The effects of manipulated somatosensory input on simulated falls during walking

Previous research has demonstrated that there is a distinct relationship between aging and instability. The somatosensory system plays a significant role in balance control in conjunction with vision and the vestibular system (Qiu et al., 2012). Evidence has shown that manipulation of the mechanoreceptors on the plantar surface of the foot has a direct effect on balance control. By manipulating these receptors with hypothermic anesthesia and vibration, researchers are capable of simulating the effect of sensory modification on healthy individuals, in order to understand the role that plantar-surface sensation has in adapting to perturbation during gait (Perry et al., 2001; Priplata et al., 2006). This study included 14 healthy young adults (mean age 23.07 (±2.43)). Within this study, participants were asked to walk the length of an 8-meter platform at a comfortable speed. Participants were required to walk with reduced, enhanced and normal levels of somatosensory information of the plantar foot surface. During walking trials the participants travelled along a raised platform that had 4 sections in which removable foam squares were placed to provide either a stable or unstable situation when stepped upon. Located underneath three of these squares were three force plates (OR-6-2000 (AMTI, Waterdown, MA)). In order to prevent learning bias the location of the foam, as well as the direction of the perturbation was randomized. Participants were perturbed in either the anterior or lateral direction based upon the direction in which the removable foam squares within the platform were placed. Moreover, participants experienced three separate conditions (control, vibration, and cooled) on the plantar surface of the foot to manipulate the sensory information received. Electromyography (AMT-8 (Bortec, Calgary, Alberta)) was used to analyze magnitude and onset changes in muscle activity within the Gastrocnemius and Tibialis Anterior of the right lower limb, and the Rectus Femoris, and Biceps Femoris muscles of the left lower limb. Three-dimensional motion analysis was also used to capture observable changes in gait (Optotrak, NDI, Waterloo, Ontario). A main effect of condition was found for the third burst of muscle activity recorded within the Tibialis Anterior (F(2,17)=2.75, p\u3c0.01), with post-hoc analysis between the cooled and vibration conditions. A significant positive correlation was found between Rectus Femoris EMG amplitude and rate of loading (r=0.94,p=0.05). Within the anterior perturbations, a main effect for condition was observed for maximum COM velocity ((F(2,35)=3.71, p=0.05), minimum COP velocity (F(2,35)=4.62, p=0.03), and for the maximum distance between COM and COP (F(2,35)=4.37, p=0.04). A trend was also observed for the maximum distance the COM travelled within the lateral direction in the BOS (F(9,35)=2.61, p=0.06). Within the lateral perturbations, a trending effect for condition was also observed for maximum COM velocity (F(2,55)=3.07, p=0.06), the maximum distance between the COM and COP (F(2,55)=2.98, p=0.06), and a main effect was observed for condition for the rate of loading (F(2,55)=3.86, p=0.03). This study provides evidence of a relationship between the plantar cutaneous mechanoreceptors and gait parameters regarding to balance control as observed by the significant effects on commonly used measurements of balance control (i.e. COP and COM velocity). A relationship between mechanoreceptors and EMG amplitude, as well as foot contact forces and EMG amplitude is also evident. These relationships may be used to further knowledge for balance control during adaptive gait, as well as provide further development of footwear and insoles to improve balance control

Pain Management

This book has seven chapters, from more than 15 authors from different countries (Korea, Poland, Saudi Arabia, Taiwan, Turkey and USA) edited by Professor Milica Prostran MD, PhD. The potential reader is shown the modern approach to pain management because the chapters deal at length and clearly with their topics. I believe that this book that I edited with great pleasure and dedication will capture the attention of many readers, from medical students to practicing doctors. All of them need to deal with this extremely important field of medicine: pain treatment. I do believe that the answers they may find in Pain Management will make their practice easier. Also, the life of their patients will be considerably more pleasant, or at least more bearable

Paresthesia

Paresthesias are spontaneous or evoked abnormal sensations of tingling, burning, pricking, or numbness of a person's skin with no apparent long-term physical effect. Patients generally describe a lancinating or burning pain, often associated with allodynia and hyperalgesia. The manifestation of paresthesia can be transient or chronic. Transient paresthesia can be a symptom of hyperventilation syndrome or a panic attack, and chronic paresthesia can be a result of poor circulation, nerve irritation, neuropathy, or many other conditions and causes. This book is written by authors that are respected in their countries as well as worldwide. Each chapter is written so that everyone can understand, treat and improve the lives of each patient

