Damage Mitigation Research Articles

Feasibility of Cognitive-Sparing Stereotactic Radiosurgery for Brain Metastases: Initial Report of Phase II COG-SRS Trial

Radiotherapy at high doses leads to white matter (WM) and hippocampal injury which can cause cognitive decline. We designed the first, to our knowledge, evidence-based cognitive sparing brain SRS trial for patients with limited brain metastases. In this report we analyze feasibility of cognitive-sparing SRS, utilizing dose constraints for eloquent WM tracts and bilateral hippocampi. This is a single-institution phase II NCI-funded clinical trial (NCT04343157) of cognitive-sparing brain SRS; eloquent regions of interest (ROI) and associated cognitive domains are outlined in Table 1. Patients underwent high-resolution quantitative diffusion and volumetric MRI at baseline and post-SRS follow-up. Comprehensive neurocognitive assessment was performed at baseline and 3 months post-SRS by a neuropsychologist evaluating different neurocognitive domains (Table 1). Clinical processing/workflow was largely automated with robust, validated segmentation tools of eloquent WM tracts and the hippocampi. Single fraction dose constraints to WM tracts were 12 Gy Dmax and 8.4 Gy to hippocampi with 3 and 5 fraction equivalent doses, based on our prior NTCP studies. Patient accrual, follow up imaging and neurocognitive testing is still active. To date, n = 59 patients and 114 lesions have been treated with cognitive-sparing Linac-based SRS on trial. Median age is 63 years. Lung cancer was the most common primary (35.6%), along with breast cancer (23.7%) and melanoma (15.3%). Patients had 1-4 brain metastases; median prescription dose was 24 Gy/1, 27 Gy/3, or 30 Gy/5 depending on target volume. Most patients were treated < 7 business days from MRI. Cognitive endpoints have been collected on 89.5% of patients. Cognitive sparing constraints were met in 79.3% of plans while maintaining standard clinical SRS plan indices and coverage benchmarks. 38.9% of the plans that failed to meet the Dmax constraint kept D0.03cc under constraints. Plans going over constraints had tumors overlying or within 1 mm of eloquent ROIs. Local control for treated lesions at 6 months was 97.9% and 95.7% at 12 months. Distant intracranial control was 68.1% at 6 and 12 months. Median OS was 18 months. Cognitive-sparing SRS treatment planning was successfully implemented for the majority of treated lesions with excellent local control. Mitigation of damage to eloquent structures has potential to further reduce cognitive decline after SRS. Full neurocognitive outcomes will be reported after accrual and testing are complete.

Epi Source-Drain Damage Mitigation During Channel Release of Stacked Nanosheet Gate-All-Around Transistors

Nanosheet gate-all-around devices have demonstrated several advantages in device performance and area scaling over finFET devices with higher device density and improved electrostatic control. Robust inner spacer (IS) and channel formation is critical for high performance, reduced variability and good yield. An isotropic dry etch of the sacrificial SiGe layer with extremely high selectivity to gate spacer, IS and Si channels is necessary for high-quality channel formation over a wide range of sheet widths. Furthermore, the nFET Si:P and pFET SiGe:B source-drain (S/D) epitaxy must be isolated using inner spacers or buffers to prevent damage during Channel Release (CR). The damage can be further mitigated with optimized CR etch chemistry, enabling IS scaling. We highlight S/D damage mechanisms during CR, then demonstrate reduced S/D damage by co-optimization of the IS, CR chemistry and S/D epitaxy.

A comprehensive analysis of electric, thermal, and structural effects of lightning strikes on CFRP composites and protective strategies

This study examines the influence of lightning strike protection (LSP) systems and lightning parameters on thermal damage and mechanical response behavior of carbon fiber-reinforced polymer (CFRP) composites. A coupled electric-thermal-structural model in COMSOL is employed to analyze the evolution of coupled electrical, thermal, and stress distribution in CFRP composites with two types of LSP systems: copper mesh (CM) and graphene-fuzzy fiber (GF). Although CM system can effectively mitigate matrix decomposition, its high density poses a drawback. Conversely, incorporating a GF layer in CFRP reduces the area and thickness of thermal damage, accompanied by minimal stress in the underlying composite. To further enhance the mitigation of thermal damage and stress, an insulated layer is integrated between the LSP layer and the composite (CM/E/CFRP and GF/E/CFRP). The study also explores how lightning parameters influence the progression of thermal damage and stress development in CFRP and GF/E/CFRP composites. By shedding light on the crucial factors governing CFRP damage, we propose novel carbon-based tailored LSP materials that are lightweight and offer high performance to effectively protect the underlying composite from lightning strikes.

