Genome-wide association study identifies loci and candidate genes for grain micronutrients and quality traits in wheat (Triticum aestivum L.).

Malnutrition due to micronutrients and protein deficiency is recognized among the major global health issues. Genetic biofortification of wheat is a cost-effective and sustainable strategy to mitigate the global micronutrient and protein malnutrition. Genomic regions governing grain zinc concentration (GZnC), grain iron concentration (GFeC), grain protein content (GPC), test weight (TW), and thousand kernel weight (TKW) were investigated in a set of 184 diverse bread wheat genotypes through genome-wide association study (GWAS). The GWAS panel was genotyped using Breeders' 35 K Axiom Array and phenotyped in three different environments during 2019-2020. A total of 55 marker-trait associations (MTAs) were identified representing all three sub-genomes of wheat. The highest number of MTAs were identified for GPC (23), followed by TKW (15), TW (11), GFeC (4), and GZnC (2). Further, a stable SNP was identified for TKW, and also pleiotropic regions were identified for GPC and TKW. In silico analysis revealed important putative candidate genes underlying the identified genomic regions such as F-box-like domain superfamily, Zinc finger CCCH-type proteins, Serine-threonine/tyrosine-protein kinase, Histone deacetylase domain superfamily, and SANT/Myb domain superfamily proteins, etc. The identified novel MTAs will be validated to estimate their effects in different genetic backgrounds for subsequent use in marker-assisted selection.

Bilateral pedicle screw fixation provides superior biomechanical stability in transforaminal lumbar interbody fusion: a finite element study.

BACKGROUND CONTEXT: Transforaminal lumbar interbody fusion (TLIF) is increasingly popular for the surgical treatment of degenerative lumbar disease. The optimal construct for segmental stability remains unknown. PURPOSE: To compare the stability of fusion constructs using standard (C) and crescent-shaped (CC) polyetheretherketone TLIF cages with unilateral (UPS) or bilateral (BPS) posterior instrumentation. STUDY DESIGN: Five TLIF fusion constructs were compared using finite element (FE) analysis. METHODS: A previously validated L3-L5 FE model was modified to simulate decompression and fusion at L4-L5. This model was used to analyze the biomechanics of various unilateral and bilateral TLIF constructs. The inferior surface of the L5 vertebra remained immobilized throughout the load simulation, and a bending moment of 10 Nm was applied on the L3 vertebra to recreate flexion, extension, lateral bending, and axial rotation. Various biomechanical parameters were evaluated for intact and implanted models in all loading planes. RESULTS: All reconstructive conditions displayed decreased motion at L4-L5. Bilateral posterior fixation conferred greater stability when compared with unilateral fixation in left lateral bending. More than 50% of intact motion remained in the left lateral bending with unilateral posterior fixation compared with less than 10% when bilateral pedicle screw fixation was used. Posterior implant stresses for unilateral fixation were six times greater in flexion and up to four times greater in left lateral bending compared with bilateral fixation. No effects on segmental stability or posterior implant stresses were found. An obliquely-placed, single standard cage generated the lowest cage-end plate stress. CONCLUSIONS: Transforaminal lumbar interbody fusion augmentation with bilateral posterior fixation increases fusion construct stability and decreases posterior instrumentation stress. The shape or number of interbody implants does not appear to impact the segmental stability when bilateral pedicle screws are used. Increased posterior instrumentation stresses were observed in all loading modes with unilateral pedicle screw/rod fixation, which may theoretically accelerate implant loosening or increase the risk of construct failure.

Do stand-alone interbody spacers with integrated screws provide adequate segmental stability for multilevel cervical arthrodesis?

