Insulin resistance in skeletal muscle is a key phenotype associated with type 2 diabetes (T2D) for which the molecular mediators remain unclear. We therefore conducted an expression analysis of human muscle biopsies from patients with T2D; normoglycemic but insulin-resistant subjects with a parental family history (FH + ) of T2D; and family history-negative control individuals (FH -). Actin cytoskeleton genes regulated by serum response factor (SRF) and its coactivator megakaryoblastic leukemia 1 (MKL1) had increased expression in T2D and FH + groups. Furthermore, striated muscle activator of Rho signaling (STARS), an activator of SRF, was upregulated in T2D and FH + and was inversely correlated with insulin sensitivity. Skeletal muscle from insulin-resistant mice recapitulated this gene expression pattern and showed reduced G-actin and increased nuclear localization of MKL1, each of which regulates SRF activity. Overexpression of MKL1 or reduction in G-actin decreased insulin-stimulated Akt phosphorylation, whereas reduction of STARS expression increased insulin signaling and glucose uptake. Pharmacological SRF inhibition by CCG-1423 reduced nuclear MKL1 and improved glucose uptake and tolerance in insulin-resistant mice in vivo. Thus, SRF pathway alterations are linked to insulin resistance, may contribute to T2D pathogenesis, and could represent therapeutic targets.

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Abstract. Near-infrared spectroscopy (NIRS) is a technique by which the interaction between light in the nearinfrared spectrum and matter can be quantitatively measured to provide information about the particular chromophore. Study into the clinical application of NIRS for traumatic brain injury (TBI) began in the 1990s with early reports of the ability to detect intracranial hematomas using NIRS. We highlight the advances in clinical applications of NIRS over the past two decades as they relate to TBI. We discuss recent studies evaluating NIRS techniques for intracranial hematoma detection, followed by the clinical application of NIRS in intracranial pressure and brain oxygenation measurement, and conclude with a summary of potential future uses of NIRS in TBI patient management. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

Object Upper cervical spine injuries in the pediatric age group have been recognized as extremely unstable from ligamentous disruption and as potentially lethal. Few measurement norms have been published for the pediatric upper cervical spine to help diagnose this pathological state. Instead, adult measurement techniques and results are usually applied inappropriately to children. The authors propose using high-resolution reconstructed CT scans to define a range of normal for a collection of selected upper cervical spine measurements in the pediatric age group. Methods Sagittal and coronal reformatted images were obtained from thin axial CT scans obtained in 42 children (< 18 years) in a 2-month period. There were 25 boys and 17 girls. The mean age was 100.9 months (range 1–214 months). Six CT scans were obtained for nontrauma indications, and 36 were obtained as part of a trauma protocol and later cleared for cervical spine injury. Six straightforward and direct linear distances—basion-dental interval (BDI); atlantodental interval (ADI); posterior atlantodental interval (PADI); right and left lateral mass interval (LMI); right and left craniocervical interval (CCI); and prevertebral soft-tissue thickness at C-2—that minimized logistical and technical distortions were measured and recorded. Statistical analysis including interobserver agreement, age stratification, and sex differences was performed for each of the 6 measurements. Results The mean ADI was 2.25 ± 0.24 mm (± SD), the mean PADI was 18.3 ± 0.07 mm, the mean BDI was 7.28 ± 0.10 mm, and the mean prevertebral soft tissue width at C-2 was 4.45 ± 0.43 mm. The overall mean CCI was 2.38 ± 0.44 mm, and the overall mean LMI was 2.91 ± 0.49 mm. Linear regression analysis demonstrated statistically significant age effects for PADI (increased 0.02 mm/month), BDI (decreased 0.02 mm/month), and CCI (decreased 0.01 mm/month). Similarly significant effects were found for sex; females demonstrated on average a smaller CCI by 0.26 mm and a smaller PADI by 2.12 mm. Moderate to high interrater reliability was demonstrated across all parameters. Conclusions Age-dependent and age-independent normal CT measurements of the upper cervical spine will help to differentiate physiological and pathological states in children. The BDI appears to change significantly with age but not sex; on the other hand, the LMI and ADI appear to be age-independent measures. This preliminary study suggests acceptable levels of interrater reliability, and further expanded study will aim to validate these measurements to produce a profile of normal upper cervical spine measurements in children.