Asphaltene Flow Assurance Risk Evaluation Case Study to Establish Guidelines for CCUS in Arabian Gulf Carbonate Oil Field

Summary In this paper, we present a case study for a comprehensive series of asphaltene flow assurance risk evaluations in the Arabian Gulf Carbonate Oil Field, where CO2 enhanced oil recovery (EOR) is recognized as one of the highest potential technologies for full-field implementation. At first, the sampling location was carefully selected considering the target reservoir’s features because the reliability of asphaltene studies highly depends on sample representativeness. After the quality assurance and quality control of collected samples, asphaltene onset pressures (AOPs) were measured at multiple temperatures under CO2 mixing conditions. The experimental design was optimized in terms of not only improving evaluation accuracy but also minimizing the experimental/sampling cost. The AOP measurements showed clear potential risks associated with CO2 injection. Subsequently, the numerical model analysis was conducted with the cubic-plus-association equation of state model to identify the risk area during CO2 injection. The analysis suggested that risk area is applicable to not only near-wellbore region at the sampling location but also tubing section/surface facility. Furthermore, risk level can be higher at the deeper location of the target reservoir. Finally, CO2-induced asphaltene formation damage risk was investigated from the viewpoints of precipitated asphaltene particle size and pore throat size in the porous media. As a result, the clogging risks from CO2-induced asphaltene were estimated to be high in the target reservoir. By virtue of the comprehensive risk evaluation, the asphaltene flow assurance risk associated with CO2 injection was identified field-wide. The findings from the evaluation encouraged us to move on to future actions, such as more detailed formation damage risk evaluation and mitigation plan development. The extended asphaltene risk evaluation covering the precipitation to deposition phenomena and the reverse engineering for sampling operations based on the experimental design made a worthy demonstration to reduce unnecessary cost and time while obtaining the key information to drive the project. The procedure in this work can contribute to establishing a subsurface part of a guideline for carbon capture, utilization, and storage (CCUS) from the viewpoint of asphaltene flow assurance risk evaluation.

Erucic acid improves the progress of pregnancy complicated with systemic lupus erythematosus by inhibiting the effector function of CD8+ Tcells.

Pathogenic CD8+ Tcells are pivotal contributors to the onset of systemic lupus erythematosus (SLE). Erucic acid (EA) has been proven to have anti-inflammatory activity. However, the capacity of EA to regulate pathogenic CD8+ Tcells in the context of pregnancy complicated with SLE (pSLE) remains unclear. In our investigation, we observed augmented CD8+ T cell effector function juxtaposed with diminished EA levels in pSLE patients relative to healthy pregnant controls. Significantly, plasma EA levels exhibited a negative correlation with the severity of pSLE-associated complications. In blood from patients with pSLE, EA inhibited the effector function of CD8+ Tcells, concurrently dampening the maintenance of stem cell-like memory CD8+ Tcells. Mechanistically, EA orchestrated the inhibition of CD8+ T cell effector function by impeding signal transducer and activator of transcription 3 phosphorylation and promoting ferroptosis. Moreover, EA supplementation in pregnant MRL/lpr mice manifested as the attenuation of uterine CD8+ T cell effector function, culminating in the mitigation of placental pathological damage. Our findings uncover the immune response modulatory effects of EA upon pathogenic CD8+ cells, thereby unveiling new perspectives for therapeutic strategies targeting pSLE patients.

