Dynamin inhibitors impair endocytosis and mitogenic signaling of PDGF.

Platelet-derived growth factor (PDGF) isoforms regulate cell proliferation, migration and differentiation both in embryonic development and adult tissue remodeling. At the cellular level, growth-factor signaling is often modulated by endocytosis. Despite important functions of PDGF, its endocytosis remains poorly studied, mainly for lack of tools to track internalized ligand by microscopy. Here, we developed such a tool and quantitatively analyzed internalization and endosomal trafficking of PDGF-BB in human fibroblasts. We further show that PDGF can be internalized in the presence of dynamin inhibitors, arguing that both dynamin-dependent and dynamin-independent pathways can mediate PDGF uptake. Although these routes operate with somewhat different kinetics, they both ultimately lead to lysosomal degradation of PDGF. Although acute inhibition of dynamin activity only moderately affects PDGF endocytosis, it specifically decreases downstream signaling of PDGF via signal transducer and activator of transcription 3 (STAT3). This correlates with reduced expression of MYC and impaired cell entry into S-phase, indicating that dynamin activity is required for PDGF-induced mitogenesis. Our data support a general view that the components governing endocytic trafficking may selectively regulate certain signaling effectors activated by a growth factor.

Impact of Superplasticizers on the Performance of Low-Grade Limestone-Based Cement Mixes.

Low-grade limestone (LGL) is not used to produce cement clinker, but this leftover material in cement quarries increases the water demand when used as a filler in concrete production. In this study, the effect of six commercial superplasticizers on the performance of cement mixes containing 35% LGL and 2% gypsum was investigated. The optimal doses of these superplasticizers were found in a range of different water/binder (w/b) ratios by conducting several Marsh cone and mini-slump tests. The addition of a superplasticizer with a higher active solid content produced a maximum cement flow, regardless of the w/b ratios. The LGL-based mortar samples admixed with this superplasticizer obtained a maximum compressive strength of about 36 MPa at the end of 28 days. SEM and XRD results showed the formation of a new calcium-rich mineral in their microstructure. These findings highlight the impact of the type and properties of superplasticizers on the performance of concrete mixes containing LGL as a supplementary cementitious material.

The use of CytoSorb in acute oral mercuric chloride poisoning at a potentially lethal dose.

INTRODUCTION: The study aims to present a case of acute mercuric chloride poisoning treated successfully with continuous renal replacement therapy using the CytoSorb filter. CASE DESCRIPTION: A 21-year-old female patient after a suicide attempt by intentional ingestion of mercuric chloride, was admitted to the hospital with features of multiple organ damage for specific treatment. The performed laboratory tests confirmed high levels of mercury in the blood (1051 µg/L) and urine (22,960 µg/L). Due to acute renal failure, continuous renal replacement therapy (CRRT) CVVHD Ci-Ca was initiated; the procedure was then converted to CVVHDF Ci-Ca with ultrafiltration to optimise therapy, and CytoSorb was added to the artificial kidney system on day 3. Specific antidote therapy (DMPS) was administered concurrently. The ongoing treatment resulted in a reduction in subjective complaints, a decrease in blood mercury levels to 580 µg/L, and an improvement in parenchymal organ function. CONCLUSION: In the event of poisoning with inorganic mercury compounds (mercuric chloride), continuous renal replacement therapy using the CytoSorb filter as an extracorporeal blood purification method may be considered.

Prevalence of life-sustaining treatment limitations in Polish very old intensive care patients (VIPs). A post-hoc analysis of two prospective observational studies.

