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Background: Chronic total occlusion rotational atherectomy (CTO RA) is an emerging intervention in coronary artery disease (CAD), although data comparing its outcomes and complications with non-CTO RA are scarce. We sought to evaluate the outcomes of RA in CTO lesions compared to those in non-CTO lesions by performing a meta-analysis. Methods: We conducted a systematic review and meta-analysis of studies comparing the clinical outcomes and complications between CTO RA and non-CTO RA in patients with CAD. We searched PUBMED, CINAHL, EMBASE and Cochrane Central Register of Clinical Trials for any studies that compared the outcomes of RA in CTO and non-CTO lesions. The outcomes analyzed included in-hospital major adverse cardiovascular events (MACE), target vessel revascularization (TVR), angiographic success, procedural success, periprocedural complications, coronary perforation, and all-cause mortality. Results: Four studies with a total of 1868 patients were included, spanning from 2018 to 2022, from Germany, Taiwan, and Korea. The median age of included patients was 71. The rate of the pooled results indicated a moderate, non-significant increase in in-hospital MACE and TVR for CTO RA compared to non-CTO RA. There was a small, non-significant decrease in angiographic and procedural success in CTO RA compared to non-CTO RA. CTO RA was associated with a non-significant increase in periprocedural complications and a significant increase in coronary perforation compared to non-CTO RA. All-cause mortality showed a non-significant increase in the CTO RA group. Conclusion: This meta-analysis provides evidence that while CTO RA may be associated with a higher risk of coronary perforation, the risk of other outcomes including MACE, TVR, and all-cause mortality is not significantly different compared to non-CTO RA. More research is needed to further understand these relationships and to optimize treatment strategies in patients with CAD undergoing CTO RA.

Abstract Laser powder bed fusion is a promising technology for local deposition and microstructure control, but it suffers from defects such as delamination and porosity due to the lack of understanding of melt pool dynamics. To study the fundamental behavior of the melt pool, both geometric and thermal sensing with high spatial and temporal resolutions are necessary. This work applies and integrates three advanced sensing technologies: synchrotron X-ray imaging, high-speed IR camera, and high-spatial-resolution IR camera to characterize the evolution of the melt pool shape, keyhole, vapor plume, and thermal evolution in Ti–6Al–4V and 410 stainless steel spot melt cases. Aside from presenting the sensing capability, this paper develops an effective algorithm for high-speed X-ray imaging data to identify melt pool geometries accurately. Preprocessing methods are also implemented for the IR data to estimate the emissivity value and extrapolate the saturated pixels. Quantifications on boundary velocities, melt pool dimensions, thermal gradients, and cooling rates are performed, enabling future comprehensive melt pool dynamics and microstructure analysis. The study discovers a strong correlation between the thermal and X-ray data, demonstrating the feasibility of using relatively cheap IR cameras to predict features that currently can only be captured using costly synchrotron X-ray imaging. Such correlation can be used for future thermal-based melt pool control and model validation.

Aim: To evaluate pharmacokinetics, efficacy and safety of fixed-dose combination (FDC) of oral capecitabine + cyclophosphamide in metastatic breast cancer (MBC) patients progressing after anthracycline and/or taxane chemotherapy. Methods: In this prospective, adaptive, phase-2/3, open-label study (CTRI/2014/12/005234), patients were randomized (1:1:1) to three FDC doses (doses/day: D1, capecitabine + cyclophosphamide 1400 mg + 60 mg; D2, 1800 mg + 80 mg; D3, 2200 mg + 100 mg) for 14 days, in 21-day cycles. In Part-I, multiple-dose pharmacokinetics and optimal dose(s) were evaluated with futility analysis. Group(s) with

Abstract A highly sensitive electrochemical method for trace‐level detection of acetaminophen (AMP) was employed using glucose‐based carbon electrode (Gu/CPE) by cyclic voltammetry (CV) and differential pulse voltammetry (DPV). Electrochemical properties of AMP were well suited in 0.2 M phosphate buffer solution (PBS) of pH 7.0 and peak intensity of AMP at the Gu/CPE was enhanced compared to the bare carbon paste electrode. Furthermore, the different parameters, such as pH of electrolyte, scan rate, accumulation time effects, were investigated by CV. The redox reaction of AMP was quasi‐reversible as controlled by a diffusion process with two protons and two electrons. As per DPV technique, a lower detection limit (LOD) of 3.72 × 10–8 M over a wide linearity range (0.6‐9.0 µM) was observed. The excipient study demonstrates the selectivity of the electrode toward the electrochemical detection of AMP. Furthermore, the electrode was utilized to quantify AMP in clinical and pharmaceutical samples.

