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Legg‐Calvé‐Perthes disease (LCPD) is a childhood hip disorder characterized by ischemic injury to the epiphysis of the femoral head, but changes to the metaphysis have also been implicated in its pathogenesis. Quantitative magnetic resonance imaging (MRI) relaxation time mapping techniques are potentially useful to detect injury in LCPD, but studies to date have focused on the epiphysis. The purpose of this study was to assess whether T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times can detect early metaphyseal changes in an LCPD piglet model. Complete epiphyseal ischemia of one femoral head was surgically induced and confirmed using contrast‐enhanced MRI in n = 10 6‐week‐old piglets; the contralateral side was unoperated. The bilateral hips were imaged 1 week after surgery in vivo at 3T MRI using relaxation time mapping and contrast‐enhanced MRI. Relaxation times and thicknesses of the metaphyseal primary and secondary spongiosa were measured and compared between the ischemic and contralateral‐control femoral heads using paired t‐tests. In the ischemic femoral heads, T2 relaxation times were significantly increased in the primary spongiosa (6.7 ± 9.8 ms, p = 0.029), and T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation times were significantly decreased in the secondary spongiosa (respectively: −13.3 ± 9.3 ms, p = 0.013; −32 ± 23 ms, p < 0.001; −43 ± 41 ms, p = 0.009; and −39 ± 13 ms, p < 0.001). The secondary spongiosa thickness was also significantly decreased in the ischemic femoral heads (p < 0.001). In conclusion, T2, T1ρ, adiabatic T1ρ, and adiabatic T2ρ relaxation time mapping techniques can detect early changes in the metaphysis following ischemic injury to the epiphysis of the femoral head in a piglet model of LCPD. [ABSTRACT FROM AUTHOR]

Background: Congenital pseudarthrosis of the tibia is a rare and challenging pediatric condition. The pre-fracture state, called congenital tibial dysplasia or anterolateral bowing of the tibia, presents a high fracture risk due to underlying bowing and dysplasia. After fracture, there is a substantial risk of nonunion. Any union achieved may be complicated by refracture, deformity, leg-length discrepancy, stiffness, pain, and dysfunction. We present the results of using distal tibial growth modulation to improve tibial alignment and to decrease fracture risk in this condition. To our knowledge, this is the first report of isolated distal tibial growth modulation as the primary surgical treatment for this condition.Methods: This is a retrospective study of 10 patients with congenital tibial dysplasia who presented prior to pseudarthrosis and underwent distal tibial growth modulation as a primary treatment. The medical records and radiographs were reviewed for age at the times of diagnosis and treatment, fracture, secondary procedures, complications, residual deformity, cystic changes, and leg-length discrepancy.Results: Ten patients had a mean follow-up (and standard deviation) of 5.1 ± 1.9 years. No patient sustained a tibial fracture, and no patient developed a tibial pseudarthrosis after guided growth was initiated. The mean age at the initiation of growth modulation was 2.6 ± 1.3 years. Six patients required a plate exchange. The mean residual tibial diaphyseal angular deformity at the most recent follow-up was 4.3° ± 3.2° of varus and 8.4° ± 5.8° in the sagittal plane. Only 1 patient had a clinically important leg-length discrepancy, with the affected leg being longer.Conclusions: In this series of 10 patients with congenital tibial dysplasia, distal tibial growth modulation delayed or possibly prevented fracture, decreased tibial malalignment, improved radiographic appearance of bone quality, and preserved leg length. No patient developed tibial fracture or pseudarthrosis after the initiation of guided growth treatment. Although early results are promising, follow-up to maturity is required to define the exact role of this simple outpatient procedure in congenital tibial dysplasia.Level Of Evidence: Therapeutic Level IV. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

Purpose: The modified lateral pillar classification (mLPC) is used for prognostication in the fragmentation stage of Legg Calvé Perthes disease. Previous reliability assessments of mLPC range from fair to good agreement when evaluated by a small number of observers with pre-selected radiographs. The purpose of this study was to determine the inter-observer and intra-observer reliability of mLPC performed by a group of international paediatric orthopaedic surgeons. Surgeons self-selected the radiograph for mLPC assessment, as would be done clinically. Methods: In total, 40 Perthes cases with serial radiographs were selected. For each case, 26 surgeons independently selected a radiograph and assigned mLPC and 21 raters re-evaluated the same 40 cases to establish intra-observer reliability. Rater performance was determined through surgeon consensus using the mode mLPC as 'gold standard'. Interobserver and intra-observer reliability data were analysed using weighted kappa statistics. Results: The weighted kappa for inter-observer correlation for mLPC was 0.64 (95% confidence interval: 0.55 to 0.74) and was 0.82 (range: 0.35 to 0.99) for intra-observer correlation. Individual surgeon's overall performance varied from 48% to 88% agreement. Surgeon mLPC performance was not influenced by years of experience (p = 0.51). Radiograph selection did not influence gold standard assignment of mLPC. There was greater agreement on cases of mild B hips and severe C hips. Conclusions: mLPC has low good inter-observer agreement when performed by a large number of surgeons with varied experience. Surgeons frequently chose different radiographs, with no impact on mLPC agreement. Further refinement is needed to help differentiate hips on the border of group B and C. [ABSTRACT FROM AUTHOR]

