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The Brief Measure of Emotional Preoperative Stress (B-MEPS) as a new predictive tool for postoperative pain: A prospective observational cohort study.
Wolmeister, AS, Schiavo, CL, Nazário, KCK, Castro, SMJ, de Souza, A, Caetani, RP, Caumo, W, Stefani, LC
PloS one. 2020;(1):e0227441
Abstract
BACKGROUND Preoperative patients' vulnerabilities such as physical, social, and psychological are implicated in postoperative pain variability. Nevertheless, it is a challenge to analyze a patient's psychological profile in the preoperative period in a practical and consistent way. Thus, we sought to identify if high preoperative emotional stress, evaluated by the Brief Measure of Emotional Preoperative Stress (B-MEPS) scale is associated with higher postoperative pain levels and poor rehabilitation in patients submitted to intermediate or major surgery. Moreover, the possible neurobiological or neurophysiological mechanisms implicated in high preoperative emotional stress, evaluated through preoperative quantitative sensory pain tests and serum biomarkers BDNF and S100B were investigated. METHODS We conducted a prospective, observational, cohort study of ASA 2 and 3 adult patients undergoing major urologic, gynecologic, proctologic and orthopedic surgeries from March 2017 to March 2018. B-MEPS and Central Sensitivity Inventory were evaluated preoperatively, followed by a sequence of experimental pain tests and serum biomarkers collection. Postoperative evaluation carried out within the first 48 hours after surgery comprehended pain at rest and movement-evoked pain, and the consumption of morphine. Quality-of-Recovery was also evaluated in the 3rd postoperative day. RESULTS 23 (15%) out of 150 patients included in the study presented high emotional preoperative stress. Variables significantly related to preoperative stress were: previous psychiatric diagnosis and Central Sensitization Inventory result. Mean movement-evoked pain in the first 12 to 48 hours was 95-105% higher than pain at rest. A mixed model for repeated measures showed a sustainable effect of B-MEPS as a movement-evoked pain predictor. Previous pain, cancer surgery, and preoperative pressure pain tolerance were also independent predictors of postoperative pain. Moderate to severe postoperative movement-evoked pain was predictive of poor rehabilitation in 48 hours after surgery. CONCLUSION We confirmed that a brief screening method of preoperative emotional states could detect individuals prone to experience severe postoperative pain. Specific interventions considering the stress level may be planned in the future to improve perioperative outcomes.
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Molecular Basis of the Beneficial Actions of Resveratrol.
Repossi, G, Das, UN, Eynard, AR
Archives of medical research. 2020;(2):105-114
Abstract
Resveratrol modulates the transcription factor NF-κB, cytochrome P450 isoenzyme CYP1A1, expression and activity of cyclooxygenase (COX) enzymes, Fas/Fas ligand mediated apoptosis, p53, mTOR and cyclins and various phospho-diesterases resulting in an increase in cytosolic cAMP levels. Cyclic AMP, in turn, activates Epac1/CaMKKβ/AMPK/SIRT1/PGC-1α pathway that facilitates increased oxidation of fatty acids, mitochondrial respiration and their biogenesis and gluconeogenesis. Resveratrol triggers apoptosis of activated T cells and suppresses tumor necrosis factor-α (TNF-α), interleukin-17 (IL-17) and other pro-inflammatory molecules and inhibits expression of hypoxia inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) that may explain its anti-inflammatory actions. Polyunsaturated fatty acids (PUFAs) and their anti-inflammatory metabolites lipoxin A4, resolvins, protectins and maresins have a significant role in obesity, type 2 diabetes mellitus (T2DM), metabolic syndrome and cancer. We observed that PUFAs (especially arachidonic acid, AA) and BDNF (brain-derived neurotrophic factor) protect against the cytotoxic actions of alloxan, streptozotocin, benzo(a)pyrene (BP) and doxorubicin. Thus, there is an overlap in the beneficial actions of resveratrol, PUFAs and BDNF suggesting that these molecules may interact and augment synthesis and action of each other. This is supported by the observation that resveratrol and PUFAs modulate gut microbiota and influence stem cell proliferation and differentiation. Since resveratrol is not easily absorbed from the gut it is likely that it may act on endocannabinoid and light, odor, and taste receptors located in the gut, which, in turn, convey their messages to the various organs via vagus nerve.
