Effects of a multi-strain probiotic supplement for 12 weeks in circulating endotoxin levels and cardiometabolic profiles of medication naïve T2DM patients: a randomized clinical trial

Background: The present randomized clinical trial characterized the beneficial effects of a multi-strain probiotics supplementation on improving circulating endotoxin levels (primary endpoint) and other cardiometabolic biomarkers (secondary endpoint) in patients with T2DM. Methods: A total of 78 adult Saudi T2DM patients (naïve and without co-morbidities) participated in this clinical trial and were randomized to receive twice daily placebo or probiotics [(2.5 × 109 cfu/g) containing the following bacterial strains: Bifidobacterium bifidum W23, Bifidobacterium lactis W52, Lactobacillus acidophilus W37, Lactobacillus brevis W63, Lactobacillus casei W56, Lactobacillus salivarius W24, Lactococcus lactis W19 and Lactococcus lactis W58 (Ecologic®Barrier)] in a double-blind manner for 12 weeks. Anthropometrics and cardiometabolic profiles were obtained at baseline and after 12/13 weeks of treatment. Results: After 12/13 weeks of intervention and using intention-to-treat analysis, no difference was noted in endotoxin levels between groups [Placebo − 9.5% vs. Probiotics − 52.2%; (CI − 0.05 to 0.36; p = 0.15)]. Compared with the placebo group however, participants in the probiotics groups had a significant but modest improvement in WHR [Placebo 0.0% vs. Probiotics 1.11%; (CI − 0.12 to − 0.01; p = 0.02)] as well as a clinically significant improvement in HOMA-IR [Placebo − 12.2% vs. Probiotics − 60.4%; (CI − 0.34 to − 0.01; p = 0.04)]. Conclusion: Using a multi-strain probiotic supplement daily for 12/13 weeks significantly improved HOMA-IR and modestly reduced abdominal adiposity among medication naïve T2DM patients

Effects of a 6-month multi-strain probiotics supplementation in endotoxemic, inflammatory and cardiometabolic status of T2DM patients: a randomized, double-blind, placebo-controlled trial

Objective The aim of this trial was to characterize the beneficial effects of probiotics on decreasing endotoxin levels and other cardiometabolic parameters in Arab patients with type 2 diabetes mellitus (T2DM). Methods Saudi adults with naïve T2DM (n=61; 12 males and 18 females) were randomly allocated to receive twice daily placebo or 2.5×109cfu/gram of Ecologic®Barrier (multi-strain probiotics; 14 males and 17 females) in a double-blind manner over a 6 month period, respectively. Anthropometrics were measured and fasting blood samples were collected to analyze endotoxin, glycemic parameters [glucose, insulin, c-peptide and homeostasis model assessment for insulin resistance (HOMA-IR)], lipids [triglycerides, total cholesterol, low and high-density lipoprotein (LDL and HDL, respectively) cholesterol and total/HDL-cholesterol ratio], inflammatory markers [tumor-necrosis factor-alpha (TNF-α), interleukin-6 (IL-6) and C-reactive protein (CRP)] and adipocytokines [leptin, adiponectin and resistin] at baseline and after 3 and 6 months of intervention. Results Multi-strain probiotics supplementation for 6 months caused a significant decrease in circulating levels of endotoxin by almost 70% over 6 months, as well as glucose (38%), insulin (38%), HOMA-IR (64%), triglycerides (48%), total cholesterol (19%), total/HDL-cholesterol ratio (19%), TNF-α (67%), IL-6 (77%), CRP (53%), resistin (53%), and a significant increase in adiponectin (72%) as compared with baseline. Only HOMA-IR had a clinically significant reduction (-3.4, 64.2%) in the probiotics group as compared to placebo group at all time points. No other clinically significant changes were observed between the probiotic or placebo group at 3 and 6 months in other markers. Conclusion Multi-strain probiotic supplementation over 6 months as a monotherapy significantly decreased HOMA-IR in T2DM patients, with the probiotic treatment group highlighting reduced inflammation and improved cardiometabolic profile. As such, multi-strain probiotics is a promising adjuvant anti-diabetes therapy

