Primary Damage Research Articles

Circulatory metabolites trigger ex vivo arterial endothelial cell dysfunction in population chronically exposed to diesel exhaust

BackgroundChronic exposure to diesel exhaust has a causal link to cardiovascular diseases in various environmental and occupational settings. Arterial endothelial cell function plays an important role in ensuring proper maintenance of cardiovascular homeostasis and the endothelial cell dysfunction by circulatory inflammation is a hallmark in cardiovascular diseases. Acute exposure to diesel exhaust in controlled exposure studies leads to artery endothelial cells dysfunction in previous study, however the effect of chronic exposure remains unknown.ResultsWe applied an ex vivo endothelial biosensor assay for serum samples from 133 diesel engine testers (DETs) and 126 non-DETs with the aim of identifying evidence of increased risk for cardiovascular diseases. Environmental monitoring suggested that DETs were exposed to high levels of diesel exhaust aerosol (282.3 μg/m3 PM2.5 and 135.2 μg/m3 elemental carbon). Surprisingly, chronic diesel exhaust exposure was associated with a pro-inflammatory phenotype in the ex vivo endothelial cell model, in a dose-dependent manner with CCL5 and VCAM as most affected genes. This dysfunction was not mediated by reduction in circulatory pro-inflammatory factors but significantly associated with a reduction in circulatory metabolites cGMP and an increase in primary DNA damage in leucocyte in a dose-dependent manner, which also explained a large magnitude of association between diesel exhaust exposure and ex vivo endothelial biosensor response. Exogenous cGMP addition experiment further confirmed the induction of ex vivo biosensor gene expressions in endothelial cells treated with physiologically relevant levels of metabolites cGMP.ConclusionSerum-borne bioactivity caused the arterial endothelial cell dysfunction may attribute to the circulatory metabolites based on the ex vivo biosensor assay. The reduced cGMP and increased polycyclic aromatic hydrocarbons metabolites-induced cyto/geno-toxic play important role in the endothelial cell dysfunction of workers chronic exposure to diesel exhaust.

Inflammatory Response and Secondary White Matter Damage to the Corpus Callosum after Focal Striatal Stroke in Rats.

Stroke is one of the leading causes of death and long-term disabilities worldwide, resulting in a debilitating condition occasioned by disturbances in the cerebral vasculature. Primary damage due to metabolic collapse is a quick outcome following stroke, but a multitude of secondary events, including excitotoxicity, inflammatory response, and oxidative stress cause further cell death and functional impairment. In the present work, we investigated whether a primary ischemic damage into the dorsal striatum may cause secondary damage in the circumjacent corpus callosum (CC). Animals were injected with endothelin-1 and perfused at 3, 7, 14, and 30 post-lesion days (PLD). Sections were stained with Cresyl violet for basic histopathology and immunolabeled by antibodies against astrocytes (anti-GFAP), macrophages/microglia (anti-IBA1/anti MHC-II), oligodendrocytes (anti-TAU) and myelin (anti-MBP), and Anti-Nogo. There were conspicuous microgliosis and astrocytosis in the CC, followed by later oligodendrocyte death and myelin impairment. Our results suggest that secondary white matter damage in the CC follows a primary focal striatal ischemia in adult rats.

Protective role of strawberry tree (Arbutus unedo L.) honey against cyto/genotoxic effects induced by ultraviolet B radiation in vitro

