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Accuracy of pedicle screw placement for lumbar fusion using anatomic landmarks versus open laminectomy: a comparison of two surgical techniques in cadaveric specimens.

OBJECTIVE: We determined whether the accuracy of lumbar pedicle screw placement is optimized by performing a laminectomy before screw placement with screw entry point and trajectory being guided by pedicle visualization and palpation (Technique 1). This technique was compared with a technique using anatomic landmarks for pedicle screw placement (Technique 2). The biomechanical stability of the instrumented constructs, in the absence and presence of a laminectomy, was also compared. METHODS: Twelve L1-L3 specimens were harvested from fresh cadavers. The intact laminectomy and instrumented spines were biomechanically tested in flexion and extension, lateral bending, and axial rotation. Laminectomies were performed in six of the 12 specimens before pedicle screw placement using Technique 1. The remaining six specimens underwent pedicle screw and rod fixation using Technique 2. Computed tomographic images were obtained for all instrumented specimens. Deviation of the screws from the ideal entry point or trajectory was analyzed to quantitatively compare the two techniques. RESULTS: Computed tomographic analysis of the specimens showed that all screw placements were within the pedicles. Scatter plot analysis demonstrated that screws placed using Technique 2 were more likely to have the combination of entry points and trajectories medial to the ideal entry point and trajectory. Laminectomy did not weaken the final pedicle screw and rod-fixated constructs. CONCLUSION: All screw placements were grossly within the confines of the pedicles, regardless of technique, as evidenced by computed tomographic analysis. Furthermore, the anatomic landmark technique and the open laminectomy technique yielded biomechanically equivalent pedicle screw and rod-fixated constructs.

Aged↗

Lateralized functional components of spatial cognition in the avian hippocampal formation: evidence from single-unit recordings in freely moving homing pigeons.

Previous research has revealed that the functional components of spatial cognition are lateralized in the forebrain of birds, including the hippocampal formation (HF). To investigate how HF cells in the left and right avian brain may differentially participate in representations of space, we recorded single-units from the HF of homing pigeons as they ran a plus maze for food. The rate maps of left HF cells often displayed elongated regions of increased activity in the center of the maze and along the maze corridors, whereas right HF cells tended to display patches at the ends of maze arms at/near goal locations. Left HF cells displayed a higher degree of spatial-specificity compared with right HF cells, including higher patch-specificity, higher reliability, and a higher incidence of location-correlated activity. Analysis of speed-correlated and trajectory-dependent activity also revealed significant HF-lateralized differences. Right HF cells tended to display significant negative correlations between spike rate and speed, although speed-dependent rate maps indicate that this relationship did not explain their space-specific activity. Left HF cells displayed a significantly higher incidence of trajectory-dependent space-specific activity than was observed in the right HF, suggesting that left HF cells may participate in navigating among goal locations. Differences in the correlates of left and right pigeon HF cells are consistent with unilateral HF-lesion data suggesting that the functional components of spatial cognition are lateralized in the avian brain, and furthermore, provide a basis for hypotheses regarding how the left and right HF support different aspects of spatial cognition.

Animals↗

A 175-psec molecular dynamics simulation of camphor-bound cytochrome P-450cam.

The structure and internal motions of cytochrome P-450cam, a monooxygenase heme enzyme with 414 amino acid residues, with camphor bound at the active site have been evaluated on the basis of a 175-psec molecular dynamics simulation carried out at 300 K. All hydrogen atoms were explicitly modeled, and 204 crystallographic waters were included in the simulation. Based on an analysis of the time course of the trajectory versus potential energy, root mean square deviation, radius of gyration, and hydrogen bonding, the simulation was judged to be stable and representative of the average experimental structure. The averaged structural properties of the enzyme were evaluated from the final 135 psec of the simulation. The average atomic displacement from the X-ray structure was 1.39 A for all heavy atoms and 1.17 A for just C-alpha atoms. The average root-mean-square (rms) fluctuations of all heavy atoms and backbone atoms were 0.42 and 0.37 A, respectively. The computed rms fluctuations were in reasonable agreement with the experimentally determined temperature factors. All 13 segments of alpha-helix and 5 segments of beta-sheet were well preserved with the exception of the N-terminal half of helix F which alternated between an alpha-helix and a 310-helix. In addition there were in general only small variations in the relative orientation of adjacent alpha-helices. The rms fluctuations of the backbone dihedral angles in the secondary structure elements were almost uniformly smaller, with the fluctuation in alpha-helices and beta-sheets, 31 and 10% less, respectively, than those in nonsecondary structure regions. The reported crystal structure contains kinks in both helices C and I. In the simulation, both of these regions showed high mobility and large deviations from their starting positions. Since the kink in the I helix is at the oxygen binding site, these motions may have mechanistic implications.

