scholarly journals Leptin and Associated Mediators of Immunometabolic Signaling: Novel Molecular Outcome Measures for Neurostimulation to Treat Chronic Pain

2019 ◽  
Vol 20 (19) ◽  
pp. 4737 ◽  
Author(s):  
Thomas Kinfe ◽  
Michael Buchfelder ◽  
Shafqat Chaudhry ◽  
Krishnan Chakravarthy ◽  
Timothy Deer ◽  
...  
Keyword(s):  
Chronic Pain ◽  
Large Scale ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Clinical Value ◽  
Failed Back Surgery ◽  
Electrical Neuromodulation ◽  
Chronic Pain Conditions ◽  
Cellular Components

Chronic pain is a devastating condition affecting the physical, psychological, and socioeconomic status of the patient. Inflammation and immunometabolism play roles in the pathophysiology of chronic pain disorders. Electrical neuromodulation approaches have shown a meaningful success in otherwise drug-resistant chronic pain conditions, including failed back surgery, neuropathic pain, and migraine. A literature review (PubMed, MEDLINE/OVID, SCOPUS, and manual searches of the bibliographies of known primary and review articles) was performed using the following search terms: chronic pain disorders, systemic inflammation, immunometabolism, prediction, biomarkers, metabolic disorders, and neuromodulation for chronic pain. Experimental studies indicate a relationship between the development and maintenance of chronic pain conditions and a deteriorated immunometabolic state mediated by circulating cytokines, chemokines, and cellular components. A few uncontrolled in-human studies found increased levels of pro-inflammatory cytokines known to drive metabolic disorders in chronic pain patients undergoing neurostimulation therapies. In this narrative review, we summarize the current knowledge and possible relationships of available neurostimulation therapies for chronic pain with mediators of central and peripheral neuroinflammation and immunometabolism on a molecular level. However, to address the needs for predictive factors and biomarkers, large-scale databank driven clinical trials are needed to determine the clinical value of molecular profiling.

scholarly journals Modelling the Effects of Boundary Walls on the Fire Dynamics of Informal Settlement Dwellings

2021 ◽  
Author(s):  
M. Beshir ◽  
M. Mohamed ◽  
S. Welch ◽  
D. Rush
Keyword(s):  
Boundary Conditions ◽  
Large Scale ◽  
Current Knowledge ◽  
Informal Settlement ◽  
Experimental Studies ◽  
Empirical Correlation ◽  
Combustion Model ◽  
Fire Tests ◽  
Fire Dynamics ◽  
Wall Boundary Conditions

AbstractCharacterising the risk of the fire spread in informal settlements relies on the ability to understand compartment fires with boundary conditions that are significantly different to normal residential compartments. Informal settlement dwellings frequently have thermally thin and leaky boundaries. Due to the unique design of these compartments, detailed experimental studies were conducted to understand their fire dynamics. This paper presents the ability of FDS to model these under-ventilated steel sheeted fire tests. Four compartment fire tests were modelled with different wall boundary conditions, namely sealed walls (no leakage), non-sealed walls (leaky), leaky walls with cardboard lining, and highly insulated walls; with wood cribs as fuel and ISO-9705 room dimensions. FDS managed to capture the main fire dynamics and trends both qualitatively and quantitatively. However, using a cell size of 6 cm, the ability of FDS to accurately model the combustion at locations with high turbulent flows (using the infinitely fast chemistry mixing controlled combustion model), and the effect of leakage, was relatively poor and both factors should be further studied with finer LES filter width. Using the validated FDS models, new flashover criteria for thermally thin compartments were defined as a combination of critical hot gas layer and wall temperatures. Additionally, a parametric study was conducted to propose an empirical correlation to estimate the onset Heat Release Rate required for flashover, as current knowledge fails to account properly for large scale compartments with thermally thin boundaries. The empirical correlation is demonstrated to have an accuracy of ≈ ± 10% compared with the FDS models.

scholarly journals Clinical Value of Complex Echocardiographic Left Ventricular Hypertrophy Classification Based on Concentricity, Mass, and Volume Quantification

2021 ◽  
Vol 8 ◽  
Author(s):  
Andrea Barbieri ◽  
Alessandro Albini ◽  
Anna Maisano ◽  
Gerardo De Mitri ◽  
Giovanni Camaioni ◽  
...  
Keyword(s):  
Left Ventricular Hypertrophy ◽  
Large Scale ◽  
Ventricular Hypertrophy ◽  
Current Knowledge ◽  
Left Ventricular ◽  
Alternative Methods ◽  
Clinical Value ◽  
Prognostic Information ◽  
Lv Mass ◽  
Wide Range