Xie Zhuo Tiao Zhi formula modulates intestinal microbiota and liver purine metabolism to suppress hepatic steatosis and pyroptosis in NAFLD therapy

BackgroundCurrent evidence indicates a rising global prevalence of Non-Alcoholic Fatty Liver Disease (NAFLD), which is closely associated to conditions such as obesity, dyslipidemia, insulin resistance, and metabolic syndrome. The relationship between the gut microbiome and metabolites in NAFLD is gaining attention understanding the pathogenesis and progression of dysregulated lipid metabolism and inflammation. The Xie Zhuo Tiao Zhi (XZTZ) decoction has been employed in clinical practice for alleviating hyperlipidemia and symptoms related to metabolic disorders. However, the pharmacological mechanisms underlying the effects of XZTZ remain to be elucidated. PurposeThe objective of this study was to examine the pharmacological mechanisms underlying the hypolipidemic and anti-inflammatory effects of XZTZ decoction in a mouse model of NAFLD, as well as the effects of supplementing exogenous metabolites on PO induced cell damage and lipid accumulation in cultured hepatocytes. MethodsA high-fat diet (HFD) mouse model was established to examine the effects of XZTZ through oral gavage. The general condition of mice and the protective effect of XZTZ on liver injury were evaluated using histological and biochemical methods. Hematoxylin and eosin staining (H&E) staining and oil red O staining were performed to assess inflammatory and lipid accumulation detection, and cytokine levels were quantitatively analyzed. Additionally, the study included full-length 16S rRNA sequencing, liver transcriptome analysis, and non-targeted metabolomics analysis to investigate the relationship among intestinal microbiome, liver metabolic function, and XZTZ decoction. ResultsXZTZ had a significant impact on the microbial community structure in NAFLD mice. Notably, the abundance of Ileibacterium valens, which was significantly enriched by XZTZ, exhibited a negative correlation with liver injury biomarkers such as, alanine transaminase (ALT) and aspartate transaminase (AST) activity. Moreover, treatment with XZTZ led to a significant enrichment of the purine metabolism pathway in liver tissue metabolites, with inosine, a purine metabolite, showing a significant positive correlation with the abundance of I. valens. XZTZ and inosine also significantly enhanced fatty acid β-oxidation, which led to a reduction in the expression of pro-inflammatory cytokines and the inhibition of liver pyroptosis. These effects contributed to the mitigation of liver injury and hepatocyte damage, both in vivo and vitro. Furthermore, the utilization of HPLC fingerprints and UPLC-Q-TOF-MS elucidated the principal constituents within the XZTZ decoction, including naringin, neohesperidin, atractylenolide III, 23-o-Acetylalisol B, pachymic acid, and ursolic acid which are likely responsible for its therapeutic efficacy. Further investigations are imperative to fully uncover and validate the pharmacodynamic mechanisms underlying these observations. ConclusionThe administration of XZTZ decoction demonstrates a protective effect on the livers of NAFLD mice by inhibiting lipid accumulation and reducing hepatocyte inflammatory damage. This protective effect is mediated by the upregulation of I.valens abundance in the intestine, highlighting the importance of the gut-liver axis. Furthermore, the presesnce of inosine, adenosine, and their derivatives are important in promoting the protective effects of XZTZ. Furthermore, the in vitro approaching, we provide hitherto undocumented evidence indicating that the inosine significantly improves lipid accumulation, inflammatory damage, and pyroptosis in AML12 cells incubated with free fatty acids.

Modeling the Budbreak in Peaches: A Basic Approach Using Chill and Heat Accumulation

Phenological shifts in peaches have been observed over the last few years due to the fluctuation of the seasonal climate conditions experienced during dormancy, affecting orchard management practices and influencing production and harvest dates. This study aimed to model the vegetative and floral budbreak of selected peach cultivars. Three peach cultivars, including “Rubyprince”, “Harvester”, and “Red Globe”, were considered in this study based on the representation of the early, early-mid, and mid-seasons. The prediction of the budbreak in peaches was assessed using different models that integrate the combination of chill and heat requirements. Models used include the Weinberger model, the modified Weinberger model, Utah, the dynamic model, and the growing degree model. The accumulation of chill varies according to the season evaluated. A model that considers both chill and heat accumulation is presented for each cultivar. Budbreak as an indicator of dormancy completion was established for each cultivar. The outcome of this study is to determine the amount of chilling accumulation and thermal time required to mark the beginning of the budbreak in selected cultivars with a model that predicts the duration of the dormancy. These results are valuable information that can be used for crop management practices and support the mitigation of cold damage during this critical period of crop development.

