scholarly journals Neuropathic Pain in Multiple Sclerosis and Its Animal Models: Focus on Mechanisms, Knowledge Gaps and Future Directions

2021 ◽  
Vol 12 ◽  
Author(s):  
Ersilia Mirabelli ◽  
Stella Elkabes
Keyword(s):  
Multiple Sclerosis ◽  
Neuropathic Pain ◽  
Animal Models ◽  
Current Knowledge ◽  
Therapeutic Interventions ◽  
Future Research ◽  
Knowledge Gaps ◽  
Autoimmune Encephalomyelitis ◽  
Increased Sensitivity ◽  
Disease Stages

Multiple sclerosis (MS) is a multifaceted, complex and chronic neurological disease that leads to motor, sensory and cognitive deficits. MS symptoms are unpredictable and exceedingly variable. Pain is a frequent symptom of MS and manifests as nociceptive or neuropathic pain, even at early disease stages. Neuropathic pain is one of the most debilitating symptoms that reduces quality of life and interferes with daily activities, particularly because conventional pharmacotherapies do not adequately alleviate neuropathic pain. Despite advances, the mechanisms underlying neuropathic pain in MS remain elusive. The majority of the studies investigating the pathophysiology of MS-associated neuropathic pain have been performed in animal models that replicate some of the clinical and neuropathological features of MS. Experimental autoimmune encephalomyelitis (EAE) is one of the best-characterized and most commonly used animal models of MS. As in the case of individuals with MS, rodents affected by EAE manifest increased sensitivity to pain which can be assessed by well-established assays. Investigations on EAE provided valuable insights into the pathophysiology of neuropathic pain. Nevertheless, additional investigations are warranted to better understand the events that lead to the onset and maintenance of neuropathic pain in order to identify targets that can facilitate the development of more effective therapeutic interventions. The goal of the present review is to provide an overview of several mechanisms implicated in neuropathic pain in EAE by summarizing published reports. We discuss current knowledge gaps and future research directions, especially based on information obtained by use of other animal models of neuropathic pain such as nerve injury.

scholarly journals Knowledge Gaps in Understanding the Etiology of Anemia in Indonesian Adolescents

2021 ◽  
Vol 42 (1_suppl) ◽  
pp. S39-S58
Author(s):  
Kesso Gabrielle van Zutphen ◽  
Klaus Kraemer ◽  
Alida Melse-Boonstra
Keyword(s):  
Current Knowledge ◽  
Vitamin A Deficiency ◽  
Public Health Problem ◽  
Population Group ◽  
Future Research ◽  
Folic Acid Deficiency ◽  
Knowledge Gaps ◽  
Local Conditions ◽  
Etiological Factors ◽  
Infection And Inflammation

Background: Anemia is a public health problem among adolescents in Indonesia. Strategies to prevent or treat anemia should be tailored to local conditions, taking into account its specific etiology and prevalence in a given setting and population group. Objective: This review aims to (1) identify and synthesize the current knowledge on the etiology of anemia among adolescents in Indonesia, (2) reveal knowledge gaps in this area, and (3) suggest directions for future research and programmatic work. Methods: We systematically searched PubMed, Web of Science, Scopus, Medline, and WorldCat databases for peer-reviewed journal articles to identify which etiological factors were related to anemia among Indonesian adolescents. Research papers were reviewed and included in the review according to inclusion criteria. Results: Of 13 studies, 8 showed that anemia was associated with iron deficiency; 4 are suggestive of vitamin A deficiency; and 2 of folic acid deficiency. Five studies underscore different etiological determinants for anemia, such as malaria, protein and energy malnutrition, vitamin B2 deficiency, calcium, and vitamin C deficiency. Based on these findings, we developed a framework on knowledge gaps on the etiology of anemia among adolescents in Indonesia, divided in 3 levels of knowledge: (1) significant knowledge gaps, (2) knowledge gaps, and (3) established knowledge. Conclusions: The knowledge gaps around the etiology of anemia among Indonesian adolescents are significant. Our framework emphasizes the need for further research across all etiological factors, namely inadequate nutritional intake and absorption, genetic hemoglobin disorders, infection and inflammation, and menstrual disorders.

scholarly journals Host Genetics and Gut Microbiome: Perspectives for Multiple Sclerosis

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1181
Author(s):  
Alessandro Maglione ◽  
Miriam Zuccalà ◽  
Martina Tosi ◽  
Marinella Clerico ◽  
Simona Rolla
Keyword(s):  
Multiple Sclerosis ◽  
Environmental Factors ◽  
Lupus Erythematosus ◽  
Gut Microbiome ◽  
Complex Disease ◽  
Current Knowledge ◽  
Association Studies ◽  
Future Research ◽  
Genome Wide Association Studies ◽  
Host Genetics