Strawberry tree (Arbutus unedo L.) honey (STH) is widely used as part of traditional medicine in the Mediterranean area, especially in the treatment of wounds, burns and infections. In this study, we investigated the cyto-/genoprotective properties of STH at cell level following short-term exposure to UVB radiation at 2 kJ/m2. Isolated human peripheral blood lymphocytes (PBL) were selected as model cells. Phenolics in STH were determined using an ultra-high-performance liquid chromatograph (UHPLC) coupled to a linear ion trap-Orbitrap hybrid mass spectrometer (LTQ Orbitrap MS), while homogentisic acid (HGA) was quantified using a gas chromatograph-mass spectrometer (GC-MS). Primary DNA damage in PBLs treated with STH before and after irradiation was assessed by alkaline comet assay, while their viability was determined using the apoptosis/necrosis assay. The levels of thiobarbituric acid reactive substances (TBARS) and glutathione (GSH) were determined in plasma samples. STH applied as pre-treatment at a concentration equivalent to its average daily portion efficiently counteracted the cytotoxic and genotoxic effects and diminished UVB-induced oxidative stress. Post-radiation treatment with STH was not as beneficial. Protective effects could be associated to the complex phytochemical profile of STH and the high content of HGA (306.8 mg/kg). It was confirmed that an intake of a complex mixture of bioactive constituents as STH prior to potential cyto/genotoxic insults stimulated a broad-spectrum of protective mechanisms, including intracellular antioxidative defence and DNA repair systems that helped pre-treated cells to counteract harmful exposures more efficiently.

Developing novel bio-nano catalyst well clean up fluid to remove formation damage induced by polymeric water-based drilling fluids

Drilling and completion fluids may cause significant formation damage in oil and gas reservoirs, directly affecting productivity. For many years, operators have applied different stimulation practices such as acidizing, oxidizers, chelating agents, and enzyme treatment to remove formation damage associated with drilling fluids filter cake. An enzyme-based biological treatment was combined with other chemicals or additives as a selective well clean-up practice to improve removing polymer content in the filter cake. However, the secondary formation damage such as deep cleaning of the invaded zone and wettability alteration remained the main concern. This paper presents the development of an innovative clean-up fluid formulation by immobilizing an enzyme and a selective nanoparticle as Bio-Nano Well Clean-Up Fluid (BNWC) in potassium chloride brine to enhance WBM filter cake removal. Several bulk experiments, including; precipitation, iodine test, and viscosity measurement, demonstrate the enzyme's optimization, the nanoparticle concentration, and base fluid brine. BNWC in potassium chloride brine showed the highest HPHT filtration rate at 200 °F and differential pressure of 100 psi and increased the filtration rate by more than 90 percent compared to the conventional enzyme in the same brine. Contact angle measurements confirmed wettability alteration of the carbonate rock to water-wet, and IFT measurements showed higher oil mobility potential. Finally, core flooding tests at reservoir conditions showed a 300 percent enhancement in injection rate and a 50% improvement in core permeability after damage. The immobilization of the enzyme with the nanoparticle has been developed successfully for other applications in bioremediation, farming, and other industries, but the novelty of this research demonstrates the application of nanobiocatalysts in drilling fluids for the first time. This innovative clean-up fluid enhances the enzymatic activity and removes primary and secondary formation damage associated with drilling fluid filter cake.

Device-related pressure ulcers: SECURE prevention. Second edition.

Device-related pressure ulcers: SECURE prevention. Second edition.

Typology, network features and damage response in worldwide urban road systems.

We survey the network properties and response to damage sustained of road networks of cities worldwide, using OpenStreetMap (OSM) data. We find that our primary damage response variable , which is the average shortest time needed to reach all nodes in a road network (which stand in for locations within a metropolitan area) from an initial node (which stands in for the location of a center for disaster relief operations), is strongly linearly–correlated with pd, the fraction of the road network segments damaged. We find that this result, previously reported for a city’s road network as opposed to grid and scale-free idealizations, is widely present across the road networks we have examined regardless of location. Furthermore, we identify three families of road networks according to their damage response, forming a typology by which we can classify city road networks. Using this typology, we identify the family of road networks which may be of most concern from a humanitarian standpoint. We also find that, of the properties of the road networks we examined, the average shortest path length, 〈lmin〉 and the average node degree, 〈k〉, proxies for city road network size and complexity respectively, are very significantly–correlated with damage susceptibility. In addition to forming a damage response typology by which city road networks could be classified, we consider five cities in detail, looking at risks and previous disaster events. Our results offer a generalizable framework in evaluating the feasibility of coursing relief efforts within disaster–affected areas using land–based transportation methods. They also provide, albeit in retrospect, a glimpse of the time difficulties which occurred, and the stakes of life involved in the humanitarian crisis which developed in the Kathmandu area due to the earthquakes of April and May 2015.