Binding Sites↗

Identification and characterization of the unfolding transition state of chymotrypsin inhibitor 2 by molecular dynamics simulations.

Temperature-induced unfolding of chymotrypsin inhibitor 2 (CI2) in water has been investigated using molecular dynamics simulations. One simulation (2.2 ns) has been analyzed in detail and three additional simulations (each > or = 1 ns) were performed to check the generality of the results. Concurrent loss of secondary and tertiary structure during unfolding was observed in all the simulations. For each simulation, the major transition state of unfolding was identified based on conformational analysis of protein structures along the unfolding trajectory. The transition state has a considerably weakened hydrophobic core and disrupted secondary structure. Nevertheless, the overall structure of the transition state is closer to the native state than to the unfolded state. The disruption of the hydrophobic core appears to be rate limiting. However, other energy barriers have to be overcome before reaching the major transition state. A method is described to quantitatively compare the structure of the simulated transition state with that characterized by protein engineering experiments. Good agreement with the experimental data is obtained for all four transition state models (the correlation coefficient R = 0.80 to 0.93) and the average over all four models gives the best correlation (R = 0.94). These simulations provide the first comprehensive atomic-level view of what the unfolding transition state of C12 may look like.

Chymotrypsin↗

Discovering the family history of Huntington disease (HD).

A considerable body of research has explored both predictive genetic test decisions for Huntington disease (HD) and the impact of receiving a test result. Extant research reveals little, however, about how and when at risk persons first discover their family history of HD. Drawing upon 24 semi-structured interviews with at risk persons and their family members, this study explored initial discovery of HD in the family. Qualitative data analysis revealed four different, though sometimes related, trajectories of discovery: (1) something is wrong, (2) out of the blue, (3) knowing, but dismissing, and 4) growing up with HD. These pathways highlighted the importance of the temporal and historical contexts in which genetic risk for HD was discovered. Notably, ignorance about HD was the most salient feature shaping participants' narratives of discovery. Implications for research and clinical practice are discussed.

Child↗

Properties of strange attractors in yeast glycolysis.

The properties of periodic and aperiodic glycolytic oscillations observed in yeast extracts under sinusoidal glucose input were analyzed by the following methods. (1) Spectral analysis, rendering sharp peaks for periodic responses and enhanced broad-band noise for aperiodic oscillations. (2) Phase plane analysis, leading to closed and to open trajectories for periodic and aperiodic oscillations, respectively. (3) Rotation of a phase plane proportionally to time, revealing strange attractors associated with the aperiodic oscillations. (4) Stroboscopic plot on the phase plane, showing that the strange attractors follow a stretch-fold-press process, if the stroboscoping phase is varied. (5) Stroboscopic transfer plot, admitting a period of three transfer processes and thus implying chaos according to the Li-Yorke theorem. (6) Determination of the rate of information production by differentiation of the transfer plot, yielding approx. 0.21 bits per min for the chaotically glycolyzing yeast extract.

Journal Article↗

Ideomotor apraxia and cerebral dominance for motor control.

Ideomotor apraxia is a symptom of left hemisphere damage. Patients with ideomotor apraxia commit errors when imitating movements with their left, non-paralyzed hand. This has been taken as evidence for a motor dominance of the left hemisphere. It has been hypothesized that the left hemisphere is dominant for internal preprogramming of skilled movements of either hand. We investigated the kinematics of movement trajectories of imitation of meaningless gestures. Group analysis confirmed that hesitant, feedback-controlled movement prevail in patients with apraxia, but analysis of single cases revealed the existence of kinematically normal movements leading to apractic errors. Enhanced reliance on feedback-control appears to be a compensatory strategy rather than the source of apractic errors. In a second study we explored the alternative hypothesis that patients with apraxia lack a general concept of the human body which is necessary to mediate the translation of a target position seen on the model into a target position on the patient's body. Imitation of movements was examined on oneself and on a mannikin. Patients with apraxia who made errors when imitating on themselves committed errors also when imitating on the mannikin. Taken together, both studies support the view that the source of errors in the imitation of gestures is to be sought at a conceptual level. This casts doubts on the alleged dominance of the left hemisphere for motor control.

