scholarly journals The Level of Oxidative Stress Markers in Generalised Periodontitis in the Setting of Bronchiectasis

2019 ◽  
Vol 26 (5) ◽  
pp. 42-51
Author(s):  
Anatoly P. Kibkalo ◽  
Artem K. Sarkisov ◽  
Ekaterina A. Polunina ◽  
Karen A. Sarkisov
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Protein Oxidation ◽  
The State ◽  
Control Group ◽  
Periodontal Tissue ◽  
Oxidative Stress Markers ◽  
Healthy Individuals ◽  
Stress Markers ◽  
Total Superoxide Dismutase

Aim. To analyse the level of oxidative stress markers and the value of dental indices characterising the state of periodontal tissue in patients with generalised periodontitis (GP) both without somatic pathology and with bronchiectasis.Materials and methods. Over the period from 2015 to 2017, a total of 90 GP patients were examined, including 40 patients without somatic pathology and 50 patients with bronchiectasis. The control group consisted of somatically healthy individuals with intact periodontium (n=40). The following indices were calculated for all examined individuals: PMA, PI, Muhlemann and OHI-s. The level of oxidative stress markers in oral fl uid was determined: total superoxide dismutase (SOD) of all three types (Cu/Zn-SOD + Mn-SOD + Fe-SOD), products of advanced protein oxidation and malondialdehyde.Results. The study established the intensifi cation of oxidative stress in GP patients without somatic pathology and with bronchiectasis. Patients with comorbid pathologies demonstrated a greater severity of oxidative stress. The analysis revealed a significant correlation between the values of dental indices (PMA, PI, Muhlemann, OHI-s) and the level of oxidative stress markers both in GP patients without somatic pathology and with bronchiectasis. Furthermore, this correlation is stronger in patients with comorbid pathologies.Conclusion. The presence of comorbid pulmonary pathologies in the form of bronchiectasis in patients with generalised periodontitis can act as an aggravating factor in the development of periodontal lesions.

scholarly journals Rosuvastatin Affects Tracheal Responsiveness, Bronchoalveolar Lavage Inflammatory Cells, and Oxidative Stress Markers in Hyperlipidemic and Asthmatic Rats

2020 ◽  
Author(s):  
Saeideh Saadat ◽  
Amin Mokhtari-Zaer ◽  
Mousa-Al-Reza Hadjzadeh ◽  
Mohammad Hossein Boskabady
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Bronchoalveolar Lavage ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Total Thiol ◽  
Stress Markers ◽  
Thiol Content ◽  
Wbc Count ◽  
And Oxidative Stress

Statins provide greater protection than predicted from just cholesterol-lowering effects, which is possibly mediated by other pleiotropic actions. This study aimed to examine the possible interaction effect of asthma on lipid profiles and evaluate the effect of rosuvastatin treatment on asthma. The animals were assigned into (1) control, (2) asthmatic, (3) hyperlipidemic, (4) asthmatic-hyperlipidemic, (5) rosuvastatin (40 mg/kg/day intraperitoneally, for 3 weeks)-treated asthmatic, (6) rosuvastatin-treated hyperlipidemic and (7) rosuvastatin-treated asthmatic-hyperlipidemic groups. Tracheal responsiveness to methacholine and ovalbumin, total and differential WBC (white blood cell) counts, and oxidative stress markers in bronchoalveolar lavage fluid (BALF) were evaluated. In the asthmatic and asthmatic-hyperlipidemic groups, tracheal responsiveness to ovalbumin, total WBC count, numbers of eosinophils, neutrophils, and monocytes were higher than the control group (p<0.001). A left-ward shift in the concentration-response curves to methacholine, an increase in nitrite and malondialdehyde concentrations, and a decrease in total thiol content, superoxide dismutase and catalase activities were also observed in the asthmatic and asthmatic-hyperlipidemic groups compared to control group (p<0.01 to p<0.001). Beyond lipid-lowering effect in the treated hyperlipidemic and asthmatic-hyperlipidemic groups, rosuvastatin treatment decreased tracheal responsiveness to methacholine, reduced total WBC count, the numbers of eosinophils, neutrophils, and monocytes, as well as decreased malondialdehyde concentration, and increased total thiol content, superoxide dismutase and catalase activities in treated asthmatic and asthmatic-hyperlipidemic groups (p<0.05 to p<0.001). The improving effect of rosuvastatin on asthmatic and asthmatic-hyperlipidemic animals was shown due to pleiotropic mechanisms including the effect on airway hyperresponsiveness, lung inflammation, and oxidative stress.

