Severe systemic inflammatory response to infection results in severe sepsis and septic shock, which are the leading causes of death in critically ill patients. Septic shock is characterised by refractory hypotension and is typically managed by fluid resuscitation and administration of catecholamine vasopressors such as norepinephrine. Vasopressin can also be administered to raise mean arterial pressure or decrease the norepinephrine dose. Endogenous norepinephrine and vasopressin are synthesised by the copper-containing enzymes dopamineβ-hydroxylase and peptidylglycine α-amidating monooxygenase, respectively. Both of these enzymes require ascorbate as a cofactor for optimal activity. Patients with severe sepsis present with hypovitaminosis C, and pre-clinical and clinical studies have indicated that administration of high-dose ascorbate decreases the levels of pro-inflammatory biomarkers, attenuates organ dysfunction and improves haemodynamic parameters. It is conceivable that administration of ascorbate to septic patients with hypovitaminosis C could improve endogenous vasopressor synthesis and thus ameliorate the requirement for exogenously administered vasopressors. Ascorbate-dependent vasopressor synthesis represents a currently underexplored biochemical mechanism by which ascorbate could act as an adjuvant therapy for severe sepsis and septic shock.

Ascorbic acid (AA) has been shown to exert beneficial effects, including mitigating oxidative stress and inhibiting inflammation. However, the preventative effect of vitamin C in chronic inflammatory diseases such as inflammatory bowel disease (IBD) remains unclear. In our study, we investigated the anti-inflammatory effects of AA and possible mechanism involved in inhibiting dextran sulfate sodium (DSS)-induced ulcerative colitis in mice. Male C57BL/6 mice were randomly divided tothree groups: control group, DSS group, and DSS plus ascorbic acid treated group. Several clinical and inflammatory parameters as well as oxidative stress were evaluated. The results demonstrated that ascorbic acid significantly reduced clinical signs, inflammatory cytokines, myeloperoxidase (MPO) and malonaldehyde (MDA) activities, whereas the activities of superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) were increased in DSS-induced mice. In addition, ascorbic acid was capable of inhibiting NF-κB, COX-2 and iNOS expression in the colonic. Taken together, these findings suggest that ascorbic acid contributes to the reduction of oxidative stress and inflammatory response in DSS-induced colitis and exerts the potential to prevent and clinical treatment of inflammatory bowel disease.

STUDY DESIGN:A rat model of multifidus muscles injury and atrophy after posterior lumbar spine surgery.

OBJECTIVE:We determined the effect of ascorbic acid (AA) on the postoperative multifidus muscles in rat model.

SUMMARY OF BACKGROUND DATA:Previous studies show oxidative stress and inflammation are two main molecular mechanisms in multifidus muscle injury and atrophy after posterior lumbar surgery. AA may have a protective effect in postoperative multifidus muscles.

METHODS:Rats were divided into sham surgery, control surgery, and surgery plus AA groups. Multifidus muscles of the control and AA groups were excised from the osseous structures. The muscles were retracted continuously for 2 h. In the sham and AA groups, AA was administered via oral gavage daily in the first week. In each group, the oxidative stress was evaluated by measuring malondialdehyde (MDA) and Total superoxide dismutase (T-SOD). The inflammation, fat degeneration or fibrosis of multifidus muscle were evaluated by Q-PCR, histology or immunohistochemical analysis.

RESULTS:T-SOD activity was significantly lower in the control group than that in the AA group in the first week. MDA levels were significantly higher in the AA group. Interleukin-6 and tumor necrosis factor-α in multifidus muscles also showed significant differences when treated with AA. The inflammation score on histology was significantly lower in the AA group postoperatively in the first week. In the long run, marker genes for fibrosis and fat degeneration, and fibrosis and fat degeneration scores,were significantly lower in the AA than the control group on days 14 and 28 postoperatively.

CONCLUSIONS:In conclusion, AA attenuated the oxidative stress and inflammation response in the postoperative multifidus muscles, and remarkable differences were observed from the histological assessment and related marker genes expression. Our results provided important insight into the anti-inflammatory and anti-oxidative effects of AA in the postoperative multifidus muscles.

LEVEL OF EVIDENCE:N/A.

