Integrated disinfection by-products mixtures research: assessment of developmental toxicity in Sprague-Dawley rats exposed to concentrates of water disinfected by chlorination and ozonation/postchlorination.

Epidemiological and animal toxicity studies have raised concerns regarding possible adverse health effects of disinfection by-products (DBPs) found in drinking water. The classes and concentrations of DBPs are influenced by the choice of disinfection process (e.g., chlorination, ozonation) as well as source water characteristics (e.g., pH, total organic carbon, bromide content). Disinfected waters were found to contain more than 500 compounds, many of which remain unidentified. Therefore, a "whole-mixture" approach was used to evaluate the toxic potential of alternative disinfection scenarios. An in vivo developmental toxicity screen was used to evaluate the adverse developmental effects of the complex mixtures produced by two different disinfection processes. Water was obtained from East Fork Lake, Ohio; spiked with iodide and bromide; and disinfected either by chlorination or by ozonation/postchlorination, producing finished drinking water suitable for human consumption. These waters were concentrated approximately 130-fold by reverse osmosis membrane techniques. To the extent possible, volatile DBPs lost in the concentration process were spiked back into the concentrates. These concentrates were then provided as drinking water to Sprague-Dawley rats on gestation days 6-16; controls received boiled, distilled, deionized water. The dams (19-20 per group) were allowed to deliver and their litters were examined on postnatal days (PD) 1 and 6. All dams delivered normally, with parturition occurring significantly earlier in the ozonation/postchlorination group. However, no effects on prenatal survival, postnatal survival, or pup weight were evident. Skeletal examination of the PD-6 pups also revealed no treatment effects. Thus, approximately 130-fold higher concentrates of both ozonated/postchlorinated and chlorinated water appeared to exert no adverse developmental effects in this study.

CAD/CAM transtibial prosthetic sockets from central fabrication facilities: how accurate are they?

This research compares transtibial prosthetic sockets made by central fabrication facilities with their corresponding American Academy of Orthotists and Prosthetists (AAOP) electronic shape files and assesses the central fabrication process. We ordered three different socket shapes from each of 10 manufacturers. Then we digitized the sockets using a very accurate custom mechanical digitizer. Results showed that quality varied considerably among the different manufacturers. Four of the companies consistently made sockets within +/-1.1% volume (approximately 1 sock ply) of the AAOP electronic shape file, while six other companies did not. Six of the companies showed consistent undersizing or oversizing in their sockets, which suggests a consistent calibration or manufacturing error. Other companies showed inconsistent sizing or shape distortion, a difficult problem that represents a most challenging limitation for central fabrication facilities.

Assessment of residual-limb volume change using bioimpedence.

We investigated electrical bioimpedance as a potential measurement modality to assess residual-limb volume change in lower-limb amputees. Four strip electrodes were positioned across the anterior lateral to posterior lateral aspects of the proximal lower leg or residual limb such that the outer pair applied current and the inner pair sensed voltage. A commercial bioimpedance analyzer supplied current at 50 fre quencies between 5 kHz and 1 MHz and then used a well-validated model to determine fluid resistance. From these data, extracellular fluid volume (V(ECF)) could be estimated. Bench test evaluation showed the instrument to have a root-mean-square error of less than 0.014% over a 1 h interval. Tests of subjects who had been transtibial amputees for at least 2 yr showed V(ECF) changes from postural adjustments well outside the instrument error and normal minute-to-minute biological variability. The rate of V(ECF) change while standing with the prosthesis donned was greater for diabetic subjects than for nondiabetic subjects. Bioimpedance analysis may have use in prosthetics research, where comparing residual-limb volume at different time points or under different treatment conditions is of interest.

Disturbed paraspinal reflex following prolonged flexion-relaxation and recovery.

STUDY DESIGN: Repeated measures experimental study of the effect of flexion-relaxation, recovery, and gender on paraspinal reflex dynamics. OBJECTIVE: To determine the effect of prolonged flexion-relaxation and recovery time on reflex behavior in human subjects. SUMMARY OF BACKGROUND DATA: Prolonged spinal flexion has been shown to disturb the paraspinal reflex activity in both animals and human beings. Laxity in passive tissues of the spine from flexion strain may contribute to desensitization of mechanoreceptors. Animal studies indicate that recovery of reflexes may take up to several hours. Little is known about human paraspinal reflex behavior following flexion tasks or the recovery of reflex behavior following the flexion tasks. METHODS: A total of 25 subjects performed static flexion-relaxation tasks. Paraspinal muscle reflexes were recorded before and immediately after flexion-relaxation and after a recovery period. Reflexes were quantified from systems identification analyses of electromyographic response in relation to pseudorandom force disturbances applied to the trunk. RESULTS: Trunk angle measured during flexion-relaxation postures was significantly higher following static flexion-relaxation tasks (P < 0.001), indicating creep deformation of passive supporting structures in the trunk. Reflex response was diminished following flexion-relaxation (P < 0.029) and failed to recover to baseline levels during 16 minutes of recovery. CONCLUSION: Reduced reflex may indicate that the spine is less stable following prolonged flexion-relaxation and, therefore, susceptible to injury. The absence of recovery in reflex after a substantial time indicates that increased low back pain risk from flexion-relaxation may persist after the end of the flexion task.

Short-term exposures to dihaloacetic acids produce dysmorphogenesis in mouse conceptuses in vitro.

