24 research outputs found
Synthesis of β-Branched Tryptophan Analogues Using an Engineered Subunit of Tryptophan Synthase
We report that l-threonine may substitute for l-serine in the β-substitution reaction of an engineered subunit of tryptophan synthase from Pyrococcus furiosus, yielding (2S,3S)-β-methyltryptophan (β-MeTrp) in a single step. The trace activity of the wild-type β-subunit on this substrate was enhanced more than 1000-fold by directed evolution. Structural and spectroscopic data indicate that this increase is correlated with stabilization of the electrophilic aminoacrylate intermediate. The engineered biocatalyst also reacts with a variety of indole analogues and thiophenol for diastereoselective C–C, C–N, and C–S bond-forming reactions. This new activity circumvents the 3-enzyme pathway that produces β-MeTrp in nature and offers a simple and expandable route to preparing derivatives of this valuable building block
A systematic review of heterosexual anal intercourse and its role in the transmission of HIV and other sexually transmitted infections in Papua New Guinea
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Management and treatment of musculoskeletal problems in adults with cerebral palsy: Experience gained from two lifespan clinics
Serial casting for early onset scoliosis and its effects on health-related quality of life during and after discontinuation of treatment.
© 2020, Scoliosis Research Society. Introduction: Serial body casting plays an important role in the treatment of early onset scoliosis (EOS), serving as a safer method compared to surgical intervention. There is no published evidence documenting the impact of casting on health-related quality of life (HRQoL) of patients and their caregivers. The purpose of this study was to utilize the 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24) to compare the HRQoL of patients with EOS and the burden of care for their caregivers before, during, and after treatment with Mehta casting. Methods: In this multicenter retrospective cohort study, two EOS databases were queried for patients with EOS who underwent serial casting from 2005 to 2016. Patients who had treatment prior to their initial cast application, including bracing or surgical intervention, were excluded from the study. Patients were stratified into two subgroups and analyzed separately: those with idiopathic etiology, and those with non-idiopathic etiology. HRQoL and burden of care were assessed using the EOSQ-24 completed before, during, and after cast treatment. Results: 91 patients were identified in this study (mean age at the index casting: 2.1 ± 1.2 years, mean age at final cast removal: 4.1 ± 1.3 years). 59 (64.8%) had EOS of idiopathic etiology, while 32 (35.2%) had EOS of non-idiopathic etiology, including 10 congenital, 6 neuromuscular, and 16 syndromic. Idiopathic patients and non-idiopathic patients experienced an improvement in the coronal deformity from 45° pre-cast to 26° post-cast, and from 59° pre-cast to 34° post-cast, respectively. Patients with idiopathic scoliosis experienced a decrease from baseline in nearly all EOSQ-24 sub-domain scores except for general health. Furthermore, even after the removal of the cast, patients with idiopathic etiology suffered residual negative effects of casting on emotion and transfer sub-domains. Among patients with non-idiopathic etiology, decreased scores from baseline were observed only in transfer and emotion sub-domains during the casting intervention. After brace removal, patients with non-idiopathic etiology had increased scores compared to their baseline scores in most sub-domains. Discussion: Serial body casting can prevent curve correction in patients with EOS. However, the psychosocial stresses secondary to this non-operative intervention can have significant negative impacts on HRQoL for both idiopathic and non-idiopathic patients during the course of treatment. Although non-idiopathic patients experience improved HRQoL following treatment, idiopathic patients do not seem to exhibit much improvement in HRQoL from baseline even years after the final cast removal
Serial casting for early onset scoliosis and its effects on health-related quality of life during and after discontinuation of treatment
© 2020, Scoliosis Research Society. Introduction: Serial body casting plays an important role in the treatment of early onset scoliosis (EOS), serving as a safer method compared to surgical intervention. There is no published evidence documenting the impact of casting on health-related quality of life (HRQoL) of patients and their caregivers. The purpose of this study was to utilize the 24-Item Early Onset Scoliosis Questionnaire (EOSQ-24) to compare the HRQoL of patients with EOS and the burden of care for their caregivers before, during, and after treatment with Mehta casting. Methods: In this multicenter retrospective cohort study, two EOS databases were queried for patients with EOS who underwent serial casting from 2005 to 2016. Patients who had treatment prior to their initial cast application, including bracing or surgical intervention, were excluded from the study. Patients were stratified into two subgroups and analyzed separately: those with idiopathic etiology, and those with non-idiopathic etiology. HRQoL and burden of care were assessed using the EOSQ-24 completed before, during, and after cast treatment. Results: 91 patients were identified in this study (mean age at the index casting: 2.1 ± 1.2 years, mean age at final cast removal: 4.1 ± 1.3 years). 