Exposure to zinc oxide nanoparticles (ZnO NPs) promotes acute pulmonary toxicity through oxidative stress and inflammation. Furthermore, dissolved zinc from ZnO NPs induces the formation of intracellular reactive oxygen species (ROS). We previously reported that supplemental ascorbic acid (AA) inhibits ZnO NP-induced acute pulmonary toxicity in a rat model; however, the mechanism of this action remains unclear. Therefore, we investigated the effects of AA on ZnO NP-induced cytotoxicity in human lung carcinoma A549 cells. AA was found to suppress intracellular production of ROS, and thus reduce the subsequent inflammation of ZnO NPs. However, intracellular Zn(2+) concentrations were higher in AA-treated cells than in AA-untreated cells. AA was found to react with Zn(2+) but not with the ZnO NPs themselves. These results suggest the possibility that AA-chelated extracellular Zn(2+) and the Zn-AA complex was readily taken up into cell. Even if the intracellular Zn(2+) level was high, cytotoxicity might be reduced because the Zn-AA complex was stable. Co-treatment of AA to A549 inhibited ROS production and subsequent intracellular inflammatory responses. These results are consistent with those previously reported from an in vivo model. Thus, two possibilities can be considered about the cytotoxicity-reducing the effect of AA: antioxidant efficacy and chelating effect.

Background:The purpose of this study was to determine the effect of blueberry supplementation on exercise performance time, inflammation markers, energy substrates, insulin, and TAS levels during two periods: non-supplemented period and supplemented period.

Methods:Eight young active participants were recruited from the Department of Physical Education at some universities in Busan City, Republic of Korea. The test period was divided into two Sections: non-supplemented period and supplemented period. Vo2 max and exercise performance time of participants were measured, with or without blueberry supplementation, with a portable gas analyzer and ECG, respectively.

Results:Vo2 max and exercise performance time were increased in the blueberry supplementation period. IL-6 and CRP levels were significantly lowered in blueberry supplementation period following exercise.

Conclusion:The blueberry supplementation can potentially increase the exercise performance and decrease the IL-6 and CRP levels caused by an increased TAS level.

The association between breastfeeding and type 1 diabetes mellitus (T1DM) is controversial. However, several recent studies have established a link between these two factors, necessitating a need to review this subject to raise public awareness. Current research indicates that breast milk contains a variety of bioactive substances including immunoglobulins, oligosaccharides, insulin, lactoferrin, lysozyme, cytokines, epidermal growth factors, leukocytes, nucleotides, beneficial bacteria and vitamins. Such substances strengthen the breastfeeding infant's immune system, both directly, by increasing gut microbiota diversity and attacking harmful bacteria and pro-inflammatory molecules, and indirectly, by increasing thymus performance. Accordingly, a lack of or inadequate breastfeeding may predispose infants to several autoimmune disorders, including T1DM. Nursing mothers and caregivers are therefore advised to follow optimal breastfeeding practices prior to introducing complementary foods.

OBJECTIVE:Vegetarian diets contain various anti-inflammatory components. We aimed to investigate the effects of vegetarianism on inflammatory biomarkers when compared with omnivores.

DESIGN:Systematic review and meta-analysis.

SETTING:Literature search was conducted in Science Direct, Proquest, MEDLINE and Google Scholar up to June 2016. Summary estimates and corresponding 95 % CI were derived via the DerSimonian and Laird method using random effects, subgroup analyses were run to find the source of heterogeneity and a fixed-effect model examined between-subgroup heterogeneity.

SUBJECTS:Studies were included if they evaluated effects of any type of vegetarianism compared with omnivores on circulating levels of inflammatory biomarkers. No restriction was made in terms of language or the date of study publications.

RESULTS:Eighteen articles were included. Pooled effect size showed no difference in high-sensitivity C-reactive protein (hs-CRP) levels in vegetarians v. omnivores (Hedges' g=-0·15; 95 % CI -0·35, 0·05), with high heterogeneity (I 2=75·6 %, P<0·01). A subgroup analysis by minimum duration of vegetarianism showed that a minimum duration of 2 years vegetarianism was associated with lower hs-CRP levels v. omnivores (Hedges' g=-0·29; 95 % CI -0·59, 0·01), with moderate heterogeneity (I 2=68·9 %, P<0·01). No significant effect was found in studies using a minimum duration of 6 months of vegetarianism, with low heterogeneity. Vegetarianism was associated with increased IL-6 concentrations (0·21 pg/ml; 95 % CI 0·18, 0·25), with no heterogeneity (I 2=0·0 %, P=0·60).

