Whiplash-Associated Dysphagia and Dysphonia: A Scoping Review.

Swallowing and voice complaints after a whiplash injury have been observed and reported in several studies; however, variability in study design complicates current understanding of whether dysphagia and dysphonia should be recognised as potential adverse outcomes. A scoping review was conducted across six databases from 1950 to March 2019. A total of 18 studies were included for review. Data regarding study purpose, design, outcome measures, participant characteristics and outcomes reported were extracted. Level of evidence (LOE) was assessed by the American Speech-Language Language Association (ASHA)'s LOE system. All studies were exploratory, with 68% rated as poor (< 3) on quality ratings. Nearly half (n = 6) were single case reports. Only three studies investigated some type of swallow-related outcome specifically within the study aim/s. Incidence of swallow-related problems ranged from 2 to 29%, with unspecified complaints of "swallowing difficulty", "dysphagia" and fatigue and pain whilst chewing reported. Neither swallowing biomechanics nor the underlying pathophysiology of swallow or voice complaints was investigated in any study. Four case studies presented post-whiplash voice complaints; two of which described loss of pitch range. Others described hoarseness, loss of control and weak phonation. Most studies only mentioned swallow- or voice-related deficits when reporting a wider set of post-injury symptomatology and six did not describe the outcome measure used to identify the swallow and voice-related problems reported. The existing literature is limited and of low quality, contributing to an unclear picture of the true incidence and underlying mechanisms of whiplash-related dysphagia and dysphonia.

Estimating recharge distribution by incorporating runoff from mountainous areas in an alluvial basin in the Great Basin region of the southwestern United States.

A method is described to estimate the distribution of ground water recharge within hydrographic basins in the Great Basin region of the southwestern United States on the basis of estimated runoff from high mountainous areas and subsequent infiltration in alluvial fans surrounding the intermontane basins. The procedure involves a combination of Geographic Information System (GIS) analysis, empirical surface-runoff modeling, and water-balance calculations. The method addresses the need to develop and incorporate constraints on the distribution of recharge in regional-scale ground water flow modeling of arid and semiarid environments. The conceptual approach and methodology were developed for Crescent Valley, Nevada. However, the concept and method are generally applicable to any region where excess precipitation in upland areas is conveyed to lower elevations before it infiltrates to recharge the ground water system. Application of the procedure to a ground water flow model of Crescent Valley appears both qualitatively and quantitatively to result in a more accurate representation of actual recharge conditions than might otherwise have been prescribed.

Solution structures of dimeric kinesin and ncd motors.

The dimeric structure of the members of the kinesin family of motor proteins determines the individual characteristics of their microtubule-based motility. Crystal structures for ncd and kinesin dimers, which move in opposite directions on microtubules, show possible states of these dimers with ADP bound but give no information about these dimers in solution. Here, low-angle X-ray and neutron scattering were used to investigate their solution structures. Scattering profiles of Drosophila ncd 281-700 (NCD281) and human kinesin 1-420 (hKIN420) were compared with models made from the crystallographically determined structures of NCD281 and rat kinesin 1-379 (rKIN379). From the low-angle region it was found that the radius of gyration (Rg) of NCD281 is 3.60 +/- 0.075 nm, which is in agreement with the crystallography-based model. Scattering by longer ncd constructs (NCD250 and NCD224) is also well fit by the appropriate crystallography-based models. However, the measured Rg of hKIN420, 4.05 +/- 0.075 nm, is significantly smaller than that of the crystallography-based model. In addition, the overall scattering pattern of NCD281 is well fit by the model, but that of hKIN420 is poorly fit. Model calculations indicate that the orientation of the catalytic cores is different from that observed in the rKIN379 crystal structure. Like the crystal structure, the best-fitting models do not show 2-fold symmetry about the neck axis; however, their overall shape more resembles a mushroom than the "T"-like orientation of the catalytic cores found in the crystal structure. The center of mass separations of the catalytic cores in the best-fitting models are 0.7-1 nm smaller than in the crystal structure.

The effect of regulatory Ca2+ on the in situ structures of troponin C and troponin I: a neutron scattering study.

