interactions with important biomolecules. Here, we investigate the binding of a graphyne nanosheet and a graphyne quantum dot to calmodulin (CaM), a dynamic Ca2+ binding protein. Simulation results show that both the graphyne nanosheet and graphyne quantum dot are able to bind both Ca2+-bound and Ca2+-free CaM with similar binding affinities. From our simulations, graphyne quantum dots appear particularly worrisome for potential toxicity as they bind to and occlude the hydrophobic binding pocket of both Ca2+-bound and Ca2+-free CaM. In both the nanosheet and quantum dot systems, the binding interactions between graphyne and CaM are markedly hydrophobic and heavily suppress the Ca2+-free CaM dynamics. Our results reiterate that graphitic nanomaterials including graphyne may have negative impacts on both the structure and dynamics of key proteins such as CaM involved in calcium signal transduction.

Propensity of a single-walled carbon nanotube-peptide to mimic a KK10 peptide in an HLA-TCR complex.

The application of nanotechnology to improve disease diagnosis, treatment, monitoring, and prevention is the goal of nanomedicine. We report here a theoretical study of a functionalized single-walled carbon nanotube (CNT) mimic binding to a human leukocyte antigen-T cell receptor (HLA-TCR) immune complex as a first attempt of a potential nanomedicine for human immunodeficiency virus (HIV) vaccine development. The carbon nanotube was coated with three arginine residues to imitate the HIV type 1 immunodominant viral peptide KK10 (gag 263-272: KRWIILGLNK), named CNT-peptide hereafter. Through molecular dynamics simulations, we explore the CNT-peptide and KK10 binding to an important HLA-TCR complex. Our results suggest that the CNT-peptide and KK10 bind comparably to the HLA-TCR complex, but the CNT-peptide forms stronger interactions with the TCR. Desorption simulations highlight the innate flexibility of KK10 over the CNT-peptide, resulting in a slightly higher desorption energy required for KK10 over the CNT-peptide. Our findings indicate that the designed CNT-peptide mimic has favorable propensity to activate TCR pathways and should be further explored to understand therapeutic potential.

Landing mechanics during single hop for distance in females following anterior cruciate ligament reconstruction compared to healthy controls.

PURPOSE: To determine possible differences in single-hop kinematics and kinetics in females with anterior cruciate ligament reconstruction compared to healthy controls. A second purpose was to make comparisons between the healthy and reconstructed limbs. METHODS: Subjects were grouped based on surgical status (33 ACLR patients and 31 healthy controls). 3D motion capture synchronized with force plates was used to capture the landing phase of three successful trials of single hop for distance during a single data collection session. Peak values during the loading phase were analysed. Subjects additionally completed three successful trials of the triple hop for distance Tegner activity scale and International Knee Document Committee 2000 (IKDC). RESULTS: Controls demonstrated greater peak knee flexion and greater internal knee extension moment and hip extension moment than ACLR subjects. Within the ACLR group, the healthy limb exhibited greater peak knee flexion, hip flexion, hip extension moment, single hop and triple hops for distance and normalized quadriceps strength. CONCLUSION: Patients who undergo anterior cruciate ligament reconstruction land in a more extended posture when compared to healthy controls and compared to their healthy limb. LEVEL OF EVIDENCE: III.

The Reliability and Discriminative Ability of the Overhead Squat Test for Observational Screening of Medial Knee Displacement.

CONTEXT: The overhead squat test (OHS) is a functional screening exam that is used to identify high-risk movement profiles such as medial knee displacement (MKD). The reliability and discriminative ability of observational screening during the OHS to identify MKD have yet to be established. OBJECTIVE: To investigate the reliability and discriminative ability of observational screening for medial knee displacement MKD during the OHS. STUDY DESIGN: Clinical measurement, cross sectional. PARTICIPANTS: 100 college students were video-recorded performing the OHS. Three certified athletic trainers classified the knee posture of each subject during the OHS on 2 different occasions using screening guidelines. MAIN OUTCOME MEASURES: Ratings were evaluated by calculating kappa coefficients for intra- and interrater levels of agreements. MKD was measured using motion analysis. RESULTS: Intrarater reliability ranged from .60-.76 with an average value of .70. Interrater reliability was substantial (kappa > .60) for both observation sessions (Fleiss kappa session 1 = .69, session 2 = .70). Sensitivity ranged was .58-.83, while specificity ranged was .70-.88. The MKD group displayed significantly more displacement than the no-MKD group (p < .001). There was a moderate positive correlation (r = .48, p < .001) between knee-posture group and MKD assessed using motion analysis. CONCLUSION: The OHS has substantial reliability and is able to assess the presence of MKD. The OHS should be used as part of a comprehensive examination that evaluates multiple movement patterns and risk levels.

Scalable improvement of SPME multipolar electrostatics in anisotropic polarizable molecular mechanics using a general short-range penetration correction up to quadrupoles.

We propose a general coupling of the Smooth Particle Mesh Ewald SPME approach for distributed multipoles to a short-range charge penetration correction modifying the charge-charge, charge-dipole and charge-quadrupole energies. Such an approach significantly improves electrostatics when compared to ab initio values and has been calibrated on Symmetry-Adapted Perturbation Theory reference data. Various neutral molecular dimers have been tested and results on the complexes of mono- and divalent cations with a water ligand are also provided. Transferability of the correction is adressed in the context of the implementation of the AMOEBA and SIBFA polarizable force fields in the TINKER-HP software. As the choices of the multipolar distribution are discussed, conclusions are drawn for the future penetration-corrected polarizable force fields highlighting the mandatory need of non-spurious procedures for the obtention of well balanced and physically meaningful distributed moments. Finally, scalability and parallelism of the short-range corrected SPME approach are addressed, demonstrating that the damping function is computationally affordable and accurate for molecular dynamics simulations of complex bio- or bioinorganic systems in periodic boundary conditions.