PURPOSE: Several initiatives have recently focused on raising awareness about limitations of treatment in Poland. We aimed to assess if the propensity to limit LST among elderly patients in 2018-2019 increased compared to 2016-2017. METHODS: We analysed Polish cohorts from studies VIP1 (October 2016 - May 2017) and VIP2 (May 2018 - May 2019) that enrolled critical patients aged >80. We collected data on demographics, clinical features limitations of LST. Primary analysis assessed factors associated with prevalence of limitations of LST, A secondary analysis explored differences between patients with and without limitations of LST. RESULTS: 601 patients were enrolled. Prevalence of LST limitations was 16.1% in 2016-2017 and 20.5% in 2018-2019. No difference was found in univariate analysis (p = 0.22), multivariable model showed higher propensity towards limiting LST in the 2018-2019 cohort compared to 2016-2017 cohort (OR 1.07;95%CI, 1.01-1.14). There was higher mortality and a longer length of stay of patients with limitations of LST compared to the patients without limitations of LST. (11 vs. 6 days, p = 0.001). CONCLUSIONS: The clinicians in Poland have become more proactive in limiting LST in critically ill patients ≥80 years old over the studied period, however the prevalence of limitations of LST in Poland remains low.

Predictors of outcomes of patients ≥ 80 years old admitted to intensive care units in Poland - a post-hoc analysis of the VIP2 prospective observational study.

INTRODUCTION: Elderly patients pose a significant challenge to intensive care unit (ICU) clinicians. In this study we attempted to characterise the population of patients over 80 years old admitted to ICUs in Poland and identify associations between clinical features and short-term outcomes. MATERIAL AND METHODS: The study is a post-hoc analysis of the Polish cohort of the VIP2 European prospective observational study enrolling patients > 80 years old admitted to ICUs over a 6-month period. Data including clinical features, clinical frailty scale (CFS), geriatric scales, interventions within the ICU, and outcomes (30-day and ICU mortality and length of stay) were gathered. Univariate analyses comparing frail (CFS > 4) to non-frail patients and survivors to non-survivors were performed. Multivariable models with CFS, activities of daily living score (ADL), and the cognitive decline questionnaire IQCODE as predictors and ICU or 30-day mortality as outcomes were formed. RESULTS: A total of 371 patients from 27 ICUs were enrolled. Frail patients had significantly higher ICU (58% vs. 44.45%, P = 0.03) and 30-day (65.61% vs. 54.14%, P = 0.01) mortality compared to non-frail counterparts. The survivors had significantly lower SOFA score, CFS, ADL, and IQCODE than non-survivors. In multivariable analysis CFS (OR 1.15, 95% CI: 1.00-1.34) and SOFA score (OR 1.29, 95% CI: 1.19-1.41) were identified as significant predictors for ICU mortality; however, CFS was not a predictor for 30-day mortality ( P = 0.07). No statistical significance was found for ADL, IQCODE, polypharmacy, or comorbidities. CONCLUSIONS: We found a positive correlation between CFS and ICU mortality, which might point to the value of assessing the score for every patient admitted to the ICU. The older Polish ICU patients were characterised by higher mortality compared to the other European countries.

Biochemical characterization of APPL endosomes: the role of annexin A2 in APPL membrane recruitment.

APPL endosomes are a recently identified subpopulation of early endosomes characterized by the presence of two homologous Rab5 effector proteins APPL1 and APPL2. They exhibit only limited colocalization with EEA1, another Rab5 effector and a marker of the canonical early endosomes. Although APPL endosomes appear to play important roles in cargo trafficking and signal transduction, their protein composition and biochemical properties remain largely unknown. Here we employed membrane fractionation methods to characterize APPL endosomes biochemically. We demonstrate that they represent heterogeneous membrane structures which can be discriminated from the canonical EEA1-positive early endosomes by their partly different physical properties and a distinct migration pattern in the continuous density gradients. In search for other potential markers of APPL endosomes we identified Annexin A2 as an interacting partner of both APPL1 and APPL2. Annexin A2 is a Ca(2+) and phosphatidylinositol 4,5-bisphosphate binding protein, previously implicated in several endocytic steps. We show that Annexin A2 co-fractionates and colocalizes with APPL endosomes. Moreover, silencing of its expression causes solubilization of APPL2 from endosomes. Although Annexin A2 is not an exclusive marker of APPL endosomes, our data suggest that it has an important function in membrane recruitment of APPL proteins, acting in parallel to Rab5.