CONCLUSIONS:The meta-analysis provides evidence that vegetarianism is associated with lower serum concentrations of hs-CRP when individuals follow a vegetarian diet for at least 2 years. Further research is necessary to draw appropriate conclusions regarding potential associations between vegetarianism and IL-6 levels. A vegetarian diet might be a useful approach to manage inflammaging in the long term.

Spinal cord injuries (SCIs) initiate a series of molecular and cellular events in which inflammatory responses can lead to major neurological dysfunctions. The present study aims to investigate whether bee venom (BV) acupuncture applied at acupoints ST36 (Zusanli) and GV3 (Yaoyangquan) could minimize locomotor deficits and the magnitude of neural tissue losses, and change the balance between pro- and anti-inflammatory cytokines after an SCI by compression. Wistar rats were subjected to an SCI model by compression in which a 2-French Fogarty embolectomy catheter was inflated in the extradural space. The effects of BV acupuncture, in which 20 μL of BV diluted in saline (0.08 mg/kg) was injected at acupoints GV3 and ST36 [BV(ST36+GV3)-SCI] was compared with BV injected at nonacupoints [BV(NP)-SCI] and with no treatment [group subjected only to SCI (CTL-SCI)]. The BV(ST36+GV3)-SCI group showed a significant improvement in the locomotorperformance and a decrease of lesion size compared with the controls. BV acupuncture at the ST36 + GV3 increased the expression of interleukin-10 (anti-inflammatory) at 6 hours and reduced the expression of interleukin-6 (proinflammatory) at 24 hours after SCI compared with the controls. Our results suggest that BV acupuncture can reduce neuroinflammation and induce recovery in the SCI compression model.

Strenuous exercise (any activity that expends six metabolic equivalents per minute or more causing sensations of fatigue and exhaustion to occur, inducing deleterious effects, affecting negatively different cells), induces muscle damage and hematological changes associated with high production of pro-inflammatory mediators related to muscle damage and sports anemia. The objective of this study was to determine whether short-term oral ubiquinol supplementation can prevent accumulation of inflammatory mediators and hematological impairment associated to strenuous exercise. For this purpose, 100 healthy and well-trained firemen were classified in two groups: Ubiquinol (experimental group), and placebo group (control). The protocol was two identical strenuous exercise tests with rest period between tests of 24 h. Blood samples were collected before supplementation (basal value) (T1), after supplementation (T2), after first physical exercise test (T3), after 24 h of rest (T4), and after second physical exercise test (T5). Hematological parameters, pro- and anti-inflammatory cytokines and growth factors were measured. Red blood cells (RBC), hematocrit, hemoglobin, VEGF, NO, EGF, IL-1ra, and IL-10 increased in the ubiquinol group while IL-1, IL-8, and MCP-1 decreased. Ubiquinol supplementation during high intensity exercise could modulate inflammatory signaling, expression of pro-inflammatory, and increasing some anti-inflammatory cytokines. During exercise, RBC, hemoglobin, hematocrit, VEGF, and EGF increased in ubiquinol group, revealing a possible pro-angiogenic effect, improving oxygen supply and exerting a possible protective effect on other physiological alterations.

Curcumin is widely consumed in Asia either as turmeric directly or as one of the culinary ingredients in food recipes. The benefits of curcumin in different organ systems have been reported extensively in several neurological diseases and cancer. Curcumin has got its global recognition because of its strong antioxidant, anti-inflammatory, anti-cancer, and antimicrobial activities. Additionally, it is used in diabetes and arthritis as well as in hepatic, renal, and cardiovascular diseases. Recently, there is growing attention on usage of curcumin to prevent or delay the onset of neurodegenerative diseases. This review summarizes available data from several recent studies on curcumin in various neurological diseases such as Alzheimer's disease, Parkinson's disease, Multiple Sclerosis, Huntington's disease, Prions disease, stroke, Down's syndrome, autism, Amyotrophic lateral sclerosis, anxiety, depression, and aging. Recent advancements toward increasing the therapeutic efficacy of curcuma/curcumin formulation and the novel delivery strategies employed to overcome its minimal bioavailability and toxicity studies have also been discussed. This review also summarizes the ongoing clinical trials on curcumin for different neurodegenerative diseases and patent details of curcuma/curcumin in India.