Dog electroencephalogram for early safety seizure liability assessments and investigation of species-specific sensitivity for neurological symptoms

Preclinical safety is an important part of drug development in animals and humans. In toxicology studies, seizure liability can be detected at high doses as convulsions. Non-convulsive seizures induce only subtle behavioral changes and their assessment in animals is challenging. Electroencephalography (EEG) is the only method to correlate animal behavior to seizure activity and video-EEG is the current gold-standard for preclinical seizure liability assessments (Authier et al., 2014b). In most cases there are no clear premonitory signs that forewarn of convulsions but epileptiform EEG activity prior to clinical manifestation has been reported during a period potentially sufficient for prophylactic anticonvulsive treatment (Dürmüller et al., 2007). Aim of this thesis was investigation of a study design for assessment of neurological symptoms in dogs. This design should optimize detection of neurological signs while minimizing study duration and animal numbers. Video-EEG was used to increase symptom detection rate and to explore the possibility to refine seizure liability testing by enabling EEG-based anticonvulsive treatment. For establishment of the EEG system in our facility, reference substances were tested first. Then, three in-house drug candidates with different modes of action and known neurological side effects were chosen. Two telemetered beagle dogs were used per experiment. Substance effects on clinical symptoms and on the EEG were investigated. CSF and blood samples for analysis of drug exposure and biomarkers were collected simultaneous to symptoms. Results were compared to previous toxicological studies thereby enabling evaluation of non-rodent species differences in sensitivity for neurological symptoms. Results showed that combination of implants for CSF collection and EEG recording is possible. In this study design, intravenous administration was superior to oral dosing as it led to a reduced variability in exposure levels. Also, experimental time was significantly reduced compared to standard toxicology studies while the same neurological symptoms were induced. This shortened duration enabled continuous clinical observations for a better evaluation of CNS effects and immediate veterinary assistance in the spirit of animal welfare. The EEG was not superior to clinical observations in forewarning of convulsion risk and did not enable convulsion prevention. This was due first to the short latency between onset of abnormal EEG activity and convulsions which was below one minute with in-house compounds. Secondly, accurate interpretation of the unfiltered EEG signal was limited, especially differentiation of artefacts and epileptiform activity. In conclusion, a study design using intravenous infusions is suitable for the characterization of neurological symptoms. All the symptoms, which were already known from studies with a longer duration, were also seen. This allowed better correlation of neurological symptoms to exposure and immediate veterinarian treatments. For substances with a high risk to induce severe neurological symptoms, such studies can guide dose selection for longer regulatory toxicological studies to prevent occurrence of severe neurological symptoms.Im Rahmen der Entwicklung von Human- und Veterinärarzneimitteln wird die Anwendersicherheit neuer Medikamente in präklinischen Sicherheitsstudien erforscht. Zentralnervöse Nebenwirkungen werden häufig erst in toxikologischen Prüfungen erkannt, wenn bei hohen Dosierungen Krampfanfälle bei den Versuchstieren auftreten. Epileptische Anfälle können allerdings auch subtilere