Cytokine mRNA Expression in Painful Radiculopathy

Inflammatory cytokines contribute to lumbar radiculopathy. Regulation of cytokines for transient cervical injuries, with or without longer-lasting inflammation, remains to be defined. The C7 root in the rat underwent compression (10gf), chromic gut suture exposure (chr), or their combination (10gf+chr). Ipsilateral C7 spinal cord and dorsal root ganglia (DRG) were harvested at 1 hour after injury for real-time PCR analysis of IL-1β, IL-6, and TNF-α. Cytokine mRNA increased after all 3 injuries. TNF-α mRNA in the DRG was significantly increased over sham after 10gf+chr (P = .026). Spinal IL-1β was significantly increased over sham after 10gf and 10gf+chr (P < .024); IL-6 was significantly increased after 10gf+chr (P < .024). In separate studies, the soluble TNF-α receptor was administered at injury and again at 6 hours in all injury paradigms. Allodynia was assessed and tissue samples were harvested for cytokine PCR. Allodynia significantly decreased with receptor administration for 10gf and 10gf+chr (P < .005). Treatment also significantly decreased IL-1β and TNF-α mRNA in the DRG for 10gf+chr (P < .028) at day 1. Results indicate an acute, robust cytokine response in cervical nerve root injury with varying patterns, dependent on injury type, and that early increases in TNF-α mRNA in the DRG may drive pain-related signaling for transient cervical injuries.PerspectiveInflammatory cytokine mRNA in the DRG and spinal cord are defined after painful cervical nerve root injury. Studies describe a role for TNF-α in mediating behavioral sensitivity and inflammatory cytokines in transient painful radiculopathy. Results outline an early response of inflammatory cytokine upregulation in cervical pain.     

Extracorporeal Shock Wave Therapy Combined With Oral Medication and Exercise for Chronic Low Back Pain: A Randomized Controlled Trial

ObjectiveTo compare extracorporeal shock wave therapy combined with oral medication and an exercise program vs sham treatment with medication and exercise for the treatment of chronic low back pain (CLBP).DesignRandomized controlled trial.SettingOutpatient clinic at a university hospital.ParticipantsEligibility criteria were age older than 18 years and duration of CLBP exceeding 3 months. Exclusion criteria were concurrent treatment or history of surgery for CLBP, cancer, fractures, infections, and disk degeneration.InterventionThe intervention group received extracorporeal shock wave therapy once a week for 4 weeks along with oral medications and an exercise program. The control group received sham extracorporeal shock wave therapy along with oral medications and an exercise program.Main Outcome MeasuresVisual analog scale and Oswestry Disability Index (ODI) were used to assess pain and disability at baseline and after 3 months.ResultsThe pain score in the intervention group (N=16) was 6.6 at baseline and 3.0 after 1 month (P<.0001) and 1.8 after 3 months (P<.0001). In the control group (N=16), the pain score was 6.8 at baseline, 4.6 after 1 month (P<.0001), and 1.1 after 3 months (P<.0001). ODI scores decreased significantly in both groups compared with baseline values (first month: P<.001, third month: P<.05). The mean ODI score did not differ significantly between the groups (P=.942).ConclusionExtracorporeal shock wave therapy combined with oral medication and exercise was safe and effective in the short-term treatment of chronic low back pain.     

A comparison between whole-body vibration and conventional training on pain and performance in athletes with patellofemoral pain

IntroductionPatellofemoral pain (PFP) is the most common cause of anterior knee pain in athletes, which affects their performance especially during single leg activities. The aim of this study was to compare the effects of whole-body vibration training (WBVT) and conventional training (CT) on pain and performance in athletes with PFP.Methods30 athletes with unilateral PFP were randomly assigned to the WBVT (6 women, 9 men) or CT (7 women, 8 men) group. All participants received training for 4 weeks in 12 sessions. The outcomes of pain and performance were measured at three points in time: baseline, immediately after training and 2 weeks after training. Pain was assessed with the Numeric Pain Rating Scale (NPRS). Performance was measured with the leg-press test and the Kujala Patellofemoral Score (KPS).ResultsIn both groups, pain intensity decreased significantly (p < 0.001) and the KPS and number of leg presses increased significantly (p < 0.001) with time. There was no significant difference between groups for changes in the pain score (p = 0.896), KPS (p = 0.463) or leg press (p = 0.796) results.ConclusionWhole-body vibration training had the same effect as exercise therapy on pain reduction and on improvements in performance in athletes with PFP.     