BACKGROUND:Optic neuropathy is a rare adverse reaction to vaccination.

CASE REPORT:A 62-year-old-woman was hospitalized for bilateral optic neuropathy with loss of vision. The symptoms occurred 15 days after a seasonal influenza vaccination. Her past medical history included a mixed connective tissue disease with no immunosuppressive treatment for several years. Investigations did not reveal any obvious cause and the hypothesis of post-influenza vaccination bilateral optic neuropathy was retained although a complication of the connective tissue disease complication could not be ruled out. The patient was given intravenous methylprednisolone 1g daily. At a cumulative dose of 8 g, oral steroids were given and tapered off.

DISCUSSION:Few similar case reports have been described in literature. The causal link between vaccination and optic neuropathy thus remains to be confirmed. Clinicians should however consider this etiology.

Poria cocos Wolf (Polyporaceae) has been used as a medicinal fungus to treat various diseases since ancient times. This study aimed to investigate the anti-inflammatory chemical constituents of the sclerotia of P. cocos. Based on bioassay-guided fractionation using lipopolysaccharide (LPS)-stimulated Raw264.7 cells, chemical investigation of the EtOH extract of the sclerotia of P. cocos resulted in the isolation and identification of eight compounds including six triterpenoids, namely poricoic acid A (1), 3-O-acetyl-16α-hydroxydehydrotrametenolic acid (2), polyporenic acid C (3), 3β-hydroxylanosta-7,9(11),24-trien-21-oic acid (4), trametenolic acid (5), and dehydroeburicoic acid (6), as well as (-)-pinoresinol (7) and protocatechualdehyde (8). The structures of the isolated compounds were determined by spectroscopic analysis, includingH andC NMR spectra, and LC/MS analysis. The anti-inflammatory activities of the isolates were evaluated by estimating their effect on the production of nitric oxide (NO) and prostaglandin E(PGE) in LPS-stimulated Raw264.7 as well as on the expression of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). Compounds 1-5 inhibited NO production and iNOS expression in LPS-stimulated Raw264.7 cells. Among them, compound 1 exerted the highest anti-inhibitory activity and reduced PGElevels via downregulation of COX-2 protein expression. The findings of this study provide experimental evidence that the sclerotia of P. cocos are a potential source of natural anti-inflammatory agents for use in pharmaceuticals and functional foods. Furthermore, the most active compound 1, seco-lanostane triterpenoid, could be a promising lead compound for the development of novel anti-inflammatory agents.

The steam-distilled essential oil of Iranian black cumin seed (Nigella sativa L.) was investigated for its composition and analgesic and antiinflammatory properties. After oil analysis by GC/MS, 20 compounds were identified in the oil, obtained in 0.4% (v/w) yield. Among them, para-cymene (37.3%) and thymoquinone (13.7%) were the major components. Acetic acid-induced writhing, formalin and light tail flick tests were used for assessment of analgesic activity. Antiinflammatory activity was evaluated using carrageenan-induced paw oedema in rats and croton oil-induced ear oedema in mice. Black cumin seed essential oil (BCSEO) was found to produce a significant analgesic effect in acetic acid-induced writhing, formalin and light tail flick tests. Naloxone, an opioid antagonist, could not reverse the analgesic effect observed in the formalin test. Although oral administration of BCSEO at doses of 100, 200 and 400 micro L/kg did not exert a significant antiinflammatory effect in the carrageenan test, i.p. injection of the same doses significantly (p < 0.001) inhibited carrageenan-induced paw oedema. BCSEO at doses of 10 and 20 micro L/ear could also reduce croton oil-induced oedema. It seems that mechanism(s) other than opioid receptors is (are) involved in the analgesic effect of BCSEO since naloxone could not reverse this effect. Both systemic and local administration of BCSEO showed antiinflammatory activity. Thymoquinone, as one of the major components of BCSEO, probably has an important role in these pharmacological effects. Copyright 2004 John Wiley & Sons, Ltd.