Dynamic stability of the Mindlin-Reissner plate using a time-modulated axial force

A time-periodic axial force acting on a continuous structure can be destabilized by parametric excitation. Moreover, it is capable of increasing the equivalent damping and shortening the transient vibrations. In this work, this concept is extended, and dynamic stability of a Mindlin-Reissner plate is analyzed. The FE formulation for the four-node plate element is derived by employing the variational approach including the action of an axial force. The stability of the time-periodic system is evaluated both numerically and analytically, using Floquet theory and first-order approximation based on the averaging method, respectively. The influence of plate length, thickness, and aspect ratio on dynamic stability is highlighted. It is demonstrated that the instability tongue at a parametric combination resonance frequency of the summation type is shifted toward higher axial force amplitudes by increasing the plate width and decreasing the plate length. Alternatively, the axial force acting in the vicinity of a parametric combination frequency of the difference type shows a parametric antiresonance which is maximized by exactly the opposite tuning of the plate design. This guideline is important when plate design under the action of a harmonic axial force is considered

Nonlinear free vibrations of Timoshenko–Ehrenfest beams using finite element analysis and direct scheme

In this work, nonlinear free vibrations of fully geometrically exact Timoshenko-Ehrenfest beams are investigated. First, the exact strong form of the Timonshenko-Ehrenfest beam, considering the geometrical nonlinearity, is derived, and the required formulations are obtained. Since the strong forms of governing equations are highly nonlinear, a nonlinear finite element analysis (FEA) is employed to obtain the weak form. The FEA is utilized to compute natural frequencies and mode shapes; the direct scheme is adopted to solve the eigenvalue problem which is obtained by eliminating nonlinear terms. Then, each eigenvector is normalized, and the nonlinear stiffness matrix is derived and the nonlinear free vibration analysis is carried out. A recursive procedure is adopted to proceed until the convergence criterion is satisfied. Finally, the applicability of the proposed formulation is provided with some examples and results are compared with those available in the literature

The Effect of Intracoronary Infusion of Bone Marrow-derived Mononuclear Cells on Clinical Outcome and Cardiac Function in Chronic Heart Failure Patients: An Uncontrolled Study

Objective: To evaluate the effect of bone marrow-derived mononuclear cells (BM-MNCs) on clinical outcome and cardiac function in chronic heart failure (HF). Methods: An uncontrolled, open-label trial was performed on symptomatic patients (New York Heart Association [NYHA] Functional Classification II–IV) receiving maximal medical therapy for at least 2 months, with a left ventricular (LV) ejection fraction <25%. Patients were divided into ischemic and nonischemic subgroups. All patients underwent BM aspiration, isolation of BM-MNCs using a standardized system, and intracoronary infusion of BM-MNCs. Primary endpoints assessed in 36 months were changes in (1) LV systolic function and LV end-diastolic diameter by echocardiography and (2) clinical improvement. Secondary measures included other echocardiography measures and major adverse cardiac events and HF hospitalization. Phenotypic and functional analyses of the cell product were performed by the Royan Institute for stem Cell Biology and Technology laboratory. Results: We enrolled 58 patients in our study. There was a significant improvement to exercise and functional capacity (evaluated by NYHA classification and 6-min walking distance) with both groups (for all P < 0.001). A significant decline in serum N-terminal Prohormone of Brain Natriuretic Peptide(NT- ProBNP) was observed in ischemic group (P = 0.01), but it was not statistically significant in nonischemic group. No significant changes were found in LV systolic and diastolic function, right ventricular size and function, severity of Mitral and Tricuspid regurgitation and pulmonary arterial pressure. There was minimal decrease in LV end-diastolic diameter which was statistically significant in ischemic and nonischemic group (P = 0.008 and P = 0.01 accordingly). Our study revealed a remarkably safe profile for BM-MNC infusion. Conclusion: It seems that intracoronary infusion of bone marrow-derived mononuclear stem cells is a safe treatment for patients with advanced HF and further studies need to address the best type of cell, route of administration, and criteria for patient selection