Inflammatory markers as related to disease severity in patients with chronic heart failure: Limited effects of exercise training

Abstract

Background. Chronic heart failure (CHF) is associated with increased inflammation, and exercise training has in some studies been shown to have anti-inflammatory effect, although controversies exist. We investigated the effects of exercise training in CHF patients on markers of inflammation, and further explored any association between inflammation and the severity and etiology of the disease. Methods. Eighty patients in stable CHF were randomized to 4 months of group-based high intensity exercise training or to a control group. Physical capacity was measured by 6-minute walk test and cycle ergometer test. Blood samples were drawn at baseline, after 4 months and after 12 months follow-up for analyses of a range of biomarkers. Results. Physical capacity was significantly inversely related to CRP, IL-6, VCAM-1 and TGF-β, and NT pro-BNP levels were significantly correlated to CRP, TNF-α, IL-6, VCAM-1, ICAM-1 and TGF-β (p < 0.05 for all). Patients with hypertension as etiology of CHF showed higher levels of CRP (p < 0.01), IL-6 (p = 0.05) and TNF-α (p = 0.02) as compared to other etiologies. No significant differences in changes between the exercise group and the control group were obtained in any of the measured variables, except in patients with idiopathic dilated cardiomyopathy (IDCM), where significant reductions in CRP, ICAM-1, TGF-β and TNF-α levels were observed (p < 0.05 for all). Conclusions. Measures of CHF severity were significantly correlated with several markers of inflammation. We could not demonstrate over-all anti-inflammatory effect of exercise in this population of CHF patients. However, the etiology of CHF affected the inflammatory profile and the effect of exercise training.     

Effects of myofascial trigger point dry cupping on pain and function in patients with plantar heel pain: A randomized controlled trial

ObjectiveTo investigate the effects of dry cupping on calf muscle myofascial trigger points (MTrPs) on pain and function in patients with plantar heel pain.MethodsSeventy-one patients were randomly divided into an intervention group or control group. Both groups performed stretching exercises for the calf muscle and plantar fascia and ankle dorsiflexion exercises. The intervention group also received dry cupping. The primary outcome measures were visual analogue scale (VAS), pressure pain threshold (PPT), and patient-specific functional scale (PSFS). The secondary outcomes were ankle dorsiflexion range of motion (ROM) and ankle plantar flexor strength. These measurements were performed at baseline, immediately after intervention, and after 2 days.ResultsCurrent VAS significantly decreased immediately in the intervention group (p = 0.002), but not in the control group (p ≥ 0.220). Morning VAS decreased significantly in both groups (p < 0.001) after 2 days, but decreased more in the intervention group (p = 0.006). Trigger point PPT significantly improved immediately in the intervention group (p = 0.003), but not in the control group (p = 0.112). Both groups improved significantly in PSFS (p < 0.001) and ankle dorsiflexion ROM (p < 0.001). Plantar flexor strength significantly increased immediately in the intervention group (p < 0.001), but not in the control group (p = 0.556).ConclusionAdding dry cupping on calf MTrPs to self-stretching and ankle dorsiflexion exercises for patients with plantar heel pain was superior to only self-stretching and active ankle dorsiflexion exercises in pain, ankle dorsiflexion ROM, and plantar flexor strength.     

Time of sampling is crucial for measurement of cell-free plasma DNA following acute aseptic inflammation induced by exercise

ObjectivesTo determine the time-course changes of cell-free plasma DNA (cfDNA) following heavy exercise.MethodscfDNA concentration, C-reactive protein levels (hs-CRP), uric acid concentration (UA), creatine kinase activity (CK) were measured before and post-exercise (immediately post, 0.5 h, 1 h, 2 h, 3 h, 4 h, 5 h, 6 h, 8 h, 10 h, 24 h).ResultscfDNA increased (15-fold) 30-min post-exercise and normalized thereafter. hs-CRP increased (56%, p < 0.001) 1 h post-exercise, remained elevated throughout recovery (52–142%, p < 0.0001), and peaked (200% rise, p < 0.0001) at 24 h post-exercise. UA and CK increased (p < 0.05), immediately post-exercise, remained elevated throughout recovery (p < 0.0001), and peaked (p < 0.0001) at 24 h of post-exercise recovery.ConclusionscfDNA sampling timing is crucial and a potential source of error following aseptic inflammation.     