BACKGROUND CONTEXT: Some postoperative complications after anterior cervical fusions have been attributed to anterior cervical plate (ACP) profiles and the necessary wide operative exposure for their insertion. Consequently, low-profile stand-alone interbody spacers with integrated screws (SIS) have been developed. Although SIS constructs have demonstrated similar biomechanical stability to the ACP in single-level fusions, their role as a stand-alone device in multilevel reconstructions has not been thoroughly evaluated. PURPOSE: To evaluate the acute segmental stability afforded by an SIS device compared with the traditional ACP in the setting of a multilevel cervical arthrodesis. STUDY DESIGN: In vitro human cadaveric biomechanical analysis. METHODS: Thirteen human cadaveric cervical spines (C2-T1) were nondestructively tested with a custom 6 df spine simulator under axial rotation, flexion-extension, and lateral bending loading. After intact analysis, eight single-levels (C4-C5/C6-C7) from four specimens were instrumented and tested with ACP and SIS. Nine specimens were tested with C5-C7 SIS, C5-C7 ACP, C4-C7 ACP, C4-C7 ACP+posterior fixation, C4-C7 SIS, and C4-C7 SIS+posterior fixation. Testing order was randomized with each additional level instrumented. Full range of motion (ROM) data were obtained and analyzed by each loading modality, using mean comparisons with repeated measures analysis of variance. Paired t tests were used for post hoc analysis with Sidak correction for multiple comparisons. RESULTS: No significant difference in ROM was noted between the ACP and SIS for single-level fixation (p>.05). For multisegment reconstructions (two and three levels), the ACP proved superior to SIS and intact condition, with significantly lower ROM in all planes (p<.05). When either the three-level SIS or ACP constructs were supplemented with posterior lateral mass fixation, there was a greater than 80% reduction in ROM under all testing modalities (p<.05), with no significant difference between the ACP and SIS constructs (p>.05). CONCLUSIONS: The SIS device may be a reasonable option as a stand-alone device for single-level fixation. However, SIS devices should be used with careful consideration in the setting of multilevel cervical fusion. However, when supplemented with posterior fixation, SIS devices are a sound biomechanical alternative to ACP for multilevel fusion constructs.

The biomechanical consequences of rod reduction on pedicle screws: should it be avoided?

BACKGROUND CONTEXT: Rod contouring is frequently required to allow for appropriate alignment of pedicle screw-rod constructs. When residual mismatch is still present, a rod persuasion device is often used to achieve further rod reduction. Despite its popularity and widespread use, the biomechanical consequences of this technique have not been evaluated. PURPOSE: To evaluate the biomechanical fixation strength of pedicle screws after attempted reduction of a rod-pedicle screw mismatch using a rod persuasion device. METHODS: Fifteen 3-level, human cadaveric thoracic specimens were prepared and scanned for bone mineral density. Osteoporotic (n=6) and normal (n=9) specimens were instrumented with 5.0-mm-diameter pedicle screws; for each pair of comparison level tested, the bilateral screws were equal in length, and the screw length was determined by the thoracic level and size of the vertebra (35 to 45 mm). Titanium 5.5-mm rods were contoured and secured to the pedicle screws at the proximal and distal levels. For the middle segment, the rod on the right side was intentionally contoured to create a 5-mm residual gap between the inner bushing of the pedicle screw and the rod. A rod persuasion device was then used to engage the setscrew. The left side served as a control with perfect screw/rod alignment. After 30 minutes, constructs were disassembled and vertebrae individually potted. The implants were pulled in-line with the screw axis with peak pullout strength (POS) measured in Newton (N). For the proximal and distal segments, pedicle screws on the right side were taken out and reinserted through the same trajectory to simulate screw depth adjustment as an alternative to rod reduction. RESULTS: Pedicle screws reduced to the rod generated a 48% lower mean POS (495±379 N) relative to the controls (954±237 N) (p<.05) and significantly decreased work energy to failure (p<.05). Nearly half (n=7) of the pedicle screws had failed during the reduction attempt with visible pullout of the screw. After reduction, decreased POS was observed in both normal (p<.05) and osteoporotic (p<.05) bone. Back out and reinsertion of the screw resulted in no significant difference in mean POS, stiffness, and work energy to failure (p>.05). CONCLUSIONS: In circumstances where a rod is not fully seated within the pedicle screw, the use of a rod persuasion device decreases the overall POS and work energy to failure of the screw or results in outright failure. Further rod contouring or correction of pedicle screw depth of insertion may be warranted to allow for appropriate alignment of the longitudinal rods.