59 (64.8%) had EOS of idiopathic etiology, while 32 (35.2%) had EOS of non-idiopathic etiology, including 10 congenital, 6 neuromuscular, and 16 syndromic. Idiopathic patients and non-idiopathic patients experienced an improvement in the coronal deformity from 45° pre-cast to 26° post-cast, and from 59° pre-cast to 34° post-cast, respectively. Patients with idiopathic scoliosis experienced a decrease from baseline in nearly all EOSQ-24 sub-domain scores except for general health. Furthermore, even after the removal of the cast, patients with idiopathic etiology suffered residual negative effects of casting on emotion and transfer sub-domains. Among patients with non-idiopathic etiology, decreased scores from baseline were observed only in transfer and emotion sub-domains during the casting intervention. After brace removal, patients with non-idiopathic etiology had increased scores compared to their baseline scores in most sub-domains. Discussion: Serial body casting can prevent curve correction in patients with EOS. However, the psychosocial stresses secondary to this non-operative intervention can have significant negative impacts on HRQoL for both idiopathic and non-idiopathic patients during the course of treatment. Although non-idiopathic patients experience improved HRQoL following treatment, idiopathic patients do not seem to exhibit much improvement in HRQoL from baseline even years after the final cast removal
Treatment of congenital pseudarthrosis of the tibia with recombinant human bone morphogenetic protein-7 (rhBMP-7). A report of five cases
Congenital pseudarthrosis of the tibia is one of the most
frustrating conditions encountered in pediatric orthopaedics
because of the difficulty in achieving healing.
Numerous treatment options have been explored with varying
degrees of success1-19. Although some reports have demonstrated
successful healing7,9,19, it is very difficult to restore the
normal structural and functional integrity of the bone such as
that which occurs after treatment of other types of fractures in
children. Advances in molecular biology have provided a better
understanding of the mechanisms of fracture-healing as well
as possible new solutions for the problem, including the use
of bone morphogenetic protein (BMP)20-24. In a controlled,
prospective, randomized study of 124 tibial nonunions (in
122 adult patients) treated with insertion of an intramedullary
rod and recombinant human (rh) BMP-7, no significant
difference (p = 0.939) was noted between the BMP group
and the group that received an intramedullary rod and autogenous
iliac crest bone grafts20. In a prospective, randomized,
controlled, single-blind study of 450 patients with an
open tibial fracture, patients who were treated with rhBMP-
2 (1.50 mg/mL) had significantly (p = 0.005) superior results
compared with patients who were treated with intramedullary
nail fixation and routine soft-tissue management as dictated
by the injury21. These two large clinical series suggest
that BMPs may be a good alternative to autogenous iliaccrest
bone-grafting.
Bone morphogenetic proteins have shown promising
results in experimental animal models, and their clinical efficacy
has been shown in the treatment of adult tibial nonunions
and in spinal fusion20-24. They have not been tested in
children because of uncertainty as to the effect on adjacent
physes and because of concern about unexpected reactions.
The use of BMP to treat congenital pseudarthrosis of the tibia
is a logical approach because the results from both animal
studies and human trials have suggested that BMP is efficacious
in bone-healing. This prospective study was undertaken
to determine the clinical efficacy and safety of the use of
rhBMP-7 for the treatment of congenital pseudarthrosis of the
tibia in skeletally immature patients and to compare the results
with those of previously published studies in which autogenous
iliac-crest bone grafts have been used in conjunction
with various fixation methods
Improvement in a post-stroke pediatric patient with hemiplegia: Use of a hand-arm bimanual intensive therapy with hybrid assistive limb
Background: Pediatric stroke is a rare medical condition that often leads to long-lasting motor and cognitive impairments. Although therapies for adults after a stroke are well described, treatments for motor deficits following a pediatric stroke are yet to be investigated. We report a case of pediatric stroke in the chronic phase, in which a combination of novel treatments resulted in a significant improvement in physical function. Case report: A seven-year-old girl with a left hemispheric cerebral infarction lost almost all right upper extremity motor function. Following onabotulinumtoxinA treatment, she underwent hand-arm bimanual intensive therapy augmented with a hybrid assistive limb for 90 h over 15 days. Evaluation after the training revealed significant improvements in physical function, daily activities, and occupational performance. Conclusions: This report highlights the importance of innovative combinations of techniques in the treatment of pediatric stroke