Suppliers play an important role in achieving an organization's sustainability goals. By engaging sustainable suppliers, an organization gets clean and green materials to ensure that their end-products are environmentally friendly. Sustainable supplier selection is a challenging task as it involves a complex decision making process involving different objectives and organization priorities. We propose a combined AHP-TOPSIS multiple criteria decision-making approach to solve this problem considering the uncertainty involved and to evaluate the quantitative and qualitative data. In this research, ethics is taken as the fourth dimension of sustainability along with Triple Bottom Line, considering that ethics plays a crucial role in purchasing activity and supplier selection. These four dimensions for sustainable supplier selection criteria have been divided into 16 sub-criteria to evaluate the suppliers. The model is demonstrated by its application to select a sustainable supplier in a real world electronics case company. The results indicate that economic factors still dominate during sustainable supplier selection. In selecting a sustainable supplier, it is found that prominence is given to human rights, safety systems and occupational health, pollution control and resource reduction and consumption, code of conduct, and transparency in suppliers' business and accounting criteria, which covers the other dimensions of sustainability. The application of the proposed model demonstrates the evaluation of tangible and intangible sustainability criteria in selecting a supplier. The result provides a ranking for the suppliers by showing their distances from the positive ideal solution of a sustainable supplier.

Abstract Background Patients with metastatic HER2/neu-positive (HER2/neu +) breast cancer (BC) often experience treatment resistance, disease recurrences and metastases. Thus, new approaches for improving the treatment of HER2/neu + BC to prevent metastatic dissemination are urgently needed. Our previous studies have shown that losartan, an angiotensin receptor blocker, increases tumor perfusion and decreases hypoxia in a number of tumor models. Hypoxia reduces the efficacy of radiation and increases metastases. We therefore hypothesized that by modifying tumor stroma and increasing oxygenation, losartan will improve the outcome of radiotherapy and inhibit disease progression in a highly metastatic HER2/neu + murine BC model. Methods We established a metastatic HER2/neu + murine BC line (MCa-M3C) and used it to generate mammary fat pad isografts in syngeneic female FVB/N mice. Starting on day 3 after orthotopic tumor implantation, we administered a 7-day losartan treatment (40 mg/kg BW, gavage daily); or a 7-day losartan treatment followed by 20 Gy single dose local irradiation (S-IR) on day 10 (tumor size ~ 100 mm3), or 20 Gy local fractionated (5 × 4 Gy daily) irradiation (F-IR) on days 10–14. We analyzed tumor-growth delay (TGD), development of spontaneous lung metastases, animal survival, tumor vascular density, and tumor hypoxia. Results Treatments with S-IR, F-IR, Losartan + S-IR, or Losartan + F-IR resulted in a significantly increased TGD (8–16 days) in MCa-M3C tumors versus controls. However, the combination of Losartan + S-IR and Losartan + F-IR further enhanced tumor response to radiation alone by increasing TGD an additional 5 to 8 days for both single and fractionated dose irradiation (P

Radiotherapy (RT) is a standard treatment for patients with advanced prostate cancer (PCa). Previous preclinical studies showed that SDF1α/CXCR4 axis could mediate PCa metastasis (most often to the bones) and cancer resistance to RT. We found high levels of expression for both SDF1α and its receptor CXCR4 in primary and metastatic PCa tissue samples. In vitro analyses using PCa cells revealed an important role of CXCR4 in cell invasion but not radiotolerance. Pharmacologic inhibition of CXCR4 using AMD3100 showed no efficacy in orthotopic primary and bone metastatic PCa models. However, when combined with RT, AMD3100 potentiated the effect of local single-dose RT (12 Gy) in both models. Moreover, CXCR4 inhibition also reduced lymph node metastasis from primary PCa. Notably, CXCR4 inhibition promoted the normalization of bone metastatic PCa vasculature and reduced tissue hypoxia. In conclusion, the SDF1α/CXCR4 axis is a potential therapeutic target in metastatic PCa patients treated with RT.

A sensitive method has been proposed for electrochemical reduction of tinidazole (TNZ) drugs employing a voltammetric approach. The supporting electrolyte, phosphate buffer solution (PBS) was prepared for different pH levels (3.0–8.0). The method involves a silica gel modified carbon paste electrode (SG/CPE) as an electrochemical sensor which demonstrated exceptional selectivity and sensitivity towards the detection of TNZ. Various parameters like the impact of accumulation time, pH of supporting buffer, scan rate, and concentration on electro-analysis of TNZ were examined. By the pH study, it was evident that the same number of protons and electrons participated in the process and by scan rate studies, we have estimated the heterogeneous rate constant and electron number. The process was irreversible and diffusion controlled. The linearity range was found to be 1.0 ​μM–10.0 ​μM from concentration variation studies. The detection and quantification limit was calculated and the practical applicability of a developed sensor is tested for tablet and urine samples. The reports obtained by studying the different parameters revealed that the electrode has good stability and sensitivity with reproducible results.