The effects of regulatory amounts of Ca2+ on the in situ structures of troponin C (TnC) and troponin I (TnI) in whole troponin have been investigated by neutron scattering. In separate difference experiments, 97% deuterated TnC and TnI within whole troponin were studied +/-Ca2+ in 41.6% 2H2O buffers in which protonated subunits were rendered "invisible". We found that the radius of gyration (Rg) of TnI decreased by approximately 10% upon addition of regulatory Ca2+ indicating that it was significantly more compact in the presence of Ca2+. The apparent cross-sectional radius of gyration (Rc) of TnI increased by about 9% when regulatory Ca2+ was bound to TnC. Modeling studies showed that the high-Q scattering patterns of TnI could be fit by a TnI which consisted of two subdomains: one, a highly oblate ellipsoid of revolution containing about 65% of the mass and the other, a highly prolate ellipsoid of revolution consisting of about 35% of the mass. No other fits could be found with this class of models. Best fits were achieved when the axes of revolution of these ellipsoids were steeply inclined with respect to each other. Ca2+ addition decreased the center of mass separation by about 1.5 nm. The Rg of TnI, its high-Q scattering pattern, and the resultant structure were different from previous results on neutron scattering by TnI in the (+Ca2+) TnC.TnI complex. The Rg of TnC indicated that it was elongate in situ. The Rg of TnC was not sensitive to the Ca2+ occupancy of its regulatory sites. However, Rc increased upon Ca2+ addition in concert with expectations from NMR and crystallography of isolated TnC. The present observations indicate that TnI acts like a molecular switch which is controlled by smaller Ca2+-induced changes in TnC.

Conformations of myosin subfragment 1 ATPase intermediates from neutron and X-ray scattering.

In order to elucidate the structural changes that occur during the hydrolysis of ATP by myosin, low-angle neutron and X-ray scattering have been used to investigate the shape of the myosin head (S1) with various bound nucleotides and nucleotide analogs. It was found that the radius of gyration (Rg) of S1.MgADP.AlF4 and of S1MgADP.Vi were similar and significantly smaller (approximately 3%) than the similar Rg values of nucleotide-free S1, S1.MgADP and S1.MgADP.BeFx. In addition, S1 in the presence of MgATP, which is predominantly in the S1.MgADP.Pi state under the experimental conditions employed, showed a change in Rg comparable with that of S1.MgADP.AlF4 and S1.MgADP.Vi. The results obtained here with BeFx and AlF4 are in close harmony with crystallographic results on truncated S1 bearing MgADP.BeFx and MgADP.AlF4. A. Fisher and co-workers have postulated that these two systems, which exhibit some structural differences, represent the pre-hydrolysis state and the transition state of ATP hydrolysis, respectively. It was postulated that this structural difference might alter the orientation of the light-chain-binding domain (tail) of intact S1 relative to the remainder of the molecule. Since this orientation is the major determinant of the Rg of S1, the current data support the hypothesis that a unitary large-scale conformational cocking of S1 for subsequent force production occurs just before or during ATP hydrolysis. Modeling changes in Rg by rigid-body rotations indicates that the longitudinal component of the force-producing throw is likely to be less than 6 nm.

The shapes of the motor domains of two oppositely directed microtubule motors, ncd and kinesin: a neutron scattering study.

The shapes of the motor domains of kinesin and ncd, which move in opposite directions along microtubules, have been investigated. Using proteins expressed in Escherichia coli, it was found that at high salt (> 200 mM) Drosophila ncd motor domain (R335-K700) and human kinesin motor domain (M1-E349) were both sufficiently monomeric to allow an accurate determination of their radii of gyration (Rg) and their molecular weights. The measured Rg values of the ncd and kinesin motor domains in D2O were 2.06 +/- 0.06 and 2.05 +/- 0.04 nm, respectively, and the molecular weights were consistent with those computed from the amino acid compositions. Fitting of the scattering curves to approximately 3.5 nm resolution showed that the ncd and kinesin motor domains can be described adequately by triaxial ellipsoids having half-axes of 1.42 +/- 0.38, 2.24 +/- 0.44, and 3.65 +/- 0.22 nm, and half-axes of 1.52 +/- 0.23, 2.00 +/- 0.25, and 3.73 +/- 0.10 nm, respectively. Both motor domains are described adequately as somewhat flattened prolate ellipsoids with a maximum dimension of approximately 7.5 nm. Thus, it appears that the overall shapes of these motor domains are not the major determinants of the directionality of their movement along microtubules.

