TBX3 is essential for establishment of the posterior boundary of anterior genes and upregulation of posterior genes together with HAND2 during the onset of limb bud development.

During limb bud formation, axis polarities are established as evidenced by the spatially restricted expression of key regulator genes. In particular, the mutually antagonistic interaction between the GLI3 repressor and HAND2 results in distinct and non-overlapping anterior-distal Gli3 and posterior Hand2 expression domains. This is a hallmark of the establishment of antero-posterior limb axis polarity, together with spatially restricted expression of homeodomain and other transcriptional regulators.

Optimized protocol for whole-mount RNA fluorescent in situ hybridization using oxidation-mediated autofluorescence reduction on mouse embryos.

Tissue autofluorescence poses significant challenges for RNA and protein analysis using fluorescence-based techniques. Here, we present a protocol that combines oxidation-mediated autofluorescence reduction with detergent-based tissue permeabilization for whole-mount RNA-fluorescence in situ hybridization (FISH) on mouse embryonic limb buds. We describe the steps for embryo collection, fixation, photochemical bleaching, permeabilization, and RNA-FISH, followed by optical clearing of RNA-FISH and immunofluorescence samples for imaging.

Utility of intraoperative neurophysiological monitoring in detecting motor and sensory nerve injuries in pediatric high-grade spondylolisthesis.

Background Context: Intraoperative neuromonitoring (IONM) during surgical correction of spinal deformity has been shown to reduce iatrogenic injury in pediatric and adult populations. Although motor-evoked potentials (MEP), somatosensory-evoked potentials (SSEP), and electromyography (EMG) have been shown to be highly sensitive and specific in detecting spinal cord and nerve root injuries, their utility in detecting motor and sensory nerve root injury in pediatric high-grade spondylolisthesis (HGS) remains unknown.

Purpose: We aim to assess the diagnostic accuracy and therapeutic impact of unimodal and multimodal IONM in the surgical management of HGS.

Compartment Syndrome of All Extremities in the Setting of COVID-19-Induced Systemic Capillary Leak Syndrome With Superimposed Myositis.

Three years following the pandemic's emergence, COVID-19 has continued to affect much of the symptomatic population with widely varied respiratory complaints, fevers, numerous unexpected prodromal manifestations, and unknown long-term consequences. Scattered cases involving myopathies, rhabdomyolysis, and compartment syndrome have also been reported throughout the pandemic. Some similar cases have been attributed to systemic capillary leak syndrome (SCLS).

A spatio-temporally constrained gene regulatory network directed by PBX1/2 acquires limb patterning specificity via HAND2.

A lingering question in developmental biology has centered on how transcription factors with widespread distribution in vertebrate embryos can perform tissue-specific functions. Here, using the murine hindlimb as a model, we investigate the elusive mechanisms whereby PBX TALE homeoproteins, viewed primarily as HOX cofactors, attain context-specific developmental roles despite ubiquitous presence in the embryo. We first demonstrate that mesenchymal-specific loss of PBX1/2 or the transcriptional regulator HAND2 generates similar limb phenotypes.

A comparison of three- and two-rod constructs in the correction of severe pediatric scoliosis.

Purpose: Managing severe scoliosis is challenging and risky with a significant complication rate regardless of treatment strategy. In this retrospective comparative study, we report our results using a three-rod compared to two-rod construct in the surgical treatment of severe spine deformities to investigate which technique is safer, and which provides superior radiological outcomes.

Methods: Forty-six consecutive patients undergoing posterior spine fusion for scoliosis between 2006 and 2017 were identified in our institutional records.

Congenital cervicothoracic dissociation: report of two cases.

Purpose: Congenital cervicothoracic dissociation (CCTD) of the spine is a rare condition while having major impacts on stability and neurological function. Surgical treatment includes decompression and instrumented fusion. Only few cases of CCTD have been reported in children.

Increased proximal vertebral rotation is associated with shoulder imbalance after posterior spinal fusion for severe adolescent idiopathic scoliosis.