Evaluation of Salivary Antioxidants and Oxidative Stress Markers in Type 2 Diabetes Mellitus: A Retrospective Cohort Study

2020 ◽  
Vol 20 (4) ◽  
pp. 584-590 ◽  
Author(s):  
Shima Fathi ◽  
Shiva Borzouei ◽  
Mohammad Taghi Goodarzi ◽  
Jalal Poorolajal ◽  
Fatemeh Ahmadi-Motamayel
Keyword(s):  
Oxidative Stress ◽  
Diabetes Mellitus ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Type 2 Dm ◽  
Patients With Diabetes ◽  
The Difference ◽  
And Oxidative Stress

Background: Diabetes Mellitus (DM) is a progressive metabolic disorder. Objective: The aim of this study was to investigate the relationship between antioxidant and oxidative stress markers in the saliva of patients with type 2 DM and a healthy control group. Methods: In this study, 20 patients with diabetes and 20 healthy individuals were evaluated. Salivary antioxidants markers consisted of total antioxidant capacity (TAC), uric acid (UA), peroxidase and catalase. Oxidative stress markers included total oxidant status (TOS), malondealdehyde (MDA) and total thiol (SH). Sialochemical analysis was performed with spectrophotometric assay. All the statistical analyses were conducted using STATA software. Results: TAC decreased significantly in patients with diabetes. Although salivary UA and peroxidase were lower in patients with diabetes compared to the control group, the difference was not significant. Salivary catalase in patients with diabetes was significantly lower than that in the control group. MDA and TOS exhibited significantly higher levels in type 2 DM. SH levels were slightly higher in DM. Conclusions: According to the results of the present study, there were some changes in the salivary levels of some antioxidants and oxidative stress markers in patients with type 2 DM and could be measured as an indicator of serum changes..

scholarly journals The Effects of Vibroacoustically Induced Microvibrations on Arterial Blood Pressure and Oxidative Stress in Rats

2014 ◽  
Vol 15 (2) ◽  
pp. 83-88
Author(s):  
Dusko Kornjaca ◽  
Vladimir Zivkovic ◽  
Nevena Barudzic ◽  
Vladimir Jakovljevic ◽  
Dragan Djuric
Keyword(s):  
Oxidative Stress ◽  
Arterial Pressure ◽  
Systolic Arterial Pressure ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Sound Waves ◽  
Initial Value ◽  
The Third ◽  
Stress Markers ◽  
Arterial Blood

ABSTRACT Vibroacoustics, a scientific field that has been intensively studied for the last thirty years, uses the properties of sound waves (infrasound, ultrasound, noise and music) to induce vibrations that, like a sound wave, may have both useful and harmful effects. Th e aim of this study was to examine the effects of vibroacoustically induced microvibrations on arterial blood pressure and markers of oxidative stress in the blood. Th e experiments were performed on Wistar male rats that had a 180-200 g body mass and were divided into control and experimental groups (6 rats in each). In the experimental group, microvibrations were induced using the Vitafon vibroacoustic apparatus (Vitafon, St. Petersburg, Russian Federation), which delivers sound waves of varying frequencies by a process called “phoning”. Up to 60 minutes of phoning time was delivered to the kidney and liver using 4 diff erent regimens that included a 5-minute stabilisation time; up to four 10-minute phoning regimens, with 5-minute breaks between each single regimen, at a 30 Hz-18000 kHz frequency range;, and 2.8 μm-12.3 μm microwave amplitudes. After the completion of a phoning regimen, animals were sacrificed and the oxidative stress markers were measured in blood samples (O2-, H2O2, nitrites, lipid peroxidation index, superoxide dismutase, catalase, and glutathione) and compared with the values of markers in the control group. Systolic arterial pressure was analysed after the acute application of up to four diff erent regimens of vibroacoustic microvibrations. Systolic arterial pressure decreased significantly during the administration of the second regimen in comparison to the control group. Systolic arterial pressure returned, almost completely, to the initial value after the administration of the third and fourth regimens. Th ere was no significant change in diastolic arterial pressure after the acute administration of up to four different regimens, although the pressure decreased slightly after the first and second regimens and returned to the initial value during the administration of the third and fourth regimens. Analysis of oxidative stress markers showed a statistically significant change in the catalase level. No statistically significant differences were found in the other oxidative stress markers analyzeanalysed. Further research is needed to clarify the physiological effects of low compared to high frequencies of vibroacoustically induced microvibrations and their possible therapeutic significance.

