Short-term changes in the physiology of the primary motor cortex following head impact exposure during a Canadian football game.

OBJECTIVE: This study investigated the association between head impact exposure (HIE) during varsity Canadian football games and short-term changes in cortical excitability of the primary motor cortex (M1) using transcranial magnetic stimulation (TMS). METHODS: Twenty-nine university-level male athletes wore instrumented mouth guards during a football game to measure HIE. TMS measurements were conducted 24 hours before and 1-2 hours after the game. Twenty control football athletes were submitted to a noncontact training session and underwent identical TMS assessments. Between-group changes in short-interval intracortical inhibition (SICI) ratios over time were conducted using two-way ANOVAs. The relationship between HIE (i.e., number, magnitude, and cumulative forces of impacts) and SICI (secondary outcome) was also investigated using Pearson correlations. RESULTS: Relative to controls, the group of athletes who had played a full-contact football game exhibited a significant intracortical disinhibition (p = 0.028) on the SICI 3-msec protocol (i.e., short interstimulus interval of 3 msec) within hours following the game. Moreover, exposure to ≥ 40g hits positively correlated with SICI disinhibition (p < 0.05). CONCLUSIONS: Athletes exposed to subconcussive hits associated with Canadian football exhibit abnormal M1 corticomotor inhibition function, particularly when the recorded impact magnitude was ≥ 40g. Given the deleterious effects of decreased inhibition on motor control and balance, systematically tracking head impact forces at each game and practice with contacts could prove useful for injury prevention in contact sports.

A New Approach to Quantifying Muscular Fatigue Using Wearable EMG Sensors during Surgery: An Ergonomic Case Study.

(1) Background: Surgeons are exposed to musculoskeletal loads that are comparable to those of industrial workers. These stresses are harmful for the joints and muscles and can lead to musculoskeletal disorders (MSD) and working incapacity for surgeons. In this paper, we propose a novel ergonomic and visualization approach to assess muscular fatigue during surgical procedures. (2) Methods: The activity of eight muscles from the shoulder girdle and the cervical/lumbar spines were evaluated using position and electromyographic wearable sensors while a surgeon performed an arthroscopic rotator-cuff surgery on a patient. The time and frequency-domain variables of the root-mean-square amplitude and mean power frequency, respectively, were calculated from an electromyographic signal. (3) Results: The entire surgical procedure lasted 73 min and was divided into 10 sub-phases associated with specific level of muscular activity and fatigue. Most of the muscles showed activity above 60%, while the middle trapezius muscles were almost constantly activated (>20%) throughout the surgical procedure. (4) Conclusion: Wearable sensors can be used during surgical procedure to assess fatigue. Periods of low-to-high activity and fatigue can be evaluated and visualized during surgery. Micro-breaks throughout surgical procedures are suggested to avoid fatigue and to prevent the risk of developing MSD.

Theory and simulations of toroidal and rod-like structures in single-molecule DNA condensation.

DNA condensation by multivalent cations plays a crucial role in genome packaging in viruses and sperm heads, and has been extensively studied using single-molecule experimental methods. In those experiments, the values of the critical condensation forces have been used to estimate the amplitude of the attractive DNA-DNA interactions. Here, to describe these experiments, we developed an analytical model and a rigid body Langevin dynamics assay to investigate the behavior of a polymer with self-interactions, in the presence of a traction force applied at its extremities. We model self-interactions using a pairwise attractive potential, thereby treating the counterions implicitly. The analytical model allows to accurately predict the equilibrium structures of toroidal and rod-like condensed structures, and the dependence of the critical condensation force on the DNA length. We find that the critical condensation force depends strongly on the length of the DNA, and finite-size effects are important for molecules of length up to 10(5)µm. Our Langevin dynamics simulations show that the force-extension behavior of the rod-like structures is very different from the toroidal ones, so that their presence in experiments should be easily detectable. In double-stranded DNA condensation experiments, the signature of the presence of rod-like structures was not unambiguously detected, suggesting that the polyamines used to condense DNA may protect it from bending sharply as needed in the rod-like structures.

Receptor clustering affects signal transduction at the membrane level in the reaction-limited regime.

