The role of epigenetics in renal ageing

An ability to separate natural ageing processes from processes specific to morbidities is required to understand the heterogeneity of age-related organ dysfunction. Mechanistic insight into how epigenetic factors regulate ageing throughout the life course, linked to a decline in renal function with ageing, is already proving to be of value in the analyses of clinical and epidemiological cohorts. Noncoding RNAs provide epigenetic regulatory circuits within the kidney, which reciprocally interact with DNA methylation processes, histone modification and chromatin. These interactions have been demonstrated to reflect the biological age and function of renal allografts. Epigenetic factors control gene expression and activity in response to environmental perturbations. They also have roles in highly conserved signalling pathways that modulate ageing, including the mTOR and insulin/insulin-like growth factor signalling pathways, and regulation of sirtuin activity. Nutrition, the gut microbiota, inflammation and environmental factors, including psychosocial and lifestyle stresses, provide potential mechanistic links between the epigenetic landscape of ageing and renal dysfunction. Approaches to modify the renal epigenome via nutritional intervention, targeting the methylome or targeting chromatin seem eminently feasible, although caution is merited owing to the potential for intergenerational and transgenerational effects

Albiglutide and cardiovascular outcomes in patients with type 2 diabetes and cardiovascular disease (Harmony Outcomes): a double-blind, randomised placebo-controlled trial

Background: Glucagon-like peptide 1 receptor agonists differ in chemical structure, duration of action, and in their effects on clinical outcomes. The cardiovascular effects of once-weekly albiglutide in type 2 diabetes are unknown. We aimed to determine the safety and efficacy of albiglutide in preventing cardiovascular death, myocardial infarction, or stroke. Methods: We did a double-blind, randomised, placebo-controlled trial in 610 sites across 28 countries. We randomly assigned patients aged 40 years and older with type 2 diabetes and cardiovascular disease (at a 1:1 ratio) to groups that either received a subcutaneous injection of albiglutide (30–50 mg, based on glycaemic response and tolerability) or of a matched volume of placebo once a week, in addition to their standard care. Investigators used an interactive voice or web response system to obtain treatment assignment, and patients and all study investigators were masked to their treatment allocation. We hypothesised that albiglutide would be non-inferior to placebo for the primary outcome of the first occurrence of cardiovascular death, myocardial infarction, or stroke, which was assessed in the intention-to-treat population. If non-inferiority was confirmed by an upper limit of the 95% CI for a hazard ratio of less than 1·30, closed testing for superiority was prespecified. This study is registered with ClinicalTrials.gov, number NCT02465515. Findings: Patients were screened between July 1, 2015, and Nov 24, 2016. 10 793 patients were screened and 9463 participants were enrolled and randomly assigned to groups: 4731 patients were assigned to receive albiglutide and 4732 patients to receive placebo. On Nov 8, 2017, it was determined that 611 primary endpoints and a median follow-up of at least 1·5 years had accrued, and participants returned for a final visit and discontinuation from study treatment; the last patient visit was on March 12, 2018. These 9463 patients, the intention-to-treat population, were evaluated for a median duration of 1·6 years and were assessed for the primary outcome. The primary composite outcome occurred in 338 (7%) of 4731 patients at an incidence rate of 4·6 events per 100 person-years in the albiglutide group and in 428 (9%) of 4732 patients at an incidence rate of 5·9 events per 100 person-years in the placebo group (hazard ratio 0·78, 95% CI 0·68–0·90), which indicated that albiglutide was superior to placebo (p<0·0001 for non-inferiority; p=0·0006 for superiority). The incidence of acute pancreatitis (ten patients in the albiglutide group and seven patients in the placebo group), pancreatic cancer (six patients in the albiglutide group and five patients in the placebo group), medullary thyroid carcinoma (zero patients in both groups), and other serious adverse events did not differ between the two groups. There were three (<1%) deaths in the placebo group that were assessed by investigators, who were masked to study drug assignment, to be treatment-related and two (<1%) deaths in the albiglutide group. Interpretation: In patients with type 2 diabetes and cardiovascular disease, albiglutide was superior to placebo with respect to major adverse cardiovascular events. Evidence-based glucagon-like peptide 1 receptor agonists should therefore be considered as part of a comprehensive strategy to reduce the risk of cardiovascular events in patients with type 2 diabetes. Funding: GlaxoSmithKline

