No abstract

The pro-apoptotic Bax isoform BaxΔ2 was originally discovered in cancer patients with a microsatellite guanine deletion (G8 to G7). This deletion leads to an early stop codon; however, when combined with the alternative splicing of exon 2, the reading frame is restored allowing production of a full-length protein (BaxΔ2). Unlike the parental Baxα, BaxΔ2 triggers apoptosis through a non-mitochondrial pathway and the expression in human tissues was unknown. Here, we analyzed over 1000 tissue microarray samples from 13 different organs using immunohistochemistry. BaxΔ2-positive cells were detected in all examined organs at low rates (1-5%) and mainly scattered throughout the connective tissues. Surprisingly, over 70% of normal colon samples scored high for BaxΔ2-positive staining. Only 7% of malignant colon samples scored high, with most high-grade tumors being negative. A similar pattern was observed in most organs examined. We also showed that both Baxα and BaxΔ2 can co-exist in the same cells. Genotyping showed that the majority of BaxΔ2-positive normal tissues contain no G7 mutation, but an unexpected high rate of G9 was observed. Although the underlying mechanism remains to be explored, the inverse correlation of BaxΔ2 expression with tissue malignancy suggests that it may have a clinical implication in cancer development and treatment.

While the peripheral nervous system has regenerative ability, restoration of sufficient function remains a challenge. Vimentin has been shown to be localized in axonal growth fronts and associated with nerve regeneration, including myelination, neuroplasticity, kinase signaling in nerve axoplasm, and cell migration; however, the mechanisms regulating its expression within Schwann cell (SC) remain unexplored. The aim of this study was to profile the spatial and temporal expression profile of microRNA (miRNA) in a regenerating rat sciatic nerve after transection, and explore the potential role of miR-138-5p targeting vimentin in SC proliferation and migration. A rat sciatic nerve transection model, utilizing a polyethylene nerve guide, was used to investigate miRNA expression at 7, 14, 30, 60, and 90 days during nerve regeneration. Relative levels of miRNA expression were determined using microarray analysis and subsequently validated with quantitative real-time polymerase chain reaction. In vitro assays were conducted with cultured Schwann cells transfected with miRNA mimics and assessed for migratory and proliferative potential. The top seven dysregulated miRNAs reported in this study have been implicated in cell migration elsewhere, and GO and KEGG analyses predicted activities essential to wound healing. Transfection of one of these, miRNA-138-5p, into SCs reduced cell migration and proliferation. miR-138-5p has been shown to directly target vimentin in cancer cells, and the luciferase assay performed here in rat Schwann cells confirmed it. These results detail a role of miR-138-5p in rat peripheral nerve regeneration and expand on reports of it as an important regulator in the peripheral nervous system.

Skeletal maturity is a critical consideration for pediatric orthopedic surgeons, general pediatricians, endocrinologists, metabolic bone disease specialists, rheumatologists, and physiatrists in the development and modification of treatment plans for growing children. Arguably the most widely utilized method of determining skeletal age, the Greulich and Pyle method (GPM), unfortunately has many shortcomings. Between the method reflecting limited population metrics and its reliance on a voluminous hard-copy radiographic atlas, the GPM may not lend itself to widespread use or optimized learning in the modern era of orthopedics. In 2013, the Shorthand Bone Age (SBA) method suggested a simpler approach by demonstrating reliability when just a single feature for each skeletal age, depending on patient sex, was sufficient in providing an accurate bone age estimate reflective of the full GPM. In addition to the SBA, an expanding body of research has emerged over the past two decades, attempting to provide the orthopedic community with simpler yet effective tools to determine skeletal age. In this review, we compare and present the spectrum of current concepts encompassing validated bone age determination methods for each of six commonly imaged anatomic locations: hand/wrist, elbow, shoulder/proximal humerus, hip/pelvis, knee, foot/ankle. All methods are presented visually in table format, with detailed graphic design, quantitative approximations to generate relative consistency between systems, and age-based color-coding for ease of memorization and use. All images are derived from patients presenting to the study institution within the past three months, so as to harness modern image quality and populations while also adhering to the principles and age-based features inherent to each system’s different categories. The purpose of this review is multifaceted: to enable better incorporation of skeletal age considerations into daily practice by caregivers in many disciplines; to enhance awareness regarding the full array of tools that may spare young patients additional and unnecessary radiation; and to serve as a springboard for a mobile application to be utilized in any clinical setting by anyone with a mobile device.

Background: Radial head and neck fracture malunion can lead to pain, stiffness, deformity, and functional limitations. This study analyzed the early radiographic and functional outcomes of corrective osteotomy for symptomatic radial head and/or neck malunion in skeletally immature patients. Methods: Thirteen pediatric patients treated with corrective osteotomy for symptomatic radial head and/or neck malunion from 2004 to 2018 were identified. Radiographic union, range of motion, pain, and complications were recorded. Functional outcomes were assessed using the Broberg and Morrey Elbow Scale. Results: The average age at the time of surgery was 12.3 years (range: 8.6 to 16.3). The mean time from injury to osteotomy was 7.5 months (range: 2 to 24.1 mo). Before osteotomy, mean radial head-shaft angulation was 23 degrees (range: 5 to 57 degrees), mean displacement was 76% (range: 0 to 55), average elbow flexion contracture was 18 degrees (range: 0 to 60 degrees), and average elbow flexion was 112 degrees (range: 95 to 135 degrees). After a mean follow-up of 14.3 months, 12 of 13 osteotomies (92%) healed; 1 patient had a painless nonunion. The number of patients reporting pain decreased from 9 to 2 (P=0.012). Radiographic alignment and range of motion improved in all patients. Mean angulation and displacement improved to 8 degrees (range: 2 to 15 degrees, P=0.001) and 3% (range: 0 to 18 degrees, P=0.001), respectively. Mean elbow flexion contracture was reduced to 5 degrees (range: 0 to 30 degrees, P=0.008), and the average elbow flexion increased to 128 degrees (range: 100 to 135 degrees, P<0.001). Three patients underwent implant removal for complications, including heterotopic ossification and avascular necrosis. Physeal arrest did not lead to any adverse sequelae. The sole case of avascular necrosis had a reduced range of motion but no pain. The mean postoperative Broberg and Morrey score was 91.1; 7 patients had excellent postoperative scores, 4 good, and 2 fair. Conclusions: Corrective osteotomy for symptomatic malunion of the radial head and/or neck in skeletally immature patients can improve elbow alignment, motion, pain, and function. Preservation of the soft-tissue attachments to the proximal epiphysis and rigid internal fixation are critical components of this surgical technique. Level of Evidence: Therapeutic Level IV.