The radius of gyration of native and reductively methylated myosin subfragment-1 from neutron scattering.

Reductive methylation of nearly all lysine groups of myosin subfragment-1 (S1) was required for crystallization and solution of its structure at atomic resolution. Possible effects of such methylation on the radius of gyration of chicken skeletal muscle myosin S1 have been investigated by using small-angle neutron scattering. In addition, we have investigated the effect of MgADP.Vi, which is thought to produce an analog of the S1.ADP.Pi state, on the S1 radius of gyration. We find that although methylation of S1, with or without SO42- ion addition, does not significantly alter the structure, addition of ADP plus vanadate does decrease the radius of gyration significantly. The S1 crystal structure predicts a radius of gyration close to that measured here by neutron scattering. These results suggest that the overall shape by crystallography resembles nucleotide-free S1 in solution. In order to estimate the effect of residues missing from the crystal structure, the structure of missing loops was estimated by secondary-structure prediction methods. Calculations using the complete crystal structure show that a simple closure of the nucleotide cleft by a rigid-body torsional rotation of residues (172-180 to 670) around an axis running along the base of the cleft alone does not produce changes as large as seen here and in x-ray scattering results. On the other hand, a rigid body rotation of either the light-chain binding domain (767 to 843 plus light chains) or of a portion of 20-kDa peptide plus this domain (706 to 843 plus light chains) is more readily capable of producing such changes.

Cross-helix separation of tropomyosin molecules in acto-tropomyosin as determined by neutron scattering.

The cross-helix separation of Tm molecules in acto-tropomyosin has been determined using neutron scattering. Deuterated Dictyostelium discoideum actin was density matched in a 93% D2O buffer so that effectively only the protonated tropomyosin was "visible" to neutrons. Analysis of the solution scattering pattern in the region of the first oscillation yielded a value for the cross-helix separation of 7.9 +/- 0.3 nm. The implications of this value for the mechanism of the regulation of muscle contraction are discussed in light of recent results by others.

Mechanism of force generation studied by neutron scattering.

Neutron scattering has been used to compare the structure of myosin S1 that is free in solution to that when it is bound to F-actin. To achieve this, deuterated actin was obtained from D. discoideum that had been fed deuterated E. coli. This deuterated actin was rendered "invisible" to neutrons when dissolved in 94% D2O. The neutron scattering patterns obtained from S1 bound to deuterated actin were identical to those of free S1 except for oscillations due to S1's bound to the same actin filament. At low S1 to actin stoichiometries, these oscillations diminish and the patterns become indistinguishable. The apparent radius of gyration of S1 bound to actin is identical to that of free S1 when the stoichiometry is low. Thus, no changes in the structure of S1 were observed to a resolution of 2.5 nm. Computer modelling studies were used to evaluate the compatibility of models for the mechanism of force generation with the neutron data. These studies show that for powerstrokes greater than 5.0 nm, the data are consistent with more than 80% of the crossbridge maintaining a rigid conformation during force generation.

Recent neutron scattering studies of muscle contraction and its control.

We have presented two applications of the method of neutron scattering utilizing selective deuteration of actin. In these experiments the actin was rendered effectively invisible to neutrons by matching the scattering-length densities of deuterated actin and the solvent. The scattering of neutrons by myosin S1 and by Tm bound to this actin was studied. For free chymotrypsin-generated S1 it was found that Rg = 4.0 +/- 0.15 nm, while for papain-generated S1 it was found that Rg = 4.6 +/- 0.2 nm. Upon binding of papain-generated S1 to actin at low NS1/N actin ratios, the change in Rg in difference experiments was delta Rg = 0.05 +/- 0.15 nm. This lack of significant change in Rg in the very low-s domain confirms and extends our earlier neutron scattering work in the higher-s domain. The longest chords of S1, as well as shorter ones, are not significantly altered upon actin binding. These results indicate that muscle contraction does not occur as a result of large-scale changes in S1 structure. In actin-Tm complexes, a measurement of the mean cross-helix separation, d, of Tm molecules has been made using neutron scattering. With deuterated actin matched out in 93% D2O buffer, it was found that d = 7.9 +/- 0.3 nm. This value is in good agreement with a model based on Tm crystallography and also with recent electron microscopy results. These experiments demonstrate the feasibility and value of neutron diffraction and scattering techniques in the study of muscle contraction and its control. One can expect that the further employment of emerging cell biology techniques for generating deuterated proteins will aid our understanding of muscle in the future.

