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1.
《Biomarkers》2013,18(4):357-364
Abstract

Objectives: To determine whether inflammation (C-reactive protein, CRP), oxidative stress (malondialdehyde, MDA) or haemodialysis (HD) affect associations between asymmetric (ADMA), symmetric (SDMA) dimethylarginine, NG-monomethyl-L-arginine (L-NMMA) and nitrite/nitrate (NOx) in end-stage renal disease (ESRD).

Method: Metabolites were measured pre-HD, after 1 hour and end-HD in 40 ESRD patients (age 63?±?14 years).

Results: Positive associations between NOx and ADMA (p?=?0.04), SDMA (p?<?0.001) and L-NMMA (p?=?0.04) were observed pre-HD. Associations weakened during HD but were not significantly influenced by CRP or MDA.

Conclusions: HD, oxidative stress or inflammation did not significantly affect the positive associations between methylated arginines and NOx in ESRD.  相似文献   

2.
Objective: To investigate the presence of oxidative stress (OS) in pregnant women with Familial Mediterranean fever (FMF) in the first trimester by evaluating thiol/disulphide homeostasis.

Study design: A total of 31 pregnant women with a diagnosis of FMF, between 110 and 136 weeks of gestation, were compared with 51 healthy pregnant controls at the same gestational weeks. A recently defined method was used to measure plasma native thiol, total thiol and disulphide levels.

Results: There were no differences between groups in terms of maternal age, body mass index and numbers of gravida and parity. Antenatal complications (45.2% vs. 9.8%, P?=?0.001) and primary caesarean section (22.6% vs. 5.9%, P?=?0.037) were higher in the FMF group. Pregnant women with FMF had significantly lower first trimester serum levels of native thiol (297.5?μmol/l (153.2–441.8) vs. 366.1?μmol/l (288.7–432.4), P?=?0.000), total thiol (327.2?μmol/l (171.0–471.0) vs. 389.9?μmol/l (317.1–449.8), P?=?0.000) and higher levels of disulphide (14.2?±?4.5?μmol/l vs. 12.4?±?3.4?μmol/l, P?=?0.045). No differences were found in these parameters among FMF patients with and without antenatal complications.

Conclusions: The main outcome demonstrates a relation between OS and pregnant women with FMF in the first trimester of gestation. OS in the first trimester may be a major aetiological factor of unfavourable pregancy outcomes in this group of patients.  相似文献   

3.
Purpose: This study aimed to determine serum YKL-40 in patients with end-stage renal disease (ESRD) on haemodialysis (HD) and to evaluate the prognostic value of serum YKL-40.

Methods: Patients >18?years on maintenance HD were included. Serum YKL-40 was measured using ELISA before and after a single HD treatment.

Results: A total of 306 patients were included. Median serum YKL-40 concentration was 238?µgL?1 (IQR: 193–291?µgL?1) before HD treatment and 198?µgL?1 (IQR: 147–258?µgL?1) after HD treatment, which corresponded to age-corrected 93th percentile in healthy subjects. All-cause mortality after 2.8?years was 35.9%. Patients with serum YKL-40 in the highest quartile compared with the lowest quartile had a univariate HR of 4.0 (95% CI: 2.2–7.3, p?p?=?0.01) in multivariate analysis. Time-dependent receiver operating characteristic curves showed that serum YKL-40 after HD treatment had significant higher area under the curves from 90?d (p?=?0.004) and throughout the rest of the follow-up period when compared to serum YKL-40 before HD treatment.

Conclusion: YKL-40 was highly elevated in patients with ESRD on HD, and dialysis reduced serum YKL-40 concentrations approximately one-sixth. YKL-40 measured after dialysis was independently associated with mortality in HD patients.  相似文献   

4.
Objective: The objective was to investigate blood-based biomarkers of type I (PRO-C1), III (PRO-C3) and VI (PRO-C6) collagen formation in systemic sclerosis (SSc) patients and examine their correlation to modified Rodnan skin score (mRSS).

Methods: Limited (lSSc, n?=?76) and diffuse SSc (dSSc, n?=?41) fulfilling the ACR/EULAR 1980 and 2013 classification criteria for SSc and asymptomatic controls (n?=?9) were included. PRO-C1, PRO-C3 and PRO-C6 were measured in serum.