Zinc sulfate biofortification enhances physio-biochemical attributes and oxidative stress tolerance in rice varieties grown in zinc deficient alkaline soil

Zinc (Zn) is a crucial trace mineral with diverse roles in plants; its deficiency in edible plant parts results in micronutrient malnutrition, leading to stunted growth. Zinc deficiency in the soil is a significant factor leading to poor rice quality. This research aimed to reveal the impact of Zn biofortification on rice productivity and to introduce rice cultivars with enriched nutrients. The effects of various zinc sulfate (ZnSO4) rates viz. 100, 200, 300, 400 and 500 mM (designated as T1, T2, T3, T4 and T5, respectively) on the germination process, chlorophyll pigments, biochemical activities, and the mitigation of oxidative damage in four different rice (Oryza sativa L.) cultivars (KSK-133, Basmati-198, Basmati-515, and PK-386) grown in alkaline Zn-deficient soil were evaluated. A control without Zn application (T0) was kept for comparison. Results demonstrated that Zn treatments significantly affected the germination rates, vegetative growth, photosynthetic attributes, and enzymatic and non-enzymatic activities of all tested cultivars. Zn application significantly ameliorated the oxidative stress by increasing antioxidant enzyme activities such as catalase (CAT), peroxidase (POD), superoxide dismutase (SOD), ascorbate peroxidase (APX), 2,2-diphenyl-1-picrylhydrazyl (DPPH), glutathione peroxidase, and non-enzymatic compounds (such as flavonoids, proline, phenolics, reducing sugar and non-reducing sugar, total carbohydrates, and free amino acid) in all tested cultivars. Among the application rates, ZnSO4 application at 400 mM depicted the highest values of the above-mentioned traits. Furthermore, recorded data also revealed that ZnSO4 had a significant impact on flavonoids, total carbohydrates, and phenolic contents where its application at 400 mM depicted significantly higher values than other treatments. Among the tested cultivars, Basmati-198 exhibited the highest values of flavonoids, total carbohydrates, and phenolic contents showing an increase of 134.53%, 103.57%, and 265.34%, respectively, over the average of other cultivars. In sum, ZnSO4 application at 400 mM significantly improved rice performance under alkaline conditions whereas its application at 500 mM onsets toxic effect on all tested cultivars. However, to gain a comprehensive understanding of the underlying mechanisms, further research is needed to conduct long-term field studies at the molecular level.

Evaluation of Physicians' Knowledge About Honey/Sucralfate Treatments in Children With Button Battery Ingestion.

Ingestion of button batteries (BBs) causes serious mortality and morbidity. We aimed to evaluate the knowledge level of physicians working in pediatric emergency departments about the updated guidelines for BB ingestion and whether they used honey and sucralfate, which have proven positive effects in preventing mucosal damage, in their daily practice. A "Google Form" questionnaire was prepared and used to evaluate the approach of physicians who worked in pediatric emergency department with questions about pediatric patients who were admitted with the suspicion of BB swallowing. A total of 263 physicians, 169 women (64.3%), with a mean age of 34.5 ± 7.3 years, participated in the study. Seventy-five percent of the participants were from tertiary care hospitals, and 60.8% had less than 5 years of pediatric emergency experience. Some 71.9% of the physicians who participated in the survey (n = 189) had no algorithm at their hospitals. Fifty-eight percent (n = 152) of the participants completely and correctly answered all our survey questions about battery swallowing. Fifty-eight (22.1%) of the participants administered sucralfate, and 12.2% (n = 32) used honey treatments in patients who swallowed BBs; 68.1% (n = 179) had never heard of the use of sucralfate, and 77.6% (n = 204) had never heard of honey applications before in the management of swallowed batteries. It was determined that the physicians who managed pediatric battery swallowing cases had deficiencies in their treatment approaches, they had no protocol in their institutions, and the use of mucosal damage mitigation and neutralization treatments, such as honey and sucralfate, was insufficient.

