The effects of voluntary contraction effort on quadriceps femoris electromyogram median frequency in humans: a muscle and sex comparison

The purpose of this study was to examine the effect of voluntary contraction efforts on the median frequency (f _med) of the electromyogram (EMG) recorded from the quadriceps femoris muscle in healthy men and women. A group of 30 healthy volunteers (15 men, 15 women) were assessed for EMG activity of the vastus medialis (VM), vastus lateralis (VL), and rectus femoris (RF) muscles during isometric contractions with the knee at 60° flexion. Subjects performed a series of 5 s maximal voluntary isometric contractions that anchored the perceptual range with a "10" on a 10-point scale. Sub-maximal isometric contractions were then separately performed at the following perceived effort levels on the 10-point scale: 1, 2, 3, 4, 5, 6, 7, 8 and 9, in a random order. Subjects were instructed to maintain the contraction at each perceived level of effort for 5 s. The f _med of the three muscles was assessed using a power spectrum analysis performed over 11 consecutive, 512 ms, epochs overlapping each other by half their length during the middle 3 s of each contraction. The f _med for each of the 11 epochs was then determined for each muscle, followed by calculation of the means and normalized coefficients of variation [(standard deviation/mean)×100%] for each contraction. The results demonstrated that the mean f _med of VL was significantly greater than those of the other two muscles, and that f _med of RF was significantly greater than that of VM. The VL muscle demonstrated a significant increase in mean f _med across the contraction efforts, compared to the VM and RF muscles that displayed a significant decrease. The men displayed significantly higher f _med values for the VM muscle than did the women, as well as showing a significantly greater increase across the contraction efforts for the VL muscle. The variability of f _med was shown to be significantly higher for the VM muscle, compared to the VL and RF muscles. The findings of this study suggest that the f _med statistic is most sensitive to contraction intensity efforts for the VL muscle, and that men display significantly higher values for the VL and VM muscles, compared to women. Electronic Publication     

A Review of: “ Handbook of Adaptive Designs in Pharmaceutical and Clinical Development,by A. Pong and S.-C. Chow (Eds.)”

In practice, there exist many disease processes with three ordinal disease classes; for example, in the detection of Alzheimer’s disease (AD) a patient can be classified as healthy (disease-free stage), mild cognitive impairment (early disease stage), or AD (full disease stage). The treatment interventions and effectiveness of such disease processes will depend on the disease stage. Therefore, it is important to develop diagnostic tests with the ability to discriminate between the three disease stages. Measuring the overall ability of diagnostic tests to discriminate between the three classes has been discussed extensively in the literature. However, there has been little proposed on how to select clinically meaningful thresholds for such diagnostic tests, except for a method based on the generalized Youden index by Nakas et al. (2010). In this article, we propose two new criteria for selecting diagnostic thresholds in the three-class setting. The numerical study demonstrated that the proposed methods may provide thresholds with less variability and more balance among the correct classification rates for the three stages. The proposed methods are applied to two real examples: the clinical diagnosis of AD from the Washington University Alzheimer’s Disease Research Center and the detection of liver cancer (LC) using protein segments.     

Relationships between inflammation,hemodynamic function and RAAS in longstanding type 1 diabetes and diabetic kidney disease

The renin angiotensin aldosterone system (RAAS) is associated with renal disease and inflammation in a diabetes setting, however, little is known about the implicated mechanisms in individuals with long standing diabetes. Accordingly, our aim was to perform an observational study to quantify urinary excretion of inflammatory biomarkers in participants with long standing type 1 diabetes (T1D) (with and without diabetic kidney disease [DKD]) and controls, at baseline and in response to RAAS activation. GFR_INULIN, ERPF_PAH, and 42 urine inflammatory biomarkers were measured in 74 participants with T1D for ≥50 years (21 with DKD and 44 without DKD [DKD resistors]) and 73 healthy controls. Additionally, inflammatory biomarkers were measured before and after an angiotensin II infusion (ANGII, 1 ng?kg^?1?min^?1). Significantly lower urinary excretion of cytokines (IL-18, IL-1RA, IL-8), chemokines (MCP1, RANTES) and growth factors (TGF-α, PDGFAA, PDGFBB, VEGF-A) was observed in participants with T1D at baseline compared to controls. Urinary IL-6 was higher in DKD than in DKD resistors in an exploratory analysis unadjusted for multiple comparisons. In T1D only, lower GFR_INULIN correlated with greater excretion of proinflammatory biomarkers (IL-18, IP-10, & RANTES), growth factors (PDGF-AA & VEGFAA), and chemokines (eotaxin & MCP-1). ANGII increased 31 of 42 inflammatory biomarkers in T1D vs controls (p < 0.05), regardless of DKD resistor status. In conclusion, lower GFR and intra-renal RAAS activation were associated with increased inflammation even after longstanding T1D. The increased urinary IL-6 in patients with DKD requires further investigation to determine whether IL-6 is a candidate protective biomarker for prognostication or targeted therapy in DKD.     