Results: LSSc compared to dSSc were significantly older, had longer disease duration and lower mRSS. PRO-C3 was higher in early dSSc compared to early lSSc (mean [95 percentile], 27.4 [13.1–39.1] ng/mL vs 14.9 [8.2–28.8] ng/mL, p?=?0.006). PRO-C6 levels were higher in early dSSc compared to early lSSc and late dSSc (early dSSc: 28.2 [10.4–92.3] ng/ml vs early lSSc: 11.0 [6.9–28.5] ng/ml; p?=?0.006 and late dSSc: 12.6 [6.5–25.3] ng/mL, p?=?0.04). No difference was observed with PRO-C1. PRO-C3 and PRO-C6 were moderately correlated with mRSS with R-partials of 0.36 (p?<?0.001) and 0.29 (p?=?0.002), respectively

Conclusion: Measures of type III and VI collagen formation are potential objective biomarkers of fibrosis in systemic sclerosis. These biomarkers could be useful in monitoring the disease and efficacy of treatment.  相似文献   


5.
Abstract

Purpose: To examine thiol-disulphide homeostasis auto painters.

Materials and methods: A total of 115 male workers, including 60 auto painters workers and 55 reference group, of the painting and assembly line units respectively, were included in the study. Thiol-disulphide parameters and ischaemia-modified albumin (IMA) of groups were determined. Urinary hippuric acid, (HA) phenol, hexanedione, trichloroacetic acid, arsenic and blood lead and manganese were analysed.

Results: The median urinary HA level was significantly higher in auto painters when compared to the reference group [(2461 (1212) vs. 520 (513) µgr/L), (p?<?0.001)] . The mean disulphide level [19.7 (4.3) vs 0.15.1(4.1) μmol/L, (p?<?0.001)], the disulphide/native thiol ratio [4.72 (1.47) vs. 3.13 (1.21, (p?<?0.001)] and the disulphide/total thiol ratio [4.31 (1.23) vs. 2.94 (1.06), (p?<?0.001)] were higher in auto painters when compared to the reference group. There was a statistically significant positive correlation between urinary HA and disulphide concentrations (r?=?0.536 and p?<?0.001), disulphide/native thiol ratio (r?=?0.564 and p?<?0.001) and the disulphide/total thiol ratio (r?=?0.564 and p?<?0.001) and IMA (r?=?0.396 and p?<?0.001).

Conclusion: The results presented in this study showed that oxidative stress can be associated with occupational exposure to toluene denoted by alteration of thiol disulphide homeostasis and ischaemia-modified albumin levels.  相似文献   

6.
Abstract

Background: Patients with hepatorenal syndrome carry a high short-term mortality. Early diagnosis and treatment are essential for patients’ outcome. Nevertheless diagnosis of HRS remains difficult. First-line therapy terlipressin is often associated with severe complications. Biomarkers become more on focus for an early diagnosis.

Objective: The aim of this study was to test the diagnostic accuracy of urinary [TIMP-2]·[IGFBP7] for HRS patients and prognostic value for therapy responding patients.

Material and methods: NephroCheck® measures urinary concentrations of TIMP-2 and IGFBP-7, both indicating stress of renal cells and associated with induction of cell cycle arrest. 22 HRS patients and 30 patients with normal kidney function were included. [TIMP-2]·[IGFBP7] was measured using NephroCheck®. HRS patients receiving terlipressin were also examined.

Results: [TIMP-2]·[IGFBP7] values did not differ significantly (1.3?±?2.09 vs. 1.03?±?1.03; p?=?0.55). Furthermore, there was no significant difference of [TIMP-2]·[IGFBP7] regarding response of terlipressin (1.32?±?2.39 vs. 0.81?±?1.05; p?=?0.56). Low [TIMP-2]·[IGFBP7] values were significantly associated with higher mortality (p?=?0.01).

Conclusions: The results of this study suggest that [TIMP-2]·[IGFBP7] is not suitable for diagnostic of HRS and prediction of therapy response, but there might be evidence for prognostic value of [TIMP-2]·[IGFBP7] in regard to mortality of liver cirrhosis patients.  相似文献   

7.
Abstract

Background: Unilateral spatial neglect (USN) is the prevalent feature in patients with right-sided stroke. It is diagnosed through the behavior inattention test (BIT) and has a negative impact on patients affecting both their functional capacity and quality of life.