As a complex disease, Multiple Sclerosis (MS)’s etiology is determined by both genetic and environmental factors. In the last decade, the gut microbiome has emerged as an important environmental factor, but its interaction with host genetics is still unknown. In this review, we focus on these dual aspects of MS pathogenesis: we describe the current knowledge on genetic factors related to MS, based on genome-wide association studies, and then illustrate the interactions between the immune system, gut microbiome and central nervous system in MS, summarizing the evidence available from Experimental Autoimmune Encephalomyelitis mouse models and studies in patients. Finally, as the understanding of influence of host genetics on the gut microbiome composition in MS is in its infancy, we explore this issue based on the evidence currently available from other autoimmune diseases that share with MS the interplay of genetic with environmental factors (Inflammatory Bowel Disease, Rheumatoid Arthritis and Systemic Lupus Erythematosus), and discuss avenues for future research.

scholarly journals Role of microRNAs in Venous Thromboembolism

2020 ◽  
Vol 21 (7) ◽  
pp. 2602 ◽  
Author(s):  
Vânia M. Morelli ◽  
Sigrid K. Brækkan ◽  
John-Bjarne Hansen
Keyword(s):  
Venous Thromboembolism ◽  
Animal Models ◽  
Statistical Power ◽  
Current Knowledge ◽  
Thrombus Formation ◽  
Therapeutic Targets ◽  
Small Sample ◽  
Future Research ◽  
Gene Expressions

MicroRNAs (miRNAs) are non-coding RNAs that execute their function by targeted downregulation of gene expressions. There is growing evidence from epidemiological studies and animal models suggesting that the expression level of miRNAs is dysregulated in venous thromboembolism (VTE). In this review, we summarize the current knowledge on the role of miRNAs as biomarkers for VTE and provide general insight into research exploring the modulation of miRNA activity in animal models of venous thrombosis. Up to now, published studies have yielded inconsistent results on the role of miRNAs as biomarkers for VTE with most of the reports focused on diagnostic research. The limited statistical power of the individual studies, due to the small sample sizes, may substantially contribute to the poor reproducibility among studies. In animal models, over-expression or inhibition of some miRNAs appear to influence venous thrombus formation and resolution. However, there is an important gap in knowledge on the potential role of miRNAs as therapeutic targets in VTE. Future research involving large cohorts should be designed to clarify the clinical usefulness of miRNAs as biomarkers for VTE, and animal model studies should be pursued to unravel the role of miRNAs in the pathogenesis of VTE and their potential as therapeutic targets.

scholarly journals MIlitary Combat Mental Health Framework

2020 ◽  
pp. bmjmilitary-2020-001439
Author(s):  
Martin Bricknell
Keyword(s):  
Mental Health ◽  
Military Service ◽  
Current Knowledge ◽  
Armed Forces ◽  
Well Being ◽  
Therapeutic Interventions ◽  
Future Research ◽  
The Subject ◽  
Mental Well Being ◽  
Military Combat

This paper describes a framework for understanding military combat mental health based on the possible mental ill-health consequences of exposure to ‘potential trauma events’ for members of the armed forces and after their military service as veterans. It uses a life course approach that maps an individual’s mental well-being against four ‘states’: fit, reacting, injured and ill. It then considers five categories of factors that influence the risk of mental illness from this exposure based on research evidence; prejoining vulnerability, resilience, precipitating, treatment and recovery. This framework offers a structure to debate current knowledge, inform policy and therapeutic interventions, provide education and to guide future research into the subject.

scholarly journals Enantiomers of Carbohydrates and Their Role in Ecosystem Interactions: A Review

Symmetry ◽  
2020 ◽  
Vol 12 (3) ◽  
pp. 470 ◽  
Author(s):  
Lea Lojkova ◽  
Valerie Vranová ◽  
Pavel Formánek ◽  
Ida Drápelová ◽  
Martin Brtnicky ◽  
...  
Keyword(s):  
Abiotic Stress ◽  
Plant Nutrition ◽  
Current Knowledge ◽  
Genetic Regulation ◽  
Future Research ◽  
Knowledge Gaps ◽  
Research Knowledge ◽  
Critical Knowledge ◽  
Ecosystem Interactions ◽  
Plant Compounds

