Abstract
Background
Fibromyalgia is a form of chronic widespread pain that is defined as a syndrome of chronic symptoms of moderate to severe intensity, including diffuse pain, fatigue, sleep ...disturbance, cognitive impairment, and numerous somatic complaints. To date, there is no specific drug treatment for fibromyalgia but only symptomatic treatments. A drug free solution based on a wristband that emits millimeter waves associated with a therapeutic coaching program was developed. The application of millimeter waves on an innervated area has been described to have a neuromodulating effect, due to endorphin release stimulation and parasympathetic activation. Coaching is carried out to improve the patient’s adherence and to increase compliance and effectiveness of the treatment. Regular use of this solution by fibromyalgia patients is expected to improve sleep quality, reduce anxiety and pain levels, and, at the end, increase the quality of life.
Methods
This trial is performed over 8 French inclusion centers for a total of 170 patients. The effectiveness of the solution is evaluated according to the primary objective, the improvement of the quality of life measured through the dedicated Fibromyalgia Impact Questionnaire after 3 months. Patients are randomized in two groups, Immediate or Delayed. The Immediate group has access to the solution just after randomization in addition to standard care, while Delayed has access to the standard of care and waits for 3 months to have the solution. The purpose of this methodology is to limit deception bias and facilitate inclusion. The solution consists in using the device for three sessions of 30 min per day and four coaching sessions spread over the first 2 months of wristband usage.
Discussion
The objective is to confirm the effect of the integrative approach based on endorphin stimulation and a therapeutic coaching program in nociplastic pain and specifically for the patient suffering from fibromyalgia. If the effectiveness of the solution is demonstrated, we will be able to respond to the demand of fibromyalgia patients for access to an effective non-medicinal treatment to improve their quality of life.
Trial registration
ClinicalTrials.gov
NCT05058092
Vaccinia virus (VACV) was used as a surrogate of Variola virus (genus
Orthopoxvirus), the causative agent of smallpox, to study orthopoxvirus infection
via the respiratory airway. Lung surfactant, a ...physiological barrier to infection encountered by the virus, is predominantly composed of phospholipids whose role during orthopoxvirus infection has not been investigated. An attenuated Lister strain, derived from the traditional smallpox vaccine and the Western Reserve (WR) strain, lethal for mice infected by the respiratory route, were examined for their ability to bind various surfactant phospholipids. Dipalmitoyl phosphatidylglycerol (DPPG) was found to interact with both VACV strains. DPPG incorporated in small unilamellar vesicle (SUV-DPPG) inhibited VACV cell infection, unlike other phospholipids tested. Both pre-incubation of virus with SUV-DPPG and pretreatment of the cell with SUV-DPPG inhibited cell infection. This specific DPPG effect was shown to be concentration and time dependent and to prevent the first step of the viral cycle, i.e. virus cell attachment. Cryo-electron microscopy highlighted the interaction between the virus and SUV-DPPG. In the presence of the phospholipid, virus particles displayed a hedgehog-like appearance due to the attachment of lipid vesicles. Mice infected intranasally with VACV-WR pre-incubated with SUV-DPPG survived a lethal infection. These data suggest that DPPG in lung surfactant could reduce the amount of orthopoxvirus particles able to infect pneumocytes at the beginning of a respiratory poxvirus infection. The knowledge acquired during this study of virus–DPPG interactions may be used to develop novel chemotherapeutic strategies for smallpox.
The lung would be the first organ targeted in case of the use of Variola virus (the causative agent of smallpox) as a bioweapon. Pulmonary surfactant composed of lipids (90%) and proteins (10%) is ...considered the major physiological barrier against airborne pathogens. The principle phospholipid components of lung surfactant were examined in an in vitro model to characterize their interactions with VACV, a surrogate for variola virus. One of them, Dipalmitoyl phosphatidylglycerol (DPPG), was recently shown to inhibit VACV cell infection.
The interactions of poxvirus particles from the Western Reserve strain (VACV-WR) and the Lister strain (VACV-List) with model membranes for pulmonary surfactant phospholipids, in particular DPPG, were studied by Electron Spin Resonance (ESR) and proton Nuclear Magnetic Resonance (1H-NMR). ESR experiments showed that DPPG exhibits specific interactions with both viruses, while NMR experiments allowed us to deduce its stoichiometry and to propose a model for the mechanism of interaction at the molecular level.
