High interindividual variability in dose-dependent reduction in speed of movement after exposing C. elegans to shock waves

In blast-related mild traumatic brain injury (br-mTBI) little is known about the connections between initial trauma and expression of individual clinical symptoms. Partly due to limitations of current in vitro and in vivo models of br-mTBI, reliable prediction of individual short-and long-term symptoms based on known blast input has not yet been possible. Here we demonstrate a dose-dependent effect of shock wave exposure on C. elegans using shock waves that share physical characteristics with those hypothesized to induce br-mTBI in humans. Increased exposure to shock waves resulted in decreased mean speed of movement while increasing the proportion of worms rendered paralyzed. Recovery of these two behavioral symptoms was observed during increasing post-traumatic waiting periods. Although effects were observed on a population-wide basis, large interindividual variability was present between organisms exposed to the same highly controlled conditions. Reduction of cavitation by exposing worms to shock waves in polyvinyl alcohol resulted in reduced effect, implicating primary blast effects as damaging components in shock wave induced trauma. Growing worms on NGM agar plates led to the same general results in initial shock wave effect in a standard medium, namely dose-dependence and high interindividual variability, as raising worms in liquid cultures. Taken together, these data indicate that reliable prediction of individual clinical symptoms based on known blast input as well as drawing conclusions on blast input from individual clinical symptoms is not feasible in br-mTBI

Hypothermia ameliorates blast-related lifespan reduction of C-elegans

Blast-related mild traumatic brain injury induces significant long-term health issues, yet treatment procedures remain underdeveloped. Therapeutic hypothermia has been postulated as a potentially effective therapy. In a Caenorhabditis elegans model, we demonstrate a dose-dependent reduction in lifespan following exposure to blast-like shock waves. Using polyvinyl alcohol, we show that cavitation is a key injurious factor in the damaging shock wave component. Short and long lifespan C. elegans mutants demonstrated the interaction of genetic and environmental longevity-determining factors. Hypothermia reduced the long term effect of shock wave exposure. Thus, we present an effective C. elegans model of long term effects of blast-related mild traumatic brain injury, as well as evidence of the merit of therapeutic hypothermia as a therapy option following blast exposure

A Prospective Case-Control Study of Radial Extracorporeal Shock Wave Therapy for Spastic Plantar Flexor Muscles in Very Young Children With Cerebral Palsy

To assess the effects of radial extracorporeal shock wave therapy (rESWT) on plantar flexor muscle spasticity and gross motor function in very young patients with cerebral palsy (CP).The design was case-control study (level of evidence 3).The setting was the Department of Pediatric Neurology and Neurorehabilitation, First Hospital of Jilin University, Changchun, China.Those with a diagnosis of CP and spastic plantar flexor muscles were recruited between April 2014 and April 2015.According to the parents' decision, patients received 1 ESWT session per week for 3 months, with 1500 radial shock waves per ESWT session and leg with positive energy flux density of 0.03mJ/mm(2), combined with traditional conservative therapy (rESWT group) or traditional conservative therapy alone (control group).The Modified Ashworth Scale (MAS) (primary outcome measure) and passive range of motion (pROM) measurements were collected at baseline (BL), 1 month (M1), and 3 months (M3) after BL. The Gross Motor Function Measure (GMFM)-88 was collected at BL and M3.Sixty-six patients completed the final review at 3 months and were included in the study. Subjects ranged in age from 12 to 60 months (mean age 27.013.6 months;median age 22.0 months;33.3% female). For the rESWT group (n=34), mean MAS grades at BL, M1, and M3 were 2.6, 1.9, and 1.5 on the left side and 1.9, 1.7, and 1.2 on the right side. For the control group (n=32), mean MAS grades at BL, M1, and M3 were 2.5, 2.4, and 2.1 on the left side and 1.8, 1.8, and 1.5 on the right side. The within-subject effects timexside and timextreatment were statistically significant (P<0.01). Similar results were found for the improvement of mean pROM. GMFM-88 improved from BL to M3, but showed no statistically significant difference between the groups. There were no significant complications.This study demonstrates that the combination of rESWT and traditional conservative therapy is more effective than traditional conservative therapy alone in the treatment of spasticity in very young patients with CP

Radial Shock Wave Devices Generate Cavitation

Background Conflicting reports in the literature have raised the question whether radial extracorporeal shock wave therapy (rESWT) devices and vibrating massage devices have similar energy signatures and, hence, cause similar bioeffects in treated tissues. Methods and Findings We used laser fiber optic probe hydrophone (FOPH) measurements, high-speed imaging and x-ray film analysis to compare fundamental elements of the energy signatures of two rESWT devices (Swiss DolorClast;Electro Medical Systems, Nyon, Switzerland;D-Actor 200;Storz Medical, Tagerwillen, Switzerland) and a vibrating massage device (Vibracare;G5/General Physiotherapy, Inc.,Earth City, MO, USA). To assert potential bioeffects of these treatment modalities we investigated the influence of rESWT and vibrating massage devices on locomotion ability of Caenorhabditis elegans (C. elegans) worms. Results FOPH measurements demonstrated that both rESWT devices generated acoustic waves with comparable pressure and energy flux density. Furthermore, both rESWT devices generated cavitation as evidenced by high-speed imaging and caused mechanical damage on the surface of x-ray film. The vibrating massage device did not show any of these characteristics. Moreover, locomotion ability of C. elegans was statistically significantly impaired after exposure to radial extracorporeal shock waves but was unaffected after exposure of worms to the vibrating massage device. Conclusions The results of the present study indicate that both energy signature and bioeffects of rESWT devices are fundamentally different from those of vibrating massage devices

