Yemisi Deborah Joseph

All Publications

• Paired Biomechanical Comparison of Cortical and Traditional Pedicle Screw Constructs Under Cyclic Loading in a Severely Destabilized Lumbar Spine Model. Spine Swinford, S. T., Yoseph, E. T., Johnston, T. R., Koltsov, J., Behn, A. W., Joseph, Y. D., Alamin, T. F. 2025

  Abstract

  Cadaveric biomechanical analysis.To compare the fatigue resistance and failure behavior of cortical bone trajectory (CBT) and traditional pedicle screw (TPS) constructs in severely destabilized lumbar segments under cyclic flexion-compression loading.CBT screw fixation is increasingly used for lumbar stabilization and offers theoretical biomechanical advantages over TPS, including higher insertional torque and increased cortical engagement. However, its fatigue behavior in unstable constructs remains poorly characterized, despite clinical reports of early failures following interbody reduction maneuvers.Fourteen lumbar motion segments (L2-L3 and L4-L5) from seven cadaveric spines were randomized to CBT or TPS fixation (n=7 per group) using a paired design. Following subtotal discectomy and bilateral facetectomy, constructs were cyclically loaded (200-750 N, 2 Hz, 50,000 cycles). Segment stiffness, flexion range of motion (ROM), and survival were compared. Bone mineral density (BMD) was quantified via dual-energy X-ray absorptiometry.In the intact state, CBT and TPS constructs showed no significant differences in stiffness or ROM. After destabilization and instrumentation, CBT constructs demonstrated reduced flexion ROM (P=0.026), with similar end-range stiffness (P=0.219). BMD significantly correlated with ROM and stiffness in the destabilized state (ρ=-0.72, P=0.007; ρ=0.65, P=0.014). Three of seven constructs in each group survived cyclic loading. While CBT constructs withstood more cycles on average (19,500±13,026 vs. 5,625±6,419), the difference was not statistically significant (P=0.710).In a highly destabilized flexion-compression model, CBT and TPS constructs demonstrated similar fatigue performance. CBT screws offered greater resistance to ROM but no significant advantage in construct stiffness or survival. These results suggest that observed clinical failures of CBT may be attributable to surgical technique or placement sensitivity rather than inferior fatigue behavior.

  View details for DOI 10.1097/BRS.0000000000005483

  View details for PubMedID 40856413

• Hand Osteoarthritis: Molecular Mechanisms, Randomized Controlled Trials, and the Future of Targeted Treatment. International journal of molecular sciences Joseph, Y. D., Ladd, A. L., Bhutani, N. 2025; 26 (10)

  Abstract

  Hand osteoarthritis (OA) is a prevalent and disabling condition, yet its pathogenesis remains less studied than OA in large weight-bearing joints. Emerging genetic, epigenetic, and microbiome research suggests that hand OA might be biologically distinct, involving joint-specific pathways not shared by knee or hip OA. This review integrates genome-wide association studies specific to hand OA, highlighting key molecular contributors such as inflammatory cytokines. These genetic insights, together with emerging data on epigenetic alterations and gut microbial dysbiosis, point to broader systemic and regulatory influences on hand OA onset and progression. We also assess pharmacologic interventions tested in randomized controlled trials that have attempted to target these pathways. While agents such as TNF and IL-6 inhibitors, hydroxychloroquine, and corticosteroids have shown limited success, emerging evidence supports the potential of methotrexate in synovitis-positive general hand OA, platelet-rich plasma in thumb carpometacarpal (CMC) OA, and prolotherapy in interphalangeal (IP) OA. These findings illustrate the persistent gap between mechanistic understanding and therapeutic success. Future work must prioritize multifactorial strategies for addressing pain and translational frameworks that link molecular mechanisms to treatment response. In summary, this review offers an update on hand OA and identifies key opportunities for more targeted and effective therapy.

  View details for DOI 10.3390/ijms26104537

  View details for PubMedID 40429679

  View details for PubMedCentralID PMC12110887

• Patient Acceptance of Reoperation Risk for Lumbar Decompression Versus Fusion. The spine journal : official journal of the North American Spine Society Pius, A. K., Joseph, Y. D., Mullis, D. M., Koduri, J., Levin, J., Alamin, T. F. 2024

