Introduction: There are almost no studies characterizing the integrative level of blood pressure (BP) regulation.
Materials and methods: 277 people of both genders aged 58.6±6.4 with stage II ...hypertension disease were randomized into six groups. The monotherapy of hypertension disease was conducted in five groups, using nebivolol, lisinopril, indapamide, amlodipine, and losartan. The sixth group had a combined therapy (lisinopril/indapamide). The therapy effectiveness was assessed at four levels of blood pressure regulation, using the following methods: 1) laser Doppler flowmetry, determination of the level of tumor necrosis factor-α and interleukin-10; 2) echocardiography and Doppler sonography, ultrasound examination of the renal blood flow, ECG, Holter monitoring of ECG; 3) an examination of the heart rate variability level and a quantitative assessment of beta-adrenoreception of erythrocyte cell membranes; 4) the regulatory and adaptive status was assessed, using the method of cardio-respiratory synchronism.
Results and discussion: A more significant BP decrease was revealed during a combination therapy (by 20.4% of the baseline daily value). At the integrative level, an index of the regulatory and adaptive status (iRAS) increased in the treatment with lisinopril/indapamide combination (by 40.5%), amlodipine (by 40.5%), losartan (by 35.3%), and lisinopril (by 30.2%). Nebivolol administration resulted in a 13.5% decrease in iRAS. Indapamide therapy had no significant effect on iRAS.
Conclusion: A comprehensive assessment of the blood pressure regulation system makes it possible to control the effectiveness of the therapy not only on a target organ or function, but also on the condition of the organism as an integral system.
In this paper, we propose a regulation-level representation for microarray data and optimize it using genetic algorithms (GAs) for cancer classification. Compared with the traditional ...expression-level features, this representation can greatly reduce the dimensionality of microarray data and accommodate noise and variability such that many statistical machine-learning methods now become applicable and efficient for cancer classification. Experimental results on real-world microarray datasets show that the regulation-level representation can consistently converge at a solution with three regulation levels. This verifies the existence of the three regulation levels (up-regulation, down-regulation and non-significant regulation) associated with a particular biological phenotype. The ternary regulation-level representation not only improves the cancer classification capability but also facilitates the visualization of microarray data.
Atrazine (ATZ) is one of the most used herbicides in the US and a known endocrine disruptor. ATZ is frequently detected in drinking water, especially in Midwestern regions of the United States, ...exceeding the EPA regulation of maximum contamination level (MCL) of 3 ppb. Epidemiology studies have suggested an association between ATZ exposure and neurodegeneration. Less, however, is known about the neurotoxic mechanism of ATZ, particularly for exposures at a developmental stage. Here, we exposed floor plate progenitors (FPPs) derived from human induced pluripotent stem cells (hiPSCs) to low concentrations of ATZ at 0.3 and 3 ppb for two days followed by differentiation into dopaminergic (DA) neurons in ATZ-free medium. We then examined the morphology, activity, pathological protein aggregation, and transcriptomic changes of differentiated DA neurons. We observed significant decrease in the complexity of neurite network, increase of neuronal activity, and elevated tau- and α-synuclein (aSyn) pathologies after ATZ exposure. The ATZ-induced neuronal changes observed here align with pathological characteristics in Parkinson's disease (PD). Transcriptomic analysis further corroborates our findings; and collectively provides a strong evidence base that low-concentration ATZ exposure during development can elicit increased risk of neurodegeneration.
Environmental exposure to fine particulate matter PM2.5 is known to be associated with many hazardous health effects, including cardiovascular diseases (CVDs). To reduce the related health burden, it ...is crucial that policy-makers throughout the world set regulation levels according to their own evidence-based study outcomes. However, there appears to be a lack of decision-making methods for the control level of PM2.5 based on the burden of disease. In this study, 117,882 CVD-free participants (≥30-years-old) of the MJ Health Database were followed-up (for a median of 9 years) between 2007 and 2017. Each participant's residential address was matched to the 3× 3 km grid PM2.5 concentration estimates with a 5-year average for long-term exposure. We used a time-dependent nonlinear weight-transformation Cox regression model for the concentration–response function (CRF) between exposure to PM2.5 and CVD incidence. Town/district-specific PM2.5-attributable years of life in disability (YLDs) in CVD incidence were calculated by using the relative risk (RR) of the PM2.5 concentration level relative to the reference level. A cost–benefit analysis was proposed by assessing the trade-off between the gain in avoidable YLDs (given a reference level at u and considering mitigation cost) versus the loss in unavoidable YLDs by not setting at the lowest observed health effect level u0. The CRF varied across different areas with dissimilar PM2.5 exposure ranges. Areas with low PM2.5 concentrations and population sizes provided crucial information for the CVD health effect at the lower end. Additionally, women and older participants were more susceptible. The avoided town/district-specific YLDs in CVD incidence due to lower RRs ranged from 0 to 3000 person-years comparing the PM2.5 concentration levels in 2019 with the levels in 2011. Based on the cost–benefit analysis, an annual PM2.5 concentration of 13 μg/m3 would be optimal, which provides a guideline for the updated regulation level (currently at 15 μg/m3). The proposed cost–benefit analysis method may be applied to other countries/regions for regulation levels that are most suitable for their air pollution status and population health.
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•C–R function varied across different areas with dissimilar PM2.5 concentrations.•The areas with low PM2.5 and population sizes provide crucial C–R information.•Women and older participants were more susceptible to PM2.5-attributed CVD incidence.•A cost–benefit analysis for the tradeoff between YLDs in CVD and mitigation cost•The cost–benefit analysis suggested an optimal PM2.5 control level of 13 μg/m3.
Knowledge and error flow from the same mental sources, only success can tell the one from the other (Mach, E., 1905. Knowledge and Error. Sketches on the Psychology of Enquiry. D. Reidel Publishing ...Company, Dordrecht (translated into English, 1976). The current paper is concerned with human actions and errors that have accidents with an injury outcome as their consequence. Its aims are to identify and describe the occurrence of risk-triggering and risk-creating human errors, and to analyze the cognitive regulation levels of risk-triggering actions. This provides a basis on which to discuss some difficulties involved in the assigning of regulation levels to actions. The empirical material employed in the paper consists of data from 76 in-depth investigations of accidents in automated production. Risk-creating errors were found in 93% of cases, and were made at various organizational levels in the companies. The amount of and character of the risk-creating errors point to the importance of interventions that promote learning at the levels of the work team and the organization. In 88% of cases there was also a human error that triggered the risk. Risk-triggering errors were made at all cognitive-regulation levels. The conclusions concern methodological issues and theoretical question marks arising. There emerged a need to distinguish between the outcome of an action and its further consequences. Classification of regulation levels involved in human error was found to be fraught with difficulties when drawing boundaries between levels. Actions at different levels appeared to intervene and take over from each other, leaving errors at category interfaces. The structural aspect of action as a composite phenomenon might mean that it is not always possible to assign any particular act to a specific level, and since a task or an action usually is composed of several behavioral components the action could be assigned to several levels simultaneously. This raises questions concerning the applicability of the Skill–Rule–Knowledge (SRK) model to triggering errors in automated production.
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