Upper body accelerations during walking are altered in adults with ACL reconstruction.

This study was designed to assess and compare the pattern of acceleration from the lower trunk, neck and head regions for individuals with reconstructed ACL compared to healthy controls during walking. Participants with unilateral ACL reconstruction and matched control persons participated in the study. Accelerations were collected using three triaxial accelerometers attached to the head, neck, and lower trunk. Measures of amplitude and signal regularity of the acceleration data were performed. Similarities were seen between both groups with regards to the general acceleration patterns in all three axes. However, the results also revealed that the individuals with ACL reconstruction had significantly greater peak power in the AP direction at higher frequencies, indicating a reduced ability to attenuate frequency signals. Further, the ACL group had a reduced ability to control head motion during gait, as indicated by reduced regularity in VT. Both groups demonstrated a similar pattern of gait-related oscillations across the head, neck and trunk segments. However, adults with a reconstructed ACL demonstrated a reduced capacity to compensate for the higher frequency components of the gait signal, which may have led to a decline in head control. Overall, these findings indicate that previous damage to the ACL is not simply localized to the knee joint, but influences upper body control, too.

Three-dimensional assessment of postural tremor during goal-directed aiming.

The performance of fine motor tasks which require a degree of precision can be negatively affected by physiological tremor. This study examined the effect of different aiming positions on anterior-posterior (AP), medial-lateral (ML) and vertical (VT) postural tremor. Participants were required to aim a mock handgun at a target located in front of them at eye level. Changes in AP, ML and VT tremor from the forearm and gun barrel were assessed as a function of limb (i.e., whether one or both arms were used) and upper arm position (elbow bent or extended). Tremor was recorded using triaxial accelerometers. Results showed that, across all tasks, the ML and VT tremor for any point was characterized by two frequency peaks (between 1-4 and 8-12 Hz) with amplitude increasing from proximal (forearm) to distal (gun barrel). Interestingly, irrespective of the posture adopted, ML accelerations were of greater amplitude than VT oscillations. AP oscillations were markedly smaller compared to VT and ML tremor, did not display consistent frequency peaks, and were not altered by the arm conditions. Altering the aiming posture resulted in changes in VT and ML tremor amplitude, with oscillations being greater when using a single arm as compared to when two arms were used together. Similarly, tremor amplitude was reduced when the task was performed with the elbow bent compared to the straight arm condition. Overall, these results highlight that ML oscillations make as significant a contribution to the overall tremor dynamics as those observed in the VT direction. However, the origin of ML tremor is not simply the product of voluntary adjustments to maintain aim on the target, but also exhibits features similar to the neural generated 8-12-Hz tremor seen under postural conditions.

Bracing of the trunk and neck has a differential effect on head control during gait.

During gait, the trunk and neck are believed to play an important role in dissipating the transmission of forces from the ground to the head. This attenuation process is important to ensure head control is maintained. The aim of the present study was to assess the impact of externally restricting the motion of the trunk and/or neck segments on acceleration patterns of the upper body and head and related trunk muscle activity. Twelve healthy adults performed three walking trials on a flat, straight 65-m walkway, under four different bracing conditions: 1) control-no brace; 2) neck-braced; 3) trunk-braced; and 4) neck-trunk braced. Three-dimensional acceleration from the head, neck (C7) and lower trunk (L3) were collected, as was muscle activity from trunk. Results revealed that, when the neck and/or trunk were singularly braced, an overall decrease in the ability of the trunk to attenuate gait-related oscillations was observed, which led to increases in the amplitude of vertical acceleration for all segments. However, when the trunk and neck were braced together, acceleration amplitude across all segments decreased in line with increased attenuation from the neck to the head. Bracing was also reflected by increased activity in erector spinae, decreased abdominal muscle activity and lower trunk muscle coactivation. Overall, it would appear that the neuromuscular system of young, healthy individuals was able to maintain a consistent pattern of head acceleration, irrespective of the level of bracing, and that priority was placed over the control of vertical head accelerations during these gait tasks.

Circular polarization in the optical afterglow of GRB 121024A.

Gamma-ray bursts (GRBs) are most probably powered by collimated relativistic outflows (jets) from accreting black holes at cosmological distances. Bright afterglows are produced when the outflow collides with the ambient medium. Afterglow polarization directly probes the magnetic properties of the jet when measured minutes after the burst, and it probes the geometric properties of the jet and the ambient medium when measured hours to days after the burst. High values of optical polarization detected minutes after the burst of GRB 120308A indicate the presence of large-scale ordered magnetic fields originating from the central engine (the power source of the GRB). Theoretical models predict low degrees of linear polarization and no circular polarization at late times, when the energy in the original ejecta is quickly transferred to the ambient medium and propagates farther into the medium as a blast wave. Here we report the detection of circularly polarized light in the afterglow of GRB 121024A, measured 0.15 days after the burst. We show that the circular polarization is intrinsic to the afterglow and unlikely to be produced by dust scattering or plasma propagation effects. A possible explanation is to invoke anisotropic (rather than the commonly assumed isotropic) electron pitch-angle distributions, and we suggest that new models are required to produce the complex microphysics of realistic shocks in relativistic jets.