scholarly journals Basic Studies on the Oxidative Stress Markers in Two Types of Horse Breed: Semi-isolated Population of Huculs Is Different from Commercially Used Arabian Horses

2020 ◽  
Vol 2020 ◽  
pp. 1-10
Author(s):  
Barbara A. Bażanów ◽  
Elżbieta Chełmecka ◽  
Ewa Romuk ◽  
Dominika M. Stygar
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Animal Health ◽  
Oxidative Stress Markers ◽  
Serum Samples ◽  
Antioxidants Activity ◽  
Stress Markers ◽  
Total Antioxidant ◽  
Basic Studies ◽  
Oxidant Status

Hucul and Arabian horses differ in the physiological constitution and exposition to environmental conditions. Oxidative stress plays a pathogenic role in many diseases and enables further injuries. The objective of this study was to compare the levels of enzymatic and nonenzymatic oxidative stress markers in Hucul horses living in seminatural conditions and in commercially handled Arabian horses. We tested the serum samples for total superoxide dismutase (total SOD), Cu-Zn-superoxide dismutase (CuZnSOD), and Mn-dependent superoxide dismutase (MnSOD) activity; for lipofuscin (LPS), ceruloplasmin (CER) and malondialdehyde (MDA) concentration; and for total antioxidant capacity (TAC) and total oxidant status (TOS). Total SOD (p<0.001), MnSOD (p<0.001), and CuZnSOD (p<0.001) activities were significantly higher whereas LPS (p<0.05), TAC (p<0.001), TOS (p<0.001), and MDA (p<0.001) concentrations were significantly lower in the serum samples collected from Huculs vs. Arabian horses, regardless of the gender. Gender, regardless of the breed, had no significant impact on the antioxidants’ activity and concentration. Total SOD and MnSOD activities were significantly higher in Hucul’s mares when compared to Hucul’s stallions. Concentrations of TAC and TOS were significantly lower in Arabian stallions than in Arabian mares. Commercially handled horses expressed a higher level of oxidative stress markers in comparison to breeds living in seminatural conditions. We conclude that antioxidants are important biomarkers of animal health, whether they are under maintenance care or performing physical exercise.

scholarly journals General, 21-Day Postoperative Rehabilitation Program Has Beneficial Effect on Oxidative Stress Markers in Patients after Total Hip or Knee Replacement

2020 ◽  
Vol 2020 ◽  
pp. 1-9
Author(s):  
Bronisława Skrzep-Poloczek ◽  
Jakub Poloczek ◽  
Elżbieta Chełmecka ◽  
Wojciech Kazura ◽  
Agnieszka Dulska ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Superoxide Dismutase ◽  
Knee Replacement ◽  
Average Distance ◽  
Rehabilitation Program ◽  
Oxidative Stress Markers ◽  
Postoperative Rehabilitation ◽  
Total Hip ◽  
Stress Markers ◽  
Successful Recovery