Methodology for assessing the probability of corrosion in concrete structures on the basis of half-cell potential and concrete resistivity measurements.

In recent years, the corrosion of steel reinforcement has become a major problem in the construction industry. Therefore, much attention has been given to developing methods of predicting the service life of reinforced concrete structures. The progress of corrosion cannot be visually assessed until a crack or a delamination appears. The corrosion process can be tracked using several electrochemical techniques. Most commonly the half-cell potential measurement technique is used for this purpose. However, it is generally accepted that it should be supplemented with other techniques. Hence, a methodology for assessing the probability of corrosion in concrete slabs by means of a combination of two methods, that is, the half-cell potential method and the concrete resistivity method, is proposed. An assessment of the probability of corrosion in reinforced concrete structures carried out using the proposed methodology is presented. 200 mm thick 750 mm × 750 mm reinforced concrete slab specimens were investigated. Potential E corr and concrete resistivity ρ in each point of the applied grid were measured. The experimental results indicate that the proposed methodology can be successfully used to assess the probability of corrosion in concrete structures.

Decreasing the hazardous effect of waste quartz powder and the toxicity of epoxy resin by its synergistic application in industrial coatings.

Quartz powder sourced from industrial wastes is very hazardous. It is because it contains large amounts of fine particles. Thus, it has the potential to cause cancer and nervous system impact on humans and animals. Furthermore, its disposal leads to water pollution and plant pollination (negative for the environment). It will not be dangerous if incorporated into a hardened epoxy resin coating. In turn, epoxy resin is very harmful to the environment, in particular to aquatic organisms; therefore, it is necessary to reduce its mass in coatings by using additives. The article describes the systematic investigation of the adhesion of an epoxy resin coating and an economic and toxicity analysis showing the cost and toxicity reduction of the epoxy resin coating by replacing a part of the epoxy resin mass with waste quartz powder. The key novelty of the following article is to highlight a new way to decrease the hazardous effect of waste quartz powder, thanks to its utilization in epoxy resin coatings. Furthermore, the novelty is to decrease the toxicity of epoxy resin by reducing its mass necessary to make the industrial coating.

Effectiveness of the Use of Polymers in High-Performance Concrete Containing Silica Fume.

The incorporation of polycarboxylate ether superplasticizer (PCE)-type polymers and silica fume (SF) in high-performance concretes (HPC) leads to remarkable rheological and mechanical improvements. In the fresh state, PCEs are adsorbed on cement particles and dispersants, promoting the workability of the concrete. Silica fume enables very well-compacted concrete to be obtained, which is characterized by high mechanical parameters in its hardened state. Some PCEs are incompatible with silica fume, which can result in slump loss and poor rheological behavior. The main objective of this research is to study the influence of three types of PCEs, which all have different molecular architectures, on the rheological and mechanical behavior of high-performance concretes containing 10% SF as a partial replacement of cement. The results show that the carboxylic density of PCE has an influence on its compatibility with SF.

Acute mercuric chloride poisoning at a potentially lethal dose ended with survival: symptoms, concentration in cerebrospinal fluid, treatment.