These results confirm the ability of DPPG to strongly bind to VACV and suggest that similar interactions occur with variola virus. Similar studies of the interactions between lipids and other airborne pathogens are warranted.
LASIK eye surgery has become a very common practice for myopic people, especially those in the military. Sometimes undertaken by people who need to keep a specific medical aptitude, this surgery ...could be performed in secret from the hierarchy and from the institute medical staff. However, even though the eyes have been previously described as one of the most sensitive organs to electromagnetic fields in the human body, no data exist on the potential deleterious effects of electromagnetic fields on the healing eye. The consequences of chronic long-lasting radar exposures at power density, in accordance with the occupational safety standards (9.71 GHz, 50 W/m2), were investigated on cornea healing. The metabolic and clinical statuses after experimental LASIK keratotomy were assessed on the different eye segments in a New Zealand rabbit model. The analysis methods were performed after 5 months of exposure (1 hour/day, 3 times/week). Neither clinical or histological examinations, nor experimental data, such as light scattering, 1H-NMR HRMAS metabolomics, 13C-NMR spectra of lipidic extracts, and antioxidant status, evidenced significant modifications. It was concluded that withdrawing the medical aptitude of people working in electromagnetic field environments (i.e., radar operators in the navy) after eye surgery was not justified.
The properties of an amorphous solid dispersion of cyclosporine A (ASD) prepared with the copolymer alpha cyclodextrin (POLYA) and cyclosporine A (CYSP) were investigated by ¹H-NMR in solution and ...its membrane interactions were studied by ¹H-NMR in small unilamellar vesicles and by sup.31P ²H NMR in phospholipidic dispersions of DMPC (dimyristoylphosphatidylcholine) in comparison with those of POLYA and CYSP alone. ¹H-NMR chemical shift variations showed that CYSP really interacts with POLYA, with possible adduct formation, dispersion in the solid matrix of the POLYA, and also complex formation. A coarse approach to the latter mechanism was tested using the continuous variations method, indicating an apparent 1: 1 stoichiometry. Calculations gave an apparent association constant of logKa = 4.5. A study of the interactions with phospholipidic dispersions of DMPC showed that only limited interactions occurred at the polar head group level (sup.31P). Conversely, by comparison with the expected chain rigidification induced by CYSP, POLYA induced an increase in the fluidity of the layer while ASD formation led to these effects almost being overcome at 298 K. At higher temperature, while the effect of CYSP seems to vanish, a resulting global increase in chain fluidity was found in the presence of ASD.
Pantothenate Kinase-Associated Neurodegeneration (PKAN) is a form of Neurodegeneration with Brain Iron Accumulation (NBIA) associated with mutations in the pantothenate kinase 2 gene (PANK2). The ...PANK2 catalyzes the first step of coenzyme A (CoA) biosynthesis, a pathway producing an essential cofactor that plays a key role in energy and lipid metabolism. The majority of PANK2 mutations reduces or abolishes the activity of the enzyme. In around 10% of cases with PKAN, the presence of deformed red blood cells with thorny protrusions in the circulation has been detected. Changes in membrane protein expression and assembly during erythropoiesis were previously explored in patients with PKAN. However, data on red blood cell membrane phospholipid organization are still missing in this disease. In this study, we performed lipidomic analysis on red blood cells from Italian patients affected by PKAN with a particular interest in membrane physico-chemical properties. We showed an increased number of small red blood cells together with membrane phospholipid alteration, particularly a significant increase in sphingomyelin (SM)/phosphatidylcholine (PC) and SM/phosphatidylethanolamine (PE) ratios, in subjects with PKAN. The membrane structural abnormalities were associated with membrane fluidity perturbation. These morphological and functional characteristics of red blood cells in patients with PKAN offer new possible tools in order to shed light on the pathogenesis of the disease and to possibly identify further biomarkers for clinical studies.
•Erythrocyte lipidomic analysis revealed alterations in membrane physico-chemical properties in Italian PKAN patients.•Membrane structural abnormalities were associated with membrane fluidity perturbation.•An increased number of small red blood cells together with membrane phospholipid alteration were found.
