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Tuning the molecular interaction between enzymes and their solvent environment through polymer modification can greatly improve activity and thus utility in biocatalytic reactions. In this work, this approach was exploited to enhance the activity of lipase A (LipA) from Bacillus subtilis in anhydrous ionic liquids (ILs), which are highly attractive solvents for biocatalysis. Specifically, we showed that the transesterification activity of LipA in anhydrous 1-butyl-3-methyl imidazolium hexafluorophosphate ([BMIM][PF6]) was improved up to 19-fold via covalently conjugating the enzyme with the IL-soluble polymer poly(4-acryloylmorpholine) (PAcMO). The increase in transesterification activity correlated with an increase in LipA solubility in [BMIM][PF6] as well as, notably, the number of conjugated PAcMO repeat units. Light scattering results further showed that the attachment of PAcMO disrupted the aggregation of LipA in aqueous buffer, which was used as a proxy to understand the mechanism of activation of LipA in the IL, where aggregation was more pronounced. Additionally, using static light scattering, the Flory-Huggins interaction parameter (χ) for the polymer-IL interactions was determined (0.457). The favorable PAcMO-IL interactions presumably compensated for the unfavorable interactions between the enzyme and IL, which resulted in the improvement in dissolution and, in turn, activity due to reduced diffusional limitations. Through rationally considering χ, a similar approach may be used to tune the molecular interaction between other enzymes and ILs with other polymers, which has widespread implications for the enhancement of biocatalysis in ILs.
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Bacillus subtilis/enzimología , Líquidos Iónicos/química , Lipasa/química , Polímeros/química , Acrilamidas/química , Biocatálisis , Esterificación , Lipasa/síntesis química , Morfolinas/química , Polímeros/síntesis química , SolubilidadRESUMEN
INTRODUCTION: Rapid recovery pathways (RRP) for adolescent idiopathic scoliosis patients undergoing posterior spinal instrumentation and fusion (PSIF) have been shown to be successful in reducing hospital length of stay (LOS). Although the majority of patients are discharged within 3 days, some patients require longer hospital admission. Previous studies in the United States have identified predictors of prolonged LOS for this patient population. The goal of this project was to determine if these predictors are the same for Canadian scoliosis patients and to identify those features which are different under this single-payer system. METHODS: A RRP for scoliosis surgery was implemented in March 2015 at a single, tertiary referral children's hospital in Canada. Previously identified features, along with numerous other patient factors, were collected. Spearman correlations were used to determine the factors most associated with hospital LOS and those factors were used in a multivariable regression model. RESULTS: A total of 161 patients were included in the analysis. Of the previously identified patient factors, only receiving a peri-operative transfusion was found to be significant (ρ = 0.24; p = 0.002). None of the other pre-identified variables were found to be significantly correlated with LOS. Variables not previously examined that were found to be significantly correlated with hospital LOS included ASA status (ρ = 0.19, p = 0.046), fusion involving both the thoracic and lumbar spine (ρ = 0.18, p = 0.025), and receiving celecoxib on post-operative day 1 (ρ = - 0.16; p = 0.038). The features that had the greatest association with LOS through multivariable regression was receiving a blood transfusion (B = 0.48; 95%CI 0.096-0.89; p = 0.017). CONCLUSIONS: In this study, we found that many of the features found to be significantly correlated with prolonged hospital LOS in the United States are not transferable to the Canadian healthcare system. This is important for the Canadian, and other surgeons in a single-payer system, in order to identify pre-operative or immediate post-operative factors that may extend patient LOS following PSIF and plan resources accordingly. LEVEL OF EVIDENCE: III; therapeutic.