This study aims to present a case of acute mercuric chloride poisoning at a potentially lethal dose treated with the antidote - 2,3-dimercapto- 1-propanesulfonic acid (DMPS) and continuous renal replacement therapy (CRRT) combined with CytoSorb. A 21-year-old woman was admitted to a hospital with abdominal pain, vomiting, and suspected gastrointestinal bleeding after taking 5000 mg of mercuric chloride for suicidal purposes. Due to the patient deteriorating general condition and multiple organ damage, on the third day she was transported to the Clinic of Anaesthesiology and Intensive Care (CAaIC), Lódz, Poland. Laboratory tests confirmed features of acute kidney injury and high mercury levels in the blood (1051 µg/l) and urine (22 960 µg/l) - DMPS therapy and CRRT combined with CytoSorb were instituted. Due to nervous system complaints (headache, dizziness), a lumbosacral puncture was performed - the mercury concentration in the cerebrospinal fluid (CSF) was 5.45 µg/l. During a colonoscopy, significant diagnostic abnormalities revealed features of colonic mucosal necrosis. The treatment resulted in a decrease in subjective complaints, decreased mercury levels in biological material, and improved parenchymal organ function. On the 15th day of therapy, the patient was transferred to the primary care center for further treatment. The case confirms the possibility of improvement of patient condition following ingestion of a potentially lethal dose (5 g) as a result of the initiation of appropriate therapy even on the third day. The presence of mercury in CSF confirms that inorganic mercury compounds (mercuric chloride) can pass through the blood-brain barrier after oral ingestion. Int J Occup Med Environ Health. 2023;36(5):685-92.

Stabilization of Chromium Waste by Solidification into Cement Composites.

This article deals with the study of hazardous chromium leaching, stabilized/solidified by cement CEM II after 28 days of curing, in an acidic environment. The mortars subjected to this study were investigated by X-ray diffraction (XRD) characterization to evaluate the influence of chromium waste on their mineralogical structure. In the study range (0.6-1.2%), increasing the mass percentage of Cr2O3 in the mortars indicates that chromium accelerates the hydration process and setting of the mortar and increases the mechanical strength of the mortars compared to the control sample. It was observed that the release of chromium during the Toxicity Characteristic Leaching Procedure (TCLP) test and the efficiency of the stabilization/solidification process depended on the initial Cr concentration and the leaching time. The use of XRD allowed the identification of new crystallized phases in the cement matrices, namely, CaCrO4·2H2O and chromium-ettringite Ca6Cr2(SO4)3(OH)12·26H2O, which confirms the immobilization of chromium and the efficiency of the stabilization/solidification process. In this research, the release mechanism was found to be primarily a surface phenomenon by modeling the experimental data (dissolution or precipitation).

Recruitment of APPL1 to ubiquitin-rich aggresomes in response to proteasomal impairment.

Inhibitors of proteasomes have been shown to affect endocytosis of multiple membrane receptors, in particular at the step of cargo sorting for lysosomal degradation. Here we demonstrate that the inhibition of proteasomes causes specific redistribution of an endosomal adaptor APPL1, which undergoes initial solubilization from APPL endosomes followed by clustering in the perinuclear region. MG132 treatment decreases APPL1 labeling of endosomes while the staining of the canonical early endosomes with EEA1 remains unaffected. Upon prolonged treatment with proteasome inhibitors, endogenous APPL1 localizes to the site of aggresome formation, with perinuclear APPL1 clusters encapsulated within a vimentin cage and co-localizing with aggregates positive for ubiquitin. The clustering of APPL1 is concomitant with increased ubiquitination and decreased solubility of this protein. We determined that the ubiquitin ligase Nedd4 enhances polyubiquitination of APPL1, and the ubiquitin molecules attached to APPL1 are linked through lysine-63. Taken together, these results add APPL1 to only a handful of endogenous cellular proteins known to be recruited to aggresomes induced by proteasomal stress. Moreover, our studies suggest that the proteasome inhibitors that are already in clinical use affect the localization, ubiquitination and solubility of APPL1.

The Design of Cement Mortar with Low Capillary Suction: Understanding the Effect of Fine Aggregate and Sodium Silicate.

The article presents the results of research that was carried out in order to analyze the capillary suction of cement mortar. Capillary suction is a common process that occurs when porous material is in free contact with moisture. The result of high capillary suction may be excessive moisture in buildings, and it is therefore important to limit the causes of such moisture. The main aim of the presented research is to show the influence of sodium silicate (in various proportions), as well as the quantity of aggregate, on capillary suction. Three different types of cement mortar and one type of fine aggregates were analyzed in the research. At the beginning, the capillary suction of the aggregates was analyzed. Afterwards, nine cement mortar bars were made, which were then used to examine the capillary suction. As a result of this study, it was proved that M15 cement mortar with basalt fine aggregate and a higher proportion of sodium silicate was the mortar with the lowest capillary suction. It was found that M15 cement mortar with basalt fine aggregate and a higher proportion of sodium silicate had 39 mm of capillary suction after 120 h of being immersed in water. M5 cement mortar without sodium silicate had the highest index of capillary suction, which shows that adding sodium silicate to cement mortar can significantly reduce capillary suction.