Comparison of the structure of myosin subfragment 1 bound to actin and free in solution. A neutron scattering study using actin made "invisible" by deuteration.

The structure of subfragment 1 (S1) bound to F-actin has been compared to the structure of free S1 using neutron scattering. The F-actin was rendered "invisible" to neutrons by selective deuteration and solvent contrast matching. Highly deuterated actin was purified from the slime mold Dictyostelium discoideum, which was fed deuterated Escherichia coli. The properties of this actin were found to be similar to those of protonated actin. The neutron-scattering pattern of S1 bound to this "invisible" actin was compared to that of free S1. At near-physiological ionic strength, a strong interference effect was observed, which arose from pairs of S1 molecules cross-linking actin filaments. However, at low ionic strength the only differences that could be observed were attributed to interference effects between neutrons scattered from S1s bound randomly to equivalent sites on an actin filament. These effects became negligible as the fraction of actin sites occupied by S1 approached zero. Thus, we conclude that the scattering by S1 attached to F-actin is identical with that of free S1, to a resolution of about 2.5 nm. The difference in apparent radii of gyration is less than 0.05 nm. Modeling calculations have been carried out to determine the sensitivity of neutron scattering to possible S1 deformations. The calculations showed that deformations of the structure of S1 that are large enough ultimately to produce a powerstroke of 5 nm or greater are only consistent with the data if they involve at most about 20% of the S1 mass. These results restrict the class of plausible models describing force generation in muscle contraction.

A three-year study of obesity and its relationship to high blood pressure in adolescents.

A sample of 356 matched cases were tracked for three years during high school. Measures taken included self-reported behavior and clinical measures of height, weight, skinfold, blood pressure, and body mass index. Data were analyzed by ethnic group, age, and sex groups. Three year (1981-1982 to 1984-1985) trends for students who were overfat, overweight, and obese revealed: a relatively greater proportion of female to male students were overfat as seniors; overweight trends for each of the four groups (ethnic group and gender) were stable over the study period; a sharp increase of obesity trends among black females was observed; and significant positive relationships existed between Percent Ideal Body Weight, skinfold thickness, Body Mass Index, and blood pressure among females of both ethnic groups. The hypothesis that the early onset of obesity is an indicator of obesity in older adolescents was supported. Students classified at risk as freshmen are more likely to remain at risk as seniors.

Toothbrushing, flossing, and dental visits in relation to socioeconomic characteristics of white American families.

This study investigated the patterns of preventive dental behaviors, including toothbrushing, flossing, and dental visits with respect to certain selected socioeconomic characteristics, namely population density, age, family income, size of family, presence of children, and level of education. The sample of the study included 685 white American families. The results indicated that an individual's preventive dental behavior is related to certain socioeconomic characteristics. The individual who lives in an urban area, possesses a higher income or who has a higher educational level is more apt to take preventive dental actions. Among the socioeconomic variables, family income and educational level made significantly stronger differences with respect to toothbrushing, flossing, and dental visits. Dental visits, compared to other dental activities appeared to be more easily influenced by socioeconomic variables.

Myosin heavy chain-light chain recombinations and interactions between the two classes of light chains.

Myosin subfragment 1 (S1) heavy chains were prepared from chicken muscle S1 by immunoadsorption in NH4Cl and from rabbit muscle S1 by ion exchange chromatography at 37 degrees C in MgATP. Both heavy chain preparations contained some intact S1, and the ATPase activities of both preparations were less than those of control S1. Recombinations of these heavy chains with alkali light chains prior to removing NH4Cl or MgATP lessened the decreases in ATPase activities. However, once NH4Cl or MgATP was removed, alkali light chain recombination did not result in any increase in ATPase activity. Thus, the lower activities appear to result from the instability of the S1 heavy chain in the absence of alkali light chain. When incubated with a 10-fold molar excess of radiolabeled alkali light chains for 1 h under approximately physiological conditions, almost all of the alkali light chains of S1 but only 8% of those of myosin or myofibrils were exchanged. Aggregation of myosin into filaments accounts for part of this difference in exchangeability. Removal of 30% of the 19,000-Da 5,5'-dithiobis-(2-nitrobenzoic acid) (DTNB) light chains from myosin increased 3-fold the amount of alkali light chain exchanged. The exchange of the alkali light chains of S1 is inhibited by the presence of DTNB light chains, and cleavage of the DTNB light chains of heavy meromyosin to 17,000-Da fragments increased the rate of alkali light chain exchange. There was no detectable difference in the exchangeability of the two different alkali light chains.

