Platelets differentially modulate CD4+ Treg activation via GPIIa/IIIb-, fibrinogen-, and PAR4-dependent pathways

CD4+FoxP3+ regulatory T cells (CD4+ Tregs) are known to dampen inflammation following severe trauma. Platelets were shown to augment their posttraumatic activation in burn injury, but the exact mechanisms remain unclear. We hypothesized that platelet activation mechanisms via GPIIb/IIIa, fibrinogen, and PAR4 have an immunological effect and modulate CD4+ Treg activation early after trauma. Therefore, C57Bl/6 N mice were injected with tirofiban (GPIIb/IIIa inhibition), ancrod (fibrinogen splitting enzyme), or tcY-NH2 (selective PAR4 antagonist peptide) before inducing a third-degree burn injury of 25% of the total body surface area. Changes in coagulation, and local and systemic CD4+ Treg activity were assessed via rotational thromboelastometry (ROTEM®) and phospho-flow cytometry 1 h post intervention. The inhibition of GPIIb/IIIa and fibrinogen locally led to a higher basic activity of CD4+ Tregs compared to non-inhibited animals. In contrast, PAR4 disruption on platelets locally led to an increased posttraumatic activation of CD4+ Tregs. Fibrinogen led to complete elimination of coagulation, whereas GPIIb/IIIa or PAR4 inhibition did not. GPIIb/IIIa receptor and fibrinogen inhibition increase CD4+ Tregs activity independently of trauma. Both are crucial for thrombus formation. We suggest platelets trapped in thrombi are unable to interact with CD4+ Tregs but augment their activity when circulating freely. In contrast, PAR4 seems to reduce CD4+ Treg activation following trauma. In summary, GPIIb/IIIa-, PAR4-, and fibrinogen-dependent pathways in platelets modulate CD4+ Treg baseline activity, independently from their hemostatic functionality. PAR4-dependent pathways modulate the posttraumatic interplay of platelets and CD4+ Tregs.

Factors associated with transitions between frailty states among older persons in Brazil, 2006-2010

Background Frailty is considered one of the major conditions faced by ageing societies. Little has been reported about the transitions between the different frailty states in developing countries. Objective This study aimed to identify the factors associated with transitions between frailty states between 2006 and 2010 among older adults in Brazil. Method The present investigation is part of the SABE study (Health, Well-being and Ageing). Frailty state was classified according to the Fried’s criteria (nonfrail, prefrail, and frail). The final study sample was composed of 1,399 individuals representing 1,019,243 older adults in the city of Sao Paulo, Brazil. Multiple logistic regression was used to identify factors associated with changes in frailty states. Results Women were more likely to present a decline in frailty states. In the prefrail-to-nonfrail model, level of education was the most strongly associated factor. Advanced age and difficulty in performing at least one basic activity of daily living reduced in 9 and 64% the risk of becoming nonfrail, respectively. Conclusion Addressing the factors associated with transition between frailty states among older adults is essential. Adequate interventions are important to reduce vulnerability and improve the health and well-being of older persons.

CHALLENGES OF APPLICATION AND INTERPRETATION OF REGULATIONS IN THE PRACTICE OF MISDEMEANOR COURTS

The author analyzes the always current issue of application and interpretation of regulations in the practice of misdemeanor courts. The scope and complexity of the matter in which misdemeanor courts act is pointed out, but also the fact that shortcomings in the regulation of regulations represent a major problem in court practice. The subject of the author's interest are the basic principles of application of law as the basic activity of misdemeanor courts, which is why the structure of the legal norm and the distinction between factual and legal issues are considered. Then, the notion of court interpretation of regulations was analyzed and attention was drawn to the dangers of applying the analogy in substantive misdemeanor law. The author considered the issues of court interpretation of regulations which provide for the objective responsibility of a natural person and different interpretations of regulations as the cause of uneven court practice. Numerous court decisions listed in the paper served as a basis to point out the importance of court interpretation of legal institutes for misdemeanor liability. Through the theoretical aspect and rich case law, the author analyzed some controversial issues and offered solutions to the problem, concluding that judges of misdemeanor courts in their daily work have great challenges related to the application and interpretation of regulations.