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Cifosis , Escoliosis , Niño , Humanos , Adolescente , Estados Unidos , Escoliosis/cirugía , Escoliosis/epidemiología , Tiempo de Internación , Sistema de Pago Simple , Canadá , Atención a la SaludRESUMEN
Cutaneous-skeletal hypophosphatemia syndrome (CSHS) is a rare bone disorder featuring fibroblast growth factor-23 (FGF23)-mediated hypophosphatemic rickets. We report a 2-year, 10-month-old girl with CSHS treated with burosumab, a novel human monoclonal antibody targeting FGF23. This approach was associated with rickets healing, improvement in growth and lower limb deformity, and clinically significant benefit to her functional mobility and motor development. This case report provides evidence for the effective use of FGF23-neutralizing antibody therapy beyond the classic FGF23-mediated disorders of X-linked hypophosphatemia and tumor-induced osteomalacia.
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PURPOSE: Posterior spinal fusion and instrumentation (PSF) and vertebral body tethering (VBT) are corrective surgical techniques used in treating adolescent idiopathic scoliosis (AIS). Comparing the preservation of spine range of motion (ROM) following PSF and VBT for treatment of AIS has yet to be explored. The purpose of this work was to retrospectively compare global spine ROM in adolescents (9-18 years of age) without spine deformity, adolescents with untreated AIS, adolescents having undergone PSF, and adolescents having undergone VBT to gain insight on the effect of VBT on spine motion. METHODS: Twenty participants were recruited into four groups including Control (n = 6), untreated AIS (n = 5), post-operative PSF (n = 4) and post-operative VBT (n = 5). Three-dimensional kinematics of the spine were collected and analyzed using an intersegmental spine model during constrained forward flexion, right-left lateral bending, and right-left axial twist movements. RESULTS: The PSF group displayed significantly lower spine ROM than the two non-operative groups during thoracic and total left axial twist (p ≤ 0.048), whereas thoracic and total ROM during right-left lateral bending is almost equally lower in the PSF (p ≤ 0.03) and VBT (p ≤ 0.01) groups when compared to the Control and AIS groups. CONCLUSION: These results suggest some preservation of spine motion in the transverse plane following VBT. This study provides initial evidence of some potential preservation of spine ROM following VBT; however, further prospective investigation of VBT is needed to assess and confirm these hypotheses.
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Cifosis , Escoliosis , Adolescente , Humanos , Escoliosis/cirugía , Proyectos Piloto , Cuerpo Vertebral , Estudios Retrospectivos , Rango del Movimiento ArticularRESUMEN
Osteomyelitis of the acetabulum is a rare condition accounting for only 12% of pelvic osteomyelitis cases. This report describes a previously healthy 10-year-old girl with subacute acetabular osteomyelitis and subsequent development of secondary septic arthritis of the hip. The patient presented with 3 weeks of groin pain, elevated erythrocyte sedimentation rate and C-reactive protein, synovial thickening of the hip on ultrasonography and diffuse signal uptake in the acetabulum on magnetic resonance imaging. Despite antibiotic therapy, her symptoms worsened clinically, and repeat Magnetic resonance imaging images showed worsening of the osteomyelitis with likely extension through the acetabulum and into the joint. A hip aspirate was positive for Fusobacterium, an atypical anaerobe. Hip arthroscopy, with identification of the site of extrusion and then extensive débridement and irrigation, was successful in helping to control and ultimately eradicate the infection. The patient regained normal hip function and returned to full activities. This case demonstrates how hip arthroscopy can serve as an important surgical treatment modality for acetabular osteomyelitis with intraarticular extension in addition to septic arthritis of the hip.