Background and aims: Smartphones have become an indelible part of a student’s life; but, their effect on academic performance of medical students is unclear with sparse data. The objective of the study was to estimate the prevalence of smartphone addiction among undergraduate medical students, pattern of its use, and the association of smartphone addiction with academic performance. Method: We conducted a cross-sectional study on all the undergraduate medical students in the Medical College Baroda, Anandpura, Vadodara, Gujarat, India, from second year to internship after getting written informed consent. Sociodemographic details, patterns of smartphone use, and scores of the final examination appeared for, were obtained to assess academic performance using a self-report semi-structured questionnaire. Smartphone addiction was diagnosed using the Smartphone Addiction Inventory (SPAI). Result: Out of the 523 students approached, 427 returned completed questionnaires. Ninety five students (22.2%) had smartphone addiction, with the addicted students being more likely to change their phone often, use it for longer periods and in restricted places. No association was found with gender, age, years of use, and academic performance. Conclusion: Nearly one-fifth of the medical undergraduate students were suffering from smartphone addiction. However, it does not seem to have an association with academic performance among undergraduate medical students.

Globalization has led organizations to think beyond economic benefit goals and move towards sustainable supply chains to address their business's societal and environmental concerns. An increasing number of companies are now committing to the cause of sustainability in their supply chain due to external pressures and foreseeing the rewards sustainable supply chains can deliver. The process of changing to a sustainable supply chain is complex, and certain enablers assist in achieving this effectively. This research aims to study the factors that act as enablers of sustainability in the electronics industries. Among these enablers, some have high causing influence while others exhibit high effecting influence. In this study, seventeen important enablers affecting the sustainability of the electronics supply chain in the Indian context have been identified from literature review and experts' opinions. The research helps in finding the causal and the effect enablers for implementing sustainable supply chain management. The interrelationship among these enablers is analyzed using a combination of Grey-DEMATEL methodology, and a diagraph depicting the causal relationship between enablers is established. Further, these enablers are ranked based on their degree of prominence. Results indicate that Government policies & legislations are the primary causal factor for sustainability, followed by culture related factors and Top Management commitment. The policy category enablers are seen to have a major causal effect on other enablers. The factor Health & safety standards have the highest net effect value. Top management commitment is the enabler demonstrating the highest correlation with other factors. Sensitivity analysis is performed to check the robustness of the results. The originality of this study stems from deriving a framework by identifying the enablers and their relationship for the implementation of a sustainable supply chain in the Indian electronics industry. The findings can help organizations to build a strategy and promptly evaluate the enablers to implement sustainability in their supply chains. The paper concludes by giving managerial implications of this research with possibilities of further research directions.

The concept of eco-efficiency is an important step in the move towards sustainable development. In the present day business, organizations have to take care of both the economic growth and environmental impact. Eco-efficiency determines the value of a product considering its environmental impact. In this research, the eco-efficiency requirements of an electronics industry are analyzed. The customer requirements (CRs) and design requirements (DRs) are identified for increasing the eco-efficiency in the industry. Seven CRs and fourteen DRs are identified for the electronics industry to improve eco-efficiency. An integrated Analytical Network Process (ANP) and Quality Function Deployment (QFD) is applied to prioritize the design requirements as per the customer's needs. QFD helps to incorporate the concept of the voice of customers for the design and development of products/services. The House of Quality developed translates the CRs to prioritize the DRs to improve eco-efficiency. The study encompasses the voice of customers in developing the sustainability performance of the electronics supply chain. It is found that design requirements to reduce greenhouse gases, air emissions, volatile organic compounds and carbon footprint is the most significant design parameter for eco-efficiency. The next design requirements with higher importance are Reduced use/consumption of resources, Use renewable energy like solar, State of the art innovative materials, Technologies for reducing use/consumption of energy, Green suppliers and green procurement, and Design for Environment. Focusing on these DRs aid in achieving the eco-efficiency goals of an organization. The paper contributes to the environmental sustainability aspect by identifying, prioritizing and creating a framework of requirements for eco-efficiency gains by an organization. The limitations and future scope of the study are also discussed.

