Background: Concomitant diffuse idiopathic skeletal hyperostosis (DISH) and cervical ossification of the posterior longitudinal ligament (cOPLL) are primarily investigated in radiographic studies of East Asian populations. This study aimed to determine clinical prevalence of concomitant DISH/cOPLL in a large U.S. sample and to compare characteristics and complications in cOPLL patients with and without concomitant DISH who were surgically treated. Methods: A retrospective database study was performed using PearlDiver. Billing codes identified cOPLL patients with and without concomitant DISH during 2010-2022. Annual prevalence was calculated. Patients undergoing cervical/thoracic spine decompression with/without fusion were included. Bivariate analyses compared patient characteristics, 1-year reoperation, and cohort-matched 90-day complications. Results: A total of 681 cOPLL patients had concomitant DISH and 28,395 did not. Prevalence of DISH in patients with cOPLL was 1.4%. cOPLL patients with DISH underwent surgery more frequently than those without (30.2% vs. 21.7%; P < 0.0001) via posterior approach (68.0% vs. 42.1%; P < 0.0001). cOPLL patients with DISH undergoing surgery were more frequently male (71.0% vs. 51.6%; P < 0.0001) with higher proportion of metabolic syndrome (61.4% vs. 37.9%; P < 0.0001). Compared with cOPLL patients without DISH, cOPLL patients with DISH had similar 1-year reoperation (8.3% vs. 9.6%; P = 0.61) and postmatch 90-day complications (17.8% vs. 14.2%; P = 0.31), but higher overall neurologic injury (14.7% vs. 6.9%; P = 0.0047) amid infrequent procedure-related neurologic injury (2.3% vs. 0.6%; P = 0.08). Conclusions: Clinical prevalence of DISH in patients with cOPLL in the United States is low; however, cOPLL patients with concomitant DISH underwent surgery more frequently than those without. Despite higher comorbidity burden, cOPLL patients with DISH may have similar short-term postsurgical risk to cOPLL patients without DISH. However, higher nonprocedural neurologic injury in cOPLL patients with DISH may indicate insidious or delayed disease sequelae.

Spina bifida is a birth defect resulting from abnormal embryonic development of the neural tube. Though spina bifida is divided into several subtypes, myelomeningocele-the most severe form of spina bifida often associated with a markedly diminished quality of life-accounts for a significant portion of cases. A broad range of genetic and environmental factors, many of which are still unknown, influence spina bifida, making it difficult to provide a comprehensive etiology for the disorder. Folic acid supplementation aided by the mandatory fortification of food is preventive; still, spina bifida persists due to numerous other confounding factors that affect risk. This article reviews the latest studies pertaining to the risk factors and genetics involved in spina bifida in an attempt to elucidate the complex background of the congenital malformation. Additionally, this review highlights the significant impact of environmental pollutants, adverse medication effects, and maternal health conditions such as diabetes and obesity on the prevalence of spina bifida. Emerging research on gene-environment interactions provides insight into how specific genetic variants may influence susceptibility to these environmental factors. We also discuss new technologies in genetic sequencing that show promise for the large-scale discovery of genes associated with spina bifida risk. Understanding these intricate interactions is crucial for developing effective prevention and intervention strategies.

Intervertebral disc (IVD) degeneration (IVDD), primarily caused by nucleus pulposus (NP) dehydration, leads to low back pain. While current treatments focus on symptom management or surgical intervention, tissue engineering using IVD-derived cells, biofactors, and scaffolds offers a promising regenerative approach. Here, human NP cells (NPCs) and annulus fibrosus cells (AFCs) are immortalized with human telomerase reverse transcriptase (hTERT), generating immortalized NPCs (iHNPCs) and AFCs (iHAFCs). These cells express NP and AF-specific markers, are reversible via FLP recombinase, and are non-tumorigenic. iHAFCs exhibit osteogenic potential, while iHNPCs show chondrogenic differentiation. A 3D-printed citrate-based scaffold was employed to develop an IVD regeneration model, with BMP9-stimulated iHAFCs in the peripheral region and BMP2-stimulated iHNPCs in the central region. Histological analysis revealed bone formation in the iHAFC region and cartilage formation in the iHNPC region, mimicking the natural IVD structure. Additionally, an ex vivo spine fusion model demonstrated robust bone formation in iHAFC-treated segments. These findings highlight the potential of iHAFCs and iHNPCs as valuable tools for IVD tissue engineering and regeneration.

