Citations

Background: The radiolunate joint is conventionally thought to be spared from radiocarpal osteoarthritis, but proximal lunate degenerative changes have been noted. An investigation of radiolunate arthrokinematics in ostensibly healthy wrists may improve understanding of posttraumatic and postoperative outcomes. We hypothesize that four-dimensional computed tomography (4DCT)-derived radiolunate arthrokinematics during motion will differ between wrists with type 1 and type 2 lunates. The clinical-translational relevance of this analysis is highlighted using a 4DCT case study of scaphoid excision with 4-corner arthrodesis (SEFCA). Methods: Four-dimensional computed tomography data were collected during flexion-extension and radioulnar deviation in 19 healthy wrists (mean [SD] age: 43.6 [11.7] years, 21.1% female) and 1 wrist 3 years after SEFCA (male, 52 years). Carpal osteokinematics and joint arthrokinematics were calculated to derive median radiolunate interosseous proximities at each 4DCT-captured timepoint. Results: Median radiolunate interosseous proximities during motion are well approximated by second-order regressions in uninjured wrists. In the arthrodesed wrist, closest proximities occurred at the extremes of motion except maximum radial deviation. Conclusions: This study quantifies a normative range of median radiolunate interosseous proximities during wrist motion. The normative 4DCT datasets provide a reference range for evaluating postoperative arthrokinematics, suggesting the clinical-translational potential of dynamic imaging. The case study highlights applications for patient-level postoperative evaluation, which can be expanded to other pathologies, surgeries, or conditions in the future.

Abstract The scaphotrapeziotrapezoid (STT) joint is involved in load transmission between the wrist and thumb. A quantitative description of baseline STT joint morphometrics is needed to capture the variation of normal anatomy as well as to guide staging of osteoarthritis. Statistical shape modeling (SSM) techniques quantify variations in three‐dimensional shapes and relative positions. The objectives of this study are to describe the morphology of the STT joint using a multi‐domain SSM. We asked: (1) What are the dominant modes of variation that impact bone and articulation morphology at the STT joint, and (2) what are the morphometrics of SSM‐generated STT joints? Thirty adult participants were recruited to a computed tomography study of normal wrist imaging and biomechanics. Segmentations of the carpus were converted to three‐dimensional triangular surface meshes. A multi‐domain, particle‐based entropy system SSM was used to quantify variation in carpal bone shape and position as well as articulation morphology. Articular surface areas and interosseous proximity distributions were calculated between mesh vertex pairs on adjacent bones within distance (2.0 mm) and surface‐normal angular (35°) thresholds. In the SSM, the first five modes of variation captured 76.2% of shape variation and contributed to factors such as bone scale, articular geometries, and carpal tilt. Median interosseous proximities—a proxy for joint space—were 1.39 mm (scaphotrapezium), 1.42 mm (scaphotrapezoid), and 0.61 mm (trapeziotrapezoid). This study quantifies morphological and articular variations at the STT joint, presenting a range of normative anatomy. The range of estimated interosseous proximities may guide interpretation of imaging‐derived STT joint space.

Abstract Background In predynamic or dynamic scapholunate (SL) instability, standard diagnostic imaging may not identify SL interosseous ligament (SLIL) injury, leading to delayed detection and intervention. This study describes the use of four-dimensional computed tomography (4DCT) in identifying early SLIL injury and following injured wrists to 1-year postoperatively. Description of Technique 4DCT acquires a series of three-dimensional volume data with high temporal resolution (66 ms). 4DCT-derived arthrokinematic data can be used as biomarkers of ligament integrity. Patients and Methods This study presents the use of 4DCT in a two-participant case series to assess changes in arthrokinematics following unilateral SLIL injury preoperatively and 1-year postoperatively. Patients were treated with volar ligament repair with volar capsulodesis and arthroscopic dorsal capsulodesis. Arthrokinematics were compared between uninjured, preoperative injured, and postoperative injured (repaired) wrists. Results 4DCT detected changes in interosseous distances during flexion-extension and radioulnar deviation. Generally, radioscaphoid joint distances were greatest in the uninjured wrist during flexion-extension and radioulnar deviation, and SL interval distances were smallest in the uninjured wrist during flexion-extension and radioulnar deviation. Conclusion 4DCT provides insight into carpal arthrokinematics during motion. Distances between the radioscaphoid joint and SL interval can be displayed as proximity maps or as simplified descriptive statistics to facilitate comparisons between wrists and time points. These data offer insight into areas of concern for decreased interosseous distance and increased intercarpal diastasis. This method may allow surgeons to assess whether (1) injury can be visualized during motion, (2) surgery repaired the injury, and (3) surgery restored normal carpal motion. Level of Evidence Level IV, Case series.

Transcutaneous (TSS) and epidural spinal stimulation (ESS) are electrophysiological techniques that have been used to investigate the interactions between exogenous electrical stimuli and spinal sensorimotor networks that integrate descending motor signals with afferent inputs from the periphery during motor tasks such as standing and stepping. Recently, pilot-phase clinical trials using ESS and TSS have demonstrated restoration of motor functions that were previously lost due to spinal cord injury (SCI). However, the spinal network interactions that occur in response to TSS or ESS pulses with spared descending connections across the site of SCI have yet to be characterized. Therefore, we examined the effects of delivering TSS or ESS pulses to the lumbosacral spinal cord in nine individuals with chronic SCI. During low-frequency stimulation, participants were instructed to relax or attempt maximum voluntary contraction to perform full leg flexion while supine. We observed similar lower-extremity neuromusculature activation during TSS and ESS when performed in the same participants while instructed to relax. Interestingly, when participants were instructed to attempt lower-extremity muscle contractions, both TSS- and ESS-evoked motor responses were significantly inhibited across all muscles. Participants with clinically complete SCI tested with ESS and participants with clinically incomplete SCI tested with TSS demonstrated greater ability to modulate evoked responses than participants with motor complete SCI tested with TSS, although this was not statistically significant due to a low number of subjects in each subgroup. These results suggest that descending commands combined with spinal stimulation may increase activity of inhibitory interneuronal circuitry within spinal sensorimotor networks in individuals with SCI, which may be relevant in the context of regaining functional motor outcomes.