Predictors of stroke in high-risk patients after acute myocardial infarction: insights from the VALIANT Trial.

AIMS: We sought to determine risk models for predicting early and late stroke in a large cohort of high-risk post-myocardial infarction (MI) patients. METHODS AND RESULTS: We prospectively analysed data from 14 703 patients in the VALIANT trial with acute MI complicated by heart failure, left ventricular (LV) systolic dysfunction, or both. Patients were randomized 0.5-10 days after acute MI to valsartan, captopril, or their combination. We evaluated risk factors for early (<45 days) and late (>45 days) stroke by using multivariable Cox proportional hazards regression analyses with stepwise variable selection techniques applied to 92 pre-specified potential predictor variables. After randomization, 463 (3.2%) patients had fatal (n = 124) or non-fatal (n = 339) strokes, with 134 strokes occurring in the first 45 days. The strokes were classified as ischaemic (348), haemorrhagic (40), or of indeterminate cause (75). Estimated glomerular filtration rate and heart rate when in sinus rhythm were the most powerful predictors of early stroke (<45 days after MI), whereas diastolic blood pressure (DBP) >90 mmHg, prior stroke, and atrial fibrillation (AF) were the most powerful predictors of stroke overall. Ejection fraction and sex were not predictive of stroke in this cohort. CONCLUSION: Among high-risk patients presenting with MI but without initial neurological symptoms, the risk of stroke 6 weeks thereafter is 0.94% (95% CI 0.78-1.09). Of the most powerful baseline predictors of stroke, DBP and AF are amenable to therapeutic interventions and thus merit special attention in these patients.     

Interaction between inflammation and thrombosis in acute coronary syndrome

BACKGROUND: Inflammation and thrombosis are important in the pathogenesis of acute coronary syndrome (ACS). Cytokines [interleukin-1beta (IL-1beta) and interleukin-6 (IL-6)] are inflammation markers which play a major role in the development of coronary heart disease. Experimental data documented that an increase of cytokine and von Willebrand factor (vWF) levels in unstable angina (UA) and non-Q wave myocardial infarction (MI) predicts an adverse outcome. AIM: To examine the correlation between the IL-1beta, IL-6 and vWF levels in patients with ACS. METHODS: We examined 92 patients (74 men, 18 women, aged from 43 to 76) divided into 3 groups. The first group included 43 patients with a Q-wave MI, the second group - 33 with a non-Q-wave MI, and the third group - 18 with UA. All patients were given 125-250 mg of aspirin and bolus of 5.000 units of unfractionated heparin, followed by heparin infusion titrated to maintain an activated partial thromboplastin time of 50-75 s. Patients with a Q-wave MI received thrombolytic therapy 1.5 million units of streptokinase. The IL-1b, IL-6 and vWF levels was measured on admission and 7 as well as 21 days later. Fifteen patients with stable angina served as the control group. RESULTS: The levels of cytokines and vWF were significantly higher in patients with ACS than in control subjects. A significant correlation between vWF and IL-6 levels, measured on admission and 7 days later, was found in patients with UA (r=+0.74 and r=+0.55, respectively). Also, a significant correlation was found between vWF and IL-1beta levels measured on admission in patients with either Q-wave or non-Q wave MI (r=+0.7 and r=+0.61, respectively). CONCLUSIONS: Our data suggest that there is a positive correlation between inflammation and thrombosis markers in patients with ACS.