Objective: Here, we aimed to evaluate the impact of USN on the quality of life of patients in the chronic phase of stroke.

Methods: This is a cross-sectional study with stroke patients with USN. After confirming the presence of stroke through neuroimaging examinations and of USN through the BIT, patients’ quality of life was evaluated by using the EUROQOL scale. Spearman’s correlation was used to validate the correlation between patients’ USN and quality of life, with a p?<?.05 representing significant results.

Results: Eighteen individuals were included. When correlating the value of each domain of the EUROQOL scale with the results of the BIT, we observed a negative correlation between mobility (r?=?–0.97; p?=?.000), self-care (r?=?–0.82; p?=?.013), usual activities (r?=?–0.87; p?=?.005); pain or discomfort (r?=?–0.88; p?=?.004), anxiety or depression (r?=?–0.97; p?=?.000), and EUROQOL total score (r?=?–0.97, p?=?.000).

Conclusion: After a correlation between the overall EUROQOL and BIT scores, we suggest that the higher the USN degree is in stroke patients, the worse their perceived quality of life tends to be.  相似文献   

8.
Yuehua Li  Hanjun Pei  Ying Lou 《Biomarkers》2020,25(2):164-170
Abstract

Background: The purpose of this meta-analysis was to evaluate the relationship between elevated cardiac troponin pre-transcatheter aortic valve replacement (TAVR) and long-term all-cause mortality.

Methods: Prospective studies with the endpoint of all-cause mortality were included. We primarily used the fixed-effect model weighted by inverse variance. Meta-regression and subgroup analyses were conducted to explore the potential sources of heterogeneity by specified study characteristics.

Results: Seven prospective studies comprising of 3049 subjects were included in our meta-analysis. Pre-procedural elevated cardiac troponin was associated with increased risk of long-term mortality post TAVR [hazard ratio (HR) 2.25, 95% CI 1.83–2.78, p?=?0.000, I2 = 30.3%, p for heterogeneity 0.197]. In addition, subgroup analyses have shown that the group with an younger age (<82?y) seemed to have a higher risk of all-cause mortality than the group with older age (≥82?y) [HR 4.08 (2.41 to 6.89) VS 2.01 (1.60 to 2.53), p?=?0.016 for subgroup difference].

Conclusions: Pre-procedural elevated cardiac troponin was associated with increased long-term all-cause mortality in patients undergoing TAVR.  相似文献   

9.
Abstract

Background: Australia implemented mandatory folic acid fortification of bread-making flour in 2009.

Objective: To assess the impact of folic acid fortification in remote vs. regional urban areas and Indigenous vs. non-Indigenous populations in northern Queensland.

Methods: Routinely collected data on folic acid measurements in remote areas and two regional urban centres in northern Queensland between 2004 and 2015 were analysed (n?=?13,929) dichotomously (folic deficient vs. non-deficient).

Results: Overall prevalence of folic acid deficiency was 3.2% (235/7282) in urban centres compared with 7.2% (480/6647) in remote areas (p?<?0.001), and 9.3% (393/4240) in the Indigenous population compared with 3.2% (273/8451) in the non-Indigenous population (p?<?0.001). Prevalence of folic acid deficiency dropped from 12.2% (n?=?481) in 2004–2008 to 1.5% (n?=?126) in 2010–2015 (p?<?0.001). This translates into a relative risk reduction (RRR) of 88%. RRR was 79% (7.2% vs. 1.5%) in urban centres, 91% (17.3% vs. 1.5%) in remote areas, 92% (20.5% vs. 1.6%) in the Indigenous population and 80% (7.4% vs. 1.5%) in the non-Indigenous population (p?<?0.001 for all).

Conclusions: Substantial declines of folic acid deficiency to low and comparable proportions in former high-risk populations indicate that mandatory folic acid fortification of flour has had a population-wide benefit in northern Queensland.  相似文献   

10.
Objective: To investigate how many patients with acute heart failure (AHF) hypersecrete relaxin-2 concentrations similar to those of pregnant women and determine their long-term outcome.

Methods: In consecutive AHF patients relaxin-2 was quantified by ELISA sandwich method. Patients were divided into pregnancy-like group (PLG, relaxin-2 ≥?500?pg/mL) and control group (CG, relaxin-2 10?days), combined endpoint (death, rehospitalisation, ED revisit) 30?days after discharge, and 30-day, one-year and three-year death rates.