In the past, industries were concentrating only on the economic aspects of a business. Many organizations are now addressing the social and environment impact of their supply chain for which they are adopting sustainability in their supply chain. The process of transformation to a sustainable supply chain will encounter some barriers which need to be eliminated or mitigated. To successfully manage these obstacles, it is crucial to know and study these barriers in specific context. This research aims to identify and analyse major barriers hampering sustainability implementation in the case of electronics industry in India. Through literature review and experts’ opinion eleven barriers are identified and classified into categories of Policy, Human resource and Technology. The hierarchical structure and interrelationship among these barriers is established using Interpretive Structural Modeling (ISM) methodology. A major finding in this research is that lack of awareness on benefits of sustainability, lack of regulations and enforcement of environment standards and lack of commitment from top management are significant barriers in implementation of a sustainable supply chain. The driving and driven powers of these barriers and their interdependence is determined. Using MICMAC analysis, five barriers were recognized to be the driver variables, three barriers as dependent variables and three as linkage variables. The barrier lack of performance metrics/evaluation standards on sustainability is having strong dependence power and least driving power implying that it is highly influenced by other variables. It is found that most of the barriers in the policy category are independent with high driving and influencing power. The research draws attention to formulate targeted policies at both government and organizational level in the electronics industry for successful implementation of sustainable supply chain management. The modeling gives an insight to organizations in confronting barriers and to manage their resources in an efficient and effective way while making their supply chains sustainable. The paper concludes with findings and future scope of research being discussed.

The ketorolac (KEC) is a non-steroidal anti-inflammatory drug (NSAID) which is a water-soluble non-opioid analgesic drug that exhibits antipyretic properties that helps in the treatment concerned with pain. The reports were found on the adverse effect of overdosage of KEC on health which makes to develop the simple, sensitive, and economic electroanalytical method for the trace level detection of KEC. In the present study, pencil graphite was employed as the electrode (PGE) for the electrochemical detection of KEC. The effects of different electrochemical parameters viz., pH of electrolyte, scan rate, and concentration etc., on KEC were explored through cyclic voltammetry (CV) and differential pulse voltammetry (DPV) techniques. The irreversible electrochemical reaction governed by the electrode process governed by the diffusion was attained by KEC at PGE. The linearity range was between 2.0 × 10−6 and 1.0 × 10−3 M, while the limit of detection was 4.59 × 10−7 M. The efficiency of the PGE was determined by analysing KEC in pharmaceutical drugs, and spiked real samples. The capability of the PGE towards the detection of KEC in presence of other chemicals was investigated by conducting an interference study. Hence, the proposed method can be applied for the determination of KEC in real biological and clinical samples.

The present study involves detecting and determining CIP by a new electrochemical sensor based on graphene (Gr) in the presence of sodium dodecyl sulfate (SDS) employing voltammetric techniques. Surface morphology studies of the sensing material were analyzed using a scanning electron microscope (SEM) and atomic force microscope (AFM). In the electroanalysis of CIP at the developed electrode, an enhanced anodic peak response was recorded, suggesting the electro-oxidation of CIP at the electrode surface. Furthermore, we evaluated the impact of the electrolytic solution, scan rate, accumulation time, and concentration variation on the electrochemical behavior of CIP. The possible electrode mechanism was proposed based on the acquired experimental information. A concentration variation study was performed using differential pulse voltammetry (DPV) in the lower concentration range, and the fabricated electrode achieved a detection limit of 2.9 × 10−8 M. The proposed sensor detected CIP in pharmaceutical and biological samples. The findings displayed good recovery, with 93.8% for tablet analysis and 93.3% to 98.7% for urine analysis. The stability of a developed electrode was tested by inter- and intraday analysis.

The antibiotic drug trimethoprim (TMP) is used to treat bacterial infections in humans and animals, and frequently TMP is used along with sulfonamides. However, a large portion of TMP is excreted in its active state, which poses a severe problem to humans and the environment. A sensitive, rapid, cost-effective analytical tool is required to monitor the TMP concentration in biological and environmental samples. Hence, this study proposed an analytical methodology to analyze TMP in clinical, biological and environmental samples. The investigations were carried out using a glucose-modified carbon paste electrode (G-CPE) employing voltammetric techniques. Electrochemical behavior was examined with 0.5 mM TMP solution at optimum pH 3.4 (Phosphate Buffer Solution, I = 0.2 M). The influence of scan rate on the electro-oxidation of TMP was studied within the range of 0.05 to 0.55 V/s. The effect of pH and scan rate variations revealed proton transfer during oxidation. Moreover, diffusion phenomena governed the irreversibility of the electrode reaction. A probable and suitable electrode interaction and reaction mechanism was proposed for the electrochemical oxidation of TMP. Further, the TMP was quantitatively estimated with the differential pulse voltammetry (DPV) technique in the concentration range from 9.0 × 10−7 to 1.0 × 10−4 M. The tablet, spiked water and urine analysis demonstrated that the selected method and developed electrode were rapid, simple, sensitive, and cost-effective.