Geosynthetic reinforced rubble mound breakwater for mitigation of tsunami-induced damage

Several rubble mound breakwaters (RMB) were damaged and even collapsed during the past tsunamis. The main reasons for the failure of the breakwaters occurred due to the combined effects of seepage and scouring. Limited articles are available dealing with the behaviour of RMB during the tsunami. Furthermore, few available articles are related to developing countermeasures for the RMB against tsunamis. Therefore, an attempt has been made in the study to determine the exact behaviour of the RMB under the action of the tsunami. In addition, the main aim of the present study is to develop countermeasures to make the breakwater tsunami resilient. The present study proposes a novel geosynthetics-reinforced RMB to mitigate tsunami-induced breakwater damage. Based on the available information, this is the first time geosynthetics have been used in the RMB to mitigate tsunami-induced damage. Geogrid layers, geobags, sheet piles and crown walls (with shear keys) are adopted as countermeasure elements against the tsunami. Since the height of a tsunami can exceed its design tsunami height, tsunami waves were allowed to overflow the breakwater in physical model tests. Comparative analyses between the reinforced and unreinforced RMB were performed by conducting physical model tests, analytical tools, and numerical simulations.

Modulation of paraoxonase-2 in human dermal fibroblasts by UVA-induced oxidative stress: A new potential marker of skin photodamage

Paraoxonase-2 (PON2) is an intracellular protein, that exerts a protective role against cell oxidative stress and apoptosis. Genetic and environmental factors (i.e. dietary factors, cigarette smoke, drugs) are able to modulate cellular PON2 levels. The effect of ultraviolet A radiation (UVA), the oxidizing component of sunlight, on PON2 in human dermal fibroblasts (HuDe) has not been previously explored. Excessive UVA radiation is known to cause direct and indirect skin damage by influencing intracellular signalling pathways through oxidative stress mediated by reactive oxygen species (ROS) that modulate the expression of downstream genes involved in different processes, e.g. skin photoaging and cancer. The aim of this study was, therefore, to investigate the modulation of PON2 in terms of protein expression and enzyme activity in HuDe exposed to UVA (270 kJ/m2). Our results show that PON2 is up-regulated immediately after UVA exposure and that its levels and activity decrease in the post-exposure phase, in a time-dependent manner (2–24 h). The trend in PON2 levels mirror the time-course study of UVA-induced ROS. To confirm this, experiments were also performed in the presence of a SPF30 sunscreen used as shielding agent to revert modulation of PON2 at 0 and 2 h post-UVA exposure where other markers of photo-oxidative stress were also examined (NF-KB, γH2AX, advanced glycation end products). Overall, our results show that the upregulation of PON2 might be related to the increase in intracellular ROS and may play an important role in mitigation of UVA-mediated damage and in the prevention of the consequences of UV exposure, thus representing a new marker of early-response to UVA-induced damage in skin fibroblasts.

Mitigating Heavy Ion Irradiation‐Induced Degradation in p‐type SnO Thin‐Film Transistors at Room Temperature

The study investigates the mitigation of radiation damage on p‐type SnO thin‐film transistors (TFTs) with a fast, room‐temperature annealing process. Atomic layer deposition is utilized to fabricate bottom‐gate TFTs of high‐quality p‐type SnO layers. After 2.8 MeV Au4+ irradiation at a fluence level of 5.2 × 1012 ions cm−2, the output drain current and on/off current ratio (Ion/Ioff) decrease by more than one order of magnitude, field‐effect mobility (μFE) reduces more than four times, and subthreshold swing (SS) increases more than four times along with a negative shift in threshold voltage. The observed degradation is attributed to increased surface roughness and defect density, as confirmed by scanning electron microscopy (SEM), high‐resolution micro‐Raman, and transmission electron microscopy (TEM) with geometric phase analysis (GPA). A technique is demonstrated to recover the device performance at room temperature and in less than a minute, using the electron wind force (EWF) obtained from low‐duty‐cycle high‐density pulsed current. At a pulsed current density of 4.0 × 105 A cm−2, approximately four times increase in Ion/Ioff is observed, 41% increase in μFE, and 20% decrease in the SS of the irradiated TFTs, suggesting effectiveness of the new annealing technique.