Purpose: Residual shoulder imbalance is associated with suboptimal outcomes following the surgical correction of adolescent idiopathic scoliosis (AIS) including poor patient satisfaction. In this retrospective study, we evaluate the radiographic parameters and the relationship between the global and local indices of spinal alignment with shoulder balance pre- and postoperatively utilizing EOS imaging and 3D reconstruction.

Methods: A retrospective radiographic analysis was performed on patients with AIS, treated with posterior spinal fusion.

The association between operating margin and surgical diversity at Critical Access Hospitals.

Context: Surgical volume is correlated with increased hospital profitability, yet many Critical Access Hospitals (CAHs) offer few or no inpatient surgical services.

Objectives: This study aims to investigate the impact of the presence of different inpatient surgical services on CAH profitability.

Methods: The study design was a cross-sectional analysis of financial data from the most recent fiscal year (FY) of 1299 CAHs.

SMAD4 target genes are part of a transcriptional network that integrates the response to BMP and SHH signaling during early limb bud patterning.

SMAD4 regulates gene expression in response to BMP and TGFβ signal transduction, and is required for diverse morphogenetic processes, but its target genes have remained largely elusive. Here, we identify the SMAD4 target genes in mouse limb buds using an epitope-tagged Smad4 allele for ChIP-seq analysis in combination with transcription profiling. This analysis shows that SMAD4 predominantly mediates BMP signal transduction during early limb bud development.

Conserved and species-specific chromatin remodeling and regulatory dynamics during mouse and chicken limb bud development.

Chromatin remodeling and genomic alterations impact spatio-temporal regulation of gene expression, which is central to embryonic development. The analysis of mouse and chicken limb development provides important insights into the morphoregulatory mechanisms, however little is known about the regulatory differences underlying their morphological divergence. Here, we identify the underlying shared and species-specific epigenomic and genomic variations.

Spatial regulation by multiple Gremlin1 enhancers provides digit development with cis-regulatory robustness and evolutionary plasticity.

Precise cis-regulatory control of gene expression is essential for normal embryogenesis and tissue development. The BMP antagonist Gremlin1 (Grem1) is a key node in the signalling system that coordinately controls limb bud development. Here, we use mouse reverse genetics to identify the enhancers in the Grem1 genomic landscape and the underlying cis-regulatory logics that orchestrate the spatio-temporal Grem1 expression dynamics during limb bud development.

Implant-Related Complications Using Uniaxial Implants In Pediatric Spinal Deformity Surgery.

Introduction:  The successful surgical treatment of paediatric spinal deformity relies on robust anchors to achieve correction. Uniaxial pedicle screws are designed with articulation between the screw head and screw shaft, thus reducing the risk of anchor failure whilst permitting corrective manoeuvres. The purpose of this study was to describe the incidence, nature, and chronology of implant-related complications in pediatric spinal deformity treated with uniaxial pedicle screws.

Correcting Scoliosis in Rett Syndrome.

Objectives Rett syndrome is a rare disorder characterised by severe scoliosis in 80% of cases. In this retrospective case series, we analysed the radiographic, clinical, and functional outcomes of consecutive patients treated for scoliosis associated with Rett syndrome. We sought to understand the results of the treatment of scoliosis in Rett syndrome and evaluate the need to fuse to the pelvis.

The Value Surgical Services Bring to Critical Access Hospitals.

Purpose Critical Access Hospitals (CAHs) serve rural populations and receive government subsidies to compensate for their relatively high overhead costs and low occupancy rates. Twenty-nine percent of all hospitalizations in the United States include a surgical procedure, and hospitalizations involving surgery accounted for nearly half of all hospital revenue in 2011. This study aims to determine the value surgical services bring to CAHs and their impact on the viability of these facilities.

Perioperative blood conservation strategies for pediatric scoliosis surgery.

Purpose: Many pediatric patients with severe scoliosis requiring surgery have baseline anemia. Pediatric scoliosis fusion surgery is associated with perioperative blood loss requiring transfusion. As such, many patients in this surgical population could benefit from a perioperative blood conservation program.