Connectomic-genetic signatures in the cerebral small vessel disease

Small vessel disease (SVD) is a disorder that causes vascular lesions in the entire parenchyma of the human brain. At present, it is not well understood how primary and secondary damage interact to give rise to the complex scenario of white matter (WM) and grey matter (GM) lesions. Using novel cross-sectional and longitudinal connectomic approaches, we unveil the bidirectional nature of GM and WM changes, that is, primary cortical neurodegeneration that leads to secondary alterations in vascular border zones, and WM lesions that lead to secondary neurodegeneration in cortical projecting areas. We found this GM-WM interaction to be essential for executive cognitive performance. Moreover, we also observed that the interlocked degeneration of GM and WM over time associates with prototypical expression levels of genes potentially linked to SVD. Among these connectomic-genetic intersections, we found that the Androgen Receptor (AR) gene, is a particularly central candidate gene that might confer key vulnerability for brain lesion development in SVD. In conclusion, this study advances in the understanding of the bidirectional relationships between GM and WM lesions, primary and secondary vascular neurodegeneration, and sheds light on the genetic signatures of SVD.

Nanoparticled Titanium Dioxide to Remediate Crude Oil Exposure. An In Vivo Approach in Dicentrarchus labrax.

The contamination of marine water bodies with petroleum hydrocarbons represents a threat to ecosystems and human health. In addition to the surface slick of crude oil, the water-soluble fraction of petroleum is responsible for the induction of severe toxic effects at different cellular and molecular levels. Some petroleum-derived hydrocarbons are classified as carcinogenic and mutagenic contaminants; therefore, the oil spill into the marine environment can have long term consequences to the biota. Therefore, new tools able to remediate crude oil water accommodation fraction pollution in marine water are highly recommended. Nanomaterials were recently proposed in environmental remediation processes. In the present in vivo study, the efficacy of pure anatase titanium nanoparticles (n-TiO2) was tested on Dicentrarchus labrax exposed to the accommodated fraction of crude oil. It was found that n-TiO2 nano-powders themselves were harmless in terms of DNA primary damage, and the capability of pure anatase n-TiO2 to lower the levels of DNA damage induced by a mixture of genotoxic pollutant was revealed. These preliminary results on a laboratory scale are the prerequisite for deepening this new technology for the abatement of the cellular effects related with oil spill pollutants released in marine environments.

Defect structure classification of neutron-irradiated graphite using supervised machine learning

Molecular dynamics simulations were performed to predict the behavior of graphite atoms under neutron irradiation using large-scale atomic/molecular massively parallel simulator (LAMMPS) package with adaptive intermolecular reactive empirical bond order (AIREBOM) potential. Defect structures of graphite were compared with results from previous studies by means of density functional theory (DFT) calculations. The quantitative relation between primary knock-on atom (PKA) energy and irradiation damage on graphite was calculated.and the effect of PKA direction on the amount of defects is estimated by counting displaced atoms. Defects are classified into four groups: structural defects, energy defects, vacancies, and near-defect structures, where a structural defect is further subdivided into six types by decision tree method which is one of the supervised machine learning techniques.

Evaluating the relationship between the respiratory exposure to the benzene with the primary damages of deoxyribonucleic acid and total antioxidant capacity in one of the oil companies in Iran.