Vitamin D deficiency in general medical inpatients in summer and winter.

BACKGROUND: Vitamin D deficiency is common in various populations worldwide. Adverse effects of vitamin D deficiency are the development of bone disorders; however, other diseases such as multiple sclerosis, type 1 diabetes, rheumatoid arthritis and certain cancers have also been linked to vitamin D deficiency. The general medical inpatient population is a group at increased risk of vitamin D deficiency. These patients often have coexistent risk factors for its consequences. This study aims to document a point prevalence of vitamin D deficiency in this population. METHODS: Two cross-sectional audits of patients admitted to general medicine units were carried out--the first in mid-November at the end of winter and the second in mid-April and May at the end of summer. Information regarding patients' comorbidities, medication usage, previous falls and fractures was obtained and serum 25-hydroxyvitamin D, parathyroid hormone and calcium levels were measured. RESULTS: A total of 129 patients was studied (65 in winter and 64 in summer). Ninety-four patients (74%) had 25-hydroxyvitamin D levels < or = 50 nmol/L. Seven patients had severe deficiency (levels < or = 12.5 nmol/L). Average vitamin D levels were lower at the end of winter (35 vs 43 nmol/L, P = 0.007). Of the 37 patients receiving vitamin D supplements, 20 (54%) had 25-hydroxyvitamin D levels < or = 50 nmol/L. CONCLUSION: Low vitamin D levels were common in this general medical inpatient population. The average vitamin D level was lower in the patient group tested in November following winter. Supplementation of vitamin D did not uniformly prevent deficiency.

Evidence-based guide to perioperative medicine.

The discipline of perioperative medicine is assuming greater importance as increasing numbers of older patients with medical comorbidity undergo complex surgical procedures. If patient outcomes and use of limited hospital resources are to be optimized, physicians with skills and interest in perioperative risk assessment and therapeutic intervention are needed. This systematic review attempts to provide an evidence-based update in several key areas in the management of the perioperative patient.

Sinusoidal visuomotor tracking: intermittent servo-control or coupled oscillations?

In visuomotor tasks that involve accuracy demands, small directional changes in the trajectories have been taken as evidence of feedback-based error corrections. In the present study variability, or intermittency, in visuomanual tracking of sinusoidal targets was investigated. Two lines of analyses were pursued: First, the hypothesis that humans fundamentally act as intermittent servo-controllers was re-examined, probing the question of whether discontinuities in the movement trajectory directly imply intermittent control. Second, an alternative hypothesis was evaluated: that rhythmic tracking movements are generated by entrainment between the oscillations of the target and the actor, such that intermittency expresses the degree of stability. In 2 experiments, participants (N = 6 in each experiment) swung 1 of 2 different hand-held pendulums, tracking a rhythmic target that oscillated at different frequencies with a constant amplitude. In 1 line of analyses, the authors tested the intermittency hypothesis by using the typical kinematic error measures and spectral analysis. In a 2nd line, they examined relative phase and its variability, following analyses of rhythmic interlimb coordination. The results showed that visually guided corrective processes play a role, especially for slow movements. Intermittency, assessed as frequency and power components of the movement trajectory, was found to change as a function of both target frequency and the manipulandum's inertia. Support for entrainment was found in conditions in which task frequency was identical to or higher than the effector's eigenfrequency. The results suggest that it is the symmetry between task and effector that determines which behavioral regime is dominant.

MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells.

Ligation of the high-affinity IgE receptor (FcepsilonRI) or of c-Kit stimulates cytokine production in mast cells. We show that MEK kinase 2 (MEKK2), a MAPK kinase kinase (MAP3K) that regulates the JNK and ERK5 pathways, is required for cytokine production in embryonic stem (ES) cell-derived mast cells (ESMC). Targeted disruption of the MEKK2 or MEKK1 gene was used to abolish expression of the respective kinases in ESMC. Transcription of specific cytokines in response to IgE or c-Kit ligand was markedly reduced in MEKK2(-/-) ESMC relative to wild-type ESMC. Cytokine production in MEKK1(-/-) ESMC was similar to that of wild-type ESMC, demonstrating the specificity of MEKK2 in signaling cytokine gene regulation. MEKK2(-/-) ESMC also lost receptor-mediated stimulation of JNK. In contrast, JNK activation in response to UV irradiation was normal, showing that MEKK2 is required for receptor signaling but not for cellular stress responses. MEKK2 is the first MAP3K shown to be required for mast cell tyrosine kinase receptor signaling controlling cytokine gene expression.