Echocardiography is the most validated, non-invasive and used approach to assess left ventricular hypertrophy (LVH). Alternative methods, specifically magnetic resonance imaging, provide high cost and practical challenges in large scale clinical application. To include a wide range of physiological and pathological conditions, LVH should be considered in conjunction with the LV remodeling assessment. The universally known 2-group classification of LVH only considers the estimation of LV mass and relative wall thickness (RWT) to be classifying variables. However, knowledge of the 2-group patterns provides particularly limited incremental prognostic information beyond LVH. Conversely, LV enlargement conveys independent prognostic utility beyond LV mass for incident heart failure. Therefore, a 4-group LVH subdivision based on LV mass, LV volume, and RWT has been recently suggested. This novel LVH classification is characterized by distinct differences in cardiac function, allowing clinicians to distinguish between different LV hemodynamic stress adaptations in various cardiovascular diseases. The new 4-group LVH classification has the advantage of optimizing the LVH diagnostic approach and the potential to improve the identification of maladaptive responses that warrant targeted therapy. In this review, we summarize the current knowledge on clinical value of this refinement of the LVH classification, emphasizing the role of echocardiography in applying contemporary proposed indexation methods and partition values.

scholarly journals Potential for endocannabinoid system modulation in ocular pain and inflammation: filling the gaps in current pharmacological options

2018 ◽  
Vol 2 (4) ◽  
Author(s):  
J. Daniel Lafreniere ◽  
Melanie E.M. Kelly
Keyword(s):  
Chronic Pain ◽  
Current Knowledge ◽  
Endocannabinoid System ◽  
Ocular Pain ◽  
Physiological Basis ◽  
Future Directions ◽  
Anti Inflammatory ◽  
Neuroprotective Actions ◽  
Chronic Pain Conditions ◽  
Ocular Safety

Challenges in the management of ocular pain are an underappreciated topic. Currently available therapeutics lack both efficacy and clear guidelines for their use, with many also possessing unacceptable side effects. Promising novel agents would offer analgesic, anti-inflammatory, and possibly neuroprotective actions; have favorable ocular safety profiles; and show potential in managing neuropathic pain. Growing evidence supports a link between the endocannabinoid system (ECS) and a range of physiological and disease processes, notably those involving inflammation and pain. Both preclinical and clinical data suggest analgesic and anti-inflammatory actions of cannabinoids and ECS-modifying drugs in chronic pain conditions, including those of neuropathic origin. This review will examine existing evidence for the anatomical and physiological basis of ocular pain, specifically, ocular surface disease and the development of chronic ocular pain. The mechanism of action, efficacy, and limitations of currently available treatments will be discussed, and current knowledge related to ECS-modulation of ocular pain and inflammatory disease will be summarized. A perspective will be provided on the future directions of ECS research in terms of developing cannabinoid therapeutics for ocular pain.

Extracellular Proteins as Enterobacterial Thermometers

2003 ◽  
Vol 86 (1-2) ◽  
pp. 139-156 ◽  
Author(s):  
Robin J. Rowbury
Keyword(s):  
Thermal Stress ◽  
Heat Shock ◽  
Stress Responses ◽  
Direct Evidence ◽  
Experimental Studies ◽  
Extracellular Proteins ◽  
Temperature Changes ◽  
Induction Components ◽  
Cellular Components ◽  
Thermal Stimuli

Biological thermometers are cellular components or structures which sense increasing temperatures, interaction of the thermometer and the thermal stress bringing about the switching-on of inducible responses, with gradually enhanced levels of response induction following gradually increasing temperatures. In enterobacteria, for studies of such thermometers, generally induction of heat shock protein (HSP) synthesis has been examined, with experimental studies aiming to establish (often indirectly) how the temperature changes which initiate HSP synthesis are sensed; numerous other processes and responses show graded induction as temperature is increased, and how the temperature changes which induce these are sensed is also of interest. Several classes of intracellular component and structure have been proposed as enterobacterial thermometers, with the ribosome and the DnaK chaperone being the most favoured, although for many of the proposed intracellular thermometers, most of the evidence for their functioning in this way is indirect. In contrast to the above, the studies reviewed here firmly establish that for four distinct stress responses, which are switched-on gradually as temperature increases, temperature changes are sensed by extracellular components (extracellular sensing components, ESCs) i.e. there is firm and direct evidence for the occurrence of extracellular thermometers. All four thermometers described here are proteins, which appear to be distinct and different from each other, and on sensing thermal stress are activated by it to four distinct extracellular induction components (EICs), which interact with receptors on the surface of organisms to induce the appropriate responses. It is predicted that many other temperature-induced processes, including the synthesis of HSPs, will be switched-on following the activation of similar extracellular thermometers by thermal stimuli.