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BDNF Met allele Is Associated With Lower Cognitive Function in Poststroke Rehabilitation.
Han, Z, Qi, L, Xu, Q, Xu, M, Cai, L, Wong, J, Hu, X, Luo, X, Wang, J, Zhang, Y, et al
Neurorehabilitation and neural repair. 2020;(3):247-259
Abstract
Background and purpose. The identification of a genetic role for cognitive outcome could influence the design of individualized treatment in poststroke rehabilitation. The aim of this study is to determine whether brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is independently associated with poststroke functional outcome. Methods. A total of 775 stroke patients with genomic data were identified from the Partners HealthCare Biobank, which contains a large number of genotypes from Biobank's consented patients. Of 775 stroke patients who met the inclusion/exclusion criteria, 86 were enrolled. Functional outcomes were assessed using the Functional Independence Measure scores at the time of admission and discharge. Logistic and linear regression models adjusted for covariate variables, including age, sex, and medical conditions, were used to evaluate the association between BDNF Val66Met and functional outcome. Results. We detected a significant correlation between Met alleles and lower cognitive function at discharge in both ischemic and hemorrhagic stroke patients. Genotyping findings confirmed that BDNF Met allele frequency was higher in contrast to Val/Val allele frequency in lower cognitive functional recovery. Furthermore, after adjusting for covariate variables, BDNF Met alleles were found to be associated with lower cognitive outcome [P = .003; odds ratio (OR) = 5.95 (1.81-19.52)] and recovery [P = .006; OR = 3.16 (1.4-7.15)], especially with lower problem solving, expression, and social recovery in all stroke patients. Conclusions. Met allele carriers exhibited impaired poststroke cognitive function. The BDNF genotype may be a useful predictor of cognitive function in inpatient poststroke rehabilitation.
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Brain-Derived Neurotrophic Factor during Oral Glucose Tolerance Test Predicts Cardiovascular Outcomes.
Lee, IT, Li, YH, Sheu, WH
International journal of molecular sciences. 2020;(14)
Abstract
We investigated if brain-derived neurotrophic factor (BDNF) accumulation after glucose intake could predict cardiovascular outcomes. We enrolled patients admitted for angiography due to angina. After their conditions stabilized, serum BDNF levels were detected at 0, 30, and 120 min during oral glucose tolerance test (OGTT). Area under the curve (AUC) of BDNF was calculated. The first occurrence of nonfatal myocardial infarction, nonfatal stroke, and all-cause mortality served as the primary composite endpoint. Of 480 enrolled patients, 428 completed the follow-up, and 36 primary endpoint events occurred during a median follow-up of 4.4 years. The area under the receiver operating characteristic curve significantly increased from 0.61 (95% confidence interval (CI): 0.52-0.73) for the Framingham risk score (FRS) alone model to 0.72 (95%CI: 0.63-0.81) for the AUC of BDNF plus FRS model (p = 0.016) for predicting the primary endpoint, but not to 0.65 (95%CI: 0.55-0.75) for the fasting BDNF plus FRS model (p = 0.160). Grouped by median AUC of BDNF of 38.0 (ng/mL) × h, the low BDNF group had a significantly higher risk of the endpoint than the high BDNF group (hazard ratio = 3.410, 95%CI: 1.520-7.653, p = 0.003). In conclusion, AUC of BDNF during OGTT could be superior to fasting BDNF for predicting a low cardiovascular risk.
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Meta-analytic method reveal a significant association of theBDNF Val66Met variant with smoking persistence based on a large samples.