D- and most L-enantiomers of carbohydrates and carbohydrate-containing compounds occur naturally in plants and other organisms. These enantiomers play many important roles in plants including building up biomass, defense against pathogens, herbivory, abiotic stress, and plant nutrition. Carbohydrate enantiomers are also precursors of many plant compounds that significantly contribute to plant aroma. Microorganisms, insects, and other animals utilize both types of carbohydrate enantiomers, but their biomass and excrements are dominated by D-enantiomers. The aim of this work was to review the current knowledge about carbohydrate enantiomers in ecosystems with respect to both their metabolism in plants and occurrence in soils, and to identify critical knowledge gaps and directions for future research. Knowledge about the significance of D- versus L-enantiomers of carbohydrates in soils is rare. Determining the mechanism of genetic regulation of D- and L-carbohydrate metabolism in plants with respect to pathogen and pest control and ecosystem interactions represent the knowledge gaps and a direction for future research.

Multiple Sclerosis: MRI and Other Imaging Approaches in MS

2017 ◽  
Author(s):  
Martina Absinta ◽  
Daniel S. Reich
Keyword(s):  
Multiple Sclerosis ◽  
Current Knowledge ◽  
Imaging Techniques ◽  
Future Research ◽  
Multiple Time ◽  
Resonance Imaging ◽  
Lesion Development ◽  
Diagnostic Role ◽  
Magnetic Resonance Imaging Mri ◽  
Multiple Time Points

Aside from its paramount diagnostic role, imaging techniques, particularly magnetic resonance imaging (MRI), provide unparalleled insights into multiple sclerosis (MS) by assessing the spatiotemporal dynamics of the associated inflammation and neurodegeneration. This dynamical view, predicated on interrogation of individuals with MS at multiple time points, is impossible with pathology. The chapter approaches MRI in MS from this perspective, describing features related to lesion development and location, as well as assessment of global and regional damage. It summarizes current knowledge, addresses the limitations of that knowledge, and suggests ways in which imaging can advance future research.

scholarly journals Aggressive multiple sclerosis (2): Treatment

2020 ◽  
Vol 26 (9) ◽  
pp. 1045-1063 ◽  
Author(s):  
Georgina Arrambide ◽  
Ellen Iacobaeus ◽  
Maria Pia Amato ◽  
Tobias Derfuss ◽  
Sandra Vukusic ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Current Knowledge ◽  
Companion Paper ◽  
Therapeutic Window ◽  
Future Research ◽  
Permanent Disability ◽  
European Committee ◽  
Efficacious Treatment ◽  
History Of ◽  
Definition Of

The natural history of multiple sclerosis (MS) is highly heterogeneous. A subgroup of patients has what might be termed aggressive MS. These patients may have frequent, severe relapses with incomplete recovery and are at risk of developing greater and permanent disability at the earlier stages of the disease. Their therapeutic window of opportunity may be narrow, and while it is generally considered that they will benefit from starting early with a highly efficacious treatment, a unified definition of aggressive MS does not exist and data on its treatment are largely lacking. Based on discussions at an international focused workshop sponsored by the European Committee for Treatment and Research in Multiple Sclerosis (ECTRIMS), we review our current knowledge about treatment of individuals with aggressive MS. We analyse the available evidence, identify gaps in knowledge and suggest future research needed to fill those gaps. A companion paper details the difficulties in developing a consensus about what defines aggressive MS.

Immunoglobulins Treatment in Multiple Sclerosis and Experimental Autoimmune Encephalomyelitis

2000 ◽  
Vol 6 (2_suppl) ◽  
pp. S6-S8 ◽  
Author(s):  
Anat Achiron ◽  
Shmuel Miron
Keyword(s):  
Multiple Sclerosis ◽  
Experimental Autoimmune Encephalomyelitis ◽  
Mechanisms Of Action ◽  
Treatment Modalities ◽  
Future Research ◽  
Disease Course ◽  
Immunomodulatory Effects ◽  
Duration Of Treatment ◽  
Autoimmune Encephalomyelitis ◽  
Experimental Autoimmune

Intravenously administered immunoglobulins (IgG) treatment has several modes of action that can regulate the immune response during different steps of the inflammatory process in experimental autoimmune encephalomyelitis (EAE) and Multiple Sclerosis (MS). The immunomodulatory effects IgG are largely dependent on their ability to interact with membrane molecules of lymphocytes and monocytes. Better understanding of these mechanisms of action in relation to the pathogenesis of MS, is important in order to decide the time of initiation and the duration of treatment in MS patients. In order to have the best beneficial effect on disease course, future research should focus on the initial events that activate the disease and on the early treatment modalities of IgG in MS.

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