Energy and Acoustic Environmental Effective Approach for a Wind Farm Location

The justification for the construction of a wind farm depends primarily on two factors. The first one is the availability of the area with significant windiness; the second one is the environmental conditions in the selected location. The aim of this paper was to demonstrate the need for parallel noise and energy analyses during the design of a turbine location and selection of its type on the wind farm. The noise analyses were performed according to ISO 9613-2. A detailed analysis of wind conditions in a given location is a basic activity to determine the profitability of a wind power plant foundation. The main environmental impact of WF is noise emission. The examples of wind turbines’ selection optimally utilizing wind resources in two particular locations are presented. Six wind turbines were analyzed for each location. The choice of a wind turbine for the examined location was determined by the parameters of the device, the results of annual wind measurements, and acceptable noise levels in the environment. The three devices that met the acoustic criteria and the most energy efficient ones are indicated. We describe how a proper process of selecting a type of WT for a specific location should proceed.

The creative personality as a subject of culture in the paradigm dimensions of understanding

The purpose of the article is to substantiate the essence of paradigmaticity, to determine the basic paradigm dimensions of cultural comprehension of the phenomenon of personality. The methodology of research consists in the application of synergetic, axiological, cultural-hermeneutic approaches and analytical, semiotic, phenomenological methods to comprehend the personality as a subject of culture, capable of representing universal cultural meanings, values and ideals through various forms of creative practices, choosing a personal vector of creative self-realization. Scientific novelty of the work lies in the fact that for the first time in the problem field of cultural studies on the basis of paradigmatic as a sign of modern postnonclassical humanitarianism is justified paradigm dimensions of comprehension of personality, based on discursiveness, multiple intellectual forms of scientific knowledge, as well as interpretive variability of artistic thinking. In the context of culturological comprehension of personality as a cultural subject universal paradigm dimensions are defined: interscientific, humanitarian, subject-value, activity-creative. Conclusions. Interscientific paradigmal dimension allows to systematize the directions of evolution of scientific views on the phenomenon of personality from the position of different spheres of scientific knowledge. Through humanitarian paradigmatic dimension the person is presented as a creative personality within phenomenological hermeneutics; in the context of discursive technologies of personality self-projection, the possession of which becomes an important condition of its successful creative self-realization. The creative personality in the context of the subject-value dimension acts as a bearer of cultural values as the works of spiritual culture. Culturological research of personality in its basic - activity-creative paradigmatic dimension allows to consider the creative personality through creative activity, on the basis of which reincarnation of the personality himself into the subject of culturecreativity takes place.

Sustainable Remediation of Soils Contaminated with Petroleum Products

In nature, it acts, simultaneously or successively, synergistically or antagonistically, on small or larger spaces, for a long or very short time, numerous natural or artificial processes that pollute, leading to the alteration of the quality of the environment. The basic activity carried out within the oil scaffolding consists in the extraction of crude oil and gases from the deposits in their exploitation, their collection, separation of phases (crude oil, reservoir water, gas), crude oil treatment, storage and sending to users. Contamination of the field related to drilling-extraction wells with crude oil, heavy petroleum products, salt water, various chemicals, etc. has a random character, but with undesirable implications on soil, surface water and / or groundwater, depending on the nature of the pollutant, its quantity and area of spread Pollution sources in the oil industry, both systematic and accidental, have a greater or lesser spread, depending on the size of the field, the type and composition of the extracted fluids, the extraction technology used, the age of oil exploitation in the area, relief and hydrographic network. Having available the data provided by the pollution diagnosis, it is possible to assess the risk that the investigated pollution represents for the people on the site and for the natural environment. If it turns out that the risk is significant, then the decision is made to switch to depollution works. The choice of an appropriate depollution path is made on the basis of relevant technical and economic criteria, which is a feasibility study. The proposed depollution technology must be the most appropriate for the case at hand and, at the same time, be available on the technology market. The most important part of the paper is dedicated to presenting the results of an experimental study on the depollution of soils contaminated with liquid petroleum products by sparging technologies, in order to ensure a sustainable remedy. The results of the soil analysis used in the experimental determination are presented, as well as the physic - chemical characteristics of the main soil pollutants. In the experimental part, laboratory decontamination of systems consisting of polluted soils was performed at the laboratory level, using air as a depollution agent. The processing of the data obtained from the experimental determinations allowed obtaining qualitative and quantitative information related to the decontamination speed depending on the nature of the soil, the nature and concentration of the pollutant and the temperature of the decontamination air. Estimating the cost places this technology at a low level compared to thermal technologies and slightly higher than microbiological technologies.