Object Quality improvement methods are being implemented in various areas of medicine. In an effort to reduce the complex (instrumented) spine infection rate in pediatric patients, a standardized protocol was developed and implemented at an institution with a high case volume of instrumented spine fusion procedures in the pediatric age group. Methods Members of the Texas Children's Hospital Spine Study Group developed the protocol incrementally by using the current literature and prior institutional experience until consensus was obtained. The protocol was prospectively applied to all children undergoing complex spine surgery starting August 21, 2012. Acute infections were defined as positive wound cultures within 12 weeks of surgery, defined in alignment with current hospital infection control criteria. Procedures and infections were measured before and after protocol implementation. This protocol received full review and approval of the Baylor College of Medicine institutional review board. Results Nine spine surgeons performed 267 procedures between August 21, 2012, and September 30, 2013. The minimum follow-up was 12 weeks. The annual institutional infection rate prior to the protocol (2007–2011) ranged from 3.4% to 8.9%, with an average of 5.8%. After introducing the protocol, the infection rate decreased to 2.2% (6 infections of 267 cases) (p = 0.0362; absolute risk reduction 3.6%; relative risk 0.41 [95% CI 0.18–0.94]). Overall compliance with data form completion was 63.7%. In 4 of the 6 cases of infection, noncompliance with completion of the data collection form was documented; moreover, 2 of the 4 spine surgeons whose patients experienced infections had the lowest compliance rates in the study group. Conclusions The standardized protocol for complex spine surgery significantly reduced surgical site infection at the authors' institution. The overall compliance with entry into the protocol was good. Identification of factors associated with post–spine surgery wound infection will allow further protocol refinement in the future.

Patients suffering from disorders of consciousness constitute a population that exists largely outside of the daily practice patterns of neurosurgeons. Historically, treatment has focused on nursing and custodial issues with limited neurosurgical intervention. Recently, however, deep brain stimulation has been explored to restore cognitive and physical function to patients in minimally conscious states. In this article, the authors characterize the physiological mechanisms for the use of deep brain stimulation in persistently vegetative and minimally conscious patients, review published cases and associated ethical concerns, and discuss future directions of this technology.

Object There are rare indications for upper cervical spine fusion in young children. Compared with nonrigid constructs, rigid instrumentation with screw fixation increases the fusion rate and reduces the need for halo fixation. Instrumentation may be technically challenging in younger children. A number of screw placement techniques have been described. Use of C-2 translaminar screws has been shown to be anatomically feasible, even in the youngest of children. However, there are few data detailing the clinical outcome. In this study, the authors describe the clinical and radiographic follow-up of 18 children 5 years of age or younger who had at least one C-2 translaminar screw as part of an occipitocervical or C1–2 fusion construct. Methods A retrospective review of all children treated with instrumented occipitocervical or C1–2 fusion between July 1, 2007, and June 30, 2013, at Riley Children's Hospital and Texas Children's Hospital was performed. All children 5 years of age or younger with incorporation of at least one C-2 translaminar screw were identified. Results Eighteen children were studied (7 boys and 11 girls). The mean age at surgery was 38.1 months (range 10–68 months). Indications for surgery included traumatic instability (6), os odontoideum (3), destructive processes (2), and congenital instability (7). A total of 24 C-2 translaminar screws were placed; 23 (95.8%) of 24 were satisfactorily placed (completely contained within the cortical walls). There was one medial cortex breach without neurological impingement. There were no complications with screw placement. Three patients required wound revisions. Two patients died as a result of their original condition (trauma, malignant tumor). The mean follow-up duration for the surviving patients was 17.5 months (range 3–60 months). Eleven (91.7%) of the 12 patients followed for 6 months or longer showed radiographic stability or completed fusion. Conclusions Use of C-2 translaminar screws provides an effective anchor for internal fixation of the upper cervical spine. In this study of children 5 years of age or younger, the authors found a high rate of radiographic fusion with a low rate of complications.