Benzene is a carcinogenic chemical substance which causes the injuries and damages through producing the free radicals in DNA (deoxyribonucleic acid) and the antioxidants are the agents which reduce the impacts of DNA damages by inhibiting the free radicals. This study was conducted aiming at determination of primary damages of DNA and level of plasma oxidative stress markers resulting from the respiratory exposure to the benzene found in petroleum compounds among the workers at loading platforms of a petroleum products distribution center. This study was an analytical (case control) research conducted among the workers in a working shift serving at the loading platforms of petroleum products. The exposure group included the workers with a history of contact with benzene and the control group was composed of the persons with no history of exposure to benzene. To investigate the level of the personnel's exposure to benzene, NIOSH-1501 method was utilized; to analyze the samples taken from the air, GC mass (gas chromatography-mass spectrometry) was applied; and to determine the average of DNA primary damages, comet assay was used. Total antioxidant capacity was determined by a photometric method. Results indicated that tail length (TL), tail density (TD), tail momentum (TM), percentage of tail in the DNA (%DNA), and %TAC in control group were 78.59, 8.35, 1.20, 10.05, and 25.58 and in the exposure group were 59.21, 75.74, 57.74, 3.5, and 16.58, respectively. The previously mentioned results showed a decrease in the TL, %DNA, and %TAC values among the workers already exposed to benzene while an increase in the TD and TM values of the same group compared to the control non-exposed group. In comparing the averages between two studied groups, all study variables had statistically meaningful difference (p < 0.05). More studies are recommended to be conducted on using the methods which identify the special places of breakage and damage in DNA chain due to the exposure to benzene and consequently prevent the complications and consequences.

LINE-1 expression in cancer correlates with p53 mutation, copy number alteration, and S phase checkpoint

Retrotransposons are genomic DNA sequences that copy themselves to new genomic locations via RNA intermediates; LINE-1 is the only active and autonomous retrotransposon in the human genome. The mobility of LINE-1 is largely repressed in somatic tissues but is derepressed in many cancers, where LINE-1 retrotransposition is correlated with p53 mutation and copy number alteration (CNA). In cell lines, inducing LINE-1 expression can cause double-strand breaks (DSBs) and replication stress. Reanalyzing multiomic data from breast, ovarian, endometrial, and colon cancers, we confirmed correlations between LINE-1 expression, p53 mutation status, and CNA. We observed a consistent correlation between LINE-1 expression and the abundance of DNA replication complex components, indicating that LINE-1 may also induce replication stress in human tumors. In endometrial cancer, high-quality phosphoproteomic data allowed us to identify the DSB-induced ATM-MRN-SMC S phase checkpoint pathway as the primary DNA damage response (DDR) pathway associated with LINE-1 expression. Induction of LINE-1 expression in an invitro model led to increased phosphorylation of MRN complex member RAD50, suggesting that LINE-1 directly activates this pathway.

On the equivalence of irradiation conditions on present and future facilities for fusion materials research and qualification: A computational study

We performed a computational study to assess the suitability and equivalence of the irradiation conditions on several test irradiation facilities (either currently operating or planned to deploy in the future) aimed at the qualification of materials for nuclear fusion reactors such as ITER and DEMO. The degradation of the material's properties is driven by the changes in its microstructure and chemistry (transmutation). The primary objective of this study is thus to perform a comparison of the microstructural pattern as predicted by means of simulations. The focus of the study is put on two materials: Eurofer97 steels and tungsten. We considered operation conditions in fusion reactors (i.e. ITER and DEMO) and in test irradiation facilities such as material test reactors (fast and mixed neutron spectrum), IFIMIF-DONES, ESS and proton accelerators. Typical irradiation conditions are addressed according to the currently available design (for DEMO) and expected operation modes (for ITER). The study is realized by means of object kinetic Monte Carlo which is parameterized and configured using state-of-the-art knowledge on irradiation spectra, neutron cross-sections, primary damage states, lattice defects mobility/cohesion and interaction of the material's microstructure with lattice defects. The irradiation defects are singled out using a dedicated post-processing tools to enable a comparison with expected findings in transmission electron microscopy (TEM) and atom probe tomography (APT). The results are discussed in terms of the equivalence of the emerging irradiation microstructure predicted to occur in test irradiation facilities if compared with the one simulated in the nuclear fusion reactors. The summary and discussion provide information on the equivalence and deviations of the microstructural patterns suggesting the suitability of the test irradiation facilities for certain irradiation regimes, as well as pointing at some limitations, e.g., originating from the difference in the neutron spectra or flux.