In humans, exposure to electromagnetic millimeter waves (MMW) has a hypoalgesic effect. In animals, this effect has been shown to depend on innervation density of the area exposed. This study aims to ...assess hypoalgesic and parasympathetic effects of MMW applied on the palmar side of the wrist in healthy participants. In a within-subject design, 10 healthy participants had the palmar side of their wrist exposed to MMW (61.25 GHz, 17 mW/cm
2
) for 30 minutes, 1 h, & 1 h30, and 30 minutes of sham exposure. Experimental pain was induced after the exposure sessions with the Cold Pressor Test, and pain threshold and pain tolerance values were compared to that of the sham condition. Participants' heart rate and blood pressure were measured before and after exposures. Finally, innocuity of the exposure system was controlled with a pre-post exposure visual examination scale and skin temperature measured by a thermal camera. Exposure to 30 minutes, but not 1 h or 1 h30, of MMW led to significant increases in pain thresholds compared to the sham condition, but no increase of pain tolerance. All conditions led to decreased heart rate, while no change in blood pressure was observed. No change in skin state or temperature was observed for any of the conditions. MMW applied on the inner part of the wrist diminish pain sensations more effectively than placebo, and seem to increase parasympathetic activities, while remaining innocuous. Building a miniaturized MMW emission system to be worn on the wrist would provide access to ambulatory MMW therapy for pain management.
Metabolic syndrome components, including obesity, dyslipidemia and impaired glucose homeostasis, become a major public health issue. Muscles play a predominant role in insulin-mediated glucose ...uptake, and high fat diets may negatively affect muscle function and homeostasis. This work aimed to study the time-course of muscle lipid accumulation, oxidative stress and mitochondrial dysfunction and their association to impaired glucose homeostasis in rats fed an obesogenic diet. Male Wistar rats were fed with a standard or a high fat/high fructose (HFHFr) diet and sacrificed on 4, 8, 12, 16, 20 weeks. Rats fed the HFHFr diet developed mild overweight, increased liver and adipose tissue weights and glucose intolerance. The impaired glucose homeostasis increased gradually with the HFHFr diet to become significant on the 12th and 16th weeks of diet. In parallel, the muscle lipid composition showed an increase in the saturated fatty acids and the monounsaturated fatty acids with a marked decrease in the polyunsaturated fatty acids. The HFHFr diet also increased muscle contents of both diacylglycerols and Ceramides. Surprisingly, HFHFr diet did not induce major muscle mitochondrial dysfunction or oxidative stress. These results indicate that muscle lipid alterations, as well as impaired glucose homeostasis occur as early as the 8th week of HFHFr diet, increase to reach a plateau around the 12th–16th weeks of diet, and then attenuate towards the end of study. At these diet treatment durations, muscle mitochondrial activity and oxidative stress remained unchanged and do not seem to have a major role in the observed impaired glucose homeostasis.
Abstract
The prevalence of metabolic syndrome (MetS) components including obesity, dyslipidemia, insulin resistance (IR), and hepatic steatosis is rapidly increasing in wealthy societies. It is ...accepted that inflammation/oxidative stress are involved in the initiation/evolution of the MetS features. The present work was designed to evaluate the effects of three major cellular ROS production systems on obesity, glucose tolerance, and hepatic steatosis development and on oxidative stress onset. To do so, 40 young male Sprague-Dawley rats were divided into 5 groups: 1-control group, 2-high fat (HF) group (60% energy from fat), 3-HF+ MitoQ (mitochondrial ROS scavenger), 4-HF+ Apocynin (NADPH oxidase inhibitor), 5-HF+ Allopurinol (xanthine oxidase inhibitor). After 8 weeks of these treatments, surrogate MetS, mitochondrial function, and oxidative stress markers were measured in blood and liver. As expected, rats that were fed the HF diet exhibited increased body weight, glucose intolerance, overt hepatic steatosis, and increased hepatic oxidative stress. The impacts of the studied ROS inhibitors on these aspects of the MetS were markedly different. MitoQ showed the most clinically relevant effects, attenuating body weight gain and glucose intolerance provoked by the HF diet. Both Apocynin and Allopurinol showed limited effects suggesting secondary roles of xanthine oxidase (XO) or NADPH oxidase-dependent ROS production in the onset of oxidative stress-dependent obesity, glucose intolerance, and hepatic steatosis process. Thus, MitoQ revealed the central role of mitochondrial oxidative stress in the development of MetS and suggested that mitochondria-targeted antioxidants may be worth considering as potentially helpful therapies for MetS features.
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