The article reflects on the need for instilling an awareness of a holistic approach to safety and health programs in the professional safety workforce. It mentions that aim is to identify where occupational safety efforts could augment such holistic wellness efforts and to establish the boundaries for occupational safety and health professionals.

Allosteric regulation is an essential function of many proteins that control a variety of different processes such as catalysis, signal transduction, and gene regulation. Structural rearrangements have historically been considered the main means of communication between different parts of a protein. Recent studies have highlighted the importance, however, of changes in protein flexibility as an effective way to mediate allosteric communication across a protein. Scapharca dimeric hemoglobin (Hbl) is the simplest possible allosteric system, with cooperative ligand binding between two identical subunits. Thermodynamic equilibrium studies of the binding of oxygen to Hbl have shown that cooperativity is an entropically driven effect. The change in entropy of the system observed upon ligand binding may arise from changes in the protein, the ligand, or the water of the system. The goal of this study is to determine the contribution of the change in entropy of the protein backbone to Hbl cooperative binding. Molecular dynamics simulations and nuclear magnetic resonance relaxation techniques have revealed that the fast internal motions of Hbl contribute to the cooperative binding to carbon monoxide in two ways: (1) by contributing favorably to the free energy of the system and (2) by participating in the cooperative mechanism at the Hbl subunit interface. The internal dynamics of the weakly cooperative Hbl mutant, F97Y, were also investigated with the same methods. The changes in backbone NH dynamics observed for F97Y Hbl upon ligand binding are not as large as for the wild type, in agreement with the reduced cooperativity observed for this mutant. The results of this study indicate that interface flexibility and backbone conformational entropy of Hbl participate in and are important for the cooperative mechanism of carbon monoxide binding. [ABSTRACT FROM AUTHOR]

Abstract: Imidazole-3-glycerol phosphate synthase is a heterodimeric allosteric enzyme that catalyzes consecutive reactions in imidazole biosynthesis through its HisF and HisH subunits. The unusually slow unfolding reaction of the isolated HisF TIM barrel domain from the thermophilic bacteria, Thermotoga maritima, enabled an NMR-based site-specific analysis of the main-chain hydrogen bonds that stabilize its native conformation. Very strong protection against exchange with solvent deuterium in the native state was found in a subset of buried positions in α-helices and pervasively in the underlying β-strands associated with a pair of large clusters of isoleucine, leucine and valine (ILV) side chains located in the α7(βα)8(βα)1–2 and α2(βα)3–6β7 segments of the (βα)8 barrel. The most densely packed region of the large cluster, α3(βα)4–6β7, correlates closely with the core of stability previously observed in computational, protein engineering and NMR dynamics studies, demonstrating a key role for this cluster in determining the thermodynamic and structural properties of the native state of HisF. When considered with the results of previous studies where ILV clusters were found to stabilize the hydrogen-bonded networks in folding intermediates for other TIM barrel proteins, it appears that clusters of branched aliphatic side chains can serve as cores of stability across the entire folding reaction coordinate of one of the most common motifs in biology. [Copyright &y& Elsevier]

OBJECTIVE: This study aimed to identify clinical measures that have been used to evaluate function, health related quality of life (HRQoL), and/or satisfaction in children who use lower limb prostheses (LLP). The data reported on psychometric properties for children who use LLP were collected for each measure. METHODS: First, PubMed, CINAHL, and Web of Science databases were searched using broad search terms to identify standardized outcome measures of function, HRQoL, and/or satisfaction with treatment used in pediatric LLP research published in 2001 or after. For each of the eligible measures found, a second search was performed to identify psychometric properties (e.g., validity, reliability) assessed with children who use LLP. RESULTS: Forty-four standardized outcome measures were identified from 41 pediatric LLP research articles. Five measures (i.e., Gait Outcomes Assessment for Lower Limb Differences, Functional Mobility Assessment, Child Amputee Prosthetics Project- Prosthesis Satisfaction Inventory, Child Amputee Prosthetics Project- Functional Scale Index, and Lower Limb Function Questionnaire) had data on psychometric properties for children who use LLP. CONCLUSIONS: Few studies report psychometric data for assessing the overall HRQoL, function, and/or satisfaction for children who use LLP. Further research is needed to validate or create new outcome measures that assess the HRQoL, satisfaction, and/or function of children who use LLP. [ABSTRACT FROM AUTHOR]

