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Towards translating research to clinical practice: Novel Strategies for Discovery and Validation of Biomarkers for Brain Injury

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193912 Year: Pages: 178 DOI: 10.3389/978-2-88919-391-2 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2015-12-03 13:02:24
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Traumatic brain injury (TBI) is a major cause of death and disability and one of the greatest unmet needs in medicine and public health. TBI not only has devastating effects on patients and their relatives but results in huge direct and indirect costs to society. Although guidelines for the management of patients have been developed and more than 200 clinical trials have been conducted, they have resulted in few improvements in clinical outcomes and no effective therapies approved for TBI. It is now apparent that the heterogeneity of clinical TBI is underlain by molecular phenotypes more complex and interactive than initially conceived and current approaches to the characterization, management and outcome prediction of TBI are antiquated, unidimensional and inadequate to capture the interindividual pathophysiological heterogeneity. Recent advances in proteomics and biomarker development provide unparalleled opportunities for unraveling substantial injury-specific and patient-specific variability and refining disease characterization. The identification of novel, sensitive, objective tools, referred to as biomarkers, can revolutionize pathophysiological insights, enable targeted therapies and personalized approaches to clinical management. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. In this Research Topic, we present novel approaches that provide an infrastructure for discovery and validation of new biomarkers of acute brain injury. These techniques include refined mass spectrometry technology and high throughput immunoblot techniques. Output from these approaches can identify potential candidate biomarkers employing systems biology and data mining methods. Finally, suggestions are provided for the way forward, with an emphasis on need for a multidimensional approach that integrate a panel of pathobiologically diverse biomarkers with clinical variables and imaging-based assessments to improve diagnosis and classification of TBI and to develop best clinical practice guidelines.

NEUROTRAUMA: From Emergency Room to Back to Day-by-Day Life

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889457243 Year: Pages: 96 DOI: 10.3389/978-2-88945-724-3 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2019-01-23 14:53:43
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Traumatic brain injury (TBI) is a nondegenerative, noncongenital insult to the brain from an external mechanical force, possibly leading to permanent or temporary impairment of cognitive, physical, and psychosocial functions, with an associated diminished or altered state of consciousness. The definition of TBI has not been consistent and tends to vary according to specialties and circumstances. The term brain injury is often used synonymously with head injury, which may not be associated with neurological deficits. The definition has also been problematic due to variations in inclusion criteria. Both American and Brazilian data indicate that more than 700,000 people suffer TBI annually, with 20% afflicted with moderate or severe TBI. According to this data, 80% of people who suffered mild TBI can return to work, whist only 20% of moderate, and 10% of victims of severe TBI can return to their daily routine. Cognitive rehabilitation, a clinical area encompassing interdisciplinary action aimed at recovery as well as compensation of cognitive functions, altered as a result of cerebral injury, is extremely important for these individuals. The aim of a cognitive and motor rehabilitation program is to recover an individual's ability to process, interpret and respond appropriately to environmental inputs, as well as to create strategies and procedures to compensate for lost functions that are necessary in familial, social, educational and occupational relationships. In general, the cognitive rehabilitation programs tend to focus on specific cognitive domains, such as memory, motor, language and executive functions. By contrast, the focus of compensatory training procedures is generally on making environmental adaptations and changes to provide grater autonomy for patients. Successful cognitive rehabilitation programs are those whose aim is both recovery and compensation based on an integrated and interdisciplinary approach. The purpose of this Research Topic is to review the basic concepts related to TBI, including mechanisms of injury, severity levels of TBI, the most common findings in mild, moderate and severe TBI survivors, and the most cognitive and motor impairments following TBI, and also to discuss the strategies used to handle patients post-TBI. Within this context, the importance of an interdisciplinary rehabilitation for TBI is underlined.

The Political Economy of Workplace Injury in Canada

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Book Series: Fabriks: Studies in the Working Class ISSN: 19256485 ISBN: 9781926836003 9781926836010 Year: Pages: 284 Language: English
Publisher: Athabasca University Press
Added to DOAB on : 2012-03-29 16:37:58
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Workplace injuries are common, avoidable, and unacceptable. The Political Economy of Workplace Injury in Canada reveals how employers and governments engage in ineffective injury prevention efforts, intervening only when necessary to maintain the standard legitimacy. Dr. Bob Barnetson sheds light on this faulty system, highlighting the way in which employers create dangerous work environments yet pour billions of dollars into compensation and treatment. Examining this dynamic clarifies the way in which production costs are passed on to workers in the form of workplace injuries.