Primary radiation damages in Li2TiO3 and Li4SiO4: a comparison study using molecular dynamics simulation

Molecular dynamics simulations are conducted on β-LiTiO and LiSiO to compare several of their radiation damage-related properties at 0 K. Overall, LiTiO was found to be more tolerant to irradiation damage than LiSiO, which is in qualitative agreement with recent experiments. For instance, LiTiO was found to amorphize at 0.55 dpa, while LiSiO amorphized at 0.25 dpa itself. Including the polarization of the O atom while modeling cascades in LiTiO was found to predict a more realistic cascade behavior and defect production. The threshold displacement energies and diffusion coefficients of atoms were calculated for both the materials. Li diffusion was found to be highest when compared to other atoms. For LiSiO, the existing interatomic potential predicted an Li diffusion coefficient which is nearly two orders of magnitude higher than what is seen for LiTiO. Moreover, this potential predicted Li diffusion at temperatures as low as 583K, making it impossible to compare finite temperature primary damage with LiTiO.

Damages in vitrified clay sewers in service for 130–142 years

The aim of the study was to analyze the damage occurring in vitrified clay sewers operated for a period of 130–142 years based on the results of their CCTV testing. In view of the fact that there are very large differences in the assessment of the forecast lifetime of sewer pipes, as reported by the different institutions, and significant differences in the survival functions developed for these pipes, particular attention has been paid to identification of the causes of this situation. One of the most important results of the research and analyses conducted is demonstration that models predicting the durability of vitrified clay pipes and the survival functions created for them should be developed separately for sewers laid in dry soils and water-saturated soils. The research has also shown that various so-called primary damages were observed in sewers, which occurred during transport, storage, and installation of pipes. Failure to take into account the possibility of these damages in the durability models being developed and in the related survival functions makes it impossible to predict the actual durability of these pipes. An analysis of the results also confirmed the thesis formulated on the basis of studies of vitrified clay pipes in Canada that the deterioration of vitrified clay pipes is not age-dependent when the pipes are properly designed and installed, with no damage during installation.

The Role of Ferroptosis in Blood-Brain Barrier Injury.

The blood-brain barrier (BBB) is an important barrier that maintains homeostasis within the central nervous system. Brain microvascular endothelial cells are arranged to form vessel walls and express tight junctional complexes that limit the paracellular pathways of the BBB and therefore play a crucial role in ensuring brain function. These vessel walls tightly regulate the movement of ions, molecules, and cells between the blood and the brain, which protect the neural tissue from toxins and pathogens. Primary damage caused by BBB dysfunction can disrupt the expression of tight junctions, transport proteins and leukocyte adhesion molecules, leading to brain edema, disturbances in ion homeostasis, altered signaling and immune infiltration, which can lead to neuronal cell death. Various neurological diseases are known to cause BBB dysfunction, but the mechanism that causes this disorder is not clear. Recently, ferroptosis has been found to play an important role in BBB dysfunction. Ferroptosis is a new form of regulatory cell death, which is caused by the excessive accumulation of lipid peroxides and iron-dependent reactive oxygen species. This review summarizes the role of ferroptosis in BBB dysfunction and the latest progress of ferroptosis mechanism, and further discusses the influence of various factors of ferroptosis on the severity and prognosis of BBB dysfunction, which may provide better therapeutic targets for BBB dysfunction.

A study of primary damage formation in collision cascades in titanium

Molecular dynamics (MD) simulations were applied to study radiation damage formation in collision cascades initiated by primary knock-on atoms (PKA) with energy EРКА = 5, 10, 15 and 20 keV in α-Ti at T = 100, 300, 600 and 900 K ambient temperatures. A series of 24 collision cascades was simulated for each (EРКА, Т) pair. The necessary sampling set size was justified by a simple a posteriori procedure. The number of Frenkel pairs and the fraction of vacancies, εv, and self-interstitial atoms (SIAs), εi in point defect clusters were evaluated as functions of (EРКА, Т). It was established that collision cascades in α-Ti are extended along PKA trajectories and tend to split into subcascades. In contrast to other elemental metals with close-packed crystal structure, εv≥ εi in collision cascades in α-Ti. Moreover, both εv and εi ௜demonstrate weak temperature dependence. This is anindirect indication that both vacancy and SIA clusters created in collision cascades in α-Ti are stable in the considered temperature range

