Probing the decelerating trajectory of a Raman soliton using temporal reflection.

Temporal reflection is a process where an optical pulse reflects off a moving boundary with different refractive indices across it. In a dispersive medium, this process creates a reflected pulse with a frequency shift that changes its speed. Such frequency shifts depend on the speed of the moving boundary. In this work, we propose and experimentally show that it is possible to probe the trajectory of the boundary by measuring the frequency shifts while changing the initial delay between the incident pulse and the boundary. We demonstrate this effect by reflecting a probe pulse off a short soliton, acting as a moving boundary that decelerates inside a photonic crystal fiber because of intrapulse Raman scattering. We deduce trajectory of the soliton from the measured spectral data for the reflected pulse.

Multilevel tandem spondylolisthesis associated with a reduced "safe zone" for a transpsoas lateral lumbar interbody fusion at L4-5.

OBJECTIVE: The aim of this study was to investigate the effect of degenerative spondylolisthesis (DS) on psoas anatomy and the L4-5 safe zone during lateral lumbar interbody fusion (LLIF). METHODS: In this retrospective, single-institution analysis, patients managed for low-back pain between 2016 and 2021 were identified. Inclusion criteria were adequate lumbar MR images and radiographs. Exclusion criteria were spine trauma, infection, metastases, transitional anatomy, or prior surgery. There were three age and sex propensity-matched cohorts: 1) controls without DS; 2) patients with single-level DS (SLDS); and 3) patients with multilevel, tandem DS (TDS). Axial T2-weighted MRI was used to measure the apical (ventral) and central positions of the psoas relative to the posterior tangent line at the L4-5 disc. Lumbar lordosis (LL), pelvic incidence (PI), pelvic tilt (PT), sacral slope (SS), and PI-LL mismatch were measured on lumbar radiographs. The primary outcomes were apical and central psoas positions at L4-5, which were calculated using stepwise multivariate linear regression including demographics, spinopelvic parameters, and degree of DS. Secondary outcomes were associations between single- and multilevel DS and spinopelvic parameters, which were calculated using one-way ANOVA with Bonferroni correction for between-group comparisons. RESULTS: A total of 230 patients (92 without DS, 92 with SLDS, and 46 with TDS) were included. The mean age was 68.0 ± 8.9 years, and 185 patients (80.4%) were female. The mean BMI was 31.0 ± 7.1, and the mean age-adjusted Charlson Comorbidity Index (aCCI) was 4.2 ± 1.8. Age, BMI, sex, and aCCI were similar between the groups. Each increased grade of DS (no DS to SLDS to TDS) was associated with significantly increased PI (p < 0.05 for all relationships). PT, PI-LL mismatch, center psoas, and apical position were all significantly greater in the TDS group than in the no-DS and SLDS groups (p < 0.05). DS severity was independently associated with 2.4-mm (95% CI 1.1-3.8 mm) center and 2.6-mm (95% CI 1.2-3.9 mm) apical psoas anterior displacement per increased grade (increasing from no DS to SLDS to TDS). CONCLUSIONS: TDS represents more severe sagittal malalignment (PI-LL mismatch), pelvic compensation (PT), and changes in the psoas major muscle compared with no DS, and SLDS and is a risk factor for lumbar plexus injury during L4-5 LLIF due to a smaller safe zone.

Discovery of two novel (4-hydroxyphenyl) substituted polycyclic carbocycles as potent and selective estrogen receptor beta agonists.

Two (4-hydroxyphenyl) substituted polycyclic carbocycles were prepared and assayed for estrogen receptor activity. 4-(4-Hydroxyphenyl)tricyclo[3.3.1.13,7]decane-1-methanol (5a/b) and 7-(4-hydroxyphenyl)spiro[3.5]nonan-2-ol ((±)-11) were found to be potent ERß agonists (1.9 ± 0.4 nM and 6.2 ± 1.4 nM respectively) in a cell-based functional assay. Furthermore, both 5a/b and 11 were highly selective for ERß over ERα (377 and 1,100-fold selective respectively). While neither compound inhibited CYP2D6 or CYP3A4 at concentrations up to 62.5 µM, 5a/b did have weak binding to CYP2C9 with an IC50 of 10 ± 0.5 µM. Computational assessment of 5a/b and 11 predicted the most probable site of metabolism would be ortho to the phenolic hydroxyl group.