Effect of Granite Powder Grain Size and Grinding Time of the Properties of Cementitious Composites.

The purpose of this article is to determine the effect of granite powder grain size and grinding time on the properties of cement paste. A series of cement pastes modified by the addition of granite powder were made and the properties of the fresh mixtures and the mechanical properties of hardened pastes were studied. Based on the study, the best results, from the point of view of the application of granite powder in cementitious composites, were obtained for a sample with granite powder ground for 3 h, in which 50% of the particles were smaller than 4 µm, and 90% were below 20 µm. Compressive strength of 55 MPa and flexural strength of 6.8 MPa were obtained on this sample after aging for 28 days. To confirm the validity of using granite powder as substitute materials, additional tests such as scanning microscopy with elemental analysis (SEM, EDS) and infrared (FTIR) studies were performed.

Effect of the Partial Replacement of Cement with Waste Granite Powder on the Properties of Fresh and Hardened Mortars for Masonry Applications.

Granite is a well-known building and decorative material, and, therefore, the amount of produced waste in the form of granite powder is a problem. Granite powder affects the health of people living near landfills. Dust particles floating in the air, which are blown by gusts of wind, can lead to lung silicosis and eye infections, and can also affect the immune system. To find an application for this kind of waste material, it was decided to study the effect of partially replacing cement with waste granite powder on the properties of fresh and hardened mortars intended for masonry applications. The authors planned to replace 5%, 10%, and 15% of cement with waste material. Series of mortar with the addition of granite powder achieved 50% to 70% of the compressive strength of the reference series, and 60% to 76% of the bending strength of the reference series. The partial replacement of cement with the granite powder significantly increased the water sorption coefficient. The consistency of the fresh mortar, and its density and water absorption also increased when compared to the reference series. Therefore, Granite powder can be used as a partial replacement of cement in masonry mortars.

Design of a machine learning model for the precise manufacturing of green cementitious composites modified with waste granite powder.

In this study, a machine learning model for the precise manufacturing of green cementitious composites modified with granite powder sourced from quarry waste was designed. For this purpose, decision tree, random forest and AdaBoost ensemble models were used and compared. A database was created containing 216 sets of data based on an experimental study. The database consists of parameters such as the percentage of cement substituted with granite powder, time of testing and curing conditions. It was shown that this method for designing green cementitious composite mixes, in terms of predicting compressive strength using ensemble models and only three input parameters, can be more accurate and much more precise than the conventional approach. Moreover, to the best of the authors' knowledge, artificial intelligence has been one of the most effective and precise methods used in the design and manufacturing industry in recent decades. The simplicity of this method makes it more suitable for construction practice due to the ease of evaluating the input variables. As the push towards decreasing carbon emissions increases, a method for designing green cementitious composites without producing waste that is more precise than traditional tests performed in a laboratory is essential.

The Assessment of Strength of Cementitious Materials Impregnated Using Hydrophobic Agents Based on Near-Surface Hardness Measurements.

