Thrombin activatable fibrinolysis inhibitor and hemostatic changes in patients with type I diabetes mellitus with and without microvascular complications.

We investigated thrombin activatable fibrinolysis inhibitor (TAFI) and its influence on fibrinolysis by measuring pro-TAFI activity and total TAFI antigen in 38 patients with type I diabetes mellitus (18 with and 20 without microvascular complications), as well as in 20 healthy controls. The pro-TAFI levels in the two groups of patients did not differ from those in the control group. Total TAFI antigen [i.e. pro-TAFI, TAFI and inactive carboxypeptidase U (TAFIi)] tended to decrease in both the patient groups (59.7 +/- 7.2 and 73.4 +/- 8.9% with and without microvascular complications, respectively) compared with controls (91.9 +/- 12.2%) (P = 0.12). We also assessed the overall hemostatic potential (OHP) in plasma, the clot lysis time and the overall fibrinolytic potential. The OHP was significantly higher in patients with complications compared with controls (8.9 +/- 0.9 versus 6.7 +/- 0.4; P < 0.05) and also higher in the diabetics without complications (7.8 +/- 0.6), although the latter difference did not reach statistical significance. Levels of clot lysis time and overall fibrinolytic potential were similar in the two groups of patients and the controls. The increased OHP in plasma from diabetic patients with microvascular complications indicates an imbalance of the hemostatic system towards a prothrombotic state. No signs of impaired fibrinolysis were observed in patients with diabetes. Using the OHP method for estimation of overall hemostasis, it seems that TAFI does not influence either fibrinolysis or the increased thrombotic potential observed in patients with type I diabetes mellitus.     

Deep spatial profiling of human COVID-19 brains reveals neuroinflammation with distinct microanatomical microglia-T-cell interactions

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The homogeneous photopolymerization of methyl methacrylate by colloidal cadmium sulfide

A completely new method of initiating the homogeneous radical polymerization of methyl methacrylate in bulk or in solution via the photogeneration of an electron hole pair in colloidal cadmium sulfide is presented. A polymerization mechanism involving an excited cadmium sulfide particle in both the initiation and termination steps is proposed. In the initiation a methyl methacrylate molecule is oxidized by a positive hole photogenerated in a CdS particle, which results in a novel chain-end structure of the poly(methyl methacrylate) (PMMA). Degradative chain transfer to reduced excited cadmium sulfide particles is responsible for chain termination. Thus, for the first time, a detailed polymerization mechanism in which all states of the polymerization, i.e., initiation, propagation, chain transfer and termination, is presented for the polymerization of vinyl monomers initiated by semiconductors. Thermogravimetry (TG) showed that the newly synthesized PMMA has greatly enhanced thermal stability when compared to normal radically prepared PMMA. In fact, the thermal stability approaches that of anionically prepared PMMA but is experimentally much easier to prepare. This technique enables the homogeneous embedding of CdS particles in a polymer matrix.     

On the monitoring of dabigatran treatment in “real life” patients with atrial fibrillation

Introduction

The oral direct thrombin inhibitor dabigatran is increasingly used to prevent thromboembolic stroke in patients with atrial fibrillation (AF). Routine laboratory monitoring is currently not recommended, but measurements of dabigatran and/or its effect are desirable in certain situations. We studied dabigatran exposure and compared different tests for monitoring of dabigatran in a real-life cohort of AF patients.

Material and methods

Ninety AF patients (68 ± 9 years, 67% men, mean CHADS₂ score 1.5) were treated with dabigatran 150 (n = 73) or 110 mg BID (n = 17). Trough plasma concentrations of total and free dabigatran by liquid chromatography-tandem mass-spectrometry (LC-MS/MS) were compared to indirect measurements by Hemoclot thrombin inhibitors (HTI) and Ecarin clotting assay (ECA), as well as PT-INR and aPTT.

Results

Total plasma dabigatran varied 20-fold (12–237 ng/mL with 150 mg BID) and correlated well with free dabigatran (r² = 0.93). There were strong correlations between LC-MS/MS and HTI or ECA (p < 0.001) but these assays were less accurate with dabigatran below 50 ng/mL. The aPTT assay was not dependable and PT-INR not useful at all. There were weak correlations between creatinine clearance (Cockcroft-Gault) and LC-MS/MS, HTI and ECA (p < 0.001 for all). A high body weight with normal kidney function was associated with low dabigatran levels.