Minocycline attenuates brain tissue levels of TNF-α produced by neurons after prolonged hypothermic cardiac arrest in rats

Neuro-cognitive disabilities are a well-recognized complication of hypothermic circulatory arrest. We and others have reported that prolonged cardiac arrest (CA) produces neuronal death and microglial proliferation and activation that are only partially mitigated by hypothermia. Microglia, and possibly other cells, are suggested to elaborate tumor necrosis factor alpha (TNF-α), which can trigger neuronal death cascades and exacerbate edema after CNS insults. Minocycline is neuroprotective in some brain ischemia models in part by blunting the microglial response. We tested the hypothesis that minocycline would attenuate neuroinflammation as reflected by brain tissue levels of TNF-α after hypothermic CA in rats. Rats were subjected to rapid exsanguination, followed by a 6 min normothermic CA. Hypothermia (30 °C) was then induced by an aortic saline flush. After a total of 20 min CA, resuscitation was achieved via cardiopulmonary bypass (CPB). After 5 min reperfusion, minocycline (90 mg kg⁻¹; n = 6) or vehicle (PBS; n = 6) was given. Hypothermia (34 °C) was maintained for 6 h. Rats were sacrificed at 6 or 24 h. TNF-α was quantified (ELISA) in four brain regions (cerebellum, CEREB; cortex, CTX; hippocampus, HIP; striatum, STRI). Naïve rats (n = 6) and rats subjected to the same anesthesia and CPB but no CA served as controls (n = 6). Immunocytochemistry was used to localize TNF-α. Naïve rats and CPB controls had no detectable TNF-α in any brain region. CA markedly increased brain TNF-α. Regional differences were seen, with the highest TNF-α levels in striatum in CA groups (10-fold higher, P < 0.05 vs. all other brain regions). TNF-α was undetectable at 24 h. Minocycline attenuated TNF-α levels in CTX, HIP and STRI (P < 0.05). TNF-α showed unique co-localization with neurons. In conclusion, we report region-dependent early increases in brain TNF-α levels after prolonged hypothermic CA, with maximal increases in striatum. Surprisingly, TNF-α co-localized in neurons and not microglia. Minocycline attenuated TNF-α by approximately 50% but did not totally ablate its production. That minocycline decreased brain TNF-α levels suggests that it may represent a therapeutic adjunct to hypothermia in CA neuroprotection.     

Effect of the Renin-Angiotensin System Inhibitors on Inflammatory Markers: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ObjectiveTo synthesize more conclusive evidence on the anti-inflammatory effects of angiotensin-converting enzyme inhibitors (ACEIs) and angiotensin receptor blockers (ARBs).MethodsPubMed, Scopus, and Embase were searched from inception until March 1, 2021. We included randomized controlled trials (RCTs) that assessed the effect of ACEIs or ARBs, compared with placebo, on any of the following markers: C-reactive protein (CRP), interleukin 6 (IL-6), or tumor necrosis factor α (TNF-α). Mean changes in the levels of these markers were pooled as a weighted mean difference (WMD) with a 95% CI.ResultsThirty-two RCTs (n=3489 patients) were included in the final analysis. Overall pooled analysis suggested that ACEIs significantly reduced plasma levels of CRP (WMD, ?0.54 [95% CI, ?0.88 to ?0.21]; P=.002; I²=96%), IL-6 (WMD, ?0.84 [95% CI, ?1.03 to ?0.64]; P<.001; I²=0%), and TNF-α (WMD, ?12.75 [95% CI, ?17.20 to ?8.29]; P<.001; I²=99%). Moreover, ARBs showed a significant reduction only in IL-6 (WMD, ?1.34 [95% CI, ?2.65 to ?0.04]; P=.04; I²=85%) and did not significantly affect CRP (P=.15) or TNF-α (P=.97) levels. The lowering effect of ACEIs on CRP levels remained significant with enalapril (P=.006) and perindopril (P=.01) as well as with a treatment duration of less than 24 weeks (WMD, -0.67 [95% CI, ?1.07 to -0.27]; P=.001; I²=94%) and in patients with coronary artery disease (WMD, ?0.75 [95% CI, ?1.17 to ?0.33]; P<.001; I²=96%).ConclusionBased on this meta-analysis, ACEIs showed a beneficial lowering effect on CRP, IL-6, and TNF-α, whereas ARBs were effective as a class in reduction of IL-6 only.     