Zhao, H, Xiong, S, Li, Z, Wu, X, Li, L
The pharmacogenomics journal. 2020;(3):398-407
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Abstract
Although numerous genetic studies have reported the link between Val66Met in BDNF gene with smoking, the findings remain controversial, mainly due to small-to-moderate sample sizes. The main aim of current investigation is to explore whether the variant of Val66Met has any genetic functions in the progress of smoking persistence. The Val-based dominant genetic model considering Val/* (namely, Val/Val + Val/Met) and Met/Met as two genotypes with comparison of the frequency of each genotype in current smokers and never smokers. There were seven genetic association articles including eight independent datasets with 10,160 participants were chosen in current meta-analytic investigation. In light of the potent effects of ethnicity on homogeneity across studies, we carried out separated meta-analyses according to the ancestry origin by using the wide-used tool of Comprehensive Meta-analysis software (V 2.0). Our meta-analyses results indicated that the Val66Met polymorphism was significantly linked with smoking persistence based on either all the chosen samples (N = 10,160; Random and fixed models: pooled OR = 1.23; 95% CI = 1.03-1.46; P value = 0.012) or Asian samples (N = 2,095; Fixed model: pooled OR = 1.25; 95% CI = 1.01-1.54; P value = 0.044; Random model: pooled OR = 1.25; 95% CI = 1.001-1.56; P value = 0.049). No significant clue of bias in publications or heterogeneity across studies was detected. Thus, we conclude that the Val66Met (rs6265) variant conveys genetic susceptibility to maintaining smoking, and smokers who carry Val/* genotypes have a higher possibility of maintaining smoking than those having Met/Met genotype.
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Effects of vitamin D and/or magnesium supplementation on mood, serum levels of BDNF, inflammatory biomarkers, and SIRT1 in obese women: a study protocol for a double-blind, randomized, placebo-controlled trial.
Abiri, B, Vafa, M
Trials. 2020;(1):225
Abstract
BACKGROUND Emerging evidence has shown that vitamin D and magnesium have anti-inflammatory and anti-depressant effects. Dietary intake of magnesium is associated with reduced body mass index, waist circumference, body fat percentage, as well as inflammatory biomarkers and depressive symptoms. Vitamin D deficiency has been linked to inflammation, obesity, and depressive symptoms. This study will test the effects of vitamin D and magnesium co-supplementation on mood, serum level of brain-derived neurotrophic factor (BDNF), inflammation, and sirtuin 1 (SIRT1) in obese women. METHODS We will conduct an 8-week, double-blind, randomized, placebo-controlled clinical trial, in a factorial design, to evaluate the individual effects of vitamin D and magnesium, and co-supplementation of them, on mood, serum level of BDNF, inflammation, and SIRT1 in 108 obese women. DISCUSSION We hypothesize that vitamin D and magnesium co-supplementation may provide a new adjuvant therapy through modulation of BDNF, inflammation, and SIRT1 in obese women. TRIAL REGISTRATION Iranian Registry of Clinical Trials, IRCT20090822002365N23. Registered on 16 August 2019.
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Serum Brain-Derived Neurotrophic Factor is Related to Platelet Reactivity and Metformin Treatment in Adult Patients With Type 2 Diabetes Mellitus.