Conclusions

HTI and ECA reflect the intensity of dabigatran anticoagulation, but LC-MS/MS is required to quantify low levels or infer absence of dabigatran. Most real life patients with a normal creatinine clearance had low dabigatran levels suggesting a low risk of bleeding but possibly limited protection against stroke.     

An extended diffraction-enhanced imaging method for implementing multiple-image radiography

Diffraction-enhanced imaging (DEI) is an analyser-based x-ray imaging method that produces separate images depicting the projected x-ray absorption and refractive properties of an object. Because the imaging model of DEI does not account for ultra-small-angle x-ray scattering (USAXS), the images produced in DEI can contain artefacts and inaccuracies in medical imaging applications. In this work, we investigate an extended DEI method for concurrent reconstruction of three images that depict an object's projected x-ray absorption, refraction and USAXS properties. The extended DEI method can be viewed as an implementation of the recently proposed multiple-image radiography paradigm. Validation studies are conducted by use of computer-simulated and synchrotron measurement data.     

Effects of Chair-Based,Low–Load Elastic Band Resistance Training on Functional Fitness and Metabolic Biomarkers in Older Women

Strength training can improve myriad health parameters in elderly cohorts. Although potentially more appropriate for the elderly, low-load resistance training protocols have been less investigated. We aimed to examine the effects of 12 weeks of chair-based, low-load resistance training with elastic band (EBT) on functional fitness and metabolic biomarkers in older women. One hundred sixty-eight women were allocated randomly to an elastic band resistance training (EBT, n = 86, 75.7 ± 8.9 years, 71.3 ± 12.2 kg) or a control group (CON, n = 82, 74.5 ± 8.2years, 70.6 ± 12.0 kg). RT protocol consisted of periodized chair-based, low-load whole-body resistance exercises (2 sets, 12-15 repetitions, 40-60% of one repetition maximum-1RM) using an elastic band, twice weekly for 12 weeks. The resistance training program was generally designed to maintain internal load over time, provided with increasing intensity using various elastic bands (Thera-Band). Functional fitness (30-s Chair Stand,30-s Arm Curl, 2-min Step Test, Chair Sit-and-Reach, Back Scratch, 8-Foot Up-and-Go, Handgrip Strength) and metabolic markers (Fasting blood glucose, triglycerides, total cholesterol, high (HDL) and low (LDL) density lipoprotein) were measured before and after the training period. To detect pre/post intervention changes and between group- differences 2x2 repeated measures ANOVA was applied. Significant improvements over time for all fitness variables for EBT comparing to CON were obtained (F = 12.78, p < 0.05 for 30-s Chair Stand; F = 14.04, p < 0.05 for 30-s Arm Curl; F = 5.18, p < 0.05 for 2-min Step Test; F = 10.90, p < 0.05 for Chair Sit-and-Reach; F = 16.57, p < 0.05 for Back Scratch; F = 11.79, p < 0.05 for 8-foot Up-and-Go; and F = 29.25, p < 0.05 for Handgrip Strength). In addition, significant improvements over time for all but one (triglycerides) biomarkers for EBT comparing to CON were obtained (F = 7.30, p < 0.05 for blood sugar levels; F = 13.36, p < 0.05 for total cholesterol; F = 8.61, p < 0.05 for HDL; and F = 11.53, p < 0.05 for LDL). Furthermore, the participants’ adherence to training sessions of over 90% was reported. In conclusion, 12 weeks of EBT is safe and beneficial for improving health-related fitness and metabolic biomarkers in older women and seems to be viable model to ensure a high training adherence rate.Key points

• EBT lead to a significant improvement in glucose, total cholesterol, HDL and LDL in older women.
• EBT lead to a significant increase in cardiorespiratory fitness, handgrip strength, lower- body strength and flexibility, upper-body strength and flexibility and agility in older women.
• EBT seems to be viable model to ensure high training adherence rate.

Key words: Aging, lipoproteins, low-intensity strength training, physical function