Symptome, deren Erkennen in Tieren schwierig ist, verursachen. Die Elektroenzephalographie (EEG) bietet in Tierstudien die einzige Möglichkeit, nicht-konvulsive Anfälle zu diagnostizieren. Daher ist die Kombination von Videoüberwachung und EEG in der präklinischen Arzneimittelentwicklung gegenwärtig der Goldstandard für die Sicherheitsbewertung einer Substanz im Hinblick auf ihr Risiko, Anfälle auszulösen (Authier et al., 2014b). Meist gibt es keine klinischen Warnzeichen vor dem Auftreten von Krampfanfällen. Allerdings wurde das Auftreten epileptiformer EEG-Aktivität vor klinischen Symptomen beobachtet. Das beschriebene Zeitfenster ist potentiell ausreichend für prophylaktische antikonvulsive Behandlung (Dürmüller et al., 2007). Ziel dieser Arbeit war es, in Pilotstudien ein neues Studiendesign für die Charakterisierung neurologischer Nebenwirkungen zu evaluieren. Dieses Studiendesign sollte die Erkennungsrate neurologischer Nebenwirkungen optimieren und dabei gleichzeitig eine Reduktion der dazu nötigen Tiere und der Studiendauer ermöglichen. Der Einsatz von EEG und Videoüberwachung sollte es ermöglichen, Substanz-induzierte Anfälle im Frühstadium zu erkennen und ihr klinisches Auftreten zu verhindern. Um das EEG-System in der Forschungseinrichtung neu zu etablieren und um zu evaluieren, ob Implantate für Liquor-Entnahme und EEG-Aufzeichnung kompatibel sind, wurden zuerst Referenzsubstanzen getestet. Zur Beantwortung der eigentlichen Fragestellung wurden drei Arzneimittelkandidaten mit unterschiedlichen Wirkmechanismen ausgewählt, von denen bekannt war, dass sie neurologische Symptome verursachen. Je Substanztest wurden zwei Hunde mit implantierten EEG-Sendern verwendet. Zwei der Substanzen wurden in eskalierenden intravenösen Dosen verabreicht, die dritte wurde als einzelne orale Dosis gegeben. Effekte der Substanzen auf klinische Symptome und auf das EEG wurden evaluiert. Parallel wurden Blut- und Liquor-Proben zur Bestimmung der Substanzspiegel und potentieller Biomarker genommen. Die Auswahl der Substanzen bot zusätzlich die Möglichkeit, die Empfindlichkeit der beiden regelmäßig in Arzneimittelprüfungen verwendeten Nicht-Nager Spezies Hund und Affe für neurologische Symptome vergleichend zu bewerten. Die Ergebnisse zeigen, dass die Kombination von Implantaten für EEG-Aufzeichnung und CSF-Probennahme möglich ist. Die intravenöse Applikation war der oralen Substanzgabe vorzuziehen, da die Variabilität der Substanz-Plasmaspiegel geringer war. Alle Symptome, die aus früheren toxikologischen Studien mit längerer Dauer bekannt waren, wurden ebenso beobachtet. Durch das Dosierungsschema war ihr Auftreten allerdings auf eine verkürzte Zeitspanne reduziert. Die kurze Studiendauer ermöglichte durchgehende klinische Beobachtung, somit die Erkennung aller Symptome und zeitnahe veterinärmedizinische Behandlungen, was im Sinne des Tierschutzes einen Vorteil darstellt. Für eine frühzeitige Erkennung von Krampfanfällen war das EEG nicht besser geeignet als klinische Beobachtung, da die Interpretation des ungefilterten EEG Signals durch das Auftreten von Artefakten erschwert war. Das Studiendesign, in dem das EEG angewendet wurde, ist zur Charakterisierung neurologischer Nebenwirkungen geeignet, da alle Symptome, die aus Studien mit längerer Dauer bekannt waren, ebenso beobachtet wurden. Durch die verkürzte Dauer wurde ermöglicht, Symptome und Substanzplasmaspiegel zu korrelieren und zeitnahe tierärztliche Behandlungen durchzuführen. Bei Substanzen, die ein hohes Risiko für neurologische Nebenwirkungen haben, kann dieses Studiendesign genutzt werden um im Vorfeld von behördlich geforderten toxikologischen Studien Dosierungen zu bestimmen, bei denen keine schweren neurologischen Nebenwirkungen zu erwarten sind