Eyileten, C, Mirowska-Guzel, D, Milanowski, L, Zaremba, M, Rosiak, M, Cudna, A, Kaplon-Cieslicka, A, Opolski, G, Filipiak, KJ, Malek, L, et al
Canadian journal of diabetes. 2019;(1):19-26
Abstract
OBJECTIVES The aim of this study was to investigate the association of serum brain-derived neurotrophic factor (BDNF) levels with platelet reactivity and antidiabetes treatment, as well as serum adipocytokine concentrations. METHODS This observational, open-label study enrolled 149 patients. Serum BDNF, hematologic, biochemical parameters and platelet reactivity were measured. Blood samples were taken after the last acetylsalicylic acid dose. RESULTS Patients with high BDNF levels were younger (65.60±8.956 vs. 68.59±8.516) and smoked cigarettes more frequently (14.6% vs. 4.1%); they were more commonly being treated by metformin (77.3% vs. 54%); had higher platelet counts (245.81±68.85 103/mm3 vs. 206.61±44.48 103/mm3); had shorter collagen-adenosine diphosphate closure time (CADP-CT) values (104.88±69.73 s vs. 140.93±86.63 s); had higher triglyceride concentrations (140.73±67.5 vs. 121.76±60.49) and had higher concentrations of serum thromboxane B2 (0.938±1.59 vs. 0.364±0.76). In univariate linear regression analyses, predictive factors for serum BDNF levels above the median were metformin treatment, current smoking, platelet count, triglyceride concentration, total cholesterol concentration and CADP-CT >74 s. In multivariate backward stepwise analysis CADP-CT >141 s; adiponectin concentration >4.22 µg/mL; total cholesterol and low-density lipoprotein levels were independently associated with serum BDNF levels above the median. CONCLUSIONS Our results suggest that BDNF may be associated with lipid metabolism and that increased production of BDNF may be related to metformin treatment. Moreover, we showed an association between BDNF levels and platelet reactivity; we found that serum BDNF levels in patients with type 2 diabetes who had high platelet reactivity were higher than in subjects with normal platelet reactivity despite antiplatelet therapy.
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Sedentarism, Physical Activity, Steps, and Neurotrophic Factors in Obese Children.
Mora-Gonzalez, J, Migueles, JH, Esteban-Cornejo, I, Cadenas-Sanchez, C, Pastor-Villaescusa, B, Molina-García, P, Rodriguez-Ayllon, M, Rico, MC, Gil, A, Aguilera, CM, et al
Medicine and science in sports and exercise. 2019;(11):2325-2333
Abstract
PURPOSE This study aimed to examine the associations of sedentary time, physical activity (PA) and step-related behaviors with neurotrophic growth factors. METHODS A total of 97 children with overweight/obesity age 8 to 11 yr participated in this study. Sedentary time, PA, and steps were measured by GT3X+ accelerometers in hip and nondominant wrist. Estimates of light, moderate, vigorous, and moderate-to-vigorous PA (MVPA) were obtained. Steps per daytime, peak 60-, 30-, and 1-min cadence were computed. The time accumulated (min·d) in different cadence bands of steps was also computed from hip accelerometer. Plasma levels of brain-derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin growth factor-1 (IGF-1) were determined by the XMap technology (Luminex IS 100/200 system, Luminex Corporation, Austin, TX). RESULTS Light PA, moderate PA, MVPA, and the peak 60-min cadence were positively related with BDNF concentrations (all P < 0.05), and only light PA to VEGF (P = 0.048). No association was observed for IGF-1 (P > 0.05). The associations of light PA with BDNF and VEGF disappeared (all P > 0.05) after performing analyses with nondominant wrist-placement data. However, moderate PA and MVPA remained significantly associated with BDNF (both P < 0.05). The time accumulated in cadence bands of 40 to 59 steps per day and 60 to 79 steps per day (i.e., walking at slow pace) was positively associated with plasma BDNF (all P < 0.05). CONCLUSIONS In conclusion, PA is positively related to plasma BDNF, whereas no relationship was observed for VEGF or IGF-1. Higher amounts of time spent in slow walking cadence bands could increment BDNF levels. Exercise-based randomized controlled trials in children with overweight/obesity should be carried out to better understand the influence of PA behaviors on the neurotrophic factors.
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Effects of medium-term green tea extract supplementation combined with CrossFit workout on blood antioxidant status and serum brain-derived neurotrophic factor in young men: a pilot study.