Recently, the surfaces of concrete structures are impregnated to protect them against the environment in order to increase their durability. It is still not known how the use of these agents affects the near-surface hardness of concrete. This is especially important for experts who use the near-surface hardness of concrete for estimating its compressive strength. The impregnation agents are colorless and, thus, without knowledge of their use, mistakes can be made when testing the surface hardness of concrete. This paper presents the results of investigations concerning the impact of impregnation on the subsurface hardness concrete measured using a Schmidt hammer. For this research, samples of cement paste with a water-cement ratio of 0.4 and 0.5 were used. The samples were impregnated with one, two, and three layers of two different agents. The first agent has been made based on silanes and siloxanes and the second agent has been made based on based on polymers. The obtained research results allow for the conclusion that impregnation affects the near-surface hardness of concrete. This research highlights the fact that a lack of knowledge about the applied impregnation of concrete when testing its near-surface hardness, which is then translated into its compressive strength, can lead to serious mistakes.

Cement Paste Mixture Proportioning with Particle Packing Theory: An Ambiguous Effect of Microsilica.

Recently, the research of innovative building materials is focused on applying supplementary materials in the form of micro- and nanopowders in cementitious composites due to the growing insistence on sustainable development. Considering above, in paper, a research on the effect of microsilica and SiO2 nanoparticles addition to cement paste, designed with Andreasen and Andersen (AA) packing density model (PDM), in terms of its physical and mechanical properties was conducted. Density, porosity, compressive strength, hardness, and modulus of indentation were investigated and compared regarding different amount of additives used in cement paste mixes. Microstructure of the obtained pastes was analyzed. The possibility of negative influence of alkali-silica reaction (ASR) on the mechanical properties of the obtained composites was analyzed. The results of the conducted investigations were discussed, and conclusions, also practical, were presented. The obtained results confirmed that the applied PDM may be an effective tool in cement paste design, when low porosity of prepared composite is required. On the other hand, the application of AA model did not bring satisfactory results of mechanical performance as expected, what was related, as shown by SEM imaging, with inhomogeneous dispersion of microsilica, and creation of agglomerates acting as reactive aggregates, what as a consequence caused ASR reaction, crack occurrence and lowered mechanical properties. Finally, the study found that the use of about 7.5% wt. of microsilica is the optimum in regards to obtain low porosity, while, to achieve improved mechanical properties, the use of 4 wt. % of microsilica seems to be optimal, in the case of tested cement pastes.

Metaheuristic Prediction of the Compressive Strength of Environmentally Friendly Concrete Modified with Eggshell Powder Using the Hybrid ANN-SFL Optimization Algorithm.

The aim of this article is to predict the compressive strength of environmentally friendly concrete modified with eggshell powder. For this purpose, an optimized artificial neural network, combined with a novel metaheuristic shuffled frog leaping optimization algorithm, was employed and compared with a well-known genetic algorithm and multiple linear regression. The presented results confirm that the highest compressive strength (46 MPa on average) can be achieved for mix designs containing 7 to 9% of eggshell powder. This means that the strength increased by 55% when compared to conventional Portland cement-based concrete. The comparative results also show that the proposed artificial neural network, combined with the novel metaheuristic shuffled frog leaping optimization algorithm, offers satisfactory results of compressive strength predictions for concrete modified using eggshell powder concrete. Moreover, it has a higher accuracy than the genetic algorithm and the multiple linear regression. This finding makes the present method useful for construction practice because it enables a concrete mix with a specific compressive strength to be developed based on industrial waste that is locally available.

Signaling from endosomes: location makes a difference.

In all transmembrane receptor systems the kinetics of receptor trafficking upon ligand stimulation is maintained in a balance between degradative and recycling pathways in order to keep homeostasis and to strictly control receptor-mediated signaling. Endocytosis is commonly considered as an efficient mechanism of uptake and transport of membrane-associated signaling molecules leading to attenuation of ligand-induced responses. Accumulating evidence, however, shows that signaling from internalized receptors not only continues in endosomal compartments, but that there are also distinct signaling events that require endocytosis. Endocytic organelles form a dynamic network of subcellular compartments, which actively control the timing, amplitude, and specificity of signaling. In this review we provide examples in which signal transduction either requires an active endocytic machinery, or directly originates from various types of endosomes. Based on recent discoveries, we emphasize the close interdependence between signaling and endocytosis, and the physiological relevance of endocytic transport in health and disease.