Electrospinning-modified Pt/CeO2 nano bandage as a promising therapy to reduce secondary brain injury

Traumatic brain injury (TBI) continues to be a major contributor to morbidity, disability, and mortality in all age groups. Initial brain damage is accompanied by acute and irreversible primary damage to the parenchyma, while subsequent secondary brain damage often progresses slowly over months to years, thus providing a window for therapeutic intervention. The most frequent case which happened is excessive oxidative stress and calcium release after brain injury. Although some traditional antioxidants have been clinically approved, the efficacy is far from satisfactory due to their low ROS-scavenging efficiency, instability, toxicity, or inadequate penetration of the blood-brain barrier. Moreover, the combination of Nanozyme based-bandage with Pt/CeO2 atom catalysis with electrospinning nanofibers N-type voltage-gated calcium channel blocker (SNX-185) is predicted to be as promising as a potential novel to reduce secondary injury of TBI. Therefore, the duo could cut down morbidity and mortality rates because of TBI in the future, noninvasively.

Effect of weave pattern on high strain rate performance of glass/polytetrafluoroethylene composites

AbstractAn investigation of the effect of strain rate on the dynamic compressive behavior of glass/polytetrafluoroethylene (PTFE) composite is presented. Experimental studies were carried out on two dimensional (2D), satin weave (SW) and three dimensional (3D) woven glass/PTFE composites using split Hopkinson pressure bar (SHPB) apparatus. Commercial grades of glass/PTFE fabrics were autoclaved to prepare the composite laminates and circular specimens were cut out using a high‐pressure water jet. High strain rate studies confirmed the rate‐dependent behavior of all the woven composite systems under consideration. The highest rates of loading were attained by 3D woven specimens for identical incident energies. The highest peak stress attained by 3D woven specimens was 501 MPa, which was trailed by 2D woven specimens with 482 MPa stress. The advantage of satin weave was not reflected in the small specimens as the peak stress attained for identical loading was limited to 405 MPa. Similarly, the highest strain and toughness were recorded for 3D woven composites. However, the SW pattern unlocked a new possibility of controlling the primary damage axis. Furthermore, an analytical method is presented based on variable rate power law to predict the dynamic compressive stress of glass/PTFE.

Можливості магнітно-резонансної томографії у ранній діагностиці прогресування м’язових дистрофій

Прогресуючі м’язові дистрофії — це генетично гетерогенна група порушень, які характеризуються прогресуючою м’язовою слабкістю, атрофією м’язів і руховими порушеннями. Це рідкісна група патологій, що являє собою діагностичну проблему в практиці лікаря-невролога. Комбінація клінічних, рентгенологічних і лабораторних методів обстеження відіграє велику роль при постановці правильного діагнозу. Магнітно-резонансна томографія (МРТ) м’язів використовується для діагностики первинного ураження м’язів, ґрунтуючись на специфічних патернах ураження м’язів. У статті ми коротко обговоримо можливості ранньої діагностики м’язових дистрофій і відзначимо роль МРТ м’язів як високоінформативного діагностичного методу при прогресуючих захворюваннях м’язів.

Assessment of Different Retrofitting Methods on Structural Performance of RC Buildings against Progressive Collapse

Progressive collapse refers to the spread of primary local damages within the structure. Following such damages due to removing one or more load-bearing columns, the failure spreads in a chain and causes structural failure. This study represents a report investigating the influence of various retrofitting methods on the progressive collapse resistance of multistorey reinforced concrete (RC) structures. To this end, eight different cases were considered. The first one included a thirteen-story RC moment-resisting frame (bare frame), while the others were frames upgraded with the application of X-brace, diagonal brace, inverted V-brace, the viscous damper in the central bay, viscous damper in two inner bays, viscous damper only in certain stories and carbon fiber reinforced polymer. Moreover, three different column removal scenarios were considered as a column failure at stories one, six, and thirteen of each case study structure. The analysis results indicated that the redistribution of loads after the column’s failure and the RC buildings’ collapse resistance was increased depending mainly on the type of approach used for upgrading the bare frame.