Long-term oral administration of a novel estrogen receptor beta agonist enhances memory and alleviates drug-induced vasodilation in young ovariectomized mice.

Development of estrogen therapies targeting the ß (ERß) but not α (ERα) estrogen receptor is critically needed for the treatment of negative menopausal symptoms, as ERα activation increases health risks like cancer. Here, we determined the effects of long-term oral treatment with EGX358, a novel highly selective ERß agonist, on memory, vasodilation, and affect in young ovariectomized mice. Mice were orally gavaged daily for 9 weeks with vehicle, 17ß-estradiol (E2), the ERß agonist diarylpropionitrile (DPN), or EGX358 at doses that enhance memory when delivered acutely. Tail skin temperature was recorded as a proxy for vasodilation following injection of vehicle or senktide, a tachykinin receptor 3 agonist used to model hot flashes. Anxiety-like behavior was assessed in the open field (OF) and elevated plus maze (EPM), and depression-like behavior was measured in the tail suspension (TST) and forced swim tests (FST). Finally, memory was assessed in object recognition (OR) and object placement (OP) tasks. E2, DPN, and EGX358 reduced senktide-mediated increases in tail skin temperature compared to vehicle. All three treatments also enhanced memory in the OR and OP tasks, whereas vehicle did not. Although E2 increased time spent in the center of the OF, no other treatment effects were observed in the OF, EPM, TST, or FST. These data suggest that long-term ERß activation can reduce hot flash-like symptoms and enhance spatial and object recognition memories in ovariectomized mice. Thus, the highly selective ERß agonist EGX358 may be a promising avenue for reducing menopause-related hot flashes and memory dysfunction.

Synthesis and evaluation of 17α-triazolyl and 9α-cyano derivatives of estradiol.

A variety of 17α-triazolyl and 9α-cyano derivatives of estradiol were prepared and evaluated for binding to human ERß in both a TR-FRET assay, as well as ERß and ERα agonism in cell-based functional assays. 9α-Cyanoestradiol (5) was nearly equipotent as estradiol as an agonist for both ERß and ERα. The potency of the 17α-triazolylestradiol analogs is considerably more variable and depends on the nature of the 4-substituent of the triazole ring. While rigid protein docking simulations exhibited significant steric clashing, induced fit docking providing more protein flexibility revealed that the triazole linker of analogs 2d and 2e extends outside of the traditional ligand binding domain with the benzene ring located in the loop connecting helix 11 to helix 12.

Severe pulmonary injury leading to death during thoracic rod removal: a case report.

PURPOSE: Removal of hardware procedures following posterior spinal fusion is most commonly performed for hardware irritation without overt infection. It is imperative that surgeons realize that serious complications may arise from this procedure. The purpose of this report is to report a case of a pneumothorax that developed in a thoracolumbar removal of hardware case that resulted in a patient death. METHODS: Retrospective review of a patient's medical record and imaging. RESULTS: A 74-year-old patient with a history of T4-10 anterior discectomy and fusion with rib autograft and T4-L2 posterior fusion underwent a removal of hardware procedure for delayed surgical site infection. During the procedure, the tip of the bolt cutter jaw broke and entered the pulmonary cavity leading to a pneumothorax. The patient developed pneumonia 1 month postoperatively and passed away. CONCLUSIONS: This case report highlights one of the rare but potential complications of spinal removal of hardware surgery. It is essential that surgeons are aware of the possibility of pulmonary complications during thoracolumbar removal of hardware cases so that they may fully counsel their patients on the potential risks.

Syntheses of spliceostatins and thailanstatins: a review.

The spliceostatins/thailanstatins are a family of linear peptides/polyketides that inhibit pre-mRNA splicing, and as such act as potent cytotoxic compounds. These compounds generally contain 9 stereocenters spread over a common (2Z,4S)-4-acetoxy-2-butenamide fragment, an (all-cis)-2,3,5,6-tetrasubstituted tetrahydropyran fragment and a terminal oxane ring joined by a dienyl chain. Due to the impressive antitumor properties of these compounds, along with their complex structure, a number of total syntheses have been reported. This review will compare the synthetic strategies reported through the end of 2019.

Broadband infrared plasmonic metamaterial absorber with multipronged absorption mechanisms.