Child Injury Prevention

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ISBN: 9783906980485 9783906980492 Year: Pages: 156 DOI: 10.3390/books978-3-906980-49-2 Language: English
Publisher: MDPI - Multidisciplinary Digital Publishing Institute
Added to DOAB on : 2015-01-12 11:21:17
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Injuries are among the leading causes of child morbidity and mortality worldwide [1]. Because injuries typically are incurred by healthy children engaging in daily activities, they can be particularly devastating to the injured child and his or her family, disrupting otherwise mentally and physically healthy lives with tragic short- and long-term consequences. Despite the implication of the lay term “accident”, injuries are preventable. The global community of scholars and practitioners is slowly creating, discovering, and implementing programs to reduce the burden of injury on the world’s youth. This volume contributes to those objectives. [1...]

Karolinska Institutet 200-Year Anniversary Symposium on Injuries to the Spinal Cord and Peripheral Nervous System - An Update on Recent Advances in Regenerative Neuroscience

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889453245 Year: Pages: 74 DOI: 10.3389/978-2-88945-324-5 Language: English
Publisher: Frontiers Media SA
Subject: Medicine (General) --- Neurology
Added to DOAB on : 2018-02-27 16:16:45
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The present E-book consists of original articles and reviews published in our Research Topic on injuries to the spinal cord and peripheral nerves and presents a wide array of novel findings and in depth discussions on topics within the field of nerve injury and repair. Our aim with this Research Topic is to bring together knowledge spanning from basic laboratory studies to clinical findings and strategies within the field of spinal cord and nerve injury and repair. We hope this publication will provide a basis for accelerated knowledge exchange within the field and hopefully a subsequent increase in research efforts and collaborations.

Traumatic Brain Injury as a Systems Neuroscience Problem

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889450985 Year: Pages: 167 DOI: 10.3389/978-2-88945-098-5 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2017-07-06 13:27:36
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Traumatic brain injury (TBI) is traditionally viewed as an anatomic and neuropathological condition. Caring for TBI patients is a matter of defining the extent of an anatomical lesion, managing this lesion, and minimizing secondary brain injury. On the research side, the effects of TBI often are studied in the context of neuronal and axonal degeneration and the subsequent deposition of abnormal proteins such as tau. These approaches form the basis of our current understanding of TBI, but they pay less attention to the function of the affected organ, the brain. Much can be learned about TBI by studying this disorder on a systems neuroscience level and correlating changes in neural circuitry with neurological and cognitive function. There are several aspects of TBI that are a natural fit for this perspective, including post-traumatic epilepsy, consciousness, and cognitive sequelae. How individual neurons contribute to network activity and how network function responds to injury are key concepts in examining these areas. In recent years, the available tools for studying the role of neuronal assemblies in TBI have become increasingly sophisticated, ranging from optogenetic and electrophysiological techniques to advanced imaging modalities such as functional magnetic resonance imaging and magnetoencephalography. Further progress in understanding the disruption and subsequent reshaping of networks is likely to have substantial benefits in the treatment of patients with TBI-associated deficits. In this Frontiers Topic, we intend to highlight the systems neuroscience approach to studying TBI. In addition to analyzing the clinical sequelae of TBI in this context, this series of articles explores the pathophysiological mechanisms underlying network dysfunction, including alterations in synaptic activity, changes in neural oscillation patterns, and disruptions in functional connectivity. We also include articles on treatment options for TBI patients that modulate network function. It is our hope that this Frontiers Topic will increase the clinical and scientific communities’ awareness of this viable framework for deepening our knowledge of TBI and improving patient outcomes.