Study Design: Retrospective case series. Objective: Describe the injury characteristics of ballistic fractures involving the atlantoaxial spine. Summary of Background Data: Civilian gunshot wounds to the spine are an increasingly common injury in the United States. Civilian studies have focused on ballistic injuries to the entire spine as opposed to a region-specific fashion. Only a single 10-patient case series investigating ballistic fractures to the upper cervical spine (C1 and C2) exists, leaving a large gap in the understanding of this injury complex. Methods: A retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. Results: Thirty-six patients were identified, with 86% being male with an average patient age of 30.0 ± 10.36 years (mean ± SD). Fracture morphology was characterized using proportional analysis. Initial neurological exams were either ASIA A or ASIA E, without any incomplete injuries noted. Patients who sustained a transcanal injury did not show any neurological improvement. The initial in-hospital mortality rate was 5.6%, with a 1-year mortality rate of 8.3%. There is a high incidence of associated vascular injury (66%) and mandible fracture (33%). Conclusions: Ballistic penetrating trauma to the atlantoaxial spine often results in complex injury patterns necessitating multidisciplinary care with high rates of morbidity and mortality. If neurological deficits are present initially, they are often complete. Two thirds of patients sustained an associated vascular injury, which should be screened for with CT angiography.

STUDY DESIGN:Retrospective cohort study performed in a nationwide insurance claims database. OBJECTIVE:To evaluate the duration and magnitude of post-operative opioid prescriptions after minimally invasive surgical sacroiliac joint fusion (MIS SIJF) as compared to other common spine surgeries. SUMMARY OF BACKGROUND DATA:MIS SIJF has been reported to significantly improve quality of life and reduce pain. However, there is a paucity of reported data on post-operative opioid use in patients undergoing MIS SIJF for sacroiliac joint dysfunction. METHODS:A nationwide insurance claims database was queried to identify 4,666 patients who underwent MIS SIJF. Patients were stratified by pre-operative opioid use: Opioid naïve, sporadic use, or chronic use were respectively defined as 0,1, or≥2 opioid prescriptions filled within 6 months prior to surgery. Duration of opioid use was defined by the time between MIS SIJF and last opioid prescription filled while magnitude of opioid use was determined by milligram morphine equivalents filled by 30 days post-operation. This opioid use data was compared to that of other common spine surgeries. RESULTS:Patients undergoing MIS SIJF continued to fill opioid prescriptions 1-year post-operatively at significantly higher proportions than those undergoing other common spine procedures assessed by prior literature within each of the pre-operative opioid use cohorts (chronic: 73% vs. 49-62%; P <0.0001, sporadic: 39% vs. 23-28%; P <0.0001, opioid naïve: 22% vs. 15-18%; P <0.0001). Chronic users filled the highest opiate dosages during the 30-day post-operative period, filling on average 64.75 MME/d compared to 19.75 MME/d and 24.25 MME/d by the opioid naïve and sporadic users, respectively. CONCLUSION:After MIS SIJF, opioid naïve patients use fewer opioids and for a shorter period of time compared to patients with sporadic or chronic pre-operative opioid use. MIS SIJF may result in less effective pain reduction when compared to other common spine surgeries evaluated via identical methodology. LEVEL OF EVIDENCE:3.

