Molecular basis for substrate recruitment to the PRMT5 methylosome.

PRMT5 is an essential arginine methyltransferase and a therapeutic target in MTAP-null cancers. PRMT5 uses adaptor proteins for substrate recruitment through a previously undefined mechanism. Here, we identify an evolutionarily conserved peptide sequence shared among the three known substrate adaptors (CLNS1A, RIOK1, and COPR5) and show that it is necessary and sufficient for interaction with PRMT5. We demonstrate that PRMT5 uses modular adaptor proteins containing a common binding motif for substrate recruitment, comparable with other enzyme classes such as kinases and E3 ligases. We structurally resolve the interface with PRMT5 and show via genetic perturbation that it is required for methylation of adaptor-recruited substrates including the spliceosome, histones, and ribosomal complexes. Furthermore, disruption of this site affects Sm spliceosome activity, leading to intron retention. Genetic disruption of the PRMT5-substrate adaptor interface impairs growth of MTAP-null tumor cells and is thus a site for development of therapeutic inhibitors of PRMT5.

Effect of four different types of vermicomposts on okra productivity and farm income.

Organic based fertilizers is crucial for maintaining soil fertility, increasing crop production, and mitigating climate change. Among various organic fertilizers, vermicompost (VC) has been found to be one of the promising options for enhancing soil fertility and productivity. However, there are limited studies on the agronomic effects of vermicomposts in Nepal. In this study, a pot culture experiment was conducted inside a greenhouse to assess the agronomic and economic effects of four different commercially available vermicomposts, available in both reduced and original moisture forms, on okra. Nine treatments with three replications were arranged in a completely randomized design (CRD). These treatments included Divya vermicompost with both reduced (DvRM: 28.82 %) and original moisture (DvOM: 62.17 %); Praramva vermicompost with reduced (PvRM: 29.63 %) and original moisture (PvOM: 54.65 %), Bio-Comp vermicompost with reduced (BvRM: 26.75 %) and original moisture (BvOM: 49.77 %), Sathi vermicompost with reduced (SvRM: 28.52 %) and original moisture (SvOM: 65.18 %), and a control (CK: non-fertilized treatment). All VC treatments, whether in reduced or original moisture forms, showed better performance on plant growth parameters and fruit yield compared to the control. There was no significant difference between the four types of VCs, in either moisture form. The average number of fruits per pot in VC treatments (ranging from 5.5 to 8.0 fruits per pot) increased by 94 % compared to CK (3.5 fruits). Similarly, total fruit yield increased by 126 % in VC treatments (ranging from 16213 kg ha-1 to 23193 kg ha-1) compared to the CK (8260 kg ha-1). The benefit to cost ratio (B:C) of all the VCs was above 1 (B:C > 1), ranging from 1.00 to 1.59, illustrating the economic benefit of using vermicompost in okra cultivation. The findings suggest that farmers should consider the widespread use of vermicomposts to increase both crop productivity and farm profitability, thereby sustaining their livelihoods.

Unilateral C1-C2 Posterior Fusion in a Patient With Right Vertebral Artery Anomaly With Intracanal Trajectory: A Case Report.

CASE: A 59-year-old woman presented with progressively worsening neck pain and radicular symptoms. Cervical radiographs revealed C1-C2 dynamic instability. Magnetic resonance imaging and computed tomographic angiogram revealed an anomalous right vertebral artery with intracanal trajectory at C1. A unilateral left C1-C2 fusion with a C1 lateral mass screw and C2 transarticular screw placement was performed due to the anomalous artery. At 14-month follow-up, the patient's cervical symptoms had resolved. CONCLUSION: In this patient with an aberrant vertebral artery who was indicated for C1-C2 fusion, a unilateral contralateral fusion with a C1 lateral mass screw and C2 transarticular screw was a satisfactory treatment option.

The Role of Perioperative Nutritional Status and Supplementation in Orthopaedic Surgery: A Review of Postoperative Outcomes.