Results: We included 814 patients [81 (SD?=?9) years; 53.0% women] followed during 1.9 (SD 2.8) years; 517 (63.5%) died. Twenty patients (2.5%) formed the PLG (median relaxin-2?=?1459?pg/mL; IQR?=?1722) and 794 the CG (median?=?26; IQR?=?44). There was no interaction with variables included on adjustment (age, sex, ischaemic cardiomyopathy, NT-proBNP, glycaemia, and sodium). PLG patients did not have better short-term secondary endpoints, but did show a significantly lower three-year mortality [ORadjusted?=?0.17 (0.05–0.5), p?=?0.003].

Conclusions: The small proportion of AHF patients achieving relaxin-2 concentrations similar to those observed in pregnancy may survive longer.  相似文献   

11.
Abstract

Background: Myocardial fibrosis in hypertrophic cardiomyopathy (HCM) is associated with worse clinical outcomes. The availability of circulating biomarkers of myocardial fibrosis and hypertrophy would be helpful in clinical practice.

Objective: The aim of this study was to evaluate usefulness of various biomarkers of myocardial fibrosis and hypertrophy in HCM.

Methods: Levels of biomarkers: soluble ST2 (sST2), galectin-3 (Gal-3), growth differentiation factor-15 (GDF-15), NT-proBNP and high-sensitivity cardiac troponin T (hs-cTnT) were measured in 60 patients with HCM. All patients underwent cardiac magnetic resonance imaging to calculate parameters of hypertrophy and fibrosis.

Results: We observed positive correlations among sST2 levels and left ventricular mass (LVM) (r?=?0.32, p?=?0.012), LV mass indexed for the body surface area (LVMI) (r?=?0.27, p?=?0.036) and maximal wall thickness (MWT) (r?=?0.31, p?=?0.015). No correlation was found between Gal-3 and GDF-15 levels and hypertrophy and fibrosis parameters. We observed positive correlations among hs-cTnT levels and LVM (r?=?0.58, p?<?0.0001), LVMI (r?=?0.48, p?=?0.0001), MWT (r?=?0.31, p?=?0.015) and late gadolinium enhancement (LGE) mass (r?=?0.37, p?=?0.003). There were positive correlations between NT-proBNP levels and LVM (r?=?0.33, p?=?0.01), LVMI (r?=?0.41, p?=?0.001), MWT (r?=?0.42, p?<?0.001) and LGE mass (r?=?0.44, p?<?0.001).

Conclusions: Although no correlation between sST2 levels and myocardial fibrosis was found, sST2 may provide some additional information about hypertrophy extension. NT-proBNP and hs-cTnT are useful biomarkers in assessment of hypertrophy and fibrosis in HCM.  相似文献   

12.
《Biomarkers》2013,18(4):326-331
Abstract

Background: There are no good biomarkers to predict renal parenchymal involvement in children with urinary tract infection (UTI).

Methods: Children (N?=?73) younger than 5 years with UTI were enrolled. Urinary levels of 8-hydroxy-2′-deoxyguanosine (8-oxodG) and total antioxidant capacity (TAC) were checked as markers of oxidative stress and antioxidant capacity, respectively. Tc99m-dimercaptosuccinic acid (DMSA) renal scintigraphy was used to find evidence of renal involvement.

Results: Patients with positive DMSA findings had higher levels of urinary 8-oxodG (p?=?0.003) and higher urinary TAC (p?=?0.001) than patients with normal DMSA findings.

Conclusions: High level of urinary 8-oxodG may be a risk factor of severe renal damage.  相似文献   

13.
《Biomarkers》2013,18(6-7):371-375
Abstract

Context: Excess growth hormone (GH) is associated with early mortality.

Objectives: We assessed the association of GH with prognosis after acute myocardial infarction (AMI), and the effects of secondary prevention therapies.

Methods: GH was measured using a high-sensitivity assay in 953 AMI patients (687 males, mean age 66.1?±?12.8 years).