A nanocomposite electrode of graphene (Gr) and zinc oxide (ZnO) nanoparticles was fabricated to study the electrochemical oxidation behavior of an anti-inflammatory drug, i.e., cetirizine (CET). The voltametric response of CET for bare CPE, Gr/CPE, ZnO/CPE, and the ZnO-Gr nanocomposite electrode was studied. The modifier materials were characterized using scanning electron microscopy (SEM), energy-dispersive X-ray spectroscopy (EDS), and X-ray powder diffraction (XRD) to comprehend the surface morphology of the utilized modifiers. The influence of pH, scan rate, and accumulation time on the electrooxidation of CET was examined. It was found that the electrochemical oxidation of CET was diffusion-controlled, in which two protons and two electrons participated. The detection limit was found to be 2.8 × 10−8 M in a linearity range of 0.05–4.0 µM. Study of excipients was also performed, and it was found that they had negligible interference with the peak potential of CET. The validation and utility of the fabricated nanocomposite sensor material were examined by analyzing clinical and biological samples. Stability testing of the nanocomposite electrode was conducted to assess the reproducibility, determining that the developed biosensor has good stability and high efficiency in producing reproducible results.

An efficient, high-yield and rapid synthesis of (E)-1,5-dimethyl-4-((2-((substituted-2-oxo-2H-chromen-4-yl)methoxy)naphthalen-1-yl)methyleneamino)-2-phenyl-1,2-dihydropyrazol-3-one derivatives (3a–3i) containing Schiff base structures under microwave-irradiation has been described. Schiff base is a potential target to discover anti-inflammatory chemotherapeutics, material science, catalysis and molecular magnetism. All the newly synthesized compounds (3a–3i) have been characterized by elemental analysis and spectroscopic techniques. The synthesized compounds (3a–3i) were evaluated for their antibacterial activity by agar-well diffusion method and anti-inflammatory activity by egg albumin denaturation method. The compounds (3e) and (3i) exhibit antibacterial effect with minimum inhibitory concentration (MIC) 0.78 µg ml−1 and MIC 1.562 µg ml−1 against Gram-positive Staphylococcus aureus bacterial strain compared with standard ciprofloxacin drug (MIC 6.25 µg ml−1). The compounds (3c) and (3f) exhibited an inhibition of heat-induced protein denaturation at the concentration (31.25 µg ml−1) as 53.65% and 67.27%, respectively, and these compounds are more active than standard aceclofenac drug (5.50%). Molecular docking study has been performed for all the synthesized compounds with S. aureus dihydropteroate synthetase and results obtained are quite promising.

The synthesis of various 3-aryl-furo[3,2-c]coumarins 4a–l has been carried out by employing two different methodologies under microwave irradiation condition. In the first method different 3-aryl-furo[3,2-c]coumarins 4a–l have been synthesized by reacting various 4-hydroxy coumarins 1a–d with appropriate 2-aryl-1-nitro ethenes 2a–c under Nef reaction condition, while in the second method the same target compounds have been synthesized by reacting various 4-hydroxy coumarins 1a–d with appropriate aroylmethyl bromides 3a–c under Feist–Benary reaction condition. All the synthesized compounds were characterized by elemental analysis and IR, 1H NMR, 13C NMR, DEPT-90 spectral analysis. All the synthesized compounds 4a–l were screened for their antimicrobial activity.

Controlled release floating metformin hydrochloride microbeads were prepared and optimized using a blend of varying concentrations of freeze-dried pregelatinized Chinese yam starch (Dioscorea oppositifolia L) and sodium alginate. Floating microbeads were prepared by the ionotropic gelation method using 10% w/v calcium chloride as the cross-linking agent and sodium bicarbonate as the gas releasing agent. A full 32 factorial design was used to investigate the influence of two variables: concentrations of starch (X1) and sodium bicarbonate (X2) on the swelling, floating lag time and amount of drug released after 1 hour (Q1) and 10 hours (Q10). Potential variables such as the concentrations of drug and total polymer were kept constant. The results showed that the properties of the floating microbeads were significantly (p

Software firms are increasingly adopting an open source strategy, allowing them to leverage the effort exerted by the open source community toward improving software quality. In addition to embracing a proprietary or fully open source strategy, several firms choose a partial openness strategy wherein only certain parts of the code are open source while the rest is proprietary. Specifically, when adopting a partial openness strategy, a firm may choose to make the core software code open source while keeping the extension software