Analysis of bird situation around airports using avian radar

To improve the ability of avian radar to process bird information, a statistical analysis method for the bird situation around airport is proposed based on avian radar data. By accumulating a large amount of avian radar data, hotspots of the activity area of bird targets can be determined and taken as a reference point to realise lifecycle management of each bird target from initiation to continuation and finally death. In the process of target tracking, combined with the particle filter method, the probability of several possible events is estimated, leading to completion of the data association and real-time statistics for the number of targets. The simulation results reveal that this method is superior to the traditional logic method regarding the timeliness of multi-target initiation. With the application of the proposed method to avian radar data, the bird population and its basic activity rules can be discovered by fixing the bird habitats around the airport.

Conservative rehabilitation for a patient presenting with severe orthostatic hypotension after surgical management of brainstem tumor: illustrative case

BACKGROUND Blood pressure (BP) dysregulation is frequently observed in patients after surgical management of brainstem lesions; however, there has been no standard rehabilitation. Considering the conflicting risks for hypoperfusion and disuse syndrome in these patients, a safe and effective rehabilitative strategy is warranted. OBSERVATIONS A 50-year-old man who had undergone craniotomy for resection of a recurrent dorsal medullary epidermoid cyst developed persistent orthostatic hypotension. It was resistant to physical exercise, pharmacological therapy, abdominal binders, and compression stockings; therefore, it inhibited postoperative rehabilitation. Although the responsible lesion was not clearly visible on the postoperative image, accompanying symptoms, including segmental sensory impairment, implied an improvement in BP control. Although there was a trade-off between the risk of developing disuse syndrome and a delay in functional recovery, the authors decided to continue a conservative rehabilitation strategy rather than increasing the workload. The patient’s BP control was gradually restored by the seventh postoperative week, and the authors proceeded with basic activity training. LESSONS A conservative prognostic prediction-based rehabilitation strategy was applied in this case. The precise evaluation of the accompanying neurological symptoms was helpful in deciding the treatment regimen. The conflicting risks for hypoperfusion and disuse syndrome in such cases must be considered.

Disruption of FOXO3a-miRNA feedback inhibition of IGF2/IGF-1R/IRS1 signaling confers Herceptin resistance in HER2-positive breast cancer

Resistance to Herceptin represents a significant challenge for successful treatment of HER2-positive breast cancer. Here, we show that in Herceptin-sensitive cells, FOXO3a regulates specific miRNAs to control IGF2 and IRS1 expression, retaining basic IGF2/IGF-1R/IRS1 signaling. The basic activity maintains expression of PPP3CB, a subunit of the serine/threonine-protein phosphatase 2B, to restrict FOXO3a phosphorylation (p-FOXO3a), inducing IGF2- and IRS1-targeting miRNAs. However, in Herceptin-resistant cells, p-FOXO3a levels are elevated due to transcriptional suppression of PPP3CB, disrupting the negative feedback inhibition loop formed by FOXO3a and the miRNAs, thereby upregulating IGF2 and IRS1. Moreover, we detect significantly increased IGF2 in blood and IRS1 in the tumors of breast cancer patients with poor response to Herceptin-containing regimens. Collectively, we demonstrate that the IGF2/IGF-1R/IRS1 signaling is aberrantly activated in Herceptin-resistant breast cancer via disruption of the FOXO3a-miRNA negative feedback inhibition. Such insights provide avenues to identify predictive biomarkers and effective strategies overcoming Herceptin resistance.

Validation of the Korean Version of the Anosognosia Questionnaire for Dementia

Objective Anosognosia is a common phenomenon in individuals with dementia. Anosognosia Questionnaire for dementia (AQ-D) is a well-known scale for evaluating anosognosia. This study aimed to establish a Korean version of the AQ-D (AQ-D-K) and to evaluate the reliability and validity of the AQ-D-K in patients with Alzheimer’s disease (AD) dementia.Methods We translated the original English version of AQ-D into Korean (AQ-D-K). Eighty-four subjects with very mild or mild AD dementia and their caregivers participated. Reliability of AQ-D-K was assessed by internal consistency and one-month test-retest reliability. Construct validity and concurrent validity were also evaluated.Results Internal consistencies of the AQ-D-K patient form and caregiver form were high (Cronbach alpha 0.95 and 0.93, respectively). The test-retest reliability of AQ-D-K measured by intra-class correlation coefficient was 0.84. Three factors were identified: 1) anosognosia of instrumental activity of daily living; 2) anosognosia basic activity of daily living; and 3) anosognosia of depression and disinhibition. AQ-D-K score was significantly correlated with the clinician-rated anosognosia rating scale (ARS), center for epidemiological studies-depression scale (CES-D) and state-trait anxiety inventory (STAI).Conclusion The findings suggest that the AQ-D-K is a reliable and valid scale for evaluating anosognosia for AD dementia patients using Korean language.