Aberrant wound healing and TGF-beta production in the autoimmune-prone MRL/+ mouse.

Wound healing is a complex process that involves inflammation, apoptosis, growth, and tissue remodeling. The autoimmune-prone inbred mouse strain MRL/+ manifests accelerated and extensive healing to ear punch wounds, suggesting a link between immune defects and wound healing. Prior studies with lupus-prone mice have shown that hematopoietic cells of lupus-prone strains can transfer disease to otherwise non-autoimmune-prone recipients. In this study we performed reciprocal bone marrow transfers between MRL and the control strain B10.BR and found that radioresistant MRL/+ host cells, rather than hematopoietic cells, are required for the healing response. We have also made the novel observations that, compared to normal controls, MRL/+ hematopoietic cells overproduce TGF-beta1 and manifest impaired inflammatory responses to lipopolysaccharide challenge. These features suggest that the aberrant wound healing phenotype of MRL mice is independent of their propensity to develop autoimmunity.

Efficient peripheral clonal elimination of B lymphocytes in MRL/lpr mice bearing autoantibody transgenes.

Peripheral B cell tolerance was studied in mice of the autoimmune-prone, Fas-deficient MRL/ lpr.H-2(d) genetic background by introducing a transgene that directs expression of membrane-bound H-2Kb antigen to liver and kidney (MT-Kb) and a second transgene encoding antibody reactive with this antigen (3-83mu delta, anti-Kk,b). Control immunoglobulin transgenic (Ig-Tg) MRL/lpr.H-2(d) mice lacking the Kb antigen had large numbers of splenic and lymph node B cells bearing the transgene-encoded specificity, whereas B cells of the double transgenic (Dbl-Tg) MRL/lpr.H-2(d) mice were deleted as efficiently as in Dbl-Tg mice of a nonautoimmune B10.D2 genetic background. In spite of the severely restricted peripheral B cell repertoire of the Ig-Tg MRL/lpr.H-2(d) mice, and notwithstanding deletion of the autospecific B cell population in the Dbl-Tg MRL/lpr.H-2(d) mice, both types of mice developed lymphoproliferation and exhibited elevated levels of IgG anti-chromatin autoantibodies. Interestingly, Dbl-Tg MRL/lpr.H-2(d) mice had a shorter lifespan than Ig-Tg MRL/lpr.H-2(d) mice, apparently as an indirect result of their relative B cell lymphopenia. These data suggest that in MRL/lpr mice peripheral B cell tolerance is not globally defective, but that certain B cells with receptors specific for nuclear antigens are regulated differently than are cells reactive to membrane autoantigens.

Enhancement of 1,25-dihydroxyvitamin D3-mediated antitumor activity with dexamethasone.

BACKGROUND: The active metabolite of vitamin D, i.e., 1,25-dihydroxycholecalciferol (1,25-D3), inhibits the growth of murine SCCVII/SF squamous cell carcinoma cells, both in vitro and in vivo. However, in vivo use of 1,25-D3 is hampered as a result of hypercalcemia (i.e., elevated levels of calcium in the blood). Glucocorticoids, such as dexamethasone, affect calcium absorption and modulate vitamin D receptor binding and have been used to treat hypercalcemia. In this study, we examined the effect of dexamethasone on tumor growth inhibition by 1,25-D3. METHODS: The effects of 1,25-D3 and dexamethasone, alone and in combination, on the growth of SCCVII/SF cells in in vitro culture or in vivo in female C3H/HeJ mice were determined by clonogenic tumor cell assay and/or by actual changes in tumor volume. Vitamin D receptor-ligand-binding activities in whole-cell extracts from cells (in culture), tumors, and normal tissues were assayed by single-point saturation analysis and equilibrium binding. RESULTS: Treatment of cultured SCCVII/SF cells with 500 nM dexamethasone for 24 hours before addition of 1,25-D3 reduced their survival. The growth of SCCVII/SF tumors was inhibited in mice treated simultaneously with dexamethasone and 1,25-D3 (as compared with no treatment or single-agent treatment); hypercalcemia was also reduced. Total vitamin D receptor content in SCCVII/SF cells was increased after treatment with dexamethasone. Treatment of tumor-bearing animals with dexamethasone (9 microg/day) for 7 days led to increased vitamin D receptor-ligand-binding activities in whole-cell extracts from tumor or kidneys and decreased activity in intestinal mucosa. CONCLUSIONS: Dexamethasone may enhance the antitumor effect of 1,25-D3 by increasing vitamin D receptor-ligand-binding activity.