Location Tracking of Drifting Container by Solitary Wave Load Using a Motion Analysis Program

Objects adrift can cause considerable damage to coastal infrastructure and property during tsunami and storm surge events. Despite the potential for harm, the drifting behavior of these objects remains poorly understood, thereby hindering effective prediction and mitigation of collision damage. To address this gap, this study employed a motion analysis program to track a drifting container's location using images from an existing laboratory experiment. The container's trajectory and velocity were calculated based on the positions of five markers strategically placed at its four corners and center. Our findings indicate that the container's maximum drift velocity and distance are directly influenced by the scale of the solitary wave and inversely related to the container's weight. Specifically, heavier containers are less likely to be displaced by solitary waves, while larger waves can damage coastal structures more. This study offers new insights into container drift behavior induced by solitary waves, with implications for enhancing coastal infrastructure design and devising mitigation strategies to minimize the risk of collision damage.

Home range sizes of red deer in relation to habitat composition: a review and implications for management in Sweden

Knowledge about deer spatial use is essential for damage mitigation, conservation, and harvest management. We assess annual and seasonal home range sizes in relation to habitat composition for red deer (Cervus elaphus) in Sweden, using GPS-data from two regions with different management systems. We compare our findings with reviewed data on red deer home range sizes in Europe. Annual and seasonal home ranges during calving, hunt, and winter-spring, decreased with increasing proportion forest. Female annual home ranges in a mixed agricultural-forest landscape were three times larger than in a forest-dominated landscape. Core areas (50% Kernels) were approximately 1/5 of the full annual and seasonal home ranges (95% Kernels) regardless of habitat composition. Home range size in the forest-dominated landscape showed little inter-seasonal variation. In the agricultural-forest landscape, home ranges were larger during calving, hunt, and winter-spring compared to summer and rut. In the forest-dominated landscape, management areas are large enough to cover female spatial use. In the agricultural-forest landscape, female spatial use covers several license units. Here, the coordinated license system is needed to reach trade-offs between goals of conservation, game management, and damage mitigation. Males had in general larger home ranges than females, and the majority of the males also made a seasonal migration to and from the rutting areas. The license system area in the agricultural-forest landscape is large enough to manage migrating males. In the forest landscape, a coordination of several management areas is needed to encompass male migrations. We conclude that management needs to adapt to deer spatial use in different types of landscapes to reach set goals.

Urban Flood Modelling under Extreme Rainfall Conditions for Building-Level Flood Exposure Analysis

The expansion of urban areas and the increasing frequency and magnitude of intense rainfall events are anticipated to contribute to the widespread escalation of urban flood risk across the globe. To effectively mitigate future flood risks, it is crucial to combine a comprehensive examination of intense rainfall events in urban areas with the utilization of detailed hydrodynamic models. This study combines extreme value analysis techniques applied to rainfall data ranging from sub-hourly to daily durations with a high-resolution flood modelling analysis at the building level in the centre of Thessaloniki, Greece. A scaling procedure is employed to rainfall return levels assessed by applying the generalised extreme value (GEV) distribution to annual maximum fine-temporal-scale data, and these scaling laws are then applied to more reliable daily rainfall return levels estimated by means of the generalised Pareto distribution (GPD), in order to develop storm profiles with durations of 1 h and 2 h. The advanced flood model, CityCAT, is then used for the simulation of pluvial flooding, providing reliable assessments of building-level exposure to flooding hazards. The results of the analysis conducted provide insights into flood depths and water flowpaths in the city centre of Thessaloniki, identifying major flowpaths along certain main streets resulting in localised flooding, and identifying around 165 and 186 buildings highly exposed to inundation risk in the study area for 50-year storm events with durations of 1 h and 2 h, respectively. For the first time in this study area, a detailed analysis of extreme rainfall events is combined with a high-resolution Digital Terrain Model (DTM), used as an input into the advanced and fully featured CityCAT hydrodynamic model, to assess critical flowpaths and buildings at high flood risk. The results of this study can aid in the planning and design of resilient solutions to combat urban flash floods, as well as contribute to targeted flood damage mitigation and flood risk reduction.