Apraxias↗

Pressure denaturation of apomyoglobin: a molecular dynamics simulation study.

The effect of pressure on the structure and mobility of Sperm Wale Apomyoglobin was studied by Molecular Dynamics computer simulation at 1 bar and 3 kbar (1 atm=1.01325 bar=101.325 kPa). The results are in good agreement with the available experimental data, allowing further analysis of other features of the effect of pressure on the protein solution. From the analysis of Secondary Structures (SS) along the trajectories it is observed that alpha-helixes are favoured under pressure at the expense of bends, turns and 3-helixes. The studies of mobility show that although the general mobility is restricted under pressure this is not true for some particular residues. The studies of tertiary structure show important conformational changes. The evolution of the Solvent Accessed Surface (SAS) with pressure shows a notorious increase due almost completely to a biased raise in the hydrophobic area exposed, which consequently shows that the hydrophobic interaction is considerably weaker under high hydrostatic pressure conditions.

Animals↗

Ability of static and statistical mechanics posturographic measures to distinguish between age and fall risk.

Traditional posturographic analysis and four statistical mechanics techniques were applied to center-of-pressure (COP) trajectories of young, older "low-fall-risk" and older "high-fall-risk" individuals. Low-fall-risk older adults were active 3 days per week in a cardiac rehabilitation program, while high-fall-risk older adults were diagnosed with perilymph fistula. Subjects diagnosed with perilymph fistula must have experienced two of the following vestibular findings: constant disequilibrium, positional vertigo and/or a positive fistula test. Non-parametric statistical tests were used to determine whether the posturographic measures could detect differences between the young and older "low-fall-risk" groups (age comparison) and between the older "low-" and "high-risk" groups (risk of falling comparison). The statistical mechanics techniques were more sensitive than the traditional measures: detecting significant differences between the young and older "low-risk" groups, while none of the traditional measures were significantly different. In addition, interpretation of the statistical mechanics techniques may offer more insight into the nature of the process controlling the COP trajectories. However, the methods offered slightly different explanations. For instance, the Hurst rescaled range analysis suggests that the movement of the COP is governed solely by anti-persistent behavior, whereas the stabilogram diffusion analysis suggests a short-term persistence balanced by a long-term anti-persistence. These discrepancies highlight the need for a model that incorporates the biological systems responsible for maintaining balance and experimental methods to directly quantify their status and roles. Until such a model exists, however, the statistical mechanics techniques appear to have some advantages over traditional posturographic measures for studying balance control.

Accidental Falls↗

Interaction of cardiac troponin C with calmodulin antagonist [corrected] W7 in the presence of three functional regions of cardiac troponin I.

W7 is a well-known calmodulin (CaM) antagonist and has been implicated as an inhibitor of the troponin C-mediated Ca(2+) activation of cardiac muscle contraction. In this study, we use NMR spectroscopy to study binding of W7 to cardiac troponin C (cTnC) free or in complex with cardiac troponin I (cTnI) peptides. Titration of cTnC.3Ca(2+) with W7 shows that residues throughout the sequence, including the N- and C-domains of cTnC and the central linker, are affected. Analysis of the binding stoichiometry and the trajectories of chemical shift changes indicate that W7 binding occurs at multiple sites. To address the issue of whether multiple-site binding is relevant within the troponin complex, W7 is titrated to a cTnC-cTnI complex (cTnC.3Ca(2+).cTnI(34)(-)(71).cTnI(128)(-)(163)). In the presence of the N-terminal (residues approximately 34-71), inhibitory (residues approximately 128-147), and switch (residues approximately 147-163) regions of cTnI, W7 induces chemical shift changes only in the N-domain and not in the C-domain or the central linker of cTnC. The results indicate that in the presence of cTnI, W7 no longer binds to multiple sites of cTnC but instead binds specifically to the N-domain, and the binding (K(D) = 0.5 +/- 0.1 mM) can occur together with the switch region of cTnI. Hence, W7 may play a role in directly modulating the Ca(2+) sensitivity of the regulatory domain of cTnC and the interaction of the switch region of cTnI and cTnC.