Results: During 2 years follow-up, there were 281 major adverse cardiac events (MACE). Patients with MACE had higher GH levels (median [range], 0.91 [0.04–26.28] μg/L) compared to event-free survivors (0.59 [0.02–21.6], p?<?0.0005). In multivariate Cox survival analysis, GH was a significant predictor of MACE (hazard ratios 1.43, p?=?0.026 and 1.49, p?=?0.01, respectively) with significant interactions with beta blocker therapy (p?=?0.047) and angiotensin converting enzyme inhibitor or angiotensin receptor blocker (ACE/ARB) therapy (p?=?0.016).

Conclusions: GH levels post-AMI are prognostic for MACE and may indicate those patients who benefit from beta blocker and ACE/ARB therapy.  相似文献   

14.
15.
《Biomarkers》2013,18(7):607-613
Abstract

Objective: The potential development of a noninvasive marker predicting nonalcoholic steatohepatitis (NASH).

Methods: Thirty patients with biopsy-proven nonalcoholic fatty liver disease were evaluated by numerous anthropometric, clinical and biochemical parameters.

Results: Serum glutamic oxaloacetic transaminase (SGOT; p?=?0.027), log (erythrocyte sedimentation rate) (ESR; p?=?0.034) and homocysteine (p?=?0.041) were associated with NASH independently from gender, age and body mass index. When combined, the regression model provided R2?=?0.563 (p?=?0.001) and area under the ROC curve?=?0.873?±?0.066 (p?<?0.001).

Conclusion: This noninvasive marker, named HSENSI (acronym of homocysteine, SGOT, ESR, Nonalcoholic Steatohepatitis Index), consists of three low cost, easily measurable parameters and may accurately predict NASH.  相似文献   

16.
Context: This study aims to explore the potential of new inflammatory markers for improving the challenging diagnosis of acute appendicitis (AA).

Methods: Levels of IL-1, IL-6, IL-8, IL-10, CRP, INF-γ, and TNF-α in serum were measured in 73 patients with AA. Oxidative stress and antioxidant enzymes were analyzed.

Results: Serum levels of interleukins, TNF-α, and INF-γ were significantly elevated in patients with appendicitis (p?<?0.0001), except for IL-10, which presented decreased levels. There were no significant differences in SOD (p?=?0.29), CAT (p?=?0.19), or TBARS levels (p?=?0.18), whereas protein carbonyls presented significant increase (p?<?0.0001).

Conclusion: Evaluating these biomarkers could aid in diagnosing AA.  相似文献   

17.
Objective: Elevated levels of arginine derivatives in the NO pathway, such as asymmetric dimethylarginine (ADMA), are related to disease severity and reduced exercise capacity in heart failure (HF). We investigated the influence of exercise intervention on these parameters and on L-arginine (L-Arg) and L-homoarginine (L-hArg) in HF with preserved ejection fraction (HFpEF) patients.

Material and methods: Sixty-two patients (65?±?6 years) were included in this analysis and randomized to supervised endurance/resistance training (ET) or to usual care (UC). EDTA-plasma was analysed for NO metabolites.

Results: There were baseline associations for adjusted values of maximum workload with ADMA (r=??0.322, p?=?0.028) and L-Arg/ADMA ratio (r?=?0.331, p?=?0.015), and for the 6-min walk test (6MWT) with ADMA (r=??0.314, p?=?0.024) and L-Arg/ADMA ratio (r?=?0.346, p?=?0.015). No significant differences between UC and ET changes of NO parameters were observed at 3-month follow-up. Higher L-hArg levels were associated with a greater improvement in peak oxygen uptake (peak O2) at follow-up: 3.4?±?2.8 vs. 1.1?±?2.9?mL/min/kg (p?=?0.005).

Conclusions: Exercise intervention did not influence NO parameters in HFpEF patients, but L-hArg was related to change in peak O2.  相似文献   

18.
Uremic patients undergoing hemodialysis (HD) are considered to face an elevated risk for atherosclerosis and cancer. This has been attributed in part to an increased oxidative stress. In this pilot study, oxidative cell damage in blood of HD-patients was compared to those of controls: total DNA damage (basic and specific oxidative DNA damage), modulation of glutathione levels (total and oxidized glutathione) and of lipid peroxidation were monitored via the Comet assay (with and without FPG), a kinetic photometric assay and HPLC quantification of plasma malondialdehyde (MDA), respectively. In some samples, leukocytes were analysed for malondialdehyde–deoxyguanosine-adducts (M1dG) with an immunoslot blot technique.