The biomechanical effect of pedicle screw hubbing on pullout resistance in the thoracic spine.

BACKGROUND CONTEXT: The biomechanical fixation strength afforded by pedicle screws has been strongly correlated with bone mineral density. It has been postulated that "hubbing" the head of the pedicle screw against the dorsal laminar cortex provides a load-sharing effect, thereby limiting cephalocaudad toggling and improving the pullout resistance of the pedicle screw. PURPOSE: To evaluate the pullout strength (POS) of monoaxial hubbed pedicle screws versus standard fixation in the thoracic spine. STUDY DESIGN: Biomechanical investigation. METHODS: Twenty-two human cadaveric thoracic vertebrae were acquired and dual-energy X-ray absorptiometry scanned. Osteoporotic (n = 16) and normal (n = 6) specimens were instrumented with a 5.0 × 35-mm pedicle screw on one side in a standard fashion. In the contralateral pedicle, 5.0 × 30-mm screw was inserted with hubbing of the screw into the dorsal lamina. A difference in screw length was used to achieve equivalent depth of insertion. After 2,000 cycles of cephalocaudad toggling, screws were pulled out with the tensile force oriented to the midline of the spine and peak POS measured in newtons (N). Four additional specimens were subjected to microcomputed tomography (micro-CT) analysis to evaluate internal pedicle architecture after screw insertion. RESULTS: Hubbed screws resulted in significantly lower POS (290.5 ± 142.4 N) compared with standard pedicle screws (511.5 ± 242.8 N; p = .00). This finding was evident in both normal and osteoporotic vertebrae based on independent subgroup post hoc analyses (p<.05). As a result of hubbing, half of the specimens fractured through the lamina or superior articular facet (SAF). No fractures occurred on the control side. There was no difference in mean POS for hubbed screws with and without fracture; however, further micro-CT analysis revealed the presence of internal fracture propagation for those specimens that did not have any external signs of failure. CONCLUSIONS: Hubbing pedicle screws results in significantly decreased POS compared with conventional pedicle screws. Hubbing predisposes toward iatrogenic fracture of the dorsal lamina, transverse process, or SAF during insertion.

Effect of graded facetectomy on biomechanics of Dynesys dynamic stabilization system.

STUDY DESIGN: Finite element (FE) method was used to compare the biomechanics of L3-S1 lumbar spine with graded facetectomy before and after placement of Dynesys. OBJECTIVE: To evaluate the biomechanics of Dynesys as a function of graded bilateral facetectomies. SUMMARY OF BACKGROUND DATA: Spinal fusion or posterior dynamic stabilization systems are used to restore stability after facetectomies. METHODS: The intact FE spine was modified to simulate decompression at L4-L5 with 50% and 75% and total facetectomy with/without dynamic stabilization with Dynesys. Biomechanics of the implanted level was investigated under different physiological loadings. RESULTS: Total facetectomy increased the motion in extension (8.7° vs. 2.7° for intact) and axial rotation (8.4° vs. 2.4° for intact). However the decrease in motion in the Dynesys model ranged from 65% in axial rotation to 80% in flexion for all facetectomies, except in the total facetectomy axial rotation case (motion higher than intact). The center of rotation of dynamic stabilized segment moved inferior/posterior in partial facetectomy and superior/posterior in total facetectomy with respect to the intact and destabilized cases. The Dynesys screws observed peak stresses up to 28% higher than those of a rigid fixation system in certain loadings, such as lateral bending and extension. The critical loosening torque applied to the screws in total facetectomy case was 6 times the partial facetectomy case in axial rotation. CONCLUSION: Partial facetectomy had a minimal effect on range of motion on the Dynesys-implanted segment. However, in the case of total facetectomy the motion increased by almost 40% in flexion and by 200% in axial rotation. The higher stresses applied to the screws in Dynesys in specific loadings may lead to higher risk of screw failure in Dynesys than in a generic rigid fixation construct.