Effect of Propolis Intake on Serum C-Reactive Protein (CRP) and Tumor Necrosis Factor-alpha (TNF-α) Levels in Adults: A Systematic Review and Meta-Analysis of Clinical Trials

BackgroundPropolis is a natural Product and the antioxidant properties of Propolis appear to be principally responsible for its therapeutic effects. However, several studies have shown the positive effect of Propolis on the reduction the levels of inflammatory markers; some others have revealed non-significant impacts on them. Hence, the present systematic review and meta-analysis aimed to investigate the effects of Propolis intake on C-reactive protein (CRP) and tumor necrosis factor-alpha (TNF-α).MethodsThe systematic search was undertaken in scientific databases that included: PubMed, Embase, Scopus and Web of Science to find studies assessing the effects of Propolis on CRP and TNF-α up to December 2019. Standardized mean difference (SMD) and 95 % confidence intervals (CI) were pooled using a random-effects model. Potential publication bias was tested using Egger’s test.ResultsSix studies comprising 406 participants were included in the meta-analysis. Compared to controls, Propolis intake significantly reduced serum TNF-α (SMD = −0.48, 95 % CI = [−0.69, −0.26], P < 0.0001, I² = 66.9 %) and CRP (SMD = −0.38, 95 % CI = [−0.68, −0.07], P = 0.01, I² = 44.4 %) levels. No evidence of publication bias was found in the meta-analyses.ConclusionThe present study concluded in the statistically and clinically reduction of serum CRP and TNF-α levels following Propolis intake.     

The effect of aerobic exercise on immune biomarkers and symptoms severity and progression in patients with COVID-19: A randomized control trial

BackgroundThe World Health Organization in March 2020 has announced that COVID-19 is a world pandemic because the number of infected cases increases rapidly. however, there are several available vaccines, their protection is limited to a certain period. Thus, the role of modalities that improve immune functions should be performed to counter COVID-19 viral load and decrease mortality rates.ObjectiveTo investigate the effect of aerobic exercise on immune biomarkers, disease severity, and progression in patients with COVID-19.DesignA randomized controlled study.ParticipantsThirty patients with COVID-19 participated in this study. Participants’ age ranged from 24 to 45 years old. Participants had a mild or moderate COVID-19. Participants were assigned randomly into two groups, exercise and control groups. There were two main dependent variables including blood immune markers and severity of respiratory symptoms.InterventionsAll participants performed 2 weeks of moderate-intensity aerobic exercise for 40 min/session, 3 sessions/week. The measurements were performed at baseline, and after 2-weeks.ResultsAt baseline measurements, there were non-significant differences between both groups in the Wisconsin scale total score, Leucocytes, Lymphocytes, Interleukin-6, Interleukin-10, Immunoglobulin-A, and TNF-α (P > .05). After the intervention, the Wisconsin scale (patient-oriented illness-specific quality-of-life) total score significantly decreased in the intervention group (P < .05); while, Leucocytes, Lymphocytes, and Immunoglobulin-A significantly increased in the intervention group (P < .05).ConclusionThe current study indicated that 2 weeks of moderate-intensity aerobic exercise decreased the severity and progression of COVID-19 associated disorders and quality of life. Also, a 2-weeks of aerobic exercise positively affected immune function by increasing the amounts of Leucocytes, Lymphocytes, Immunoglobulin A.     

Reference Values for the Headache Impact Test-6 Questionnaire

ObjectiveTo determine reference values for the Headache Impact Test-6 (HIT-6) in a young, physically active cohort and to examine the influence of sex, concussion history, headache history, and competitive sport level on HIT-6 scores.DesignCross-sectional.SettingUnited States Service Academy.ParticipantsUnited States Service Academy cadets (N=2678) completed an HIT-6 questionnaire as part of their annual concussion baseline assessment. Cadets with a recent concussion were excluded from baseline testing.InterventionsNot applicable.Main Outcome MeasuresReference values were calculated and stratified by sex, concussion history, headache history, and competitive sport level. Mann-Whitney U and Kruskal-Wallis tests were used to examine the effect of sex, concussion history, headache history, and competitive sport level on HIT-6 scores (P<.05).ResultsOf the 3599 cadets baselined, 2687 cadets (23% female) agreed to participate in the study and completed the HIT-6. Female participants reported significantly worse HIT-6 scores compared with male participants both with (P<.001) and without (P<.001) a concussion history. In both sexes, participants with a headache history reported worse scores than those with no headache/concussion history and a concussion history (all P<.005). Female cadets who participated in intramural athletics reported worse HIT-6 scores at baseline than female intercollegiate athletes (P=.003).ConclusionsThis is the first study to stratify HIT-6 data by sex, concussion history, headache history, and sport level in a collegiate population at risk for concussions. Sex and headache history appear to influence HIT-6 scores and should be given special consideration when interpreting health-related quality of life deficits due to headache.     