BACKGROUND CONTEXT Civilian gunshot injuries to the spine are increasingly common in the US. However, most studies are focused on a military population sustaining high energy ballistic injuries. Civilian studies have focused on ballistic injuries to the entire spine as opposed to a region-specific fashion, with no reports of upper cervical spine (C1 and C2) ballistic fractures. PURPOSE Characterize our centers' experience with ballistic fractures to the axial cervical spine at C1 and C2 and their associated injuries. STUDY DESIGN/SETTING Retrospective chart review. PATIENT SAMPLE Consecutive patients presenting to an urban level 1 trauma center suffering a ballistic fracture to the C1 and C2 that received orthopedic spine surgery consultation from 5/2018 to 1/2023. OUTCOME MEASURES Fracture morphology, neurological status, and associated injuries. METHODS IRB approval was obtained and retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. RESULTS Twenty-two patients were identified in the study period. Fractures were classified based on the involved levels and fracture morphology including location affected, vertebral artery foramen fracture extension, and canal involvement. A single patient required halo immobilization due to comminuted dens fracture and angulation. Of the patients sustaining a trans-canal bullet trajectory, all presented with an associated ASIA A spinal cord injury. All other patients were classified as ASIA E and had no neurologic deficit except for a single patient with an ASIA C injury due to an additional ballistic injury through the temporal bone into the brain parenchyma. Forty-five percent (10) of patients sustained an arterial injury to either the vertebral, internal carotid, or external carotid artery with 2 patients emergently going to the operating room for neck exploration; 64% (14) patients sustained facial fractures with 10 patients undergoing surgical fixation; 18% (4) patients were found to have additional intracranial injuries. CONCLUSIONS This is the first cohort of patients reported to have sustained ballistic C1 and C2 fractures. A single patient sustained an unstable fracture pattern requiring halo immobilization. The low likelihood of bony instability is likely, given the penetrating mechanism of a relatively low energy missile that does not cause ligamentous instability. Interestingly, patients either suffered a devastating ASIA A spinal cord injury or had no neurologic deficit. All ASIA A injuries were associated with a trans-canal trajectory. Significant rates of associated arterial injuries, brain injuries, and facial fractures requiring surgical fixation were found showing these are complex injury patterns in polytraumatized patients. Due to the severity of the associated injuries, including brain and high-level spinal cord injury, it is possible that patients expire before full trauma evaluation or obtaining complete imaging, limiting our sample size. Further research is needed to formulate a classification system to better direct optimal care for these injury patterns. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs. Civilian gunshot injuries to the spine are increasingly common in the US. However, most studies are focused on a military population sustaining high energy ballistic injuries. Civilian studies have focused on ballistic injuries to the entire spine as opposed to a region-specific fashion, with no reports of upper cervical spine (C1 and C2) ballistic fractures. Characterize our centers' experience with ballistic fractures to the axial cervical spine at C1 and C2 and their associated injuries. Retrospective chart review. Consecutive patients presenting to an urban level 1 trauma center suffering a ballistic fracture to the C1 and C2 that received orthopedic spine surgery consultation from 5/2018 to 1/2023. Fracture morphology, neurological status, and associated injuries. IRB approval was obtained and retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. Twenty-two patients were identified in the study period. Fractures were classified based on the involved levels and fracture morphology including location affected, vertebral artery foramen fracture extension, and canal involvement. A single patient required halo immobilization due to comminuted dens fracture and angulation. Of the patients sustaining a trans-canal bullet trajectory, all presented with an associated ASIA A spinal cord injury. All other patients were classified as ASIA E and had no neurologic deficit except for a single patient with an ASIA C injury due to an additional ballistic injury through the temporal bone into the brain parenchyma. Forty-five percent (10) of patients sustained an arterial injury to either the vertebral, internal carotid, or external carotid artery with 2 patients emergently going to the operating room for neck exploration; 64% (14) patients sustained facial fractures with 10 patients undergoing surgical fixation; 18% (4) patients were found to have additional intracranial injuries. This is the first cohort of patients reported to have sustained ballistic C1 and C2 fractures. A single patient sustained an unstable fracture pattern requiring halo immobilization. The low likelihood of bony instability is likely, given the penetrating mechanism of a relatively low energy missile that does not cause ligamentous instability. Interestingly, patients either suffered a devastating ASIA A spinal cord injury or had no neurologic deficit. All ASIA A injuries were associated with a trans-canal trajectory. Significant rates of associated arterial injuries, brain injuries, and facial fractures requiring surgical fixation were found showing these are complex injury patterns in polytraumatized patients. Due to the severity of the associated injuries, including brain and high-level spinal cord injury, it is possible that patients expire before full trauma evaluation or obtaining complete imaging, limiting our sample size. Further research is needed to formulate a classification system to better direct optimal care for these injury patterns.