The haloacetic acids (HAAs) are a family of xenobiotics found in tap water as a result of drinking water disinfection. Administration of HAAs to rats produces a variety of adverse effects, including developmental toxicity. The dysmorphogenic potencies of all nine bromo/chloro-acetic acids have been determined in rodent whole embryo culture using standard 26-h exposure. Since the half-lives of the HAAs in vivo are typically <8 h, the developmental effects of short-term exposures to dihaloacetates were evaluated. Gestation day 8 (3-6 somite pairs) CD-1 mouse conceptuses were exposed to 11,000 microM dichloroacetic acid (DCA), 300 microM dibromoacetic acid (DBA) or 300 microM bromochloroacetic acid (BCA) for culture periods of 1, 3, 6 or 26 h. Following 1, 3 or 6 h of exposure to HAAs, conceptuses were transferred to control medium to complete a 26-h culture period. The amounts of HAAs present in embryos after 1, 3 and 6h of exposure were determined. Increased incidences of dysmorphic embryos were produced by 6 or 26-h exposures to DCA; a 26-h exposure to DBA; or 3, 6 or 26-h exposures to BCA. The dysmorphology produced was dependent upon the length of exposure and chemical. The embryonic concentration of each HAA (104.5, 2.5 and 2.6 pmol/microg protein for DCA, DBA and BCA, respectively) was reached by 1h of exposure and did not change at the subsequent time points examined. The current studies demonstrate that BCA is more potent than DBA or DCA at disrupting embryogenesis since shorter exposures alter morphogenesis. Since the embryonic HAA concentrations were the same at the three time points measured, the time-dependence in dysmorphogenesis does not appear to be a simple function of increasing embryonic concentration of these chemicals. These studies demonstrate that for these dihaloacetic acids relatively high concentrations and long exposures are needed to alter rodent development in vitro.

Active trunk stiffness increases with co-contraction.

Trunk dynamics, including stiffness, mass and damping were quantified during trunk extension exertions with and without voluntary recruitment of antagonistic co-contraction. The objective of this study was to empirically evaluate the influence of co-activation on trunk stiffness. Muscle activity associated with voluntary co-contraction has been shown to increase joint stiffness in the ankle and elbow. Although biomechanical models assume co-active recruitment causes increase trunk stiffness it has never been empirically demonstrated. Small trunk displacements invoked by pseudorandom force disturbances during trunk extension exertions were recorded from 17 subjects at two co-contraction conditions (minimal and maximal voluntary co-contraction recruitment). EMG data were recorded from eight trunk muscles as a baseline measure of co-activation. Increased EMG activity confirms that muscle recruitment patterns were different between the two co-contraction conditions. Trunk stiffness was determined from analyses of impulse response functions (IRFs) of trunk dynamics wherein the kinematics were represented as a second-order behavior. Trunk stiffness increased 37.8% (p < 0.004) from minimal to maximal co-activation. Results support the assumption used in published models of spine biomechanics that recruitment of trunk muscle co-contraction increases trunk stiffness thereby supporting conclusions from those models that co-contraction may contribute to spinal stability.

Bromochloro-haloacetic acids: effects on mouse embryos in vitro and QSAR considerations.

The haloacetic acids (HAA) are a family of chemicals that are drinking water disinfection by-products. We previously reported that haloacetic acids, including several bromo- and chloro-HAAs, alter embryonic development when mouse conceptuses are directly exposed to these xenobiotics in whole embryo culture. Craniofacial dysmorphogenesis was observed in exposed embryos and a quantitative structure activity relationship (QSAR) for induction of cranial neural tube dysmorphogenesis was established for a series of 10 HAAs, which also included fluoro- and iodo-HAA representatives. In the current study, we evaluate the effects of exposing neurulation staged (3-6 somite pairs) CD-1 mouse conceptuses to bromochloro- (BCA), dibromochloro- (DBCA) and bromodichloro-acetic (BDCA) acids in whole embryo culture at concentrations ranging from 50 to 2500 microM. Morphological development was assessed after a 26 h exposure period. Exposure of conceptuses to these HAAs produced dysmorphogenesis, including prosencephalic and pharyngeal arch hypoplasia as well as eye and heart tube abnormalities. Benchmark concentrations for induction of neural tube dysmorphogenesis were 63, 500 and 536 microM for BCA, DBCA and BDCA, respectively. Our previously developed HAA QSAR accurately predicted placement of these three chemicals in the larger context of the previously tested di- and tri-HAAs, also correctly predicting that BCA would be more potent than DBCA and BDCA, and that the latter two HAAs would be near equi-potent. This study describes the concentration-dependent induction of dysmorphogenesis in whole embryo culture by three mixed chloro/bromo-HAAs and demonstrates the ability of the HAA QSAR to predict relative potencies within this family of xenobiotics.

Effects of static flexion-relaxation on paraspinal reflex behavior.

BACKGROUND: Static trunk flexion working postures and disturbed trunk muscle reflexes are related to increased risk of low-back pain. Animal studies conclude that these factors may be related; passive tissue strain in spinal ligaments causes subsequent short-term changes in reflex. Although studies have documented changes in the myoelectric onset angle of flexion-relaxation following prolonged static flexion and cyclic flexion we could find no published evidence related to the human reflex response of the trunk extensor muscles following a period of static flexion-relaxation loading. METHODS: Eighteen subjects maintained static lumbar flexion for 15 min. Paraspinal muscle reflexes were elicited both before and after the flexion-relaxation protocol using pseudorandom stochastic force disturbances while recording EMG. Reflex gain was computed from the peak value of the impulse response function relating input force perturbation to EMG response using time-domain deconvolution analyses. FINDINGS: Reflexes showed a trend toward increased gain after the period of flexion-relaxation (P < 0.055) and were increased with trunk extension exertion (P < 0.021). Significant gender differences in reflex gain were observed (P < 0.01). INTERPRETATIONS: Occupational activities requiring extended periods of trunk flexion contribute to changes in reflex behavior of the paraspinal muscles. Results suggest potential mechanisms by which flexed posture work may contribute to low-back pain. Significant gender differences indicate risk analyses should consider personal factors when considering neuromuscular behavior.