Exercise is a potent stimulus for enhancing circulating DNase activity

Objectives

To elucidate cell free DNA (cfDNA) clearance kinetics following an acute bout of high intensity exercise by measuring circulating DNase activity reduction (AR).

Design and methods

Serum cfDNA concentration and DNase-AR were measured prior to and post (immediately post, 7 and 30 min post) an acute bout of rowing exercise until exhaustion.

Results

Serum cfDNA concentration was significantly (P ≤ .001) elevated immediately post (2.5-fold) and 7 min post exercise (2.3-fold) with a return close to baseline at 30 min post exercise (1.5-fold). The rise in cfDNA was accompanied by a concomitant, significant (P ≤ .001) decrease in serum DNase-AR from 15.1% prior to exercise to 3.1% AR at cessation of the exercise test and 7 min post exercise (3.9% AR). DNase-AR returned close to baseline at 30 min post exercise (5.2% AR).

Conclusions

A single bout of high intensity exercise is a potent stimulus for enhancing circulating DNase activity in healthy people. Acute exercise may therefore be considered as a non-pharmacological stimulus to trigger DNase activity.This finding may be relevant for pathological conditions associated with increased cfDNA concentrations like cystic fibrosis, where pharmacological recombinant human DNase (rhDNase) treatment has been successfully used to improve patients' health and physical function.     

Activation of adenosine A1 receptor attenuates tumor necrosis factor-α induced hypertrophy of cardiomyocytes

Tumor necrosis factor (TNF)-α has been implicated in the pathogenesis of cardiac hypertrophy, while the activation of adenosine receptors has been shown to exert antihypertrophic effect on the heart. However, it remains unknown whether adenosine can attenuate hypertrophy induced by TNF-α. This study was aimed to address this issue using transverse aortic constriction (TAC) mouse models and cultured neonatal rat cardiomyocytes. Plasma TNF-α was significantly increased in hypertrophied hearts (Sham vs TAC group: 46.8 ± 2.5 vs 67.0 ± 1.6 pg/ml, P = 0.021), while myocardial TNF-α level, expression of TNF receptor 1 and TNF-α-converting enzyme were positively correlated with heart weight to body weight ratio (r = 0.930, 0.676 and 0.891, respectively, P < 0.01-0.05). Myocardial adenosine levels were increased significantly at 4 weeks (Sham vs TAC group: 16.15 ± 1.59 vs 86.54 ± 13.49 nmol/mg protein, P < 0.01) and decreased from 6 to 11 weeks after TAC. N6-cyclopentyladenosine, an adenosine A1 receptor agonist inhibited protein synthesis of cardiomyocytes induced by TNF-α in a dose-dependent manner. This antihypertrophic effect could not be mimicked by agonists of A2a, A2b and A3 adenosine receptors. These findings indicate that TNF-α signal system plays important role in the process of cardiac hypertrophy, and activation of adenosine receptor 1 inhibits hypertrophy of cardiomyocytes induced by TNF-α.     