Many types of membrane receptors are found to be organized as clusters on the cell surface. We investigate the potential effect of such receptor clustering on the intracellular signal transduction stage. We consider a canonical pathway with a membrane receptor (R) activating a membrane-bound intracellular relay protein (G). We use Monte Carlo simulations to recreate biochemical reactions using different receptor spatial distributions and explore the dynamics of the signal transduction. Results show that activation of G by R is severely impaired by R clustering, leading to an apparent blunted biological effect compared to control. Paradoxically, this clustering decreases the half maximal effective dose (ED50) of the transduction stage, increasing the apparent affinity. We study an example of inter-receptor interaction in order to account for possible compensatory effects of clustering and observe the parameter range in which such interactions slightly counterbalance the loss of activation of G. The membrane receptors' spatial distribution affects the internal stages of signal amplification, suggesting a functional role for membrane domains and receptor clustering independently of proximity-induced receptor-receptor interactions.

Impact of receptor clustering on ligand binding.

BACKGROUND: Cellular response to changes in the concentration of different chemical species in the extracellular medium is induced by ligand binding to dedicated transmembrane receptors. Receptor density, distribution, and clustering may be key spatial features that influence effective and proper physical and biochemical cellular responses to many regulatory signals. Classical equations describing this kind of binding kinetics assume the distributions of interacting species to be homogeneous, neglecting by doing so the impact of clustering. As there is experimental evidence that receptors tend to group in clusters inside membrane domains, we investigated the effects of receptor clustering on cellular receptor ligand binding. RESULTS: We implemented a model of receptor binding using a Monte-Carlo algorithm to simulate ligand diffusion and binding. In some simple cases, analytic solutions for binding equilibrium of ligand on clusters of receptors are provided, and supported by simulation results. Our simulations show that the so-called "apparent" affinity of the ligand for the receptor decreases with clustering although the microscopic affinity remains constant. CONCLUSIONS: Changing membrane receptors clustering could be a simple mechanism that allows cells to change and adapt its affinity/sensitivity toward a given stimulus.

Quantitative structure-activity relationship for 4-hydroxy-2-alkenal induced cytotoxicity in L6 muscle cells.

Lipid peroxidation is one of the most important sources of endogenous toxic metabolites. 4-Hydroxy-2-nonenal (HNE) and 4-hydroxy-2-hexenal (HHE) are produced in several oxidative stress associated diseases from peroxidation of n-6 and n-3 polyunsaturated fatty acids, respectively. Both are able to form covalent adducts with many biomolecules. Particularly, proteins adduction can induce structural and conformational changes and impair biological function, which may be involved in the toxicity of hydroxy-alkenals. The aim of this study was to compare the effect of 4-hydroxy-2-alkenals to several chemically related derivatives in order to clarify the physico-chemical requirement of their toxicity. L6 muscle cells were treated with HHE, HNE and parent derivatives (acetal derivative, trans-alkenals and alkanals). Viability and necrosis were estimated using MTT, LDH and caspase-3 tests. LogLC50 (Lethal Concentration 50) was then tested for correlation with adducts formation (estimated using dinitrophenylhydrazine) and several molecular descriptors in order to establish quantitative structure-toxicity relationship (QSTR) models. The rank of derivatives toxicity, based on LC50 was: hydroxy-alkenals>acetal derivatives approximately 2-alkenals>alkanals and a high correlation was found between logLC50 and protein carbonylation. Moreover, logLC50 was correlated to the electrophilic descriptor LUMO (lowest unoccupied molecular orbital) as well as with electronegativity-related molecular descriptors such as number of oxygen atoms, partial negative surface area (PNSA3) and partial positive surface area (PPSA3). Together, these results point out the important role of the electrophilic structure and adduct formation in hydroxy-alkenals toxicity. Our present study demonstrates that 4-hydroxy-2-alkenals dramatic effects on cell viability are due to covalent adducts formation, particularly Michael adducts. This capacity is related to the electrophilic structure and reactive CC double bond, making it highly accessible for nucleophilic addition. The present study suggests that nucleophilic scavengers might protect cells against electrophile compounds and might be of possible therapeutic value in oxidative stress associated diseases.