The evolutionarily conserved Wnt signaling pathway plays a central role in development and adult tissue homeostasis across species. Wnt proteins are secreted, lipid-modified signaling molecules that activate the canonical (β-catenin dependent) and non-canonical (β-catenin independent) Wnt signaling pathways. Cellular behaviors such as proliferation, differentiation, maturation, and proper body-axis specification are carried out by the canonical pathway, which is the best characterized of the known Wnt signaling paths. Wnt signaling has emerged as an important factor in stem cell biology and is known to affect the self-renewal of stem cells in various tissues. This includes but is not limited to embryonic, hematopoietic, mesenchymal, gut, neural, and epidermal stem cells. Wnt signaling has also been implicated in tumor cells that exhibit stem cell-like properties. Wnt signaling is crucial for bone formation and presents a potential target for the development of therapeutics for bone disorders. Not surprisingly, aberrant Wnt signaling is also associated with a wide variety of diseases, including cancer. Mutations of Wnt pathway members in cancer can lead to unchecked cell proliferation, epithelial-mesenchymal transition, and metastasis. Altogether, advances in the understanding of dysregulated Wnt signaling in disease have paved the way for the development of novel therapeutics that target components of the Wnt pathway. Beginning with a brief overview of the mechanisms of canonical and non-canonical Wnt, this review aims to summarize the current knowledge of Wnt signaling in stem cells, aberrations to the Wnt pathway associated with diseases, and novel therapeutics targeting the Wnt pathway in preclinical and clinical studies.

While progenitor cell-based cardiomyocyte regeneration holds great promise of repairing an injured heart,primary cardiomyogenic progenitors(CPs)have a limited life span in culture,hampering the use of CPs for in vitro and in vivo studies.We previously isolated primary CPs from mouse E15.5 fetal heart,and reversibly immortalized them with SV40 large T antigen(SV40 LTA),resulting in immortalized CPs(iCPs),which maintain long-term proliferation and ex-press cardiomyogenic markers and retain differentiation potential under appropriate differentiation conditions.1