This investigation determined the efficacy of black currant nectar (BCN) in reducing symptoms of exercise-induced muscle damage (EIMD). Sixteen college students were randomly assigned to drink either 16 oz of BCN or a placebo (PLA) twice a day for eight consecutive days. A bout of eccentric knee extensions (3× 10 sets @ 115% of 1RM) was performed on the fourth day. Outcome measures included muscle soreness (subjective scale from 0 to 10) and blood markers of muscle damage (creatine kinase, CK), inflammation (interleukin-6, IL-6), and oxygen radical absorbance capacity (ORAC). Although there were no differences in reported soreness between groups, consumption of BCN reduced CK levels at both 48 (PLA = 82.13% vs. BCN = -6.71%, p = .042) and 96 h post exercise (PLA = 74.96% vs. BCN = -12.11%, p = .030). The change in IL-6 was higher in the PLA group (PLA = 8.84% vs. BCN = -6.54%, p = .023) at 24 h post exercise. The change in ORAC levels was higher in the treatment group (BCN = 2.68% vs. PLA = -6.02%, p = .039) at 48 h post exercise. Our results demonstrate that consumption of BCN prior to and after a bout of eccentric exercise attenuates muscle damage and inflammation.

INTRODUCTION:The neuroprotective effects of hypothermia in acute ischemic stroke are well documented. However, the mechanisms involved in the effects remain to be clearly elucidated and the role of hypothermia on long-term white matter integrity after acute ischemic stroke has yet to be investigated.

AIMS:To investigate the role of mild focal hypothermia on long-term white matter (WM) integrity after transient cerebral ischemia.

RESULTS:Mild focal hypothermia treatment immediately after ischemic stroke significantly promotes WM integrity 28 days after the occlusion of the middle cerebral artery (MCAO) in mice. Higher integrity of white matter, lower activation of total microglia, less infarct volume, and better neurobehavioral function were detected in hypothermia-treated mice compared to normothermia-treated mice. Furthermore, we found that hypothermia could decrease detrimental M1 phenotype microglia and promote healthy M2 phenotype microglia. In vitro, results also indicated that hypothermia promoted oligodendrocytes differentiation and maturation after oxygen glucose deprivation.

CONCLUSION:Hypothermia promotes long-term WM integrity and inhibits neuroinflammation in a mouse model of ischemic brain injury.

OBJECTIVE:Pro-inflammatory cytokines have been implicated in the pathophysiology and maintenance of depression. This study investigated the effects of a brief mindfulness intervention on salivary pro-inflammatory correlates of depression (IL-6, TNF-α) and self-reported symptoms of depression in college women.

METHODS:Sixty-four females with a cut score of≥16 on the Center for Epidemiological Studies for Depression Scale (CES-D) were assigned to a 4-week mindfulness-based intervention (MBI; N = 31) or a contact-control group (N = 33). For both groups, salivary cytokines and depressive symptoms were assessed at baseline and posttreatment. For the mindfulness group only, salivary cytokines were also assessed at a 3-month follow-up.

RESULTS:Both groups showed similar reductions in depression. However, MBI (vs. control) predicted greater reductions in IL-6 and TNF-α; changes in IL-6 were sustained at 3-month follow-up. Higher baseline depressive symptoms predicted greater reductions in inflammation in the mindfulness group.

CONCLUSION:MBIs may reduce inflammatory immune markers commonly implicated in depression. Individuals with greater depressive symptoms may benefit more from mindfulness training. Although reductions in salivary cytokines in the mindfulness condition were not attributable to changes in depressive symptoms, future work should examine the possibility that such reductions are protective against the development of future depressive episodes. (PsycINFO Database Record

OBJECTIVE:Pro-inflammatory cytokines have been implicated in the pathophysiology and maintenance of depression. This study investigated the effects of a brief mindfulness intervention on salivary pro-inflammatory correlates of depression (IL-6, TNF-α) and self-reported symptoms of depression in college women.

METHODS:Sixty-four females with a cut score of≥16 on the Center for Epidemiological Studies for Depression Scale (CES-D) were assigned to a 4-week mindfulness-based intervention (MBI; N = 31) or a contact-control group (N = 33). For both groups, salivary cytokines and depressive symptoms were assessed at baseline and posttreatment. For the mindfulness group only, salivary cytokines were also assessed at a 3-month follow-up.