Calcium↗

DNA deformability at the base pair level.

A complete set of harmonic force constants describing the DNA deformation energetics at the base pair level was obtained using unrestrained atomic-resolution molecular dynamics simulations of selected duplex oligonucleotides and subsequent analysis of structural fluctuations from the simulated trajectories. The deformation was described by the six base pair conformational parameters (buckle, propeller, opening, shear, stretch, stagger). The results for 13 AT pairs and 11 GC pairs in different sequence contexts suggest that buckle and propeller are very flexible (more than roll in TA dinucleotide steps), while stretch is exceptionally stiff. Only stretch and opening stiffness were found to depend unambiguously on the base pair identity (AT vs GC). The relationship of the results to a simple plates-and-springs model of base-base interactions is discussed.

Base Pairing↗

Progress Testing for Postgraduate Medical Education: a Four-Year Experiment of American College of Osteopathic Surgeons Resident Examinations.

An experiment of progress testing for postgraduate medical education was evaluated for the psychometric properties and evaluation utilities of its outcome. Psychometric analysis emphasized reliability, construct validity, exam structure, and equating quality, while analysis of evaluation value focused on growth trajectories of several cohorts of residents. The analyses concluded that progress testing for postgraduate education was feasible. The value of progress testing for postgraduate medical education assessment was unique and promising.

Journal Article↗

Adaptive modification of saccadic eye movements.

Experiments are reported in which the target for a saccadic eye movement was displaced during the saccade. Subjects adapted to the displacement by altering the amplitudes of subsequent saccades to compensate for it. Analysis of kinematic details of the saccade trajectories revealed that the adaptation did not arise from a simple remapping of perceived target locations. Instead, the adaptation appeared to be accomplished by a change in the gain of the saccadic system. The gain change arose primarily from a change in the magnitude of the force pulse for the saccade, not a change in the duration of the pulse. These results have implications for the mechanisms that underlie saccades in normal situations. In particular, people can separately adjust the magnitudes and durations of the force pulses used to produce saccades.

Adaptation, Ocular↗

Chemical and electrical synapses perform complementary roles in the synchronization of interneuronal networks.

Electrical and chemical synapses exist within the same networks of inhibitory cells, and each kind of synapse is known to be able to foster synchrony among oscillating neurons. Using numerical and analytical techniques, we show here that the electrical and inhibitory coupling play different roles in the synchronization of rhythms in inhibitory networks. The parameter range chosen is motivated by gamma rhythms, in which the gamma-aminobutyric acid type A (GABAA)-mediated inhibition is relatively strong. Under this condition, addition of a small electrical conductance can increase the degree of synchronization far more than a much larger increase in inhibitory conductance. The inhibitory synapses act to eliminate the effects of different initial conditions, whereas the electrical synapses mitigate suppression of firing due to heterogeneity in the network. Analytical techniques include tracking trajectories of coupled cells between spikes; the analysis shows that, in networks in which the degree of excitability is heterogeneous, inhibition can increase the dispersion of the voltages between spikes, whereas electrical coupling reduces such dispersion.

Action Potentials↗

Dynamics and binding modes of free cdk2 and its two complexes with inhibitors studied by computer simulations.

This article presents a molecular dynamics (MD) study of the cdk2 enzyme and its two complexes with the inhibitors isopentenyladenine and roscovitine using the Cornell et al. force field from the AMBER software package. The results show that inserting an inhibitor into the enzyme active site does not considerably change enzyme structure but it seemingly changes the distribution of internal motions. The inhibitor causes differences in the domain motions in free cdk2 and in its complexes. It was found out that repulsion of roscovitine N9 substituent causes conformational change on Lys 33 side chain. Isopentenyladenine forms with Lys 33 side chain terminal amino group a hydrogen bond. It implies that the cavity, where N9 substituent of roscovitine is buried, can adopt larger substituent due to Lys 33 side chain flexibility. The composition of electrostatic and van der Waals interactions between the inhibitor and the enzyme were also calculated along both cdk2/inhibitor MD trajectories together with MM-PB/GBSA analysis. These results show that isopentenyladenine-like inhibitors could be more effective after modifications leading to an increase in their van der Waals contact with the enzyme. We suggest that a way leading to better inhibitors occupying isopentenyladenine binding mode could be: to keep N9 and N7 purine positions free, to keep 3,3-dimethylallylamino group at C6 position, and to add, e.g., benzylamino group at C2 position. The results support the idea that the isopentenyladenine binding mode can be used for cdk2 inhibitors design and that all possibilities to improve this binding mode were not uncovered yet.