Potentiation of cisplatin antitumor activity using a vitamin D analogue in a murine squamous cell carcinoma model system.

In a murine squamous cell carcinoma (SCC) model, we have demonstrated that both 1,25-dihydroxycholecalciferol (1,25-D3) and the analogue 1,25-dihydroxy-16-ene-23-yne-cholecalciferol (Ro23-7553) have significant in vitro and in vivo antitumor activity. We have examined here the cell cycle effect of 1,25-D3 and Ro23-7553 on SCCVII/SF tumor cells by quantitating nuclear DNA using a detergent-trypsin method via flow cytometry analysis. Both 1,25-D3 and Ro23-7553 resulted in a significant increase of cells in G0-G1, with an accompanying decrease of cells in S phase. The ability to arrest cells in G0-G1 has been exploited by combining Ro23-7553 with the cytotoxic agent cisplatin (cis-diamminodichloroplatinum; cDDP). Using the in vitro clonogenic assay, pretreatment with Ro23-7553 for 24-48 h significantly enhanced cDDP-mediated tumor cell kill as compared to concurrent treatment with Ro23-7553 and cDDP or cDDP alone. To examine the effect of Ro23-7553 and cDDP in vivo, C3H/HeJ mice with 9-14-day SCC tumors were treated either for 3 days with varying i.p. doses of Ro23-7553 or for 7 days continuously through the use of Alzet pumps, and on the last day of Ro23-7553 treatment, cDDP (1-6 mg/kg) was administered. Using the in vivo excision tumor cell clonogenic assay, in which tumors were removed from animals 24 h after cDDP treatment and plated in a clonogenic assay, pretreatment with Ro23-7553 markedly enhanced cDDP-mediated clonogenic tumor cell kill, even at low doses of cDDP as compared to cDDP treatment alone. Similarly, a significant decrease in fractional tumor volume and increase in tumor regrowth delay was observed when animals were pretreated before cDDP with Ro23-7553 as compared to either agent alone. These results demonstrate a significant enhanced antitumor effect with Ro23-7553 pretreatment before cDDP both in vitro and in vivo and suggest that Ro23-7553 may potentiate cDDP cytotoxicity through effects on cell cycle progression.

Thermographic assessment of dentine pin placement.

OBJECTIVE: This in-vitro study aimed to examine the change in surface temperature induced by the actions of drills for the placement of dentine pins. METHODS: Ten decoronated extracted premolar teeth were embedded by the apical tip of their roots in orthoresin. They were held in a bench vice and allowed to reach the ambient temperature of 24 degrees C. A thermal imaging camera, Agema Thermovision 900 series, was positioned 0.05 m perpendicular to the decoronated surface. Sequential recording of a series of images was stored at a rate of three per second during each stage of the pin placement procedure. This included a pilot drill, a channel cutting drill and the pin placement. All pins were 0.675 mm diameter x 2 mm in length and were placed 1 mm from the amelo-dentinal junction using a Kavo handpiece rotating at 4000 rpm. RESULTS: The mean baseline temperature for the thermally stabilized teeth was 23.9 degrees C. The action of the round pilot drill changed the temperature from baseline by 25 degrees C. The action of the channel drill generated the greatest heat, with a mean maximum temperature recorded during these procedures of 94 degrees C +/- 9 degrees C. The pilot drill produced a mean change from baseline of 31.3 degrees C +/- 17.7 degrees C during pin placement. CONCLUSIONS: The placement of dentine pins produced a high temperature increase on the surface of the dentine. All stages of pin placement gave rise to an increased temperature, but this was maximal with the channel drill. Further studies are required to determine whether these surfaces temperatures are transferred to the pulpal chamber.

Analysis of central B cell tolerance in autoimmune-prone MRL/lpr mice bearing autoantibody transgenes.