Epidural electrical stimulation (EES) of the spinal cord has been shown to restore function after spinal cord injury (SCI). Characterization of EES-evoked motor responses has provided a basic understanding of spinal sensorimotor network activity related to EES-enabled motor activity of the lower extremities. However, the use of EES-evoked motor responses to guide EES system implantation over the spinal cord and their relation to post-operative EES-enabled function in humans with chronic paralysis attributed to SCI has yet to be described. Herein, we describe the surgical and intraoperative electrophysiological approach used, followed by initial EES-enabled results observed in 2 human subjects with motor complete paralysis who were enrolled in a clinical trial investigating the use of EES to enable motor functions after SCI. The 16-contact electrode array was initially positioned under fluoroscopic guidance. Then, EES-evoked motor responses were recorded from select leg muscles and displayed in real time to determine electrode array proximity to spinal cord regions associated with motor activity of the lower extremities. Acceptable array positioning was determined based on achievement of selective proximal or distal leg muscle activity, as well as bilateral muscle activation. Motor response latencies were not significantly different between intraoperative recordings and post-operative recordings, indicating that array positioning remained stable. Additionally, EES enabled intentional control of step-like activity in both subjects within the first 5 days of testing. These results suggest that the use of EES-evoked motor responses may guide intraoperative positioning of epidural electrodes to target spinal cord circuitry to enable motor functions after SCI.

ABSTRACTMitotic bookmarking is an epigenetic control mechanism that sustains gene expression in progeny cells; it is often found in genes related to the maintenance of cellular phenotype and growth control. RUNX transcription factors regulate a broad spectrum of RNA Polymerase (Pol II) transcribed genes important for lineage commitment but also regulate RNA Polymerase I (Pol I) driven ribosomal gene expression, thus coordinating control of cellular identity and proliferation. In this study, using fluorescence microscopy and biochemical approaches we show that the principal RUNX co‐factor, CBFβ, associates with nucleolar organizing regions (NORs) during mitosis to negatively regulate RUNX‐dependent ribosomal gene expression. Of clinical relevance, we establish for the first time that the leukemogenic fusion protein CBFβ‐SMMHC (smooth muscle myosin heavy chain) also associates with ribosomal genes in interphase chromatin and mitotic chromosomes to promote and epigenetically sustain regulation of ribosomal genes through RUNX factor interactions. Our results demonstrate that CBFβ contributes to the transcriptional regulation of ribosomal gene expression and provide further understanding of the epigenetic role of CBFβ‐SMMHC in proliferation and maintenance of the leukemic phenotype. J. Cell. Biochem. 115: 2155–2164, 2014. © 2014 Wiley Periodicals, Inc.

AbstractCore Binding Factor β (CBFβ) is complexed with the RUNX family of transcription factors in the nucleus to support activation or repression of genes related to bone (RUNX2), hematopoiesis (RUNX1) and gastrointestinal (RUNX3) development. Furthermore, RUNX proteins contribute to the onset and progression of different types of cancer. Although CBFβ localizes to cytoskeletal architecture, its biological role in the cytoplasmic compartment remains to be established. Additionally, the function and localization of CBFβ during the cell cycle are important questions relevant to its biological role. Here we show that CBFβ dynamically distributes in different stages of cell division and importantly is present during telophase at the midbody, a temporal structure important for successful cytokinesis. A functional role for CBFβ localization at the midbody is supported by striking defects in cytokinesis that include polyploidy and abscission failure following siRNA‐mediated downregulation of endogenous CBFβ or overexpression of the inv(16) fusion protein CBFβ‐SMMHC. Our results suggest that CBFβ retention in the midbody during cytokinesis reflects a novel function that contributes to epigenetic control. J. Cell. Physiol. 229: 1466–1474, 2014. © 2014 Wiley Periodicals, Inc.

Abstract The regulatory information for phenotype, proliferation, and growth of normal and tumor cells must be maintained through genome replication in the S phase and cell division during mitosis. Epigenetic mechanisms that include DNA methylation, posttranslational modifications of histones, selective utilization of histone variants, and inheritable RNA molecules play pivotal roles in maintaining cellular identity through mitotic divisions. Recent studies demonstrate that mitotic occupancy of genes, which are determinants of cell fate, growth, and proliferation, by lineage-restricted transcription factors is a key epigenetic mechanism for retention and transmission of cellular expression memory. Evidence is emerging for the presence of distinct transcriptional regulatory microenvironments in mitotic chromosomes in which the genes bookmarked for reactivation postmitotically reside. Importantly, some oncoproteins are present in mitotic microenvironments where they occupy target genes during mitosis and may contribute to perpetuating the transformed phenotype. We discuss emerging regulatory implications of epigenetically bookmarking genes during mitosis for physiologic control as well as for the onset and progression of cancer. Cancer Res; 74(2); 420–5. ©2014 AACR.