Imbalance in prooxidant-antioxidant equilibrium plays an important role in the progression of osteoarthritis (OA). Postoperative rehabilitation significantly improves the functional activity of patients with OA. We aimed to assess the effect of the general 21-day postoperative rehabilitation on the oxidative stress markers in patients after total hip arthroplasty or knee replacement. Patients (n =41) started individually designed postoperative rehabilitation ca. 90 days after endoprosthesis implantation. We used the six-minute walk test (6MWT) to quantify the changes in their exercise capacity. We analyzed the oxidative stress markers: total antioxidant capacity (TAC), total superoxide dismutase (SOD), Cu-Zn-superoxide dismutase (CuZnSOD) and ceruloplasmin (Cp) activity, malondialdehyde (MDA) and lipofuscin (LPS) concentration in patients serum to asses changes in the oxidative stress intensity. We found that after 21-days postoperative rehabilitation program: the average distance walked by patients increased by 69 m; TAC increased by 0.20 ± 0.14 mmol/l; both SOD isoforms activities increased by 1.6 (±1.7) and 1.72 (±1.5) NU/ml, respectively; but Cp activity decreased by 1.8 (0.7-3.7) mg/dl. Also, we observed lower concentrations of lipid peroxidation markers: by 19.6 ± 24.4 μmol/l for MDA and by 0.4 ± 0.5 RF for LPS. A 21-day postoperative rehabilitation program effectively reduces oxidative processes, which helps the patients after total hip or knee replacement in a successful recovery.

scholarly journals Effects of Resistance, Endurance, and Concurrent Exercise on Oxidative Stress Markers and the Histological Changes of Intestine After Morphine Withdrawal in Rats

2018 ◽  
Vol 6 (2) ◽  
pp. 44-49
Author(s):  
Iraj Salehi ◽  
Ebrahim Zarrinkalam‎ ◽  
Fatemeh Mirzaei ◽  
Ebrahim Abbasi Oshaghi ◽  
Kamal Ranjbar ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Morphological Changes ◽  
Morphine Withdrawal ◽  
Morphological Alteration ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Histological Changes ◽  
Protein Levels ◽  
Stress Markers ◽  
Concurrent Exercise

Objectives: The aim of this study was to evaluate the effects of resistance, endurance, and concurrent exercise on oxidative stress markers and histological changes of the intestine after morphine withdrawal in rats. Methods: A total of 30 male Wistar rats were randomly divided into 5 groups (n=6) including healthy control, withdrawal (rat received morphine for 21 days and 8 weeks of withdrawal period), withdrawal + endurance exercises, withdrawal + resistance exercises, and withdrawal + concurrent exercises. The rats practiced endurance, resistance, and concurrent exercises for 10 weeks. Then, their intestines were removed and used for biochemical and histological analysis. Next, several factors were measured such as total protein levels, malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAC), and total oxidant status (TOS). Finally, the morphological alteration of intestine was examined under the light microscope. Results: Morphine withdrawal significantly increased the levels of MDA in the intestine of withdrawal rats compared to those of the control group while endurance, resistance, and concurrent exercise reduced the MDA levels in the intestine. In addition, morphine withdrawal led to a decrease in TAC and GSH levels in the intestine compared to control rats whereas endurance, resistance, and concurrent exercise noticeably increased TAC and GSH levels. Interestingly, the change in the concurrent group was more significant. Moreover, the levels of TOS demonstrated a significant increase in the addicted rat as compared to the control group. Conversely, endurance, resistance, and concurrent exercise significantly decreased TOS levels and the reduction was more significant in the concurrent group. Finally, the intestine of withdrawal rat was morphologically abnormal while it restored by the exercise. Conclusion: Overall, endurance, resistance, and concurrent exercise significantly normalized oxidative stress and the morphological changes of the intestine in withdrawal rats.

scholarly journals THE PROTECTIVE EFFECTS OF ECHINOPS HETEROPHYLLUS AQUEOUS EXTRACT AGAINST METHOTREXATE-INDUCED HEPATOTOXICITY IN RABBITS

2019 ◽  
Vol 12 (1) ◽  
pp. 384 ◽  
Author(s):  
Heba Abdulmohsin ◽  
Ahmed Abu Raghif ◽  
Mohammed Jabbar Manna
Keyword(s):  
Oxidative Stress ◽  
Liver Damage ◽  
Crude Extract ◽  
Negative Control ◽  
Control Group ◽  
Protective Effects ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Study Results ◽  
Flavonoid Fraction