¼ Identification of malnourished and at-risk patients should be a standardized part of the preoperative evaluation process for every patient.¼ Malnourishment is defined as a disorder of energy, protein, and nutrients based on the presence of insufficient energy intake, weight loss, muscle atrophy, loss of subcutaneous fat, localized or generalized fluid accumulation, or diminished functional status.¼ Malnutrition has been associated with worse outcomes postoperatively across a variety of orthopaedic procedures because malnourished patients do not have a robust metabolic reserve available for recovery after surgery.¼ Screening assessment and basic laboratory studies may indicate patients' nutritional risk; however, laboratory values are often not specific for malnutrition, necessitating the use of prognostic screening tools.¼ Nutrition consultation and perioperative supplementation with amino acids and micronutrients are 2 readily available interventions that orthopaedic surgeons can select for malnourished patients.

Comparison of CT-Guided needle biopsy versus percutaneous endoscopic debridement and drainage in pathogen identification and pain outcomes for spondylodiscitis patients: A systematic review and literature review.

Introduction: Spondylodiscitis (SD) is an infection of the intervertebral disc with involvement of the adjacent vertebral bodies. Diagnostic tests with CT-guided biopsy only provide a positive yield in 14%-48% of cases. Percutaneous endoscopic debridement and drainage (PEDD) has recently shown promise in the treatment of spondylodiscitis. Research question: The purpose of this study is to determine differences in pathogen identification and clinical outcomes for PEDD versus CT-guided needle biopsy in SD patients. Materials and methods: We conducted a systematic review of the literature using PRISMA guidelines to determine differences in positive microbiology results, perioperative complications, pain control, and long-term clinical outcomes for PEDD vs. CT-guided needle biopsy in SD patients. Results: 1078 studies were evaluated, 87 of which underwent full review. 15 studies met the inclusion and exclusion criteria, including 7 PEDD, 7 CT-guided biopsy, and 1 CT-guided biopsy vs. PEDD article, for a total of 192 PEDD patients and 604 CT-guided biopsy patients. We found 36.59% of CT-guided biopsy patients had positive microbiology results, compared to 84.38% of PEDD patients. No major perioperative complications occurred as a result of the PEDD procedure. Of the five PEDD studies that reported pain outcomes, greater than 80% of patients experienced relief after intervention. Discussion and conclusion: These results suggest that PEDD may improve pathogen identification while simultaneously reducing pain compared to CT-guided needle biopsy in SD. Although current treatment guidelines recommend CT-guided biopsy, in patients with severe back pain and suspected SD, PEDD can be considered an alternative intervention.

A case report of robotic-guided prone transpsoas lumbar fusion in a patient with lumbar pseudarthrosis, adjacent segment disease, and degenerative scoliosis.

BACKGROUND: Surgical treatment of scoliosis includes long and invasive multi-level instrumentation and correction which may result in high rates of postoperative complications, especially in elderly patients with osteopenia or multiple comorbidities. Minimally invasive surgical options may benefit these patients. CASE DESCRIPTION: A 73-year-old female patient with a history of degenerative lumbar scoliosis, L4-5 pseudarthrosis, and resulting L5-S1 adjacent segment following prior unsuccessful lateral L4-5 interbody fusion presented to the clinic with severe lower back pain and lower extremity radiculopathy. The decision was made to proceed with surgical correction via a robotic-guided prone transpsoas (PTP) approach, which is a novel approach similar to lateral lumbar interbody fusion (LLIF) with the patient in a prone decubitus position. Excellent spinal alignment was achieved with no complications. On two-month follow-up, imaging revealed pedicle screws at the L3, L4, L5 levels and at the sacrum without change and continued interbody cages position with no signs or symptoms of infection. DISCUSSION: Minimally invasive procedures have demonstrated benefit in spine surgery especially for at risk populations. The LLIF procedure has been well established for use in a wide range of spinal pathologies given its noted benefits in increasing spinal column stability through posterior fixation and indirect decompression. However, only marginal improvements in segmental lordosis are expected and there are reports of neurological complications. The PTP procedure has emerged as an alternative to LLIF for the treatment of spinopelvic pathologies. This approach enables greater improvements to spinal lordosis through single-position surgery while simultaneously reducing intraoperative repositioning and providing the known benefits of lateral interbody surgery. CONCLUSION: Our experience suggests that the PTP approach is safe and effective because it does not require patient repositioning, easily interfaces with robotic guidance, and achieves increased lordosis gains via the prone positional effect compared to LLIF and comparable approaches.