BACKGROUND CONTEXT Civilian gunshot wounds to the spine are an increasingly common injury in the USA. A majority of the available research is focused on a military population suffering high energy missiles. Minimal research has focused on civilian ballistic injuries to the lumbosacral spine as the available studies focus on the entire spine due to limited numbers PURPOSE Characterize our centers experience with lumbosacral ballistic fractures and their associated injuries in order to inform fracture management. STUDY DESIGN/SETTING Retrospective chart review. PATIENT SAMPLE Consecutive patients presenting to an urban level 1 trauma center suffering a ballistic fracture to the L1-S2 level that received spine surgery consultation from 5/2018 to 11/2022. OUTCOME MEASURES Outcomes included neurological status at presentation and final follow up. METHODS IRB approval was obtained and retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation and final follow up, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. RESULTS A total of 149 patients were identified in the study period with an average follow-up of 12.4 weeks. Fractures were classified based upon the involved levels, Denis 3-column classification, and fracture morphology including location affected and spinal canal involvement. Of the patients sustaining a trans-canal bullet trajectory, 7 did not have a neurological deficit. Neurological deficits were classified at presentation according to the ASIA classification with modifiers including unilateral deficit and root injury. ASIA grade at final follow-up exam was also recorded. There were 11 patients that underwent surgical decompression, 9 of which included fusion, and 7 included foreign body removal. Only a single patient underwent surgical intervention for instability. Two of the patients improved to an ASIA grade of E at final follow-up. In terms of associated injuries, 110 patients underwent emergent exploratory laparotomy upon presentation. CONCLUSIONS This is the largest reported cohort of civilian lumbosacral spine ballistic fractures. These fractures are largely stable given the penetrating injury mechanism with a relatively low energy missile that does not cause gross ligamentous instability. In our cohort, only a single patient was found to have an unstable injury pattern necessitating fusion. The remainder of the injuries were stable (99.3%). There is also a relatively high frequency of unilateral and nerve root injuries. Trans-canal trajectory is also not always associated with a severe neurologic injury with 7 patients in our cohort sustaining no deficit. These are complex injury patterns that do not often correlate to traditional fracture or neurologic injury classification systems making operative indications difficult to define. Further, the patients are often polytraumatized and necessitating emergent exploratory laparotomy to treat life threatening injuries which can significantly delay both diagnosis and treatment. Further research is needed to formulate a classification schema to better direct optimal care for lumbosacral ballistic injuries and better inform operative indications for decompression and foreign body removal. FDA Device/Drug Status This abstract does not discuss or include any applicable devices or drugs. Civilian gunshot wounds to the spine are an increasingly common injury in the USA. A majority of the available research is focused on a military population suffering high energy missiles. Minimal research has focused on civilian ballistic injuries to the lumbosacral spine as the available studies focus on the entire spine due to limited numbers Characterize our centers experience with lumbosacral ballistic fractures and their associated injuries in order to inform fracture management. Retrospective chart review. Consecutive patients presenting to an urban level 1 trauma center suffering a ballistic fracture to the L1-S2 level that received spine surgery consultation from 5/2018 to 11/2022. Outcomes included neurological status at presentation and final follow up. IRB approval was obtained and retrospective chart review was performed. Extracted data included patient demographics, neurological status on presentation and final follow up, fracture morphology, assessment of stability, other associated injuries, and surgical procedures performed. Proportional analysis was performed to characterize the fractures and their associated neurological injuries. A total of 149 patients were identified in the study period with an average follow-up of 12.4 weeks. Fractures were classified based upon the involved levels, Denis 3-column classification, and fracture morphology including location affected and spinal canal involvement. Of the patients sustaining a trans-canal bullet trajectory, 7 did not have a neurological deficit. Neurological deficits were classified at presentation according to the ASIA classification with modifiers including unilateral deficit and root injury. ASIA grade at final follow-up exam was also recorded. There were 11 patients that underwent surgical decompression, 9 of which included fusion, and 7 included foreign body removal. Only a single patient underwent surgical intervention for instability. Two of the patients improved to an ASIA grade of E at final follow-up. In terms of associated injuries, 110 patients underwent emergent exploratory laparotomy upon presentation. This is the largest reported cohort of civilian lumbosacral spine ballistic fractures. These fractures are largely stable given the penetrating injury mechanism with a relatively low energy missile that does not cause gross ligamentous instability. In our cohort, only a single patient was found to have an unstable injury pattern necessitating fusion. The remainder of the injuries were stable (99.3%). There is also a relatively high frequency of unilateral and nerve root injuries. Trans-canal trajectory is also not always associated with a severe neurologic injury with 7 patients in our cohort sustaining no deficit. These are complex injury patterns that do not often correlate to traditional fracture or neurologic injury classification systems making operative indications difficult to define. Further, the patients are often polytraumatized and necessitating emergent exploratory laparotomy to treat life threatening injuries which can significantly delay both diagnosis and treatment. Further research is needed to formulate a classification schema to better direct optimal care for lumbosacral ballistic injuries and better inform operative indications for decompression and foreign body removal.