A broadband plasmonic metamaterial absorber with near perfect multiband absorption in the infrared region is designed using a metal-insulator-metal configuration and fabricated using photolithography. The metal-insulator-metal configuration consists of a Ti microdisk array, a SiO2 insulator spacer, and an Al bottom layer. The multiband absorption occurs with near perfect absorption at 4.8-7.5 µm and 9.7-10.5 µm. Ultra-broadband absorption in the mid-IR wavelength range between 3-14 µm is realized by adding a rough photoresist layer on top of the periodic microdisk structures. The multiband absorption is achieved through the combined mechanisms including plasmonic surface lattice resonance, gap plasmon resonance, Fabry-Perot cavity resonance, and the intrinsic phonon-polariton absorption of SiO2.

Evaluation of α-hydroxycinnamic acids as pyruvate carboxylase inhibitors.

Through a structure-based drug design project (SBDD), potent small molecule inhibitors of pyruvate carboxylase (PC) have been discovered. A series of α-keto acids (7) and α-hydroxycinnamic acids (8) were prepared and evaluated for inhibition of PC in two assays. The two most potent inhibitors were 3,3'-(1,4-phenylene)bis[2-hydroxy-2-propenoic acid] (8u) and 2-hydroxy-3-(quinoline-2-yl)propenoic acid (8v) with IC50 values of 3.0 ±â€¯1.0 µM and 4.3 ±â€¯1.5 µM respectively. Compound 8v is a competitive inhibitor with respect to pyruvate (Ki = 0.74 µM) and a mixed-type inhibitor with respect to ATP, indicating that it targets the unique carboxyltransferase (CT) domain of PC. Furthermore, compound 8v does not significantly inhibit human carbonic anhydrase II, matrix metalloproteinase-2, malate dehydrogenase or lactate dehydrogenase.

ISSLS PRIZE IN BIOENGINEERING SCIENCE 2018: dynamic imaging of degenerative spondylolisthesis reveals mid-range dynamic lumbar instability not evident on static clinical radiographs.

PURPOSE: Degenerative spondylolisthesis (DS) in the setting of symptomatic lumbar spinal stenosis is commonly treated with spinal fusion in addition to decompression with laminectomy. However, recent studies have shown similar clinical outcomes after decompression alone, suggesting that a subset of DS patients may not require spinal fusion. Identification of dynamic instability could prove useful for predicting which patients are at higher risk of post-laminectomy destabilization necessitating fusion. The goal of this study was to determine if static clinical radiographs adequately characterize dynamic instability in patients with lumbar degenerative spondylolisthesis (DS) and to compare the rotational and translational kinematics in vivo during continuous dynamic flexion activity in DS versus asymptomatic age-matched controls. METHODS: Seven patients with symptomatic single level lumbar DS (6 M, 1 F; 66 ± 5.0 years) and seven age-matched asymptomatic controls (5 M, 2 F age 63.9 ± 6.4 years) underwent biplane radiographic imaging during continuous torso flexion. A volumetric model-based tracking system was used to track each vertebra in the radiographic images using subject-specific 3D bone models from high-resolution computed tomography (CT). In vivo continuous dynamic sagittal rotation (flexion/extension) and AP translation (slip) were calculated and compared to clinical measures of intervertebral flexion/extension and AP translation obtained from standard lateral flexion/extension radiographs. RESULTS: Static clinical radiographs underestimate the degree of AP translation seen on dynamic in vivo imaging (1.0 vs 3.1 mm; p = 0.03). DS patients demonstrated three primary motion patterns compared to a single kinematic pattern in asymptomatic controls when analyzing continuous dynamic in vivo imaging. 3/7 (42%) of patients with DS demonstrated aberrant mid-range motion. CONCLUSION: Continuous in vivo dynamic imaging in DS reveals a spectrum of aberrant motion with significantly greater kinematic heterogeneity than previously realized that is not readily seen on current clinical imaging. LEVEL OF EVIDENCE: Level V data These slides can be retrieved under Electronic Supplementary Material.

Reactivity of (1-methoxycarbonylpentadienyl)iron(1+) cations with hydride, methyl, and nitrogen nucleophiles.