A BIONIC EYEBLINK: MANAGEMENT OF FACIAL PALSY

This thesis highlights the current gold-standard surgical procedures for the rehabilitation of mimicry in individuals with facial paralysis and explores the potential application of functional electrical stimulation (FES) as a novel treatment restoring the face mimicry. Closed-loop facial pacing represents an innovative solution for prosthetically assisted movements. In particular, blinking is typically symmetrical, enabling healthy eye blink on one side of the face to serve as a trigger to pace assisted blinks on the contralateral side, in case of unilateral peripheral facial palsy. The goals of this research are developing an eyeblink detection system and advancing the understanding of performing surface FES of the facial nerve in order to elicit artificial eyeblinks. The application of a biomimetic device to individuals with acute reversible facial palsy would provide immediate restoration of the periocular function and could be used until either the patient recovers sufficient function to no longer require assistance for eye closure, or the decision is made to proceed with further surgery

Modulation of Noxious Stimuli: Mechanisms Underlying the Human Experience of Pain

The aim of the current study was to explore the effects of sympathetic arousal on a healthy individual’s experience of pain, and how the presence of central sensitization, experimentally induced using electrical conditioning of the forearm, effects this interaction. It was hypothesized that following electrical conditioning, sympathetic arousal would lead to higher subjective ratings of pain and heightened nociceptive reflexes. Furthermore, it was expected this effect would be more pronounced in participants classified as high in pain catastrophizing. To test these hypotheses, the study used a repeated-measures design, comparing ratings of pain and blink reflex data to a nociceptive stimulus at baseline and post-conditioning. On a number of trials, the nociceptive stimulus was presented with concurrent acoustic stimulation, intended to evoke arousal. Results did not support the hypotheses, as electrical conditioning did not lead to an increase in pain or nociceptive reflexes during heightened states of arousal. Catastrophizing was also found not to have a significant result on the outcome. Alternative explanations, and the implications of these findings are discussed, along with suggestions for future research

Enhancing Biomechanical Function through Development and Testing of Assistive Devices for Shoulder Impairment and Total Limb Amputation

Assistive devices serve as a potential for restoring sensorimotor function to impaired individuals. My research focuses on two assistive devices: a passive shoulder exoskeleton and a muscle-driven endoprosthesis (MDE). Previous passive shoulder exoskeletons have focused on testing during static loading conditions in the shoulder. However, activities of daily living are based on dynamic tasks. My research for passive shoulder exoskeletons analyzes the effect that a continuous passive assistance has on shoulder biomechanics. In my research I showed that passive assistance decreases the muscular activation in muscles responsible for positive shoulder exoskeleton. An MDE has the potential to have accurate and precise control of movement as well as restore a sense of proprioception to the user. Such a transformative and invasive device has never previously been tested. Therefore, my research focused on analyzing fundamental principles of the MDE in an in-vivo rabbit model. The two concepts I tested in my research were the feasibility of implanting an orthopedic device underneath the skin at the distal end of a limb following amputation and the locomotor restorative capabilities of an artificial tendon used for muscle-device connection. In my work I proved the feasibility of implanting fully-footed rigid endoprostheses underneath the skin and isolated the primary factors for a successful surgery and recovery. In addition, my research showed that although artificial tendons have the potential to restore locomotor function, proper in-situ tendon lengths must be achieved for optimal movement. This research informed the design and testing of a fully jointed muscle-driven endoprosthesis prototype

Flexor Dysfunction Following Unilateral Transient Ischemic Brain Injury Is Associated with Impaired Locomotor Rhythmicity

Functional motor deficits in hemiplegia after stroke are predominately associated with flexor muscle impairments in animal models of ischemic brain injury, as well as in clinical findings. Rehabilitative interventions often employ various means of retraining a maladapted central pattern generator for locomotion. Yet, holistic modeling of the central pattern generator, as well as applications of such studies, are currently scarce. Most modeling studies rely on cellular neural models of the intrinsic spinal connectivity governing ipsilateral flexor-extensor, as well as contralateral coupling inherent in the spinal cord. Models that attempt to capture the general behavior of motor neuronal populations, as well as the different modes of driving their oscillatory function in vivo is lacking in contemporary literature. This study aims at generating a holistic model of flexor and extensor function as a whole, and seeks to evaluate the parametric coupling of ipsilateral and contralateral half-center coupling through the means of generating an ordinary differential equation representative of asymmetric central pattern generator models of varying coupling architectures. The results of this study suggest that the mathematical predictions of the locomotor centers which drive the dorsiflexion phase of locomotion are correlated with the denervation-type atrophy response of hemiparetic dorsiflexor muscles, as well as their spatiotemporal activity dysfunction during in vivo locomotion on a novel precise foot placement task. Moreover, the hemiplegic solutions were found to lie in proximity to an alternative task-space solution, by which a hemiplegic strategy could be readapted in order to produce healthy output. The results revealed that there are multiple strategies of retraining hemiplegic solutions of the CPG. This solution may modify the hemiparetic locomotor pattern into a healthy output by manipulating inter-integrator couplings which are not damaged by damage to the descending drives. Ultimately, some modeling experiments will demonstrate that the increased reliance on intrinsic connectivity increases the stability of the output, rendering it resistant to perturbations originating from extrinsic inputs to the pattern generating center

A Textbook of Advanced Oral and Maxillofacial Surgery

The scope of OMF surgery has expanded; encompassing treatment of diseases, disorders, defects and injuries of the head, face, jaws and oral cavity. This internationally-recognized specialty is evolving with advancements in technology and instrumentation. Specialists of this discipline treat patients with impacted teeth, facial pain, misaligned jaws, facial trauma, oral cancer, cysts and tumors; they also perform facial cosmetic surgery and place dental implants. The contents of this volume essentially complements the volume 1; with chapters that cover both basic and advanced concepts on complex topics in oral and maxillofacial surgery