The importance of engaging technology in education has never been more obvious than during the COVID-19 pandemic-driven era of distance learning. In this paper, we examine how an entertaining animated reward within a live online college classroom (using Facebook Group Messaging) affects students' participation and engagement. Students who answered questions correctly were rewarded with wearing an augmented reality (AR) filter of an animated college graduation cap until a subsequent student answered a question correctly and received the cap. We found that this reward system resulted in enhanced classroom engagement when it was used, particularly for students with little prior interest in the course material. Alternatively, however, students who were already interested in and studying the material prior to that class showed to be distracted by the same AR technique.

OBJECTIVE Minimally invasive surgery (MIS) techniques can effectively stabilize and decompress many thoracolumbar injuries with decreased morbidity and tissue destruction compared with open approaches. Nonetheless, there is limited direction regarding the breadth and limitations of MIS techniques for thoracolumbar injuries. Consequently, the objectives of this study were to 1) identify the range of current practice patterns for thoracolumbar trauma and 2) integrate expert opinion and literature review to develop an updated treatment algorithm. METHODS A survey describing 10 clinical cases with a range of thoracolumbar injuries was sent to 12 surgeons with expertise in spine trauma. The survey results were summarized using descriptive statistics, along with the Fleiss kappa statistic of interrater agreement. To develop an updated treatment algorithm, the authors used a modified Delphi technique that incorporated a literature review, the survey results, and iterative feedback from a group of 14 spine trauma experts. The final algorithm represented the consensus opinion of that expert group. RESULTS Eleven of 12 surgeons contacted completed the case survey, including 8 (73%) neurosurgeons and 3 (27%) orthopedic surgeons. For the 4 cases involving patients with neurological deficits, nearly all respondents recommended decompression and fusion, and the proportion recommending open surgery ranged from 55% to 100% by case. Recommendations for the remaining cases were heterogeneous. Among the neurologically intact patients, MIS techniques were typically recommended more often than open techniques. The overall interrater agreement in recommendations was 0.23, indicating fair agreement. Considering both literature review and expert opinion, the updated algorithm indicated that MIS techniques could be used to treat most thoracolumbar injuries. Among neurologically intact patients, percutaneous instrumentation without arthrodesis was recommended for those with AO Spine Thoracolumbar Classification System subtype A3/A4 (Thoracolumbar Injury Classification and Severity Score [TLICS] 4) injuries, but MIS posterior arthrodesis was recommended for most patients with AO Spine subtype B2/B3 (TLICS > 4) injuries. Depending on vertebral body integrity, anterolateral corpectomy or mini-open decompression could be used for patients with neurological deficits. CONCLUSIONS Spine trauma experts endorsed a range of strategies for treating thoracolumbar injuries but felt that MIS techniques were an option for most patients. The updated treatment algorithm may provide a foundation for surgeons interested in safe approaches for using MIS techniques to treat thoracolumbar trauma.

Appears in: ICERI2022 Proceedings Publication year: 2022Pages: 3017-3026ISBN: 978-84-09-45476-1ISSN: 2340-1095doi: 10.21125/iceri.2022.0750Conference name: 15th annual International Conference of Education, Research and InnovationDates: 7-9 November, 2022Location: Seville, Spain

As more people turn to discretionary online tools to learn new skills such as computer programming, exploring how to better support a wide range of learners is becoming increasingly essential to train the next generation of highly skilled technology workers. In our prior work, users with high learner autonomy complained that most online resources they used to learn more programming did not provide them with the flexibility they preferred to navigate through learning materials, locking them into a set sequence of topics/concepts. To explore this, we implemented a level-jumping feature into an online educational programming game. We tested it with 350 new users, tracking their progress through the game for 7 days each. We found that those with high learner autonomy did use the level jumping feature more than those with low learner autonomy. We also found that males were more likely to use this new feature, regardless of learner autonomy level, compared to their female counterparts. Finally, we found that those with low learner autonomy ultimately completed more levels than their high autonomy counterparts, and that this was particularly true of female learners (who completed the most levels overall). Based on these findings, we believe that autonomous-supportive features such as flexible navigation may be beneficial to all users of online educational tools, and that encouraging its use by a wider group of users (particularly females), may increase positive effects.