RESULTS:Both groups showed similar reductions in depression. However, MBI (vs. control) predicted greater reductions in IL-6 and TNF-α; changes in IL-6 were sustained at 3-month follow-up. Higher baseline depressive symptoms predicted greater reductions in inflammation in the mindfulness group.

CONCLUSION:MBIs may reduce inflammatory immune markers commonly implicated in depression. Individuals with greater depressive symptoms may benefit more from mindfulness training. Although reductions in salivary cytokines in the mindfulness condition were not attributable to changes in depressive symptoms, future work should examine the possibility that such reductions are protective against the development of future depressive episodes. (PsycINFO Database Record

Background::C-reactive protein is an inflammatory biomarker and its level increases in the serum of psoriatic patients. Its level is also associated with Psoriasis Area and Severity Index score.

Objective::The aim of this study was to assess the decrement of serum C-reactive protein level with narrow-band ultraviolet B (NB-UVB) therapy.

Methods::C-reactive protein serum levels in psoriasis patients were measured before and after treatment with NB-UVB and the data were analyzed in relation to the Psoriasis Area and Severity Index score improvement.

Results::Baseline C-reactive protein levels among psoriatic patients were higher than normal. These levels decreased significantly after treatment (P<0.001). At the beginning of the study, patients with higher levels of C-reactive protein also had more extensive and severe skin involvement. The highest decrease in C-reactive protein was observed in patients who responded better to the treatment and achieved a higher Psoriasis Area and Severity Index 75%. There was an association between baseline Psoriasis Area and Severity Index scores and C-reactive protein levels.

Conclusion::Patients with moderate to severe plaque-type psoriasis had active systemic inflammation, which was demonstrated by increased levels of C-reactive protein. Furthermore, skin disease severity was correlated with C-reactive protein levels. Phototherapy healed the psoriatic skin lesions and reduced inflammation, while decreasing C-reactive protein levels.

The brain can generate new neurons from neural stem cells throughout life. However, the capacity for neurogenesis declines with age, reducing the potential for learning and repair. We explored the effects of calorie restriction, an established anti-aging intervention, on neural stem cells in the subventricular zone of young and aged mice. Calorie restriction transiently enhanced proliferation of neural progenitor cells in young, but not aged mice. However, calorie restriction prevented the age-related loss of neurogenesis in the aged brain. Calorie-restricted mice showed enhanced olfactory memory compared withfed controls, suggesting that calorie restriction can produce functional improvements in the aged brain. Calorie restriction also mitigated the age-related activation of microglia and subsequent increase in pro-inflammatory cytokines. Likewise, calorie restriction prevented increases in senescent cells normally observed in the subventricular zone in aged mice, further protecting this neurogenic niche from pro-inflammatory signals. Together, these data suggest that calorie restriction protects the subventricular zone microenvironment from age-related inflammation, thereby preserving neurogenesis into old age.

A previous study demonstrated that connecting the human body to the earth during sleep (earthing) normalizes the daily cortisol rhythm and improves sleep. A variety of other benefits were reported, including reductions in pain and inflammation. Subsequent studies have confirmed these earlier findings and documented virtually immediate physiologic and clinical effects of grounding or earthing the body. It is well established, though not widely known, that the surface of the earth possesses a limitless and continuously renewed supply of free or mobile electrons as a consequence of a global atmospheric electron circuit. Wearing shoes with insulating soles and/or sleeping in beds that are isolated from the electrical ground plane of the earth have disconnected most people from the earth's electrical rhythms and free electrons. The most reasonable hypothesis to explain the beneficial effects of earthing is that a direct earth connection enables both diurnal electrical rhythms and free electrons to flow from the earth to the body. It is proposed that the earth's diurnal electrical rhythms set the biological clocks for hormones that regulate sleep and activity. It is also suggested that free electrons from the earth neutralize the positively charged free radicals that are the hallmark of chronic inflammation. A relationship between cortisol and inflammation was established in the pioneering work of H. Selye published in the 1950s. Current biomedical research has led to an inflammation hypothesis that is establishing chronic inflammation as the culprit behind almost every modern chronic illness. The research summarized here and in subsequent reports provides a basis for a number of earthing technologies that restore and maintain natural electrical contact between the human body and the earth throughout the day and night in situations where going barefoot on the earth is impractical. It is proposed that free or mobile electrons from the earth can resolve chronic inflammation by serving as natural antioxidants.