Amruthapala (Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter): A Comprehensive Review on Diversity, Therapeutic Uses, and Valorization of Bioactive Constituents

2019 ◽  
Vol 20 (5) ◽  
pp. 376-389 ◽  
Author(s):  
Sonali Mishra ◽  
Nupur Srivastava ◽  
Velusamy Sundaresan ◽  
Karuna Shanker
Keyword(s):  
Secondary Metabolite ◽  
Current Knowledge ◽  
Experimental Studies ◽  
Critical Discussion ◽  
Future Research ◽  
Bioactive Constituents ◽  
Medicinal Uses ◽  
Comprehensive Review ◽  
Therapeutic Uses ◽  
Decalepis Arayalpathra

Background: Decalepis arayalpathra (J. Joseph and V. Chandras.) Venter is used primarily for nutrition besides its therapeutic values. Traditional preparations/formulations from its tuber are used as a vitalizer and blood purifier drink. The folklore medicinal uses cover inflammation, cough, wound healing, antipyretic, and digestive system management. A comprehensive review of the current understanding of the plant is required due to emerging concerns over its safety and efficacy. Objective: The systematic collection of the authentic information from different sources with the critical discussion is summarised in order to address various issues related to botanical identity, therapeutic medicine, nutritional usage, phytochemical, and pharmacological potentials of the D. arayalpathra. Current use of traditional systems of medicine can be used to expand future research opportunities. Materials and Methods: Available scripted information was collected manually, from peered review research papers and international databases viz. Science Direct, Google Scholar, SciFinder, Scopus, etc. The unpublished resources which were not available in database were collected through the classical books of ‘Ayurveda’ and ‘Siddha’ published in regional languages. The information from books, Ph.D. and MSc dissertations, conference papers and government reports were also collected. We thoroughly screened the scripted information of classical books, titles, abstracts, reports, and full-texts of the journals to establish the reliability of the content. Results: Tuber bearing vanilla like signature flavor is due to the presence of 2-hydroxy-4-methoxybenzaldehyde (HMB). Among five other species, Decalepis arayalpathra (DA) has come under the ‘critically endangered’ category, due to over-exploitation for traditional, therapeutic and cool drink use. The experimental studies proved that it possesses gastro-protective, anti-tumor, and antiinflammatory activities. Some efforts were also made to develop better therapeutics by logical modifications in 2-Hydroxy-4-methoxy-benzaldehyde, which is a major secondary metabolite of D. arayalpathra. ‘Amruthapala’ offers the enormous opportunity to develop herbal drink with health benefits like gastro-protective, anti-oxidant and anti-inflammatory actions. Results: The plant has the potential to generate the investigational new lead (IND) based on its major secondary metabolite i.e. 2-Hydroxy-4-methoxy-benzaldehyde. The present mini-review summarizes the current knowledge on Decalepis arayalpathra, covering its phytochemical diversity, biological potentials, strategies for its conservation, and intellectual property rights (IPR) status. Chemical Compounds: 2-hydroxy-4-methoxybenzaldehyde (Pubchem CID: 69600), α-amyrin acetate (Pubchem CID: 293754), Magnificol (Pubchem CID: 44575983), β-sitosterol (Pubchem CID: 222284), 3-hydroxy-p-anisaldehyde (Pubchem CID: 12127), Naringenin (Pubchem CID: 932), Kaempferol (Pubchem CID: 5280863), Aromadendrin (Pubchem CID: 122850), 3-methoxy-1,2-cyclopentanedione (Pubchem CID: 61209), p-anisaldehyde (Pubchem CID: 31244), Menthyl acetate (Pubchem CID: 27867), Benzaldehyde (Pubchem CID: 240), p-cymene (Pubchem CID: 7463), Salicylaldehyde (Pubchem CID: 6998), 10-epi-γ-eudesmol (Pubchem CID: 6430754), α -amyrin (Pubchem CID: 225688), 3-hydroxy-4-methoxy benzaldehyde (Pubchem CID: 12127).

Retrospective analysis on the effect of spinal cord stimulation on opioid consumption

2020 ◽  
Author(s):  
Awinita Barpujari ◽  
Michael A Erdek
Keyword(s):  
Spinal Cord ◽  
Chronic Pain ◽  
Retrospective Analysis ◽  
Spinal Cord Stimulation ◽  
Alternative Therapy ◽  
Opioid Consumption ◽  
Opioid Use ◽  
Number Of Patients ◽  
Chronic Pain Conditions ◽  
Post Trial