Impact of dual neutralization of TNF-α and IL-1β along with Gentamicin treatment on the functions of blood and splenic neutrophils and its role on improvement of S. aureus induced septic arthritis

Researches of recent past years have emphasized potential of antibiotics to improve septic arthritis but as multi-drug resistant strains like MRSA are emerging fast, new alternative therapeutic advances are high in demand. This study aims to figure out the role of neutrophils in regulating inflammatory responses of S. aureus induced septic arthritis while using TNF-α Ab or IL-1β Ab along with antibiotic gentamicin or both in combination. In this study, role of anti-oxidant enzymes were investigated and correlated with generated ROS level. While expression of TLR2, TNFR2, MMP2, RANKL, SAPK/JNK in the spleen were evaluated through western blot. Serum activity of IL-8, IL-10, IL-12, OPG, OPN, CRP was assessed using ELISA. Flow cytometry study evaluated inflamed neutrophil population. Results have shown TNF-α neutralization along with gentamicin was able to reduce arthritic swelling prominently. While combination therapy effectively reduced blood neutrophil ROS activity, arginase activity, MPO activity along with spleen bacterial burden. Serum OPG, CRP, IL-10 level got reduced while serum OPN, IL-8 and IL-12 level enhanced in treatment groups, showing mitigation of inflammatory damage. Overall, it is a novel work that observed how antibiotic and antibody therapy enhanced neutrophil function positively to combat sepsis. This study may not be fully applicable in clinical trials as it is performed with animal model. Clinical trials include crystalline and inflammatory arthritides, trauma, neoplasm. Interdisciplinary collaboration between radiology, orthopaedic surgery and knowledge of animal system responses may give better idea to find proper therapeutic approach in future research works.

Role of Mesenchymal Stem Cells (MSCs) individually and with combination of cherry extract against antiepileptic drug induced hepatotoxicity

ObjectivesAntiepileptic drugs (ADEs) are now used to treat a wide range of neurological problems, although their usage is still restricted due to their side effects, particularly hepatotoxicity. Thus, this study consists of the therapeutic effects of non-conditioned Mesenchymal Stem Cells (MSCs) and the MSCs preconditioned with cherry extract (MSCs CM) on mitigation of liver damage induced by the dual administration of antiepileptic drugs such as Levetiracetam (L) and Oxcarbazepine (O). MethodsThe toxicity was induced in male albino rats by the means of the ADEs administration and was examined with the help of different paraments such as biochemical (total protein, albumin, globulin levels, A/G ratio level ALT, and GGTP), Oxidative stress (MDA, NO, and GSH), western blotting assay, immune-histopathology, and histopathological examinations. ResultsThe results revealed that rats treated with LO showed an increase in the level of ALT, GGTP, MDA, NO, Bax, and the protein expression of AKT and BI3K, caspase 3 level along with a decrease in GSH, total protein, albumin levels as well as, the level of Bcl2. MSCs or MSC CM with cherry extract treatment post antiepileptic drug administration ameliorate these parameters. Our findings suggest that MSCs and MSCs CM could be used in the disparity purpose of dual antiepileptic drugs induced towards normal. ConclusionsThus, it may be deduced that MSCs and MSC CM can hepatoprotection against ADEs-mediated hepatotoxicity and hence signifying that they could be a used as a valuable natural remedy for treating liver damage caused by drugs.

Ethylene and spermine attenuate chromium-inhibited photosynthetic functions by improving nitrogen and sulfur assimilation and antioxidant system in mustard