No Evidence of Persisting Unrepaired Nuclear DNA Single Strand Breaks in Distinct Types of Cells in the Brain, Kidney, and Liver of Adult Mice after Continuous Eight-Week 50 Hz Magnetic Field Exposure with Flux Density of 0.1 mT or 1.0 mT

BACKGROUND: It has been hypothesized in the literature that exposure to extremely low frequency electromagnetic fields (50 or 60 Hz) may lead to human health effects such as childhood leukemia or brain tumors. In a previous study investigating multiple types of cells from brain and kidney of the mouse (Acta Neuropathologica 2004; 107: 257-264), we found increased unrepaired nuclear DNA single strand breaks (nDNA SSB) only in epithelial cells of the choroid plexus in the brain using autoradiographic methods after a continuous eight-week 50 Hz magnetic field (MF) exposure of adult mice with flux density of 1.5 mT. METHODS: In the present study we tested the hypothesis that MF exposure with lower flux densities (0.1 mT, i.e., the actual exposure limit for the population in most European countries, and 1.0 mT) shows similar results to those in the previous study. Experiments and data analysis were carried out in a similar way as in our previous study. RESULTS: Continuous eight-week 50 Hz MF exposure with 0.1 mT or 1.0 mT did not result in increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice. MF exposure with 1.0 mT led to reduced unscheduled DNA synthesis (UDS) in epithelial cells in the choroid plexus of the fourth ventricle in the brain (EC-CP) and epithelial cells of the cortical collecting duct in the kidney, as well as to reduced mtDNA synthesis in neurons of the caudate nucleus in the brain and in EC-CP. CONCLUSION: No evidence was found for increased persisting unrepaired nDNA SSB in distinct types of cells in the brain, kidney, and liver of adult mice after continuous eight-week 50 Hz magnetic field exposure with flux density of 0.1 mT or 1.0 mT

Advanced Behavioral Analyses Show that the Presence of Food Causes Subtle Changes in C. elegans Movement

As a widely used and studied model organism, Caenorhabditis elegans worms offer the ability to investigate implications of behavioral change. Although, investigation of C. elegans behavioral traits has been shown, analysis is often narrowed down to measurements based off a single point, and thus cannot pick up on subtle behavioral and morphological changes. In the present study videos were captured of four different C. elegans strains grown in liquid cultures and transferred to NGM-agar plates with an E coil lawn or with no lawn. Using an advanced software, WormLab, the full skeleton and outline of worms were tracked to determine whether the presence of food affects behavioral traits. In all seven investigated parameters, statistically significant differences were found in worm behavior between those moving on NGM-agar plates with an E coli lawn and NGM-agar plates with no lawn. Furthermore, multiple test groups showed differences in interaction between variables as the parameters that significantly correlated statistically with speed of locomotion varied. In the present study, we demonstrate the validity of a model to analyze C. elegans behavior beyond simple speed of locomotion. The need to account for a nested design while performing statistical analyses in similar studies is also demonstrated. With extended analyses, C. elegans behavioral change can be investigated with greater sensitivity, which could have wide utility in fields such as, but not limited to, toxicology, drug discovery, and RNAi screening

A Prospective Case-Control Study of Radial Extracorporeal Shock Wave Therapy for Spastic Plantar Flexor Muscles in Very Young Children With Cerebral Palsy

To assess the effects of radial extracorporeal shock wave therapy (rESWT) on plantar flexor muscle spasticity and gross motor function in very young patients with cerebral palsy (CP).The design was case-control study (level of evidence 3).The setting was the Department of Pediatric Neurology and Neurorehabilitation, First Hospital of Jilin University, Changchun, China.Those with a diagnosis of CP and spastic plantar flexor muscles were recruited between April 2014 and April 2015.According to the parents' decision, patients received 1 ESWT session per week for 3 months, with 1500 radial shock waves per ESWT session and leg with positive energy flux density of 0.03mJ/mm(2), combined with traditional conservative therapy (rESWT group) or traditional conservative therapy alone (control group).The Modified Ashworth Scale (MAS) (primary outcome measure) and passive range of motion (pROM) measurements were collected at baseline (BL), 1 month (M1), and 3 months (M3) after BL. The Gross Motor Function Measure (GMFM)-88 was collected at BL and M3.Sixty-six patients completed the final review at 3 months and were included in the study. Subjects ranged in age from 12 to 60 months (mean age 27.013.6 months;median age 22.0 months;33.3% female). For the rESWT group (n=34), mean MAS grades at BL, M1, and M3 were 2.6, 1.9, and 1.5 on the left side and 1.9, 1.7, and 1.2 on the right side. For the control group (n=32), mean MAS grades at BL, M1, and M3 were 2.5, 2.4, and 2.1 on the left side and 1.8, 1.8, and 1.5 on the right side. The within-subject effects timexside and timextreatment were statistically significant (P<0.01). Similar results were found for the improvement of mean pROM. GMFM-88 improved from BL to M3, but showed no statistically significant difference between the groups. There were no significant complications.This study demonstrates that the combination of rESWT and traditional conservative therapy is more effective than traditional conservative therapy alone in the treatment of spasticity in very young patients with CP

Cavitation bubbles generated by the D-Actor 200 and the Swiss DolorClast devices.

<p>The panels show the frames with the highest number of labeled pixels (from the corresponding high-speed imaging film sequences described in the main text) generated by the D-Actor 200 (A-D) operated at 3 bar and 1 Hz (A), 3 bar and 15 Hz (B), (maximum) 5 bar and 1 Hz (C), and 5 bar and 15 Hz (D), as well as with the Swiss DolorClast (E-H) operated at 3 bar and 1 Hz (E), 3 bar and 15 Hz (F), (maximum) 4 bar and 1 Hz (G), and 4 bar and 15 Hz (H). The scale bar represents 5 mm.</p