  Abstract

  Lumbar decompression and lumbar fusion are effective methods of treating spinal compressive pathologies refractory to conservative management. These surgeries are typically used to treat different spinal problems, but there is a growing body of literature investigating the outcomes of either approach for patients with lumbar degenerative spondylolisthesis and stenosis. Different operations are associated with different risks and different potential needs for reoperation. Patient acceptance of reoperation rates after spinal surgery is currently not well understood.The purpose of this study is to identify patient tolerance for reoperation rates following lumbar decompression and lumbar fusion surgery.A qualitative and quantitative survey intended to capture information on patient preferences was administered.Written informed consent was obtained from patients presenting to two spinal clinics.Patients were asked their threshold tolerance for reoperation rates in the context of choosing a smaller (decompression) versus larger (fusion) spinal surgery.A survey was administered to patients at two spinal clinics-one surgical and one non-surgical. A consecutive series of new patients over multiple clinic days who agreed to participate in the study and filled out the survey are reported on here. Patients were asked to assess, contemplating a problem that could either be treated with lumbar decompression or lumbar fusion, the level at which 1) the likelihood that needing a repeat surgery within 3-5 years would change their mind about choosing the decompression operation and cause them to choose the fusion operation and then 2) the likelihood of needing a repeat surgery within 3-5 years that would be acceptable to them after the fusion operation. The distribution of patient responses was assessed with histograms and descriptive statistics.Ninety patients were surveyed, and of these, 73 patients (81.1%) returned fully completed questionnaires. The median reoperation acceptance rates after a decompression was <60%, while the median acceptable revision rate when contemplating the fusion surgery was 10%.Patient acceptance for the potential need for revision surgery is higher when considering a decompression compared to a fusion operation. Reoperation risk rates along with the magnitude of the surgical intervention are important considerations in determining patients' surgical preferences. Understanding patient preferences and risk tolerances can aid clinicians in shared decision-making, potentially improving patient satisfaction and outcomes in the several lumbar pathologies which can be ameliorated with either decompression or fusion.

  View details for DOI 10.1016/j.spinee.2024.09.003

  View details for PubMedID 39303829

• Nicotinamide Mononucleotide Prevents Free Fatty Acid-Induced Reduction in Glucose Tolerance by Decreasing Insulin Clearance INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES Nahle, A., Joseph, Y., Pereira, S., Mori, Y., Poon, F., Ghadieh, H. E., Ivovic, A., Desai, T., Ghanem, S. S., Asalla, S., Muturi, H. T., Jentz, E. M., Joseph, J. W., Najjar, S. M., Giacca, A. 2021; 22 (24)

  Abstract

  The NAD-dependent deacetylase SIRT1 improves β cell function. Accordingly, nicotinamide mononucleotide (NMN), the product of the rate-limiting step in NAD synthesis, prevents β cell dysfunction and glucose intolerance in mice fed a high-fat diet. The current study was performed to assess the effects of NMN on β cell dysfunction and glucose intolerance that are caused specifically by increased circulating free fatty acids (FFAs). NMN was intravenously infused, with or without oleate, in C57BL/6J mice over a 48-h-period to elevate intracellular NAD levels and consequently increase SIRT1 activity. Administration of NMN in the context of elevated plasma FFA levels considerably improved glucose tolerance. This was due not only to partial protection from FFA-induced β cell dysfunction but also, unexpectedly, to a significant decrease in insulin clearance. However, in conditions of normal FFA levels, NMN impaired glucose tolerance due to decreased β cell function. The presence of this dual action of NMN suggests caution in its proposed therapeutic use in humans.

  View details for DOI 10.3390/ijms222413224

  View details for Web of Science ID 000737988600001

  View details for PubMedID 34948019

  View details for PubMedCentralID PMC8709165

• 4-Phenylbutyric acid improves free fatty acid-induced hepatic insulin resistance <i>in vivo</i> ENDOCRINE CONNECTIONS Pereira, S., Moore, J., Li, J., Yu, W., Ghanim, H., Vlavcheski, F., Joseph, Y., Dandona, P., Volchuk, A., Cummins, C. L., Tsiani, E., Giacca, A. 2021; 10 (8): 861-872

  Abstract

  Plasma free fatty acids (FFAs) are elevated in obesity and can induce insulin resistance via endoplasmic reticulum (ER) stress. However, it is unknown whether hepatic insulin resistance caused by the elevation of plasma FFAs is alleviated by chemical chaperones. Rats received one of the following i.v. treatments for 48 h: saline, intralipid plus heparin (IH), IH plus the chemical chaperone 4-phenylbutyric acid (PBA), or PBA alone and a hyperinsulinemic-euglycemic clamp was performed during the last 2 h. PBA co-infusion normalized IH-induced peripheral insulin resistance, similar to our previous findings with an antioxidant and an IκBα kinase β (IKKβ) inhibitor. Different from our previous results with the antioxidant and IKKβ inhibitor, PBA also improved IH-induced hepatic insulin resistance in parallel with activation of Akt. Unexpectedly, IH did not induce markers of ER stress in the liver, but PBA prevented IH-induced elevation of phosphorylated eukaryotic initiation factor-2α protein in adipose tissue. PBA tended to decrease circulating fetuin-A and significantly increased circulating fibroblast growth factor 21 (FGF21) without affecting markers of activation of hepatic protein kinase C-δ or p38 mitogen-activated protein kinase that we have previously involved in hepatic insulin resistance in this model. In conclusion: (i) PBA prevented hepatic insulin resistance caused by prolonged plasma FFA elevation without affecting hepatic ER stress markers; (ii) the PBA effect is likely due to increased FGF21 and/or decreased fetuin-A, which directly signal to upregulate Akt activation.

  View details for DOI 10.1530/EC-21-0248

  View details for Web of Science ID 000689728200002

  View details for PubMedID 34319253

  View details for PubMedCentralID PMC8346193

• P38 MAPK Inhibition Protects against FFA-Induced Insulin Resistance and Hepatic Fat Accumulation Joseph, D. Y., Rivers, S. L., Giacca, A. AMER DIABETES ASSOC. 2020

  View details for DOI 10.2337/db20-1858-P

  View details for Web of Science ID 000554509804116