The effect of the autoimmune prone MRL/lpr (H-2k) genetic background on central B cell tolerance was studied in mice bearing 3-83 (anti-H-2Kk) Ig heavy and light chain transgenes. B cells bearing the dominant, transgene-encoded anti-H-2Kk specificity were tolerized appropriately on the MRL/lpr genetic background. Nevertheless, mice developed disease traits characteristic of the MRL/lpr strain, including lymphadenopathy and elevated levels of IgG dsDNA autoantibodies. Two transgenic lines were examined in this analysis: 3-83 mu delta, which expresses IgM and IgD forms of the 3-83 Ab, and Tol 1, which expresses only the IgM form of 3-83. The results obtained differed somewhat between the two transgenic lines. Crosses using 3-83 mu(delta) mice never demonstrated any defects in B cell self-tolerance to H-2Kk. Similarly, no Kk autoantibody production was seen in Tol 1 mice that were backcrossed onto the MRL/lpr genetic background and maintained in a specific pathogen-free facility. However, a subset of Tol 1/MRL/lpr mice that were housed in a conventional mouse facility demonstrated significant transgene-derived anti-Kk autoantibodies. Overall, these results suggest that there is no general defect in central B cell tolerance in MRL/lpr mice, despite their defect in the fas gene. These findings suggest similarities between the MRL/lpr T and B cell systems, because both fail to manifest clear central tolerance defects, but they nevertheless promote hyperplasia and autoimmunity in the peripheral immune system.

Interleukin 1 alpha and gamma-interferon induction of nitric oxide production from murine tumor-derived endothelial cells.

The role of nitric oxide (NO) in vascular function, host tumoricidal activity, and antiinflammatory effects is well documented. A number of cytokines induce NO from a variety of cell types. We have demonstrated in murine models that interleukin 1 alpha (IL-1 alpha) induces acute hemorrhagic necrosis, microvascular injury, and enhanced clonogenic tumor cell kill. Effects on the vasculature are observed only in tumor and not in normal tissues. Using methods established previously in our laboratory, murine tumor-derived and normal endothelial cells were cultured with IL-1 alpha, IFN-gamma, or IL-1 alpha/IFN-gamma at various doses with NO production quantitated through the measurement of nitrite by the Griess reaction. In tumor-derived endothelial cells, we demonstrated that neither cytokine alone was capable of inducing nitrite but that the combination of IL-1 alpha/IFN-gamma induced dose-dependent nitrite, with peak levels observed after 4 days incubation. When tumor-derived, normal yolk sac, mouse brain, or mouse aortic endothelial cells were treated with IL-1 alpha (100 units/ml)/IFN-gamma (10 units/ml), tumor-derived endothelial cells produced significantly more nitrite when compared to the normal endothelial cells. Nitrite production from IL-1 alpha/IFN-gamma was sensitive to the nitric oxide synthase inhibitors, NG-methyl-L-arginine or NG-nitro-L-arginine in a dose-dependent manner. In addition, dexamethasone significantly inhibited nitrite production from IL-1 alpha/IFN-gamma-treated, tumor-derived endothelial cells. These studies suggest that the antitumor activity of IL-1 alpha may be mediated through the production of NO from tumor-derived endothelial cells.

Extractions in support of orthodontic treatment.

Extractions in support of orthodontic therapy may be done in any combination of teeth. The more common extraction patterns are: 1. Maxillary and mandibular first premolars; 2. Maxillary first and mandibular second premolars; 3. Maxillary and mandibular second premolars; 4. Maxillary first premolar; 5. Maxillary second permanent molar; 6. Maxillary first permanent molars; 7. Maxillary permanent lateral incisors; 8. Mandibular permanent incisors; or 9. Any possible combination and variation for other considerations. Extractions have been proven to support changes in the profile, helping in the alignment of teeth and in reducing lower facial height. The decision as to whether or not to extract requires a great deal of thoughtful application of diagnostic skills.

Activities associated with drownings in Imperial County, CA, 1980-90: implications for prevention.

Statewide surveillance in California determined that the highest drowning rate from 1980 through 1989 was for the rural, desert county of Imperial (21.9 drownings per 100,000 population). To identify activities associated with drowning in this county, the authors abstracted data from the county sheriff-coroner's reports. From 1980 through 1990, there were 317 unintentional drownings; 85 percent occurred in irrigation canals. The activity prior to drowning was known for 262 persons (83 percent), and the most common activity was illegal entry into the United States. Overall, 140 persons (53 percent) were illegal entrants. Ninety-three percent of illegal entrants drowned in the All American Canal; the monthly drowning rate increased as the monthly average water velocity in the canal increased (r = 0.36; P < 0.001). Forty-eight persons (18 percent) drowned while riding in or on a land vehicle (automobile, pick-up truck, motorcycle, dune buggy, or tractor), the second most common activity associated with drowning. Seventy percent of the 23 drivers had an alcohol concentration of 100 milligrams per deciliter or more, California's limit for intoxication. To reduce drownings in Imperial County, prevention strategies should target persons engaged in at-risk activities near bodies of water. These strategies should include the identification and use of effective canal safety devices.