Objective: The aim of this study was to investigate antioxidant and hepatoprotective properties of Iraqi Echinops heterophyllus aqueous crude extract and its flavonoid fraction against methotrexate (MTX)-induced hepatotoxicity in rabbits.Methods: MTX-induced hepatotoxicity by administration of 20 mg/kg MTX intraperitoneally for 3 successive days was used as animal model, and animals were arrayed in four groups with eight animals in each group: Group 1 was the healthy control, Group 2 - the negative control receiving MTX only, Group 3 received MTX+crude extract of E. heterophyllus, and Group 4 administered MTX+flavonoid fraction of E. heterophyllus. The study duration was 10 days; at day 11, animals were sacrificed, and the blood samples were obtained for the measurement of serum aspartate aminotransferase, alanine aminotransferase, alkaline phosphatase, total bilirubin, total protein, and albumin as well as ELISA assay of the oxidative stress markers such as glutathione (GSH) and malondialdehyde (MDA). The liver was dissected and processed for histopathological investigation and scoring. Statistical analysis was performed to investigate the significance of each result.Results: The study results revealed severe liver damage due to MTX administration in the negative control (induced-non treated) group in comparison with healthy group, also there was significant hepatoprotective effect after administration of the crude extract of E. heterophyllus, and flavonoid fraction from E. heterophyllus shown after biochemical liver function tests and anti-oxidant properties demonstrated by the measurement of oxidative stress markers MDA and GSH. The crude extract of E. heterophyllus shown superior hepatoprotective and antioxidant effect. Histopathological scoring showed a remarkable decrease in the scores of the treatment groups in comparison with the high score in the MTX only treated group.Conclusions: MTX administered in a dose of 20 mg/kg for 3 successive days causes marked liver injury, while treatment with the crude extract and flavonoid fraction of E. heterophyllus significantly ameliorates MTX-induced liver damage, although the crude extract of E. heterophyllus seems to have the most hepatoprotective properties.

scholarly journals Correlation between the Activity of Aldehyde Dehydrogenase and Oxidative Stress Markers in the Saliva of Diabetic Patients

2019 ◽  
Vol 27 (1) ◽  
pp. 67-73
Author(s):  
Hina Younus ◽  
Sumbul Ahmad ◽  
Md. Fazle Alam
Keyword(s):  
Oxidative Stress ◽  
Aldehyde Dehydrogenase ◽  
Early Stage ◽  
Control Group ◽  
Diabetic Patients ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Patients With Diabetes ◽  
Markers Of Oxidative Stress ◽  
And Oxidative Stress

Background: Reactive aldehydes are involved in diseases associated with oxidative stress, including diabetes. Human salivary aldehyde dehydrogenase (hsALDH) presumably protects us from many toxic ingredient/contaminant aldehydes present in food. Objective: This study aimed to probe the activity of hsALDH in patients with diabetes and than to correlate it with various oxidative stress markers in the saliva. Methods: The saliva samples were collected from total 161 diabetic patients from Rajiv Gandhi Centre for Diabetes, Jawaharlal Nehru Medical College (JNMC), AMU, Aligarh, (India). HsALDH activity and markers of oxidative stress [8-hydroxydeoxyguanosine (8-OHDG), malondialdehyde (MDA) and advanced glycation end products (AGEs)] were measured in the saliva samples. Results: Patients with early stage of diabetes had higher activity of hsALDH when compared with the control group. As the history of diabetes increases, the activity of the enzyme decreases and also higher oxidative stress markers (8-OHDG, MDA and AGEs) are detected in the saliva samples. Negative significant correlation between hsALDH activity and oxidative stress markers were observed (p <0.0001). Conclusion: The activity of hsALDH increases in early stages of diabetes most probably to counter the increased oxidative stress associated with diabetes. However, in later stages of diabetes, the activity of the enzyme decreases, possibly due to its inactivation resulting from glycation.