HD-patients (n=21) showed a significant increase of total DNA damage (p<10-12), compared to controls (n=12). In a subset of patients and controls, GSSG levels and M1dG, however, only increased slightly, while tGSH and MDA levels did not differ. The influence of different low flux HD-membranes was tested in a pilot study with nine patients consecutively dialysed on three membrane types for four weeks each. In addition to the individual disposition of the patient, the dialyser membrane had a significant impact on oxidative stress. Total DNA damage was found to be almost identical for polysulfone and vitamin E coated cellulosic membranes, whereas a slight, but significant increase was observed with cellulose-diacetate (p<0.001). In patients receiving iron infusion during HD, MDA-formation (n=11) and total DNA damage (n=10) were additionally increased (p<0.005).

Our results show an increased oxidative damage in HD-patients, compared to healthy volunteers. Significant influences were found for the dialyser membrane type and iron infusion.  相似文献   

19.
Ying Bai  Shi-Dong Guo  Yue Liu 《Biomarkers》2018,23(6):512-517
Objective: To explore the association between the levels of troponin (Tn) and incident atrial fibrillation (AF) occurrence, AF recurrence after radiofrequency ablation (RFA), and the risk trend of AF related prognosis (stroke, major bleeding and mortality).

Methods: Twenty-seven studies were included after a systematic search in PubMed from 2005 to 2017, including 13 associated with incident AF occurrence, 8 associated with AF recurrence after RFA and 6 studies evaluating the risk trend of AF-related prognosis with increased Tn levels.

Results: Compared with ‘no incident AF occurrence’ patients, the incident AF occurrence group had similar baseline troponin I (TnI) levels (standardized mean differences [SMD]?=?0.42, 95% CI: ?0.02–0.86, p?=?0.06; I2?=?87.0%, N?=?6), but higher troponin T (TnT) levels (SMD?=?3.77, 2.13–5.42, p?<0.001; I2=99.7%, N?=?8). AF recurrence patients had similar peri-ablation TnI levels, but higher peri-ablation TnT levels compared to the ‘no AF recurrence’ group with pooled SMD. (TnI: SMD: ?0.61, ?1.22to 0, p?=?0.049; I2?=?87.1%; TnT: 0.38, 0.14–0.62, p?=?0.002; I2?=?64.7%). On meta-regression, there was an increased risk trend for stroke/systemic embolism (SE) (r2?=?0.93, p?=?0.04) or major bleeding (r2?=?0.99, p?r2?=?0.09, p?=?0.25) or TnT (r2?=?0.20, p?=?0.31), and stroke/SE (r2?=?0.02, p?=?0.74) or major bleeding (r2?=?0.002, p?=?0.92) was non-significantly related to increasing TnI levels.

Conclusions: In our systematic review, meta-analysis and meta-regression, TnT was associated with both incident AF occurrence and AF recurrence after RFA, as well as stroke/SE and major bleeding. In contrast, TnI was not associated with incident AF occurrence, AF recurrence after RFA or prognosis (stroke/SE, major bleeding).  相似文献   

20.
Aim of study: To examine the resting motor threshold of the tongue in healthy adults and stroke survivors.

Methods: Thirty-five healthy adults were classified into three groups: Group 1 (19–38?years; n?=?11), Group 2 (50–64?years; n?=?12) and Group 3 (66–78?years; n?=?12). Six chronic stroke survivors (mean age =59?years, SD?=?9.1?years) were recruited (Group 4). The resting motor thresholds (RMTs) of the tongue were measured and compared (i) among the four groups and (ii) between stroke survivors and age-matched healthy adults.

Results: Group 3 showed significantly higher RMTs than Group 1 (p?=?.001) and 2 (p =?0.007). Group 4 showed significantly higher RMTs than Group 1 (p =?.003) and 2 (p?=?.001). The RMTs of Group 3 and 4 were not significantly different (p =?.385). The RMT was positively correlated with age (r?=?0.534; p =?.001). Group 4 showed significantly higher RMTs than the age-matched controls (U?= 2.5, p?=?.009, r?=?0.77).

Conclusions: The resting motor threshold of the tongue is significantly increased in adults aged above 65 and in stroke survivors when compared with healthy adults. The findings suggested that the cortical excitability of the tongue deteriorates in the elderly and the stroke population.  相似文献   

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