Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Main indicators of population migration in the Russian Federation and their dynamics

The dynamics of internal and international migration processes in the Russian Federation in 2015–2019 is studied. The results of a comparative statistical study carried out for three process indicators and 120 factors are presented. The indicators for 2020 are not included in the comparative analysis, as they are not typical for Russia and are caused by the pandemic

Youth Policy And The Development of Quality Education As Factors In Reducing The Level of Radicalization In Society

The article is devoted to the consideration of youth and youth policy as factors of terrorism in the 21st century. The authors have identified factors that increase the effectiveness of recruiters of terrorist organizations in attracting young people, as well as formulated and justified the principles of improving the effectiveness of youth policy in the framework of anti-terrorist activities of the authorities. According to the authors, an important factor in the radicalization of young people is the low level of education in the country. The authors draw attention to the fact that the low level of education does not create opportunities for the development of young people. This, in turn, leads to a radicalization of the relationship between the authorities and students. If graduates are unable to find jobs that meet their expectations, then the risk of radicalization of young people increases. A good education not only allows the state to train qualified specialists, which effectively affects the social and economic development of society. Specialists in demand do not belong to social groups prone to violent and radical actions in relation to other citizens, both within the country and abroad. Therefore, it is necessary, on the one hand, to develop educational programs that allow college and university graduates to be in demand in the labor market, constantly improve their skills, and increase the level of knowledge. On the other hand, it is necessary to develop students' skills, such as critical thinking, creativity, respect for the institutions of society, and skills in solving social and professional problems

Theory of health: successful translation into the real life

The paper reveals logical relationships between events, facts and results of research studies and exemplary materials of practical applications of the adaptational reactions. It is demonstrated that the stress reaction by H. Selye and the anti-stressor type adaptational reactions by L. Kh. Garkavi, E.B. Kvakina and M.A. Ukolova have become the cornerstone in development of scientifically grounded approaches to control of the organism states

Synthesis and photophysical properties of copolyfluorenes for light-emitting applications: Spectroscopic experimental study and theoretical DFT consideration

Текст статьи не публикуется в открытом доступе в соответствии с политикой журнала

Neurometabolic effect of altaian fungus Ganoderma lucidum (Reishi Mushroom) in rats under moderate alcohol consumption

Background The medications produced from natural products are widely used as prophylactics for sickness induced by alcohol consumption. One such prophylactic is produced from the Reishi mushroom, Ganoderma lucidum. Because of the antioxidant properties of these preparations, we expect neuroprotective prophylactic effects of Reishi-based medications in alcohol-treated animals.Methods The Reishi (R) suspension was produced as water extract from Altaian mushrooms. Sprague–Dawley male rats were separated into the following 3 experimental groups: Group A + R received R (6 days per week) starting 1 week before alcohol exposure, and during the next 3 weeks, they received both R and alcohol; group A received alcohol; and group C received water. At the end of experiment, we determined the metabolic profile using proton magnetic resonance spectroscopy (1H MRS) of the brain cortex and phosphorus magnetic resonance spectroscopy of the liver. Additionally, the blood cells were collected, and the serum biochemistry and liver histology were performed after euthanasia.ResultsPartial least squares discriminant analysis processing of the brain 1H MRS gave 2 axes, the Y1 axis positively correlated with the level of taurine and negatively correlated with the level of lactate, and the Y2 axis positively correlated with the content of GABA and glycine and negatively correlated with the sum of the excitatory neurotransmitters, glutamate and glutamine. The Y1 values reflecting the brain energetics for the A + R group exceeded the corresponding values for groups C and A. The maximal level of Y2 reflecting the prevalence of inhibitory metabolites in the brain was observed in the rats exposed to alcohol. Moderate alcohol consumption did not cause significant pathological changes in the livers of the experimental animals. However, 20 days of alcohol consumption significantly increased the number of binuclear hepatocytes compared to the control. This effect was mitigated in the rats that received the Reishi extract.Conclusions Regular administration of the Reishi suspension improved the energy supply to the brain cortex and decreased the prevalence of inhibitory neurotransmitters that are characteristic of alcohol consumption. The alcohol-induced increase in liver proliferation was significantly suppressed by regular administration of the G. lucidum water suspension

