Omecamtiv mecarbil in chronic heart failure with reduced ejection fraction, GALACTIC‐HF: baseline characteristics and comparison with contemporary clinical trials

Aims: The safety and efficacy of the novel selective cardiac myosin activator, omecamtiv mecarbil, in patients with heart failure with reduced ejection fraction (HFrEF) is tested in the Global Approach to Lowering Adverse Cardiac outcomes Through Improving Contractility in Heart Failure (GALACTIC‐HF) trial. Here we describe the baseline characteristics of participants in GALACTIC‐HF and how these compare with other contemporary trials. Methods and Results: Adults with established HFrEF, New York Heart Association functional class (NYHA) ≥ II, EF ≤35%, elevated natriuretic peptides and either current hospitalization for HF or history of hospitalization/ emergency department visit for HF within a year were randomized to either placebo or omecamtiv mecarbil (pharmacokinetic‐guided dosing: 25, 37.5 or 50 mg bid). 8256 patients [male (79%), non‐white (22%), mean age 65 years] were enrolled with a mean EF 27%, ischemic etiology in 54%, NYHA II 53% and III/IV 47%, and median NT‐proBNP 1971 pg/mL. HF therapies at baseline were among the most effectively employed in contemporary HF trials. GALACTIC‐HF randomized patients representative of recent HF registries and trials with substantial numbers of patients also having characteristics understudied in previous trials including more from North America (n = 1386), enrolled as inpatients (n = 2084), systolic blood pressure < 100 mmHg (n = 1127), estimated glomerular filtration rate < 30 mL/min/1.73 m2 (n = 528), and treated with sacubitril‐valsartan at baseline (n = 1594). Conclusions: GALACTIC‐HF enrolled a well‐treated, high‐risk population from both inpatient and outpatient settings, which will provide a definitive evaluation of the efficacy and safety of this novel therapy, as well as informing its potential future implementation

Impact strength of underground cement materials

The article presents the results of a study of impact strength of underground cement materials with different water content activated by mixing water with the addition of high range plasticizers, biocidal agents, pigments, ground quartz, silica fume and fine aggregate. Samples for testing are formed in plates of size 150×100×10 mm. Testing was conducted at impact drop-weight method ASTM D7136. The maximum contact force, contact duration and magnitude of the pulse of the drummer were considered as the test parameters. The good results of the studied parameters showed highly filled plasticized compositions of the new generation. The use of iron oxide with yellow and green glauconitic pigments allows obtaining good results. Activation of the mixing water led to a rise in the maximum contact force in the case of the processing mode of E+М (3–3) while reducing the duration of the contact and the magnitude of the impulse. During the test of the biocidal composites with different biocidal preparations, it was established that the best indicators of the impact strength correspond to materials with the addition of «Teflex Antiplesen»

Pathomorphologic evaluation of intra-articular injections of soluble platelet‑rich plasma for treatment of experimental osteoarthritis

Introduction Non-surgical treatment of osteoarthritis is aimed at managing joint degeneration and inflammation to prolong the life of the original joint and delay total joint replacement. The objective was to pathomorphologically substantiate preclinical effectiveness of PRP in OA using comparative analysis of depleted plasma and serum. Material and methods The experiment was performed in 120 Wistar rats, divided into 4 groups. Osteoarthritis was simulated using an original method. Knee joint injection given to the animals after skin dissection under inhalation anesthesia and visual control two weeks later contained 0.05 ml PRP in group 1, 0.05 ml plasma in groups 2 and 0.05 ml blood serum in groups 3. The same volume of physiological saline solution was used for the injections produced for control animals. Injections were administered three times at 2-week intervals. Animals were sacrificed in groups of 10 at 2 weeks of each injection. Results The median MANKIN value scored 2.0 (1.0; 2.0) in group 1, 6.0 (5.0; 7.0) in group 2 and 7.0 (6.0; 7.0) in group 3 at 6 weeks. The median MANKIN value scored 7.5 (7.0, 8.0) in the control group. Statistically significant differences were determined between the groups at p < 0.001. Discussion Literature data on preclinical evaluation of the effectiveness of PRP therapy in biological models of OA are controversial. An original, low-traumatic functional method was used for simulating knee OA to reproduce major pathogenetic mechanisms in rats. Conclusion The findings suggested a pronounced therapeutic effect with improved morphofunctional features of the hyaline cartilage and MANKIN score of 2 at 6 days of intra-articular administration of modified PRP as compared with plasma and serum

The regioselective synthesis of spirooxindolo pyrrolidines and pyrrolizidines via three-component reactions of acrylamides and aroylacrylic acids with isatins and α-amino acids

The regioselective three-component condensation of azomethine ylides derived from isatins and α-amino acids with acrylamides or aroylacrylic acids as dipolarophiles has been realized through a one-pot 1,3-dipolar cycloaddition protocol. Decarboxylation of 2'-aroyl-2-oxo-1,1',2,2',5',6',7',7a'-octahydrospiro[indole-3,3'-pyrrolizine]-1'-carboxylic acids is accompanied by cyclative rearrangement with formation of dihydropyrrolizinyl indolones

Releases and recoveries of U.S. and NPRB salmonid data storage tags, and recoveries of high seas tags in North America and Russia, 2005. (NPAFC Doc. 904.) SAFS-UW-0504.

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