Ferulic acid attenuates osteoporosis induced by glucocorticoid through regulating the GSK-3β/Lrp-5/ERK signalling pathways

2021 ◽  
Author(s):  
Wei Zhou ◽  
Bo Chen ◽  
Jingbo Shang ◽  
Renbo Li
Keyword(s):  
Oxidative Stress ◽  
Ferulic Acid ◽  
Saline Control ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Expression Ratio ◽  
Stress Markers ◽  
Osteogenic Markers ◽  
Gsk 3Β

Abstract Objective To evaluate in-vivo and in-vitro effects of ferulic acid (FA) on glucocorticoid-induced osteoarthritis (GIO) to establish its possible underlying mechanisms. Methods The effects of FA on cell proliferation, cell viability (MTT assay), ALP activity, and mineralization assay, and oxidative stress markers (ROS, SOD, GSH LDH and MDA levels) were investigated by MC3T3-E1 cell line. Wistar rats received standard saline (control group) or dexamethasone (GC, 2 mg−1 kg) or DEX+FA (50 and 100 mg−1 kg) orally for 8 weeks. Bone density, micro-architecture, bio-mechanics, bone turnover markers and histo-morphology were determined. The expression of OPG, RANKL, osteogenic markers, and other signalling proteins was assessed employing quantitative RT-PCR and Western blotting. Results The findings indicated the elevation of ALP mRNA expressions, osteogenic markers (Runx-2, OSX, Col-I, and OSN), and the β-Catenin, Lrp-5 and GSK-3β protein expressions. FA showed the potential to increase MC3T3-E1 cell differentiation, proliferation, and mineralization. FA increased oxidative stress markers (SOD, MDA, and GSH) while decreasing ROS levels and lactate dehydrogenase release in GIO rats. The OPG/RANKL mRNA expression ratio was increased by FA, followed by improved GSK-3β and ERK phosphorylation with enhanced mRNA expressions of Lrp-5 and β-catenin. Conclusion These findings showed that FA improved osteoblasts proliferation with oxidative stress suppression by controlling the Lrp-5/GSK-3β/ERK pathway in GIO, demonstrating the potential pathways involved in the mechanism of actions of FA in GIO therapy.

scholarly journals ANTIHYPERGLYCEMIC AND ANTIOXIDATIVE EFFECTS OF LYGODIUM MICROPHYLLUM IN ALLOXAN INDUCED DIABETIC RATS

2018 ◽  
Vol 10 (12) ◽  
pp. 75
Author(s):  
D. G. Syahidah Nadiah Binti Abdull Majid ◽  
Mohammad Iqbal
Keyword(s):  
Oxidative Stress ◽  
Body Weight ◽  
Blood Glucose ◽  
Fasting Blood Glucose ◽  
Diabetic Rats ◽  
Control Group ◽  
Oxidative Stress Markers ◽  
Stress Markers ◽  
Antioxidative Effects ◽  
And Oxidative Stress

Objective: The antihyperglycemic and antioxidative effects of L. microphyllum were evaluated by using in vivo methods in normal and alloxan induced diabetic rats.Methods: Diabetes was induced in Sprague Dawley rats by injecting alloxan through intravenous (i. v) at a dose of 100 mg/kg of body weight. Aqueous extract of L. microphyllum at different doses (400, 200 and 100 mg/kg of body weight) was administered orally (orogastric intubation) for 14 d. Blood glucose and oxidative stress markers were measured. Hematoxylin and eosin staining method were used to examine the pancreatic tissues.Results: At the 14 d interval, fasting blood glucose showed a reduction in serum glucose levels in animals pretreated with L. microphyllum compared with alloxan alone treated group. Oxidative stress was noticed in rat’s pancreatic tissue as evidenced by a significant decrease in glutathione level, glutathione reductase, glutathione-S-transferase, and catalase activities. Malondialdehyde showed a significant increase compared to the normal saline-treated control group. Serum biochemistry and oxidative stress markers were consistent with the pancreatic histopathological studies. Treatment of diabetic rats with L. microphyllum at a dose level of 100, 200 and 400 mg/kg body weight leaves extract for 14 d significantly prevented these alterations and attenuated alloxan-induced oxidative stress (P<0.05).Conclusion: The results of the present study indicated that the antihyperglycemic potential of L. microphyllum might be ascribable to its antioxidant and free radical scavenging properties. Thus, it is concluded that L. microphyllum may be helpful in the prevention of diabetic complications associated with oxidative stress.

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