The reaction of tricarbonyl and (dicarbonyl)triphenylphosphine (1-methoxycarbonyl-pentadientyl)iron(1+) cations 7 and 8 with methyl lithium, NaBH3CN, or potassium phthalimide affords (pentenediyl)iron complexes 9a-c and 11a-b, while reaction with dimethylcuprate, gave (E,Z-diene)iron complexes 10 and 12. Oxidatively induced-reductive elimination of 9a-c gave vinylcyclopropanecarboxylates 17a-c. The optically active vinylcyclopropane (+)-17a, prepared from (1S)-7, undergoes olefin cross-metathesis with excess (+)-18 to yield (+)-19, a C9-C16 synthon for the antifungal agent ambruticin. Alternatively reaction of 7 with methanesulfonamide or trimethylsilylazide gave (E,E-diene)iron complexes 14d and e. Huisgen [3+2] cyclization of the (azidodienyl)iron complex 14e with alkynes afforded triazoles 25a-e.

Cervical spine bone density in young healthy adults as a function of sex, vertebral level and anatomic location.

PURPOSE: Bone mineral density (BMD) measured using quantitative computed tomography (QCT) has been shown to correlate with bone mechanical properties. Knowledge of BMD within specific anatomic regions of the spine is valuable to surgeons who must secure instrumentation to the vertebrae, to medical device developers who design screws and disc replacements, and to researchers who assign mechanical properties to computational models. The objective of this study was to comprehensively characterize BMD in the cervical spine of young healthy adults. METHODS: QCT was used to determine BMD in the cervical spines of 31 healthy adults (age 20-35). Subject-specific 3D models of each vertebra were created from CT scans, and anatomic regions of interest were identified in each bone (C1: 3 regions; C2: 9 regions, C3-C7: 13 regions). Statistical tests were performed to identify differences in BMD according to vertebral level, anatomic regions within vertebrae, and sex. RESULTS: BMD varied significantly among vertebral levels and among anatomic regions within each vertebra. Females had higher BMD than males (p = .041) primarily due to higher BMD in the posterior regions of each vertebra. CONCLUSIONS: These data can serve as a baseline to identify BMD changes in older and symptomatic patients. This data set is also the first report of volumetric bone density within different anatomic regions of the atlas and axis of the cervical spine. The finding of higher BMD in females is in agreement with the previous QCT results but contradicts DEXA results that are known to be dependent upon bone size.

Generation of Molecular Complexity from Cyclooctatetraene: Preparation of Aminobicyclo[5.1.0]octitols.

A series of eight stereoisomeric N-(tetrahydroxy bicyclo-[5.1.0]oct-2S*-yl)phthalimides were prepared in one to four steps from N-(bicyclo[5.1.0]octa-3,5-dien-2-yl)phthalimide (±)-7, which is readily available from cyclooctatetraene (62 % yield). The structural assignments of the stereoisomers were established by (1) H NMR spectral data as well as X-ray crystal structures for certain members. The outcomes of several epoxydiol hydrolyses, particularly ring contraction and enlargement, are of note. The isomeric phthalimides as well as the free amines did not exhibit ß-glucosidase inhibitory activity at a concentration of less than 100 µM.

Prevalence of venous thromboembolic events after elective major thoracolumbar degenerative spine surgery.

STUDY DESIGN: A case-control study. OBJECTIVE: The purposes of this study were to establish the prevalence of venous thromboembolic disease in patients undergoing elective major thoracolumbar degenerative spine surgery and identify risk factors. SUMMARY OF BACKGROUND DATA: Venous thromboembolic events (VTE) are a serious complication of orthopedic surgery, but the prevalence of VTE after elective thoracolumbar degenerative spine surgery is not well known. METHODS: This was a case-control study of 5766 consecutive elective thoracolumbar degenerative spine surgeries. Symptomatic pulmonary emboli (PE) were diagnosed by spiral chest CT scans, nuclear scintigraphic ventilation-perfusion, and angiography. Deep vein thromboses (DVT) were diagnosed by venous duplex scans. The prevalence of VTE was analyzed according to patient demographic variables and type of surgery performed. RESULTS: The prevalence of developing a VTE was 1.5% (89/5766), with a prevalence of symptomatic PE of 0.88% (51/5766) and DVT of 0.66% (38/5766). There were 47% males and 53% females with a mean age of 60.3 years. In patients undergoing 5-segment fusions the prevalence of PE was 3.1% (P=0.022). Patients who had ≥4 segments fused had a prevalence of PE of 1.7% (P=0.014). The odds of having a PE in those above 65 years at the time of surgery were 2.196 times as large as for those below 65 years. Noncontributory factors included sex, instrumentation, and revision surgery. CONCLUSIONS: This case-control study of 5766 patients who underwent elective thoracolumbar degenerative spine surgery revealed a prevalence of VTE of 1.5%, with a prevalence of PE of 0.88% and DVT of 0.66%. Patients with increasingly extensive surgery had a higher risk of PE, specifically those undergoing fusion of ≥5 segments.