There is a clinical need for alternatives to gadolinium contrast‐enhanced magnetic resonance imaging (MRI) to facilitate early detection and assessment of femoral head ischemia in pediatric patients with Legg‐Calvé‐Perthes disease (LCPD), a juvenile form of idiopathic osteonecrosis of the femoral head. The purpose of this study was to determine if intravoxel incoherent motion (IVIM), a noncontrast‐enhanced MRI method to simultaneously measure tissue perfusion and diffusion, can detect femoral head ischemia using a piglet model of LCPD. Twelve 6‐week‐old piglets underwent unilateral hip surgery to induce complete femoral head ischemia. The unoperated, contralateral femoral head served as a perfused control. The bilateral hips of the piglets were imaged in vivo at 3T MRI using IVIM and contrast‐enhanced MRI 1 week after surgery. Median apparent diffusion coefficient (ADC) and IVIM parameters (diffusion coefficient: Ds; perfusion coefficient: Df; perfusion fraction: f; and perfusion flux: f*Df) were compared between regions of interest comprising the epiphyseal bone marrow of the ischemic and control femoral heads. Contrast‐enhanced MRI confirmed complete femoral head ischemia in 11/12 piglets. IVIM perfusion fraction (f) and flux (f*Df) were significantly decreased in the ischemic versus control femoral heads: on average, f decreased 47 ± 27% (Δf = −0.055 ± 0.034; p = 0.0003) and f*Df decreased 50 ± 27% (Δf*Df = −0.59 ± 0.49 × 10−3 mm2/s; p = 0.0026). In contrast, IVIM diffusion coefficient (Ds) and ADC were significantly increased in the ischemic versus control femoral heads: on average, Ds increased 78 ± 21% (ΔDs = 0.60 ± 0.14 × 10−3 mm2/s; p < 0.0001) and ADC increased 60 ± 36% (ΔADC = 0.50 ± 0.23 × 10−3 mm2/s; p < 0.0001). In conclusion, IVIM is sensitive in detecting bone marrow ischemia in a piglet model of LCPD. [ABSTRACT FROM AUTHOR]

Hepatitis C NS3/4A protease is a prime therapeutic target that is responsible for cleaving the viral polyprotein at junctions 3-4A, 4A4B, 4B5A, and 5A5B and two host cell adaptor proteins of the innate immune response, TRIF and MAVS. In this study, NS3/4A crystal structures of both host cell cleavage sites were determined and compared to the crystal structures of viral substrates. Two distinct protease conformations were observed and correlated with substrate specificity: (i) 3-4A, 4A4B, 5A5B, and MAVS, which are processed more efficiently by the protease, form extensive electrostatic networks when in complex with the protease, and (ii) TRIF and 4B5A, which contain polyproline motifs in their full-length sequences, do not form electrostatic networks in their crystal complexes. These findings provide mechanistic insights into NS3/4A substrate recognition, which may assist in a more rational approach to inhibitor design in the face of the rapid acquisition of resistance. [ABSTRACT FROM AUTHOR]

Background: We examined long-term outcomes across the domains of the International Classification of Functioning, Disability and Health for 2 groups of participants with cerebral palsy who demonstrated crouch gait at clinical gait analysis. One group underwent a distal femoral extension osteotomy with patellar tendon advancement (DFEO + PTA). The other group received other treatments (non-DFEO + PTA).Methods: Fifty-one participants returned for a long-term gait analysis, physical examination, energy consumption test, knee radiographs, and questionnaires (median, 13 years post-DFEO + PTA or post-baseline [range, 8 to 21 years]). A subset of participants in the DFEO + PTA group also had a short-term analysis (9 to 24 months postoperatively).Results: Participants were reasonably well-matched at baseline, although the DFEO + PTA group demonstrated greater crouch: minimum knee flexion, a median of 37° (width of the interquartile range, 12°) compared with 27° (9°); and knee flexion contracture, a median of 15° (10°) compared with 10° (5°). The gait deviation index (GDI) and sagittal plane knee kinematics were most improved at short term for the DFEO + PTA participants, with a subsequent slight decline at long-term analysis. Fewer DFEO + PTA participants were in crouch at long term (37% compared with 65%). At the long-term assessment, group scores for function, mobility, participation, quality of life, and most pain questionnaires were similar. Knee pain and osteoarthritis ratings did not differ between the groups.Conclusions: At long-term analysis, DFEO + PTA improves stance phase knee extension and knee flexion contracture compared with conventional treatment, but these benefits do not translate to improved activity, participation, or knee pain in early adulthood.Level Of Evidence: Therapeutic Level III. See Instructions for Authors for a complete description of levels of evidence. [ABSTRACT FROM AUTHOR]