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Artritis Infecciosa , Osteomielitis , Acetábulo/diagnóstico por imagen , Artritis Infecciosa/diagnóstico , Artroscopía , Niño , Femenino , Humanos , Imagen por Resonancia Magnética , Osteomielitis/diagnóstico por imagenRESUMEN
PURPOSE: The purpose of this project was to determine if it is feasible to implement a rapid recovery pathway (RRP) for the surgical treatment of adolescent idiopathic scoliosis (AIS) within a single-payer universal healthcare system while simultaneously decreasing length of stay (LOS) without increasing post-operative complications. METHODS: A retrospective analysis was completed for all patients who underwent posterior spinal fusion for AIS at a tertiary children's hospital in Canada between March 2010 and February 2019, with date of implementation of the RRP being March 1st, 2015. Patient demographic information was collected along with a variety of outcome variables including: LOS, wound complication, infection, 30-day return to the OR, 30-day emergency department visit, and 30-day hospital readmission. An interrupted time series analysis was utilized to determine if any benefits were associated with the implementation of the RRP. RESULTS: A total of 244 patients were identified, with 113 patients in the conventional pathway and 131 in the RRP. No significant differences in demographic features or post-operative complications were found between the two cohorts (p > 0.05). Using a robust linear time series model, LOS was found to be significantly shorter in the RRP group, with the average LOS being 5.2 [95% IQR 4.3-6.1] days in the conventional group and 3.4 [95% IQR 3.3-3.5] days in the RRP group (p < 0.05). CONCLUSION: This study shows that it is possible to implement a RRP for the surgical treatment of AIS within a single-payer universal healthcare system. Use of the pathway can effectively reduce hospital LOS without increasing the risk of developing a post-operative complication. This has the upside potential to reduce healthcare and family costs. LEVEL OF EVIDENCE: Therapeutic III.
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Vías Clínicas , Atención a la Salud , Recuperación de la Función , Escoliosis/cirugía , Fusión Vertebral/instrumentación , Columna Vertebral/cirugía , Atención de Salud Universal , Adolescente , Factores de Edad , Canadá , Ahorro de Costo , Atención a la Salud/economía , Estudios de Factibilidad , Femenino , Humanos , Tiempo de Internación/estadística & datos numéricos , Masculino , Escoliosis/fisiopatología , Fusión Vertebral/métodos , Factores de TiempoRESUMEN
BACKGROUND CONTEXT: Although 40% of adolescent idiopathic scoliosis (AIS) patients present with chronic back pain, the pathophysiology and underlying pain mechanisms remain poorly understood. We hypothesized that development of chronic pain syndrome in AIS is associated with alterations in pain modulatory mechanisms. PURPOSE: To identify the presence of sensitization in nociceptive pathways and to assess the efficacy of the diffuse noxious inhibitory control in patients with AIS presenting with chronic back pain. STUDY DESIGN: Cross-sectional study. PATIENT SAMPLE: Ninety-four patients diagnosed with AIS and chronic back pain. OUTCOME MEASURES: Quantitative sensory testing (QST) assessed pain modulation and self-reported questionnaires were used to assess pain burden and health-related quality of life. METHODS: Patients underwent a detailed pain assessment using a standard and validated quantitative sensory testing (QST) protocol. The measurements included mechanical detection thresholds (MDT), pain pressure threshold (PPT), heat pain threshold (HPT), heat tolerance threshold (HTT), and a conditioned pain modulation (CPM) paradigm. Altogether, these tests measured changes in regulation of the neurophysiology underlying the nociceptive processes based on the patient's pain perception. Funding was provided by The Louise and Alan Edwards Foundation and The Shriners Hospitals for Children. RESULTS: Efficient pain inhibitory response was observed in 51.1% of patients, while 21.3% and 27.7% had sub-optimal and inefficient CPM, respectively. Temporal summation of pain was observed in 11.7% of patients. Significant correlations were observed between deformity severity and pain pressure thresholds (p=.023) and CPM (p=.017), neuropathic pain scores and pain pressure thresholds (p=.015) and temporal summation of pain (p=.047), and heat temperature threshold and pain intensity (p=.048). CONCLUSIONS: Chronic back pain has an impact in the quality of life of adolescents with idiopathic scoliosis. We demonstrated a high prevalence of impaired pain modulation in this group. The association between deformity severity and somatosensory dysfunction may suggest that spinal deformity can be a trigger for abnormal neuroplastic changes in this population contributing to chronic pain syndrome.