Surgical management of a rare myxopapillary ependymoma of the gluteal region: A case report.

BACKGROUND: Ependymomas are rare tumors originating from neuroepithelial cells lining the wall of the ventricles or central canal of the spinal cord. While these tumors mainly occur within the central nervous system (CNS), there are occasional reports in children and young adult patients with a primary tumor occurrence outside of the CNS. Ependymomas of the sacrococcygeal region have been infrequently described in the literature with no standard of care established. We present a case report and review of the literature regarding this rare entity. CASE DESCRIPTION: A 24-year-old woman presented with right gluteal pain worsened by sitting and a palpable soft tissue mass of the sacrococcygeal region. Magnetic resonance imaging revealed a 3.7 cm cystic mass centered in the right gluteal region. She underwent a biopsy at an outside institution, with histology revealing myxopapillary ependymoma. The patient was referred to our hospital and underwent an interdisciplinary neurosurgical and orthopedic oncology en bloc resection of the ependymoma, which intraoperatively appeared to originate from the coccygeal nerve. CONCLUSION: In the present report, the authors demonstrate that a myxopapillary ependymoma may present as an isolated gluteal mass attached to the coccygeal nerve, without frank CNS involvement. Furthermore, an interdisciplinary approach to surgical resection of this lesion appears to represent an effective treatment modality.

Comparison of Minimally Invasive Total versus Subtotal Resection of Spinal Tumors: A Systematic Review and Meta-Analysis.

OBJECTIVE: With the advent of minimally invasive techniques, minimally invasive spine surgery (MISS) has become a realistic option for many spine cases. This study aims to evaluate the operative and clinical outcomes of MISS for total versus subtotal tumor resection from current evidence. METHODS: A literature search was performed using the search term (Minimally invasive surgery OR MIS) AND (spine tumor OR spinal tumor). Studies including both minimally invasive total and subtotal resection cases with operative or clinical data were included. RESULTS: Seven studies describing 159 spinal tumor cases were included. Compared with total resection, subtotal resection showed no significant differences in surgical time (mean difference (MD), 9.44 minutes; 95% confidence interval [CI], -47.66 to 66.55 minutes; P = 0.37), surgical blood loss (MD, -84.72 mL; 95% CI, -342.82 to 173.39 mL; P = 0.34), length of stay (MD, 1.38 days; 95% CI, -0.95 to 3.71 days; P = 0.17), and complication rate (odds ratio, 9.47; 95% CI, 0.34-263.56; P = 0.12). Pooled analyses with the random-effects model showed that neurologic function improved in 89% of patients undergoing total resection, whereas neurologic function improved in 61% of patients undergoing subtotal resection. CONCLUSIONS: Our analyses show that there is no significant difference in operative outcomes between total and subtotal resection. Patients undergoing total resection showed slightly better improvement in neurologic outcomes compared with patients undergoing subtotal resection. Overall, this study suggests that both total and subtotal resection may result in comparable outcomes for patients with spinal tumors. However, maximal safe resection remains the ideal treatment because it provides the greatest chance of long-term benefit.

NELL2-Robo3 complex structure reveals mechanisms of receptor activation for axon guidance.

Axon pathfinding is critical for nervous system development, and it is orchestrated by molecular cues that activate receptors on the axonal growth cone. Robo family receptors bind Slit guidance cues to mediate axon repulsion. In mammals, the divergent family member Robo3 does not bind Slits, but instead signals axon repulsion from its own ligand, NELL2. Conversely, canonical Robos do not mediate NELL2 signaling. Here, we present the structures of NELL-Robo3 complexes, identifying a mode of ligand engagement for Robos that is orthogonal to Slit binding. We elucidate the structural basis for differential binding between NELL and Robo family members and show that NELL2 repulsive activity is a function of its Robo3 affinity and is enhanced by ligand trimerization. Our results reveal a mechanism of oligomerization-induced Robo activation for axon guidance and shed light on Robo family member ligand binding specificity, conformational variability, divergent modes of signaling, and evolution.