Sadowska-Krępa, E, Domaszewski, P, Pokora, I, Żebrowska, A, Gdańska, A, Podgórski, T
Journal of the International Society of Sports Nutrition. 2019;(1):13
Abstract
BACKGROUND Potential health benefits are attributed to the antioxidant properties of green tea polyphenolic compounds. The main aim of the study was to evaluate the effects of a six-week green tea extract (GTE) supplementation combined with CrossFit workout on blood antioxidant status and serum brain-derived neurotrophic factor (BDNF) in men. METHODS Sixteen young males involved in CrossFit training were randomized into two groups supplemented with GTE or placebo for six weeks. Each participant performed an exercise test for the evaluation of maximum oxygen uptake (VO2max) twice, i.e., before starting (1st trial) and after completing the supplementation combined with CrosFit workout (2nd trial). Venous blood samples were drawn at rest, immediately post-test and after one hour of recovery in order to estimate activities of antioxidant enzymes (superoxide dismutase [SOD], catalase [CAT], glutathione peroxidase [GPx], reduced glutathione [GR]), non-enzymatic antioxidants (reduced glutathione [GSH], uric acid [UA], total phenolics), total antioxidant capacity (FRAP), lipid peroxidation products (TBARS), and BDNF. RESULTS Except for a significantly higher SOD activity and FRAP level recorded at rest and post-exercise in the 2nd trial compared to the corresponding values in the 1st trial, no significant differences were recorded among other assayed measures such as CAT, GPx, GR, GSH and BDNF. Moreover, a percentage increase in FRAP level was twice as high after six weeks' GTE consumption than after placebo. Regardless of the trial, an increase in plasma UA concentration and a decrease in plasma total phenolics level were observed after exercise test. Plasma TBARS concentrations were significantly higher in PLA group after six weeks' CrossFit training, while in GTE group they were slightly lower compared to the corresponding values in the 1st trial. Moreover, there was a significant inverse correlation between FRAP and TBARS in the GTE-supplemented group (r = - 0.40, p < 0.05). CONCLUSIONS A six weeks' consumption of GTE had marginal effect on aerobic capacity and serum BDNF level in CrossFit-trained men, but it caused a marked increase in the blood antioxidant capacity and a moderate attenuation of the training-induced lipid peroxidation.
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A Pilot Study of the Use of Dexmedetomidine for the Control of Delirium by Reducing the Serum Concentrations of Brain-Derived Neurotrophic Factor, Neuron-Specific Enolase, and S100B in Polytrauma Patients.
Li, Y, Yu, ZX, Ji, MS, Yan, J, Cai, Y, Liu, J, Yang, HF, Jin, ZC
Journal of intensive care medicine. 2019;(8):674-681
Abstract
BACKGROUND Delirium is very common among patients with polytrauma, although no suitable means exist to feasibly reduce the incidence and duration of delirium in these patients. Recent reports have suggested that continuous intravenous (IV) infusions of dexmedetomidine, rather than benzodiazepine, be administered for sedation to reduce the duration of delirium in this population. However, serum neuron-specific enolase (NSE), S100 calcium binding protein B (S100B), and brain-derived neurotrophic factor (BDNF) levels have not yet been investigated in polytrauma patients who received sedation with dexmedetomidine rather than other conventional sedatives. The aim of this study was to assess the association of blood BDNF, NSE, and S100B with the occurrence of delirium among polytrauma patients who had been sedated with dexmedetomidine. MATERIALS AND METHODS Consecutive patients were randomly assigned to 1 of 2 treatment study groups, namely the "dexmedetomidine group" or the "common group." This case-control study included 18 patients with delirium and 34 matched controls in a 63-bed general intensive care unit (ICU). Blood samples were collected from all patients upon ICU admission, on the day when delirium was diagnosed, and on days 3 and 5 following diagnosis. The serum levels of S100B, BDNF, and NSE were determined by enzyme-linked immunosorbent assay. The sedation levels and delirium were assessed using the Richmond Agitation and Sedation Scale and the Confusion Assessment Method for the ICU. RESULTS The median BDNF, NSE, and S100B concentrations were significantly lower in the dexmedetomidine group than in the common group on the day when delirium was diagnosed and on the third day after delirium was diagnosed. The rate of delirium was significantly lower in the dexmedetomidine group than in the common group. There were clear differences in the BDNF, NSE, and S100B levels between the 2 groups on the fifth day after delirium was diagnosed. CONCLUSIONS Our randomized controlled study suggests that the sedation of polytrauma patients with dexmedetomidine could help reduce the serum BDNF, S100B, and NSE levels, which appear to be associated with the occurrence of delirium in the dexmedetomidine group.