Aim: Spinal cord stimulation (SCS) is used to clinically manage and/or treat several chronic pain etiologies. A limited amount is known about the influence on patients' use of opioid pain medication. This retrospective analysis evaluated SCS effect on opioid consumption in patients presenting with chronic pain conditions. Materials & methods: Sixty-seven patients underwent a temporary trial device, permanent implant or both. Patients were divided for assessment based on the nature of their procedure(s). Primary outcome was change in morphine equivalent dose (MED), ascertained from preoperative and postoperative medication reports. Results: Postoperative MED was significantly lower in patients who received some form of neuromodulation therapy. Pretrial patients reported an average MED of 41.01 ± 10.23 mg per day while post-trial patients reported an average of 13.30 ± 5.34 mg per day (p < 0.001). Pre-implant patients reported an average MED of 39.14 ± 13.52 mg per day while post-implant patients reported an average MED of 20.23 ± 9.01 mg per day (p < 0.001). There were no significant differences between pre-trial and pre-implant MED, nor between post-trial and post-implant MED. Of the 42 study subjects who reported some amount of pre-intervention opioid use, 78.57% indicated a lower MED (n = 33; p < 0.001), 16.67% indicated no change (n = 7) and 4.76% (n = 2) indicated a higher MED, following intervention. Moreover, SCS therapy resulted in a 26.83% reduction (p < 0.001) in the number of patients with MED >50 mg per day. Conclusion: Spinal cord stimulation may reduce opioid use when implemented appropriately. Neuromodulation may represent alternative therapy for alleviating chronic pain which may avoid a number of deleterious side effects commonly associated with opioid consumption.

scholarly journals Leisure Time Sports Activities and Life Satisfaction: Deeper Insights Based on a Representative Survey from Germany

2020 ◽  
Author(s):  
Michael Mutz ◽  
Anne K. Reimers ◽  
Yolanda Demetriou
Keyword(s):  
Life Satisfaction ◽  
Large Scale ◽  
Leisure Time ◽  
Organizational Context ◽  
Experimental Studies ◽  
Well Being ◽  
Activity Level ◽  
Leisure Satisfaction ◽  
General Life Satisfaction ◽  
Sports Activities

Abstract Observational and experimental studies show that leisure time sporting activity (LTSA) is associated with higher well-being. However, scholars often seem to assume that 1) LTSA fosters “general” life satisfaction, thereby ignoring effects on domain satisfaction; 2) the effect of LTSA on well-being is linear and independent of a person’s general activity level; 3) the amount of LTSA is more important than the repertoire of LTSA, i.e. the number of different activities; 4) all kinds of LTSA are equal in their effects, irrespective of spatial and organisational context conditions. Using data from the German SALLSA-Study (“Sport, Active Lifestyle and Life Satisfaction”), a large-scale CAWI-Survey (N = 1008) representing the population ≥ 14 years, the paper takes a closer look on these assumptions. Findings demonstrate that LTSA is associated with general life satisfaction and domain-specific satisfaction (concerning relationships, appearance, leisure, work and health), but that the relationship is most pronounced for leisure satisfaction. Associations of sport with life satisfaction, leisure satisfaction and subjective health are non-linear, approaching an injection point from which on additional LTSA is no longer beneficial. Moreover, findings lend support to the notion that diversity in LTSA matters, as individuals with higher variation in sports activities are more satisfied. Finally, results with regard to spatial and organizational context suggest that outdoor sports and club-organized sports have additional benefits.

scholarly journals Immune Actions on the Peripheral Nervous System in Pain

2021 ◽  
Vol 22 (3) ◽  
pp. 1448
Author(s):  
Jessica Aijia Liu ◽  
Jing Yu ◽  
Chi Wai Cheung
Keyword(s):  
Chronic Pain ◽  
Nervous System ◽  
Peripheral Nervous System ◽  
Immune Cells ◽  
Molecular Mechanisms ◽  
Process Integration ◽  
Current Knowledge ◽  
Therapeutic Strategies ◽  
Lipid Mediators ◽  
Cellular Changes

Pain can be induced by tissue injuries, diseases and infections. The interactions between the peripheral nervous system (PNS) and immune system are primary actions in pain sensitizations. In response to stimuli, nociceptors release various mediators from their terminals that potently activate and recruit immune cells, whereas infiltrated immune cells further promote sensitization of nociceptors and the transition from acute to chronic pain by producing cytokines, chemokines, lipid mediators and growth factors. Immune cells not only play roles in pain production but also contribute to PNS repair and pain resolution by secreting anti-inflammatory or analgesic effectors. Here, we discuss the distinct roles of four major types of immune cells (monocyte/macrophage, neutrophil, mast cell, and T cell) acting on the PNS during pain process. Integration of this current knowledge will enhance our understanding of cellular changes and molecular mechanisms underlying pain pathogenies, providing insights for developing new therapeutic strategies.

scholarly journals The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

2021 ◽  
Vol 22 (7) ◽  
pp. 3566
Author(s):  
Chae Bin Lee ◽  
Soon Uk Chae ◽  
Seong Jun Jo ◽  
Ui Min Jerng ◽  
Soo Kyung Bae
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Metabolism ◽  
Gut Microbiome ◽  
Metabolic Disorders ◽  
Current Knowledge ◽  
Potential Target ◽  
The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

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