Teeth arise from the tooth germ through sequential and reciprocal interactions between immature epithelium and mesenchyme during development. However, the detailed mechanism underlying tooth development from tooth germ mesenchymal cells (TGMCs) remains to be fully understood. Here, we investigate the role of Wnt/β‐catenin signalling in BMP9‐induced osteogenic/odontogenic differentiation of TGMCs. We first established the reversibly immortalized TGMCs (iTGMCs) derived from young mouse mandibular molar tooth germs using a retroviral vector expressing SV40 T antigen flanked with the FRT sites. We demonstrated that BMP9 effectively induced expression of osteogenic markers alkaline phosphatase, collagen A1 and osteocalcin in iTGMCs, as well as in vitro matrix mineralization, which could be remarkably blunted by knocking down β‐catenin expression. In vivo implantation assay revealed that while BMP9‐stimulated iTGMCs induced robust formation of ectopic bone, knocking down β‐catenin expression in iTGMCs remarkably diminished BMP9‐initiated osteogenic/odontogenic differentiation potential of these cells. Taken together, these discoveries strongly demonstrate that reversibly immortalized iTGMCs retained osteogenic/odontogenic ability upon BMP9 stimulation, but this process required the participation of canonical Wnt signalling both in vitro and in vivo. Therefore, BMP9 has a potential to be applied as an efficacious bio‐factor in osteo/odontogenic regeneration and tooth engineering. Furthermore, the iTGMCs may serve as an important resource for translational studies in tooth tissue engineering.

Study Design: Retrospective analysis using the PearlDiver national insurance claims database. Objective: To investigate the relationship between chronic preoperative selective serotonin reuptake inhibitor (SSRI) prescriptions and nonunion following spine fusion surgery. Summary of Background Data: Contemporary literature has linked SSRIs to decreased bone mineral density and increased rates of future bone fracture. Furthermore, a recent murine model has suggested a potential role in the quality of fracture healing itself. Methods: All single-level lumbar fusion patients were identified. The rate of nonunion diagnosis between 6 and 24 months following surgery was assessed. A stratified analysis of chronic SSRI use and a number of comorbidities was conducted, followed by a multiple logistic regression analysis of nonunion accounting for qualifying risk factors. Finally, subanalyses of individual procedure codes were carried out. Results: In total, 7905 single-level lumbar fusion patients were included. In the multivariate analysis, chronic SSRI [odds ratio (OR): 1.558, P=0.004] and tobacco use (OR: 1.500, P=0.011) were identified as independent risk factors for nonunion, whereas patient age over 60 years (OR: 0.468, P<0.001) was observed to be negatively associated with nonunion. In the individual procedure subanalyses, SSRIs were significantly associated with nonunion in 2 of 3 univariate analyses and observed to be an independent risk factor for nonunion in 2 of the 3 procedure populations. Conclusions: These data suggest that patients treated concomitantly for mental health disorders with SSRIs before arthrodesis may be at an increased risk of postoperative nonunion. Closer follow-up may be indicated in this patient population.