Endomorphins and ohmefentanyl in the inhibition of immunosuppressant function in rat peritoneal macrophages: An experimental in vitro study

Background: The potential immunosuppressant effects of opioids might have clinical implications. The effects of endomorphins (EMs) and ohmefentanyl (OMF) on cultured rat peritoneal macrophages remain unclear.Objective: The aim of this study was to investigate the immunosuppressant effects of EMs and OMF on cultured rat peritoneal macrophages in vitro.Methods: Purified rat peritoneal macrophages, from healthy adult male Sprague-Dawley rats, were cultured with EM-1 (EM-1 group), EM-2 (EM-2 group), OMF (OMF group), and saline (saline group). We measured the concentrations of tumor necrosis factor (TNF)-α and interleukin (IL)-β in supernatant when macrophages were cultured with 10⁻⁶ mol/L of EM-1, EM-2, OMF, or saline for 0, 6, 12, and 24 hours (time-effect relationship) or with 10⁻¹⁰, 10⁻⁹, 10⁻⁸, 10⁻⁷, and 10⁻⁶ mol/L of these substances for 24 hours (concentration-effect relationship). We also determined the phagocytic and bactericidal activities of macrophages using isotope markers when macrophages were cultured with 10⁻⁶ mol/L of EM-1, EM-2, OMF, or saline for 24 hours.Results: Compared with the saline group, TNF-α concentration decreased significantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Compared with the saline group, IL-1β concentration decreased signifcantly in the OMF, EM-2, and EM-1 groups at 12 hours (P < 0.05, P < 0.05, and P < 0.01, respectively) and at 24 hours (P < 0.05, P < 0.01, and P < 0.01, respectively). Decreased TNF-α and IL-1β concentrations were observed in the supernatant at 24 hours when cultured with 10⁻⁸, 10⁻⁷, and 10⁻⁶ mol/L in the OMF and EM-2 groups (all, P < 0.05) and in the EM-1 group (all, P < 0.01). Compared with the saline group, macrophage phagocytic activity (all, P < 0.05) and macrophage bactericidal activity (all, P < 0.01) were significantly lower in the 3 experimental groups compared with the saline group.Conclusion: In this in vitro experiment, EM-1, EM-2, and OMF inhibited the immunosuppressant function of cultured rat peritoneal macrophages, including decreasing TNF-α and IL-1β concentrations and phagocytic and bactericidal activities.     

Changes in infraspinatus cross-sectional area and shoulder range of motion with repetitive eccentric external rotator contraction

Background

Repetitive eccentric loading results in muscle damage and subsequent changes in muscle stiffness and edema accumulation, which manifest as reduced joint range of motion and increased muscle cross-sectional area. The purpose of the study was to evaluate changes in shoulder range of motion and the infraspinatus cross-sectional area with repetitive eccentric contraction.

Methods

Twenty physically active participants performed 9 sets of 25 repetitions of eccentric external rotator contractions. The ultrasonographic measurement of the infraspinatus cross-sectional area, and shoulder internal/external rotation and horizontal adduction range of motion were measured before, immediately after, and 24 h after the intervention.

Findings

Infraspinatus cross-sectional area significantly increased from baseline immediately after exercise (P < 0.001), and remained elevated from baseline at the 24-hour follow up (P < 0.001). Internal rotation and horizontal adduction range of motion did not change significantly between baseline and post-exercise (P > 0.05), but were significantly decreased at the 24-hour follow up from the baseline (internal rotation: P < 0.001, horizontal adduction: P < 0.001) and the immediate post-exercise (internal rotation: P = 1.012, horizontal adduction: P = 0.016).

Interpretation

These changes observed after the eccentric contractions may have implications for injury development in pitchers, because 1) the infraspinatus endures repetitive eccentric loading with pitching and 2) decreased internal rotation and horizontal adduction range of motion have been linked to upper extremity injuries. However, since the muscle response after eccentric loading varies by the task and previous exposure to similar stress, future study needs to investigate the time course of recovery of the muscle cross-sectional area and range of motion after pitching in competitive pitchers.     

Acute effects of cold spray application on mechanical properties of the rectus femoris muscle in athletes

IntroductionCold spray is a form of cryotherapy used in acute injuries at sports medicine. In the current study, we aimed to investigate the acute effect of cold spray application as a treatment strategy for acute sports injuries on the mechanical properties of the rectus femoris muscle in athletes.MethodsThe study included 23 volunteer active male athletes between the ages of 18–23 with a subepidermal fold thickness of the rectus femoris muscle between 5 mm and 15 mm. Skin temperature (thermal camera) and mechanical property evaluations of the muscle (Myoton Pro) were measured before, immediately after, and in 2 min, 5 min, 10 min and 15 min intervals following cold spray application.ResultsThe skin temperature value of the athletes were significantly lower even in the 15-min interval following application (p < 0.001). Muscle tone increased significantly after the application and in the second minute compared to the pre-application (p < 0.001). Muscle stiffness increased significantly only after the second and fifth minutes compared to the pre-application (p < 0.001). Muscle decrement showed an increase in all time-points compared to the pre-application (p < 0.05).ConclusionIn athletes, the rectus femoris muscle has been observed to become harder and less elastic following cooling with cold spray. These changes did not improve completely following the 5 min. The muscle regained its mechanical properties at the earliest approximately 10 min after the cold spray application.     