Probing the human estrogen receptor-α binding requirements for phenolic mono- and di-hydroxyl compounds: a combined synthesis, binding and docking study.

Various estrogen analogs were synthesized and tested for binding to human ERα using a fluorescence polarization displacement assay. Binding affinity and orientation were also predicted using docking calculations. Docking was able to accurately predict relative binding affinity and orientation for estradiol, but only if a tightly bound water molecule bridging Arg394/Glu353 is present. Di-hydroxyl compounds sometimes bind in two orientations, which are flipped in terms of relative positioning of their hydroxyl groups. Di-hydroxyl compounds were predicted to bind with their aliphatic hydroxyl group interacting with His524 in ERα. One nonsteroid-based dihdroxyl compound was 1000-fold specific for ERß over ERα, and was also 25-fold specific for agonist ERß versus antagonist activity. Docking predictions suggest this specificity may be due to interaction of the aliphatic hydroxyl with His475 in the agonist form of ERß, versus with Thr299 in the antagonist form. But, the presence of this aliphatic hydroxyl is not required in all compounds, since mono-hydroxyl (phenolic) compounds bind ERα with high affinity, via hydroxyl hydrogen bonding interactions with the ERα Arg394/Glu353/water triad, and van der Waals interactions with the rest of the molecule.

Mortality in elderly patients following operative and nonoperative management of odontoid fractures.

STUDY DESIGN: Retrospective matched cohort study. OBJECTIVE: To compare mortality in elderly patients with odontoid fractures after operative and nonoperative treatment. In addition, to evaluate potential factors that may increase the risk of mortality in the geriatric population after odontoid fracture. SUMMARY OF BACKGROUND DATA: Odontoid fractures represent the most common cervical spine fracture in patients over 70. In this population controversy exists as to the optimal treatment of odontoid fractures, especially type II fractures. METHODS: A retrospective review of all odontoid fractures in patients 75 years of age or older at our institution from 1996 to 2010 was performed. Comorbidities were stratified using the Charlson comorbidity index. Mortality was determined at 3 months, 1, and 5 years. RESULTS: A total of 96 patients were identified of which 75 met inclusion criteria. The average age of patients included was 82.3 years. The average Charlson comorbidity score for those operated on (2.37) was not significantly different from the nonoperative group (2.46), (P=0.45). At 3 months the operative group had a significantly lower mortality rate than the nonoperative group (P=0.024). There was no significant difference in 1-year (P=0.42) or 5-year (P=0.21) mortality between the operative and nonoperative cohorts. Of the patients treated nonoperatively, those who died within 3 months of treatment had a significantly higher Charlson score (3.98) than those who survived (2.14). Patients who survived at least 1 year after surgery had a significantly lower Charlson score (1.53) than those who died (3.22) within that time frame after surgery (P=0.05). CONCLUSIONS: There was no significant difference between 1- and 5-year mortality in patients treated operatively or nonoperatively. Regardless of treatment Charlson score had a significant impact on mortality. Age significantly affected mortality in patients treated surgically.

Synthesis and Evaluation of 5-(Heteroarylmethylene)hydantoins as Glycogen Synthase Kinase-3ß Inhibitors.

Glycogen synthase kinase-3 (GSK-3) is a serine/threonine kinase which plays a center role in the phosphorylation of a wide variety of proteins, generally leading to their inactivation. As such, GSK-3 is viewed as a therapeutic target. An ever-increasing number of small organic molecule inhibitors of GSK-3 have been reported. Phenylmethylene hydantoins are known to exhibit a wide range of inhibitory activities including for GSK-3ß. A family of fourteen 2-heterocycle substituted methylene hydantoins (14, 17-29) were prepared and evaluated for the inhibition of GSK-3ß at 25 µM. The IC50 values of five of these compounds was determined; the two best inhibitors are 5-[(4'-chloro-2-pyridinyl)methylene]hydantoin (IC50 = 2.14 ± 0.18 µM) and 5-[(6'-bromo-2-pyridinyl)methylene]hydantoin (IC50 = 3.39 ± 0.16 µM). The computational docking of the compounds with GSK-3ß (pdb 1q41) revealed poses with hydrogen bonding to the backbone at Val135. The 5-[(heteroaryl)methylene]hydantoins did not strongly inhibit other metalloenzymes, demonstrating poor inhibitory activity against matrix metalloproteinase-12 at 25 µM and against human carbonic anhydrase at 200 µM, and were not inhibitors for Staphylococcus aureus pyruvate carboxylase at concentrations >1000 µM.