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

Solution to error source model selection problem in IS EASECC

Introduction. The development of error-correcting techniques in digital transmission channels is considered. This is a multiparameter problem the solution of which through the analytical methods is rather difficult. This problem is solved within the framework of an information system for evaluating the applicability of noise-immune coding schemes based on an error sequence obtained from a real communication channel. The work objective is to develop methods for selecting the means of noise-immune protection in the data transmission systems. The key problem is to modify an information system evaluating the applicability of error-correcting coding so that it can choose the most appropriate error-source model for the error flow registered in the particular channel, and coordinate error-correcting codec parameters and characteristics of the communication channel based on the simulation experiments. Note that the choice of error-correcting methods involves selecting not only an algebraic code, but also algorithms for its coding and decoding. The results of using the error-correcting methods depend on the intensity and structure of the errors acting in the transmission channel. Materials and Methods. The basis of the described information system is a specialized software package based on the noise-immune communication channels simulation. To construct such a modification, we suggest adding a new module responsible for the error-source model selection. The module involves a special algorithm for the adequate error-source model selection constructed on the basis of the hidden semi-Markov models theory methods, particularly, on the evaluation problem solution. Research Results. The result of the work is a built-in modification of the information system for assessing the applicability of noise-immune coding schemes which allows, in an automatic mode, selecting a suitable method for a particular data transmission system from a list of the available methods of the anti-jamming protection. Discussion and Conclusions . The results obtained can be applied under designing digital transmission channels. The constructed information system allows for the automation of the process of selecting algorithmic methods of the noise-proof protection in the data transmission systems

Determination of Characteristic Peroids of Suppression of Thermal Decomposition Reaction of Forest Fuel Material by Specialized Software

Experimental studies determining periods of suppression of thermal decomposition reaction of forest combustible materials was carried out by high-speed, cross-correlation cameras and panoramic techniques PIV and IPI under influence of water steam. Conditions and characteristics of reaction termination of thermal decomposition of forest combustible materials under reaction with steam cloud were defined

Determination of Characteristic Peroids of Suppression of Thermal Decomposition Reaction of Forest Fuel Material by Specialized Software

Experimental studies determining periods of suppression of thermal decomposition reaction of forest combustible materials was carried out by high-speed, cross-correlation cameras and panoramic techniques PIV and IPI under influence of water steam. Conditions and characteristics of reaction termination of thermal decomposition of forest combustible materials under reaction with steam cloud were defined

Results of experimental studies operation chamber pump

At the moment there is a problem of high power consumption functioning pneumatic systems for bulk materials. A mathematical model of the motion of two-phase flow of fine materials with regard to the interaction of particles, uneven filling feeding pipeline and flow turbulence. The mathematical model can be used to calculate the motion of two-phase flow in pipelines, as well as in bulk pumps, subject to the incorporation of geometric design features and properties of the solid material in a stationary state. For adapting the mathematical model made industrial experiment and change the parameters obtained according to the time of discharge

Study of Brain Circadian Rhythms in Patients with Chronic Disorders of Consciousness and Healthy Individuals Using Microwave Radiometry

The study of circadian rhythms in the human body using temperature measurements is the most informative way to assess the viability of the body’s rhythm-organizing systems. Pathological processes can affect circadian rhythm dynamics in damaged organs. Severe brain damage that caused the development of disorders of consciousness (DOC) (strokes, traumatic brain injury) disrupts the activity of central oscillators, by directly damaging or destroying the periphery links, and the level of preservation of circadian rhythms and the dynamics of their recovery can be informative diagnostic criteria for patient’s condition assessment. This study examined 23 patients with DOC by using a non-invasive method for obtaining body and cerebral cortex temperature to compare with healthy controls. Measurements were made with a 4 h interval for 52 h beginning at 08:00 on day 1 and ending at 08:00 on day 3. The profile of patients with DOC showed complete disruption compared to healthy controls with rhythmic patterns. The results indicate that the mechanisms for maintaining brain circadian rhythms are different from general homeostasis regulation of the body. Use of microwave radio thermometry for the identification of rehabilitation potential in patients with DOC is a promising area of investigation