Calcium-sensitive binding of heavy meromyosin to regulated actin requires light chain 2 and the head-tail junction.

Sedimentation in a preparative ultracentrifuge was used to determine the affinity of heavy meromyosin, HMM, for regulated actin, F-actin plus troponin-tropomyosin, in the presence of MgATP at pH 7.0, 20 degrees C, and mu = 18 mM. HMM was prepared from vertebrate striated muscle myosin by a mild chymotryptic digestion. This HMM contained 85-90% intact 19 000-dalton light chains, LC2. In the presence of calcium, 90% of the HMM bound to regulated actin with an association constant of (2-4) X 10(4) M-1. In the absence of calcium, while one-third of the HMM bound with an affinity similar to that observed in the presence of calcium, the rest bound much more weakly. It was not possible to accurately determine the association constant for this weakly binding HMM, but a 20-fold reduction in affinity is consistent with the binding data. The binding of single-headed heavy meromyosin to regulated actin was similarly sensitive to the calcium concentration. Since removal of calcium inhibits the regulated actin-activated ATPase of HMM greater than 20-fold, troponin-tropomyosin must be capable of inhibiting both the binding of HMM to regulated actin and a step which occurs after binding but prior to product release. Removal of LC2 increased the fraction of HMM with calcium-insensitive binding, and adding LC2 back to this depleted HMM restored most of the calcium sensitivity. Chymotryptic cleavage of LC2 to a 17 000-dalton fragment destroyed the calcium-sensitive binding of HMM to regulated actin. Phosphorylation of LC2, however, had no detectable effect on this binding. Thus, the calcium-sensitive binding of HMM to regulated actin requires that both the head-tail junction and the N-terminal part of LC2 be intact. Binding studies with cross-linked regulated actins and kinetic measurements of the rates of change in turbidity demonstrate that this calcium sensitivity is due to calcium binding to troponin and not to LC2.

EPR and fluorescence depolarization studies on bovine cardiac myosin.

To test for possible differences in local conformation and S1 flexibility, bovine cardiac and rabbit skeletal myosins were labeled with a fluorophore (1,5-IAEDANS) and a spin label having iodoacetamide reactivity. The marked activation of the Ca2+-ATPase (6- to 8-fold) and inhibition of the K+ (EDTA)-ATPase (80-90%) by both labels indicated specific labeling of the fast-reacting thiols (SH1) of both myosins. Fluorescence depolarization studies of 1,5-IAEDANS-labeled cardiac myosin indicated that, like skeletal myosin, the SI moieties of cardiac myosin exhibit considerable segmental flexibility with respect to the rod portion of the molecule. This indicates that segmental flexibility may be a property of all myosins. Cardiac and skeletal myosins immobilized spin labels to approximately the same extent, indicating a similarity in steric restraints around the SH1 thiol of the two myosins. The magnitude of the changes in spin label mobility accompanying binding of MgADP and hydrolysis of MgATP was reduced in cardiac myosin relative to skeletal myosin. This suggests that the lower catalytic center activity of cardiac myosin is associated with more restricted conformational changes accompanying formation of M.ADP and M.ADP.Pi. From measurements of spin label mobility, the affinity of cardiac and skeletal myosin for ADP were similar: Kd (ADP) = 7 microM, n = 1.6. The EPR spectrum of spin labels attached to cardiac and skeletal myosin showed similar saturation effects upon actin binding indicating immobilization of myosin heads occurs with both proteins.

An evaluation of the behavioral aspect of a prevention-oriented oral health program.

The teaching and learning program is not effective in the behavioral dimension, given the data of this evaluation. The Navy Plaque Index was shown to be an unreliable instrument, when utilized with a relatively large number of upper elementary level students by more than one dentist, due to differences in the level of plaque recorded by the dentists.