Mesenchymal stem cells (MSCs) are capable of differentiating into bone, cartilage and adipose tissues. We identified BMP9 as the most potent osteoinductive BMP although detailed mechanism underlying BMP9-regulated osteogenesis of MSCs is indeterminate. Emerging evidence indicates that autophagy plays a critical role in regulating bone homeostasis. We investigated the possible role of autophagy in osteogenic differentiation induced by BMP9. We showed that BMP9 upregulated the expression of multiple autophagy-related genes in MSCs. Autophagy inhibitor chloroquine (CQ) inhibited the osteogenic activity induced by BMP9 in MSCs. While overexpression of ATG5 or ATG7 did not enhance osteogenic activity induced by BMP9, silencing Atg5 expression in MSCs effectively diminished BMP9 osteogenic signaling activity and blocked the expression of the osteogenic regulator Runx2 and the late marker osteopontin induced by BMP9. Stem cell implantation study revealed that silencing Atg5 in MSCs profoundly inhibited ectopic bone regeneration and bone matrix mineralization induced by BMP9. Collectively, our results strongly suggest a functional autophagy pathway may play an essential role in regulating osteogenic differentiation induced by BMP9 in MSCs. Thus, restoration of dysregulated autophagic activity in MSCs may be exploited to treat fracture healing, bone defects or osteoporosis.

As multipotent progenitor cells, mesenchymal stem cells (MSCs) can renew themselves and give rise to multiple lineages including osteoblastic, chondrogenic and adipogenic lineages. It's previously shown that BMP9 is the most potent BMP and induces osteogenic and adipogenic differentiation of MSCs. However, the molecular mechanism through which BMP9 regulates MSC differentiation remains poorly understood. Emerging evidence indicates that noncoding RNAs, especially microRNAs, may play important roles in regulating MSC differentiation and bone formation. As highly conserved RNA binding proteins, Argonaute (AGO) proteins are essential components of the multi-protein RNA-induced silencing complexes (RISCs), which are critical for small RNA biogenesis. Here, we investigate possible roles of AGO proteins in BMP9-induced lineage-specific differentiation of MSCs. We first found that BMP9 up-regulated the expression of Ago1, Ago2 and Ago3 in MSCs. By engineering multiplex siRNA vectors that express multiple siRNAs targeting individual Ago genes or all four Ago genes, we found that silencing individual Ago expression led to a decrease in BMP9-induced early osteogenic marker alkaline phosphatase (ALP) activity in MSCs. Furthermore, we demonstrated that simultaneously silencing all four Ago genes significantly diminished BMP9-induced osteogenic and adipogenic differentiation of MSCs and matrix mineralization, and ectopic bone formation. Collectively, our findings strongly indicate that AGO proteins and associated small RNA biogenesis pathway play an essential role in mediating BMP9-induced osteogenic differentiation of MSCs.

Many college students struggle to adjust academically because they never learned how to study effectively. In our first study, we developed a web-based application that enabled students to record when and how long they were studying. 29 college undergraduates used this tracking application for two weeks, then reflected on how the app affected their self-awareness and/or behavior. Analyses of participant diaries and application logs indicate that tracking applications are far from accurate, but the act of tracking itself, paired with analysis of one's own data through reflection, enables students to have stronger self-awareness of their studying habits. Our second study, a 13-week long field experiment with 162 first-year students participating in 5 groups with varying combinations of tracking and reflection, showed that the tracking+ self-reflection group scored significantly higher on their final exam than tracking with social reflection.

Virtual reality (VR) computer interfaces show promise for improving societal communication and representation of information due to their unique ability to be placed spatially around the user in three-dimensional (3D) space. This opens new possibilities for presentation and user interaction with the target information, and may be especially impactful for the education of science, technology, engineering, and mathematics (STEM) professionals. Simulations and visualizations have been shown in research studies to improve the efficiency of STEM learners compared to the less sensorimotor rich learning mediums of live instruction and textbook reading. Yet, learning science research into immersive computer simulation environments for educational applications remains limited. To address this research gap, we analyzed a fundamental VR interface capability, virtual environmental traversal, and its impact on participants' learning. We altered the traversal ability between two groups of STEM learners within the same virtual environment and compared their performance. Findings point that VR computer interfaces, regardless of environmental traversal, are suitable STEM learning environments, but that environmental traversal can increase learning efficiency.