Modified Clavien-Dindo-Sink Classification System for operative complications in adult spine surgery.

OBJECTIVE: Currently there is no standardized mechanism to describe or compare complications in adult spine surgery. Thus, the purpose of the present study was to modify and validate the Clavien-Dindo-Sink complication classification system for applications in spine surgery. METHODS: The Clavien-Dindo-Sink complication classification system was evaluated and modified for spine surgery by four fellowship-trained spine surgeons using a consensus process. A distinct group of three fellowship-trained spine surgeons completed a randomized electronic survey grading 71 real-life clinical case scenarios. The survey was repeated 2 weeks after its initial completion. Fleiss' and Cohen's kappa (κ) statistics were used to evaluate interrater and intrarater reliabilities, respectively. RESULTS: Overall, interobserver reliability during the first and second rounds of grading was excellent with a κ of 0.847 (95% CI 0.785-0.908) and 0.852 (95% CI 0.791-0.913), respectively. In the first round, interrater reliability ranged from good to excellent with a κ of 0.778 for grade I (95% CI 0.644-0.912), 0.698 for grade II (95% CI 0.564-0.832), 0.861 for grade III (95% CI 0.727-0.996), 0.845 for grade IV-A (95% CI 0.711-0.979), 0.962 for grade IV-B (95% CI 0.828-1.097), and 0.960 for grade V (95% CI 0.826-1.094). Intraobserver reliability testing for all three independent observers was excellent with a κ of 0.971 (95% CI 0.944-0.999) for rater 1, 0.963 (95% CI 0.926-1.001) for rater 2, and 0.926 (95% CI 0.869-0.982) for rater 3. CONCLUSIONS: The Modified Clavien-Dindo-Sink Classification System demonstrates excellent interrater and intrarater reliability in adult spine surgery cases. This system provides a useful framework to better communicate the severity of spine-related complications.

Generation of molecular complexity from cyclooctatetraene: preparation of optically active protected aminocycloheptitols and bicyclo[4.4.1]undecatriene.

The racemic (6-cyclo-heptadienyl)Fe(CO)(3)(+) cation ((±)-7), prepared from cyclooctatetraene, was treated with a variety of carbon and heteroatom nucleophiles. Attack took place at the less hindered C(1) dienyl carbon and decomplexation of the (cycloheptadiene)Fe(CO)(3) complexes gave products rich in functionality for further synthetic manipulation. In particular, a seven-step route was developed from racemic (6-styryl-2,4-cycloheptadien-1-yl)phthalimide ((±)-9 d) to afford the optically active aminocycloheptitols (-)-20 and (+)-20.

Subject-specific inverse dynamics of the head and cervical spine during in vivo dynamic flexion-extension.

The effects of degeneration and surgery on cervical spine mechanics are commonly evaluated through in vitro testing and finite element models derived from these tests. The objectives of the current study were to estimate the load applied to the C2 vertebra during in vivo functional flexion-extension and to evaluate the effects of anterior cervical arthrodesis on spine kinetics. Spine and head kinematics from 16 subjects (six arthrodesis patients and ten asymptomatic controls) were determined during functional flexion-extension using dynamic stereo X-ray and conventional reflective markers. Subject-specific inverse dynamics models, including three flexor muscles and four extensor muscles attached to the skull, estimated the force applied to C2. Total force applied to C2 was not significantly different between arthrodesis and control groups at any 10 deg increment of head flexion-extension (all p values ≥ 0.937). Forces applied to C2 were smallest in the neutral position, increased slowly with flexion, and increased rapidly with extension. Muscle moment arms changed significantly during flexion-extension, and were dependent upon the direction of head motion. The results suggest that in vitro protocols and finite element models that apply constant loads to C2 do not accurately represent in vivo cervical spine kinetics.