Protective Effect of Exercise in Pregnant Women Including Those Who Exceed Weight Gain Recommendations: A Randomized Controlled Trial

ObjectiveTo investigate the effect of supervised moderate to vigorous exercise on gestational weight gain, its related risks (gestational diabetes [GD]), macrosomia, and type of delivery), and the preventive effects on women who exceed the weight gain recommendations.Patients and MethodsWe conducted a single-center, 2-armed, randomized controlled trial between October 1, 2009, and June 30, 2011, in which 678 women were assessed and 345 were randomized by a central computer system to an intervention group (N=115) or a standard care group (N=230). The intervention exercise program consisted of 70 to 78 sessions (24 weeks, 3 times per week, 60-65 minutes per session, moderate to vigorous intensity). The standard care group received usual care. Excessive gestational weight (EGW) gain was calculated on the basis of the 2009 Institute of Medicine (IOM) recommendations.ResultsOf the 345 women randomized for treatment, 44 were lost to follow-up, leaving 301 women for analysis (intervention, 100; standard care, 201). Fewer women in the intervention group exceeded IOM recommendations (22 [22.0%] vs 69 [34.3%]; P=.03), including overweight and obese women (15 of 35 [42.9%] vs 40 of 50 [80.0%]; P=.001). Analysis of women exceeding weight recommendations revealed that the 3 main related risks were directly related to EGW gain in the standard care group (GD, P=.003; macrosomia, P<.001; type of delivery, P<.001) but not in the intervention group (GD, P>.99; macrosomia, 0%; type of delivery, P=.46).ConclusionSupervised moderate to vigorous exercise performed throughout gestation was effective in the prevention of EGW gain even for women with a pregestational body mass index greater than 25 kg/m². It also prevented its related risks (GD, macrosomia, and type of delivery) including for women exceeding the IOM recommendations, so we suggest that being active outweighs the effect of possible weight gain.Trial RegistrationClinicalTrials.gov Identifier: NCT01477372     

The Effects of Folic Acid Supplementation on Pro-inflammatory Mediators: a Systematic Review and Dose–Response Meta‐Analysis of Randomized Controlled Trials

PurposeDespite extensive research, findings regarding the effects of folic acid supplementation on inflammatory mediators have been controversial and inconclusive. This study therefore aimed to summarize the findings of all available clinical trials regarding the effects of folic acid supplementation on inflammatory biomarkers in adults.MethodsA systematic search was conducted of PubMed/MEDLINE, Scopus, Web of Science, EMBASE, and Google Scholar until April 2020. All randomized controlled trials that examined the influence of folic acid supplementation on C-reactive protein, interleukin 6 (IL-6), and tumor necrosis factor-α (TNF-α) were included. Pooled effect sizes were calculated based on the random effects model, and dose–response analysis was modeled by using a fractional polynomial model.FindingsIn total, 18 randomized controlled trials involving 2286 participants were analyzed. Folic acid supplementation significantly reduced serum levels of C-reactive protein (mean difference [MD], –0.21 mg/L; 95% CI, –0.41 to –0.01; n = 16), TNF-α (MD, –14.88 pg/mL; 95% CI, –23.68 to –6.09; n = 10), and IL-6 (MD, –0.93 pg/mL; 95% CI, –1.72 to –0.14; n = 11). Subgroup analyses suggested a significant reduction at doses ≤5 mg/d and studies longer than 12 weeks in duration. A significant nonlinear association was also found between folic acid dosage (P_nonlinearity <0.001) and duration of administration (P_nonlinearity <0.001) with serum TNF-α levels.ImplicationsThis meta-analysis indicates the beneficial effects of folic acid supplementation on pro-inflammatory cytokines. Further studies with a longer duration of administration, higher doses, and larger sample sizes should be performed exclusively on patients with chronic inflammatory disorders to elucidate the favorable role of folate intake on inflammatory biomarkers. International Prospective Register of Systematic Reviews identifier: CRD42021249947.