The Use of Halo Gravity Traction in Severe, Stiff Scoliosis.

Purpose: The correction of severe, stiff scoliosis in children is challenging. One method used to reduce the risk is preoperative halo gravity traction (HGT). In this study, the authors sought to define the efficiency and safety of HGT and characterize the chronology of the correction seen.

The use of three rods in correcting severe scoliosis.

Purpose: The three-rod technique, utilising a short apical concavity rod is an option to achieve controlled correction in severe scoliosis. We describe this technique, the complications encountered, and the long-term outcomes.

Method: All paediatric patients who had at least 2 years follow-up after undergoing corrective surgery for scoliosis ≥ 100° using 3 parallel rods were included.

Congenital Kyphosis: Progressive Correction With an Instrumented Posterior Epiphysiodesis: A Preliminary Report.

Purpose: Congenital kyphosis is a rare condition. In this case series we sought to identify the outcomes and complications of posterior instrumented fusion and the resultant epiphysiodesis effect in uniplanar congenital kyphosis in pediatric patients.

Method: Pediatric patients were included if treated for a uniplanar congenital kyphotic deformity treated with posterior instrumented spinal fusion between October 2006 and August 2017, with a minimum of 2 years of follow-up.

What is the Optimal Surgical Method for Achieving Correction and Avoiding Neurological Complications in Pediatric High-grade Spondylolisthesis?

Background: Controversy persists in the treatment of high-grade spondylolisthesis (HGS). Surgery is recommended in patients with intrusive symptoms and evidence debates the competing strategies. This study compares the radiologic outcomes and postoperative complications at a minimum of 2 years follow-up for patients with HGS treated with instrumented fusion with partial reduction (IFIS) with those treated with reduction, decompression, and instrumented fusion (RIF).

Gli3 utilizes Hand2 to synergistically regulate tissue-specific transcriptional networks.

Despite a common understanding that Gli TFs are utilized to convey a Hh morphogen gradient, genetic analyses suggest craniofacial development does not completely fit this paradigm. Using the mouse model (), we demonstrated that rather than being driven by a Hh threshold, robust Gli3 transcriptional activity during skeletal and glossal development required interaction with the basic helix-loop-helix TF Hand2. Not only did genetic and expression data support a co-factorial relationship, but genomic analysis revealed that Gli3 and Hand2 were enriched at regulatory elements for genes essential for mandibular patterning and development.

Impact of Various Weights in the Intraoperative Skull-Skeletal Traction on Correction of Adolescent Idiopathic Scoliosis.

Study Design: A retrospective study.

Objectives: Intraoperative skull-skeletal traction (ISST) facilitates the surgical scoliosis correction, but it is also associated with neurological risk. The objective of the present study was to investigate the impact of various traction weights on neurophysiological change and curve correction in surgery for adolescent idiopathic scoliosis (AIS).

Adolescent idiopathic scoliosis detection and referral trends: impact treatment options.

Study Design: Retrospective cross-sectional study.

Objective: To analyze the patient demographic referred for scoliosis to the Hospital for Sick Children to determine the proportion of patients suitable for brace treatment, as per the Scoliosis Research Society guidelines. There is level 1 evidence that bracing in adolescent idiopathic scoliosis (AIS) decreases the risk of curve progression and need for surgery, but optimal brace treatment requires early curve detection.

Spinal Casting for the Treatment of Severe Early Onset Scoliosis: Utilization of a Nonsurgical Health Care Provider for Cast Application.

Background: Spinal casting with the aim of delaying surgical intervention is a widely accepted but resource intensive conservative management strategy used by spine surgeons to treat severe early onset scoliosis. Opting to use a nonsurgical health care provider for cast application may be an effective use of human resources if the quality of care is not compromised. This study aimed to evaluate the outcomes of spinal cast treatment utilizing a nonsurgical health care provider for cast application.