A distal femoral extension osteotomy with patellar tendon advancement (DFEO+PTA) is a common treatment for individuals with cerebral palsy (CP) who walk in crouch. Musculoskeletal modeling suggests that the typical patella baja position post-DFEO+PTA may limit one's abilities to perform sit-to-stand (STS) tasks; however, STS function has not been assessed. Our purpose was to compare how well individuals who received a DFEO+PTA can perform a 5-times STS test (FTSST) eight or more years after surgery compared to their peers who did not receive a DFEO+PTA (non-DFEO+PTA group). Twenty-one participants completed the task (12 DFEO+PTA, 9 non-DFEO+PTA). Three-dimensional kinematics and kinetics were captured. Kinetics were non-dimensionalized to facilitate group comparisons. Non-DFEO+PTA participants performed the FTSST moderately faster than the DFEO+PTA group (median(IQR), 14.6(9.3) seconds vs. 20.3(10.1) seconds, non-parametric effect size ɣ=0.97, p=0.241). Peak negative knee power was larger for the non-DFEO+PTA group (Mean±SD, -0.063±0.025 vs. -0.048± 0.020, Cohen's d=0.66, p=0.165). A similar but weaker trend was observed for negative hip power (median(IQR) -0.120(0.066) vs. -0.105(0.044), ɣ=0.43, p=0.671). Both groups used their hips approximately twice as much as their knees to perform the task. The functional deficit among DFEO+PTA participants may be due to patella baja decreasing the knee extensor moment arm, which concurs with the modeling prediction. The group differences may also be due to the non-DFEO+PTA group being slightly higher functioning. Future research is warranted to determine if optimizing patella position during a DFEO+PTA may improve unaided STS function without compromising gait improvements. [ABSTRACT FROM AUTHOR]

BACKGROUND Pediatric musculoskeletal infection (MSKI) is a common cause of hospitalization with associated morbidity. To improve the care of pediatric MSKI, our objectives were to achieve 3 specific aims within 24 months of our quality improvement (QI) interventions: (1) 50% reduction in peripherally inserted central catheter (PICC) use, (2) 25% reduction in sedations per patient, and (3) 50% reduction in empirical vancomycin administration. METHODS: We implemented 4 prospective QI interventions at our tertiary children's hospital: (1) provider education, (2) centralization of admission location, (3) coordination of radiology-orthopedic communication, and (4) implementation of an MSKI infection algorithm and order set. We included patients 6 months to 18 years of age with acute osteomyelitis, septic arthritis, or pyomyositis and excluded patients with complex chronic conditions or ICU admission. We used statistical process control charts to analyze outcomes over 2 general periods: baseline (January 2015-October 17, 2016) and implementation (October 18, 2016-April 2019). RESULTS: In total, 224 patients were included. The mean age was 6.1 years, and there were no substantive demographic or clinical differences between baseline and implementation groups. There was an 81% relative reduction in PICC use (centerline shift 54%-11%; 95% confidence interval 70-92) and 33% relative reduction in sedations per patient (centerline shift 1.8-1.2; 95% confidence interval 21-46). Empirical vancomycin use did not change (centerline 20%). CONCLUSIONS: Our multidisciplinary MSKI QI interventions were associated with a significant decrease in the use of PICCs and sedations per patient but not empirical vancomycin administration. [ABSTRACT FROM AUTHOR]

Background Pelvic injuries in young children are rare, and it has been difficult to establish clinical guidelines to assist providers in managing blunt pelvic trauma, especially in non-Level 1 trauma centers. Objective Our aim was to describe the relationship among clinical findings, mechanism of injury, and the radiographic resources utilized in children with pelvic fractures presenting to a non-Level 1 trauma center. Methods A retrospective review of patients with a pelvic fracture treated in two urban pediatric Level 3 emergency departments was performed. Results Between 2001 and 2010, a total of 208 patients were identified. Avulsion/iliac wing fractures were the most common fractures (58.7%), and sports-related injuries were the most common mechanism of injury (50.0%). Children with sports-related injuries were more likely to sustain an avulsion fracture (p < 0.001), less likely to have a computed tomography scan obtained in the emergency department (p < 0.001), and less likely to have an associated injury (p < 0.001) than other children. Children struck by a motor vehicle (p < 0.001) or involved in a motor vehicle accident (p < 0.001) were more likely to receive a computed tomography scan (p < 0.001) and have associated head and extremity injuries (p < 0.001). Mechanism of injury was associated with abnormal computed tomography scans. Nearly all patients were treated nonoperatively (98.1%) and no deaths were reported in this study. Conclusions Patterns of injury, based on mechanism of injury, have been reported to assist the assessment and management of children with minor pelvic injuries. [ABSTRACT FROM AUTHOR]