X-ray structural studies of the fungal laccase from Cerrena maxima

Laccases are members of the blue multicopper oxidase family. These enzymes oxidize substrate molecules by accepting electrons at a mononuclear copper centre and transferring them to a trinuclear centre. Dioxygen binds to the trinuclear centre and following the transfer of four electrons is reduced to two molecules of water. The X-ray structure of a laccase from Cerrena maxima has been elucidated at 1.9 angstrom resolution using synchrotron data and the molecular replacement technique. The final refinement coefficients are R-cryst = 16.8% and R-free = 23.0%, with root mean square deviations on bond lengths and bond angles of 0.015 angstrom and 1.51 degrees, respectively. The type 1 copper centre has an isoleucine residue at the axial position and the &quot;resting&quot; state of the trinuclear centre comprises a single oxygen (OH) moiety asymmetrically disposed between the two type 3 copper ions and a water molecule attached to the type 2 ion. Several carbohydrate binding sites have been identified and the glycan chains appear to promote the formation of well-ordered crystals. Two tyrosine residues near the protein surface have been found in a nitrated state.</p

Measurement of the branching fractions for Cabibbo-suppressed decays D+→K+K−π+π0D^{+}\to K^{+} K^{-}\pi^{+}\pi^{0} and D(s)+→K+π−π+π0D_{(s)}^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0} at Belle

International audienceWe present measurements of the branching fractions for the singly Cabibbo-suppressed decays $D^+\to K^{+}K^{-}\pi^{+}\pi^{0}$ and $D_s^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0}$, and the doubly Cabibbo-suppressed decay $D^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0}$, based on 980 ${\rm fb}^{-1}$ of data recorded by the Belle experiment at the KEKB $e^{+}e^{-}$ collider. We measure these modes relative to the Cabibbo-favored modes $D^{+}\to K^{-}\pi^{+}\pi^{+}\pi^{0}$ and $D_s^{+}\to K^{+}K^{-}\pi^{+}\pi^{0}$. Our results for the ratios of branching fractions are $B(D^{+}\to K^{+}K^{-}\pi^{+}\pi^{0})/B(D^{+}\to K^{-}\pi^{+}\pi^{+}\pi^{0}) = (11.32 \pm 0.13 \pm 0.26)\%$, $B(D^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0})/B(D^{+}\to K^{-}\pi^{+}\pi^{+}\pi^{0}) = (1.68 \pm 0.11\pm 0.03)\%$, and $B(D_s^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0})/B(D_s^{+}\to K^{+}K^{-}\pi^{+}\pi^{0}) = (17.13 \pm 0.62 \pm 0.51)\%$, where the uncertainties are statistical and systematic, respectively. The second value corresponds to $(5.83\pm 0.42)\times\tan^4\theta_C$, where $\theta_C$ is the Cabibbo angle; this value is larger than other measured ratios of branching fractions for a doubly Cabibbo-suppressed charm decay to a Cabibbo-favored decay. Multiplying these results by world average values for $B(D^{+}\to K^{-}\pi^{+}\pi^{+}\pi^{0})$ and $B(D_s^{+}\to K^{+}K^{-}\pi^{+}\pi^{0})$ yields $B(D^{+}\to K^{+}K^{-}\pi^{+}\pi^{0})= (7.08\pm 0.08\pm 0.16\pm 0.20)\times10^{-3}$, $B(D^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0})= (1.05\pm 0.07\pm 0.02\pm 0.03)\times10^{-3}$, and $B(D_s^{+}\to K^{+}\pi^{-}\pi^{+}\pi^{0}) = (9.44\pm 0.34\pm 0.28\pm 0.32)\times10^{-3}$, where the third uncertainty is due to the branching fraction of the normalization mode. The first two results are consistent with, but more precise than, the current world averages. The last result is the first measurement of this branching fraction