Interaction of BCI with the underlying neurological conditions in patients: pros and cons

Authors: --- --- --- --- et al.
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889194896 Year: Pages: 129 DOI: 10.3389/978-2-88919-489-6 Language: English
Publisher: Frontiers Media SA
Subject: Neurology --- Science (General)
Added to DOAB on : 2015-11-16 15:44:59
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The primary purpose of Brain Computer Interface (BCI) systems is to help patients communicate with their environment or to aid in their recovery. A common denominator for all BCI patient groups is that they suffer from a neurological deficit. As a consequence, BCI systems in clinical and research settings operate with control signals (brain waves) that could be substantially altered compared to brain waves of able-bodied individuals. Most BCI systems are built and tested on able-bodied individuals, being insufficiently robust for clinical applications. The main reason for this is a lack of systematic analysis on how different neurological problems affect the BCI performance. Neurological problems interfering with BCI performance are either a direct cause of a disability (e.g. stroke, autism, epilepsy ) or secondary consequences of a disability, often overlooked in design of BCI systems (chronic pain, spasticity and antispastic drugs, loss of cognitive functions, drowsiness, medications which are increasing/decreasing brain activity in certain frequency range) . While some of these deficits may decrease the performance of a BCI, others may potentially improve its performance compared to BCI tested on a healthy population (e.g. overactivation of motor cortex in patients with Central neuropathic pain (CNP), increased alpha activity in some patient groups). Depending on the neurological condition, a prolonged modulation of brain waves through BCI might produce both positive or detrimental effects. Thus some BCI protocols might be more suitable for a short term use (e.g. rehabilitation of movement) while the others would be more suitable for a long term use. Prolonged self-regulation of brain oscillation through BCI could potentially be used as a treatment for aberrant brain connections for conditions ranging from motor deficits to Autism Spectrum Disorders (ASD). Currently, ASD is an increasingly prevalent condition in the U.S. with core deficits in imitation learning, language, empathy, theory of mind, and self-awareness. Understanding its neuroetiology is not only critical and necessary but should provide relevant insights into the relationship between neuroanatomy, physiology and behaviour. In this Research Topic we welcome studies of the highest scientific quality highlighting how BCI systems based on different principles (SSVEP, P300, slow cortical potential, auditory potential, operant conditioning, etc) interact with the underlying neurological problems and how performance of these BCI system differ compared to similar systems tested on healthy individuals. We also welcome studies defining signatures of neurological disorders and proposing BCI based treatments. We expect to generate a body of knowledge valuable both to researchers working with clinical populations, but also to a vast majority of BCI researchers testing new algorithms on able-bodied people. This should lead towards more robust or tailor-made BCI protocols, facilitating translation of research from laboratories to the end users.

Plasticity of primary afferent neurons and sensory processing after spinal cord injury

Authors: --- ---
Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889193967 Year: Pages: 221 DOI: 10.3389/978-2-88919-396-7 Language: English
Publisher: Frontiers Media SA
Subject: Science (General) --- Physiology
Added to DOAB on : 2015-12-03 13:02:24
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Traumatic injury of the spinal cord affects the entire organism directly and indirectly. Primary injury destroys neurons and severs axons which participate in neural circuits. Secondary injuries and pathologies arise from numerous sources including systemic inflammation, consequential damage of cutaneous, muscular, and visceral tissues, and dysregulation of autonomic, endocrine and sensory- motor functions. Evidence is mounting that spinal cord injury (SCI) affects regions of the nervous system spatially remote from the injury site, as well as peripheral tissues, and alters some basic characteristics of primary afferent cell biology and physiology (cell number, size/frequency, electrophysiology, other). The degree of afferent input and processing above the lesion is generally intact, while that in the peri-lesion area is highly variable, though pathologies emerge in both regions, including a variety of pain syndromes. Primary afferent input to spinal regions below the injury and the processing of this information becomes even more important in the face of complete or partial loss of descending input because such spared sensory processing can lead to both adaptive and pathological outcomes. This issue hosts review and research articles considering mechanisms of plasticity of primary afferent neurons and sensory processing after SCI, and how such plasticity contributes to sparing and/or recovery of functions, as well as exacerbation of existing and/or emergent pathologies. A critical issue for the majority of the SCI community is chronic above-, peri-, and below-level neuropathic pain, much of which may arise, at least in part, from plasticity of afferent fibers and nociceptive circuitry. For example, autonomic dysreflexia is common hypertensive syndrome that often develops after SCI that is highly reliant on maladaptive nociceptive sensory input and processing below the lesion. Moreover, the loss of descending input leaves the reflexive components of bladder/bowel/sexual function uncoordinated and susceptible to a variety of effects through afferent fiber plasticity. Finally, proper afferent feedback is vital for the effectiveness of activity-dependent rehabilitative therapies, but aberrant nociceptive input may interfere with these approaches since they are often unchecked due to loss of descending modulation.

Brain-immune interactions in health and disease

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195145 Year: Pages: 109 DOI: 10.3389/978-2-88919-514-5 Language: English
Publisher: Frontiers Media SA
Subject: Internal medicine --- Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2015-12-10 11:59:06
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Brain-immune interactions are essential to maintain health and their dysfunction contributes to diverse human diseases. Recent data show that haematopoietic processes and immune organs are under central autonomic control. Deficient regulation of inflammatory events contributes to brain diseases, whereas acute or chronic brain injury is linked with the development of systemic inflammatory conditions or immunosuppression. At present, common disorders with high socio-economic burden such as cancer, cardiovascular-, neuroinflammatory- and neurodegenerative diseases, asthma, allergies, autism, psychiatric conditions and sepsis are believed to be influenced, at least in part, by the dysfunction of brain-immune communication. Since the median age of the world's population is increasing rapidly, it is expected that the burden of common non-communicable diseases will further increase, which represents a huge challenge to the health care systems worldwide. Thus, there is an increasing demand to understand and treat complex diseases, many of which are age-related, and this is not possible unless the fine-tuned communication between large systems -such as the nervous and the immune system- is comprehensively understood. Although it is impossible to cover all areas of relevant research in this field, papers in this eBook give some insight to a few important aspects of brain-immune interactions and their contribution to disease. We hope that this collection could stimulate further relevant research and facilitate discussions to support the understanding of the highly complex interactions between the immune system and the brain in health and disease.

Glycolysis at 75: Is it time to tweak the first elucidated metabolic pathway in history?

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Book Series: Frontiers Research Topics ISSN: 16648714 ISBN: 9782889195862 Year: Pages: 126 DOI: 10.3389/978-2-88919-586-2 Language: English
Publisher: Frontiers Media SA
Subject: Nutrition and Food Sciences --- Medicine (General) --- Neurology --- Science (General)
Added to DOAB on : 2016-03-10 08:14:32
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Glycolysis, the pathway of enzymatic reactions responsible for the breakdown of glucose into two trioses and further into pyruvate or lactate, was elucidated in 1940. For more than seven decades, it has been taught precisely the way its sequence was proposed by Embden, Meyerhof and Parnas. Accordingly, two outcomes of this pathway were proposed, an aerobic glycolysis, with pyruvate as its final product, and an anaerobic glycolysis, identical to the aerobic one, except for an additional reaction, where pyruvate is reduced to lactate. Several studies in the 1980s have shown that both muscle and brain tissues can oxidize and utilize lactate as an energy substrate, challenging this monocarboxylate’s reputation as a useless end-product of anaerobic glycolysis. These findings were met with great skepticism about the idea that lactate could be playing a role in bioenergetics. In the past quarter of a century monocarboxylate transporters (MCTs) were identified and localized in both cellular and mitochondrial membranes. A lactate receptor has been identified. Direct and indirect evidence now indicate that the enzyme lactate dehydrogenase (LDH) resides not only in the cytosol, as part of the glycolytic pathway machinery, but also in the mitochondrial outer membrane. The mitochondrial form of the enzyme oxidizes lactate to pyruvate and concomitantly produces the reducing agent NADH. These findings have shed light on a major drawback of the originally proposed aerobic version of the glycolytic pathway i.e., its inability to regenerate NAD+, as opposed to anaerobic glycolysis that features the cyclical ability of regenerating NAD+ upon pyruvate reduction to lactate by the cytosolic form of LDH. The malate-aspartate shuttle (MAS), a major redox shuttle in the brain, was proposed as an alternative pathway for NAD+ generation for aerobic glycolysis. Nonetheless, would MAS really be necessary for that function if glycolysis always proceeds to the end-products, lactate and NAD+? An additional dilemma the originally proposed aerobic glycolysis presents has to do with the glycolytic pathway of erythrocytes, which despite its highly aerobic environment, always produces lactate as its end-product. It is time to reexamine the original, dogmatic separation of glycolysis into two distinct pathways and put to test the hypothesis of a unified, singular pathway, the end-product of which is lactate, the real substrate of the mitochondrial TCA cycle.

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