Phytohormones signaling is known for the regulation of metabolites synthesis, photosynthetic performance and abiotic stress acclimation in plants. We investigated the influence of ethylene (sourced as ethephon; 2-chloroethyl phosohonic acid, ETH) and spermine (Spm; polyamine) in alleviating the chromium (Cr)-triggered oxidative stress in the mustard (Brassica juncea cv. Varuna). The individual additions of 200 µL L−1 ETH and 1 mM Spm improved photosynthetic and growth parameters in the absence of Cr, but the Cr presence increased oxidative stress and the formation of stress (excess) ethylene, inhibiting photosynthesis, and growth. The application of ETH and Spm together in the absence of Cr, improved photosynthesis conspicuously. In the presence of Cr, ETH and Spm application improved photosynthesis by upregulation of psbA and psbB genes expression, and reducing oxidative stress, stress ethylene formation, and increase in activity of antioxidant enzymes, upregulation of ascorbate peroxidase (APX) and glutathione reductase (GR) genes, and nitrogen (N) and sulfur (S) assimilation. The possible ways in which ethylene and Spm interact in the mitigation of Cr-triggered oxidative damage are discussed. The study will provide insight into the mechanisms of N and S assimilation, antioxidant system, and regulation of ethylene production under the influence of ETH and Spm, and the strategy may be adopted for the sustainability of mustard plants under Cr stress.

LMAP-17 FEASIBILITY OF COGNITIVE-SPARING STEREOTACTIC RADIOSURGERY FOR BRAIN METASTASES: INITIAL REPORT OF PHASE II COG-SRS TRIAL

Abstract Radiotherapy at high doses leads to white matter (WM) and hippocampal injury which can cause cognitive decline. We designed the first, to our knowledge, evidence-based cognitive-sparing brain SRS trial for patients with limited brain metastases. In this report we analyze feasibility of cognitive-sparing SRS, utilizing dose constraints for eloquent WM tracts and bilateral hippocampi. Patients underwent high-resolution quantitative diffusion and volumetric MRI at baseline and post-SRS follow-up. Comprehensive neurocognitive assessment was performed at baseline and 3 months post-SRS evaluating multiple neurocognitive domains. Clinical workflow was largely automated with robust, validated segmentation of eloquent WM tracts and the hippocampi. Single fraction max dose constraints to WM tracts and hippocampi were 12 Gy and 8.4 Gy, respectively, with 3 and 5 fraction equivalent doses based on our prior NTCP studies. Patient accrual, follow-up imaging and neurocognitive testing is still active. To date, 59 patients and 114 lesions have been treated with cognitive-sparing linac-based SRS on trial. Median age is 63 years. Patients had 1-4 brain metastases; median prescription dose was 24Gy/1, 27Gy/3, or 30Gy/5 depending on target volume. Most patients were treated &amp;lt;7 business days from MRI. Cognitive endpoints have been collected on 89.5% of patients. Cognitive-sparing constraints were met in 79.3% of plans while maintaining standard clinical SRS plan indices and coverage benchmarks. Plans going over constraints had tumors overlying or within 1 mm of eloquent ROIs. Local control for treated lesions at 6 months was 97.9% and 95.7% at 12 months. Distant intracranial control was 68.1% at 6 and 12 months. Median OS was 18 months. Cognitive-sparing SRS treatment planning was successfully implemented for the majority of treated lesions with excellent local control. Mitigation of damage to eloquent structures has potential to further reduce cognitive decline after SRS. Full neurocognitive outcomes will be reported after accrual and testing are complete.

Applying three decades of research to mitigate the impacts of hemlock woolly adelgid on Ontario’s forests

Over the past 70 years, the introduced, invasive hemlock woolly adelgid (Adelges tsugae Annand) has become established and caused considerable decline and mortality of eastern hemlock (Tsuga canadensis (L.) Carr.) across much of the tree’s natural range. Hemlock is a foundation tree species with little inherent resistance to this exotic species and infestation by this sap-feeding insect results in progressive crown decline and tree mortality within 4 to 15 years. Continued climate warming favours the spread of this insect to Ontario and other areas at the northern edge of hemlock’s range. More than 30 years of basic and applied research directed towards control and mitigation of damage by this insect indicates that the rate of development of hemlock decline and mortality depends on climate, site, and stand factors that affect both insect performance and hemlock vigour. Here we synthesize these research findings to provide science-based management recommendations to (1) increase the resilience of Ontario’s hemlock forest resource to this insect before it spreads, (2) mitigate hemlock woolly adelgid damage once it gets established, and (3) facilitate degraded hemlock forest restoration.