Adenine↗

Adolescents' smoking expectancies: psychometric properties and prediction of behavior change.

Outcome expectancies have been related to smoking behavior among adults, but less attention has been given to expectancies about smoking among adolescents at differing levels of smoking experience. The present study reports the psychometric properties and predictive validity of a brief expectancy scale across two samples of adolescents. Sample 1 (N = 349) consisted of high school students (54% female) who were regular smokers enrolled in a cessation program. Sample 2 (N = 273) consisted of 8th- and 10th-grade early experimenters (54% female) involved in a natural history study of smoking trajectories. In both samples, a principal component analysis of a 13-item expectancy scale yielded four factors (taste, weight control, boredom relief, and negative affect management), each with high internal consistency (coefficient alphas >.77) and accounting for 73% and 80% of the total variance for each sample, respectively. Expectancies were significantly higher among current smokers than among early initiators. In Sample 1, boredom relief and weight management expectancies predicted smoking status 6 months later. In Sample 2, students whose smoking increased over 18 months had higher overall expectancies at baseline compared with those who tried smoking and did not escalate. These findings support the predictive validity of expectancies in predicting escalation and cessation. Implications for the importance of expectancies in understanding adolescent smoking behavior are considered.

Adolescent↗

Investigation of saddle trajectories for cardiac CT imaging in cone-beam geometry.

This paper investigates cone-beam tomography for a wide class of x-ray source trajectories called saddles. In particular, a mathematical analysis of the number of intersections between a saddle and an arbitrary plane is given. This analysis demonstrates that axially truncated cone-beam projections acquired along a saddle can be used for exact reconstruction at any point in a large volume. The reconstruction can be achieved either using a new algorithm presented herein or using a formula recently introduced by Katsevich (2003 Int. J. Math. Math. Sci. 21 1305-21). The shape of the reconstructed volume and the properties of saddles make saddles attractive for cardiac imaging. Three examples of saddles are presented with a discussion of implementation on devices similar to modern C-arm systems and multislice CT scanners. Reconstruction with one of these saddles has been tested using computer-simulated data, with and without truncation. The imaged phantom for the truncated data is a FORBILD head phantom (representing the heart) that has been modified and embedded inside the FORBILD thorax phantom. The non-truncated data were generated by excluding the thorax. The reconstructed images demonstrate the accuracy of the mathematical results.

Algorithms↗

Methodology for evaluation of possible consequences of accidental atmospheric releases of hazardous matter.

Sites exist with high levels of risk of accidental atmospheric releases. These releases can be hazardous nuclear, chemical, and biological matter. Such accidents may occur during transport of waste, or they may be due to natural hazards, human errors, terror acts or various operations at high risk. Considering the operation of lifting and transport of the sunken Kursk nuclear submarine as an example, a methodology for risk assessment is described. This methodology includes two approaches: (1) probabilistic analysis of possible atmospheric transport pathways using trajectory modelling, and (2) evaluation of possible contamination and consequences using real-time operational atmospheric dispersion modelling. The first approach can be applied in advance of an operation during the preparation stage, the second in real time during the operation stage. For the cases considered in this study, the results of trajectory modelling are supported by the operational dispersion modelling, i.e., the westerly flow is dominant during fall occurring 79% of the time. Hence, September-October 2001 was more appropriate for the lifting and transport of the Kursk nuclear submarine in comparison with summer months, when atmospheric transport toward the populated regions of the Kola and Scandinavian Peninsulas was dominant. The suggested methodology may be applied to any potentially dangerous object involving a risk of atmospheric release of hazardous material of nuclear, chemical or biological nature.

Accidents↗