Multiple Sclerosis From Bench To Bedside Currents Insights Into Pathophysiological Concepts And Their Potential Impact On Patients

Research and advances in the treatment of Multiple Sclerosis (MS) is a story of growing success. Great progress has been made in identifying the molecular mechanisms that can be utilized to develop highly efficacious treatments for MS patients. Since the middle of the last century, when studies using an inflammatory autoimmune model of MS i.e. experimental autoimmune encephalitis (EAE) were initiated, research on MS has since led to an enormous growth of knowledge. The limitations arising from these animal models have been partially compensated by insights generated from histopathological, immunological, genetic, imaging and clinical studies of MS. The importance of T cells and, recently of B cells, in MS has been elucidated and the significance of CNS resident cells, particularly in the progressive course of MS has been highlighted. The importance of environmental factors and genetic predisposition have also been recognized and the interaction between th e individual and its environment seems to play key roles in the pathogenesis of this disease. However, definite causative agent(s) or single gene(s) involved in MS still remain unidentified. A deeper understanding of the immunological pathways involved goes hand in hand with further improving therapy for MS. Focal inflammation in MS, caused by de novo CNS infiltration, can be prevented effectively using peripherally-acting drugs. However, diffuse CNS intrinsic inflammation and neurodegeneration are not targeted by the current arsenal of therapeutics and patients with progressive disease courses remain difficult to treat. Generating insights into pathophysiological processes and the clinical translation of this knowledge have been a formula of success for treating inflammatory diseases. The future will show whether this will hold true for CNS-trapped inflammation and neurodegeneration and whether the ultimate goal - truly curing MS - will be possible.

Multiple Sclerosis (MS) is one of the main causes of disability in young adult population. The estimated burden of the disease worldwide is about three million people. The pathogenic mechanism of MS involves both auto immune and degenerative processes. These two mechanisms are thought to determine a combination of events leading to several clinical pattern of disease onset and course. Multiple Sclerosis: Bench to Bedside provides the most up-to-date and concise reviews on the critical issues of multiple sclerosis from around the world. This book is written by leaders and experts in the field of multiple sclerosis research and is divided into easy to read sections. Section I focuses on basic science aspects of Multiple Sclerosis, including potential biomarkers, molecular biology, heat shock proteins, oxidative stress, genetic and epigenetics. Section II focuses on clinical and epidemiological aspects of Multiple Sclerosis, including remyelination therapy, neuroplasticity-based technologies and interventions. This is an important reference book and a must-read for Postgraduate Medical Scholars, Basic Science Researchers and Neurologists in Clinical Practice.

Tobacco smoking is a major risk factor for a number of chronic diseases, including a variety of cancers, lung disease and damage to the cardiovascular system. The World Health Organization recently calculated that there were 6 million smoking-attributable deaths per year and that this number is due to rise to about eight million per year by the end of 2030. Recent work has demonstrated that habitual smoking in adults is not only associated with a range of health problems, but may also contribute to a number of neurocognitive deficits, including deficits in memory and attention. One area of growing concern is the health and neurocognitive consequences of exposure to second-hand smoke or “passive smoking” (where a non-smoker inhales another person’s smoke, mainly in the form of side-stream smoke). In terms of tackling smoking-related problems, there has been a rise in the amount and range of smoking cessation and interventions techniques, including the emergence of e-cigarettes as one of the most popular forms of nicotine replacement therapies. The present book comprises a collection of manuscripts discussing (1) the impact of active and passive smoking upon health and neurocognitive function, (2) smoking cessation techniques and interventions used to tackle smoking-related problems, and (3) a critical consideration of current issues surrounding the use of e-cigarettes as nicotine-replacement therapy. This collection of papers includes empirical, theoretical, and review papers. This Research Topic demonstrates the broad nature of research currently being undertaken in this field and should pave the way for future work.

Three distinct types of contractions perform colonic motility functions. Rhythmic phasic contractions (RPCs) cause slow net distal propulsion with extensive mixing/turning over. Infrequently occurring giant migrating contractions (GMCs) produce mass movements. Tonic contractions aid RPCs in their motor function. The spatiotemporal patterns of these contractions differ markedly. The amplitude and distance of propagation of a GMC are several-fold larger than those of an RPC. The enteric neurons and smooth muscle cells are the core regulators of all three types of contractions. The regulation of contractions by these mechanisms is modifiable by extrinsic factors: CNS, autonomic neurons, hormones, inflammatory mediators, and stress mediators. Only the GMCs produce descending inhibition, which accommodates the large bolus being propelled without increasing muscle tone. The strong compression of the colon wall generates afferent signals that are below nociceptive threshold in healthy subjects. However, these signals become nociceptive; if the amplitudes of GMCs increase, afferent nerves become hypersensitive, or descending inhibition is impaired. The GMCs also provide the force for rapid propulsion of feces and descending inhibition to relax the internal anal sphincter during defecation. The dysregulation of GMCs is a major factor in colonic motility disorders: irritable bowel syndrome (IBS), inflammatory bowel disease (IBD), and diverticular disease (DD). Frequent mass movements by GMCs cause diarrhea in diarrhea predominant IBS, IBD, and DD, while a decrease in the frequency of GMCs causes constipation. The GMCs generate the afferent signals for intermittent short-lived episodes of abdominal cramping in these disorders. Epigenetic dysregulation due to adverse events in early life is one of the major factors in generating the symptoms of IBS in adulthood.

World-renowned economist Klaus Schwab, Founder and Executive Chairman of the World Economic Forum, explains that we have an opportunity to shape the fourth industrial revolu­tion, which will fundamentally alter how we live and work. Schwab argues that this revolution is different in scale, scope and complexity from any that have come before. Characterized by a range of new technologies that are fusing the physical, digital and biological worlds, the developments are affecting all disciplines, economies, industries and governments, and even challenging ideas about what it means to be human. Artificial intelligence is already all around us, from supercomputers, drones and virtual assistants to 3D printing, DNA sequencing, smart thermostats, wear­able sensors and microchips smaller than a grain of sand. But this is just the beginning: nanomaterials 200 times stronger than steel and a million times thinner than a strand of hair and the first transplant of a 3D printed liver are already in development. Imagine “smart factories” in which global systems of manu­facturing are coordinated virtually, or implantable mobile phones made of biosynthetic materials. The fourth industrial revolution, says Schwab, is more significant, and its ramifications more profound, than in any prior period of human history. He outlines the key technologies driving this revolution and discusses the major impacts expected on government, business, civil society and individu­als. Schwab also offers bold ideas on how to harness these changes and shape a better future—one in which technology empowers people rather than replaces them; progress serves society rather than disrupts it; and in which innovators respect moral and ethical boundaries rather than cross them. We all have the opportunity to contribute to developing new frame­works that advance progress.

The present book contains the Proceedings of a two day Symposium on Uremic Toxins organized at the University of Ghent in Belgium. A series of guest lectures, free communications and posters have been presented. An international audience of 163 scientists from 16 nationalities listened to and discussed extensively a spectrum of topics brought forward by colleagues and researchers who worked for many years in the field of Uremic Toxins. There is a striking contrast between all the new dialysis strategies available in the work to "clean" the uremic patients and the almost non-progression of our knowledge on uremic toxins in the past decade. In this sense the symposium was felt by all participants as a new start for the research in the biochemical field of the definition of uremia. If the present volume would stimulate new work in this field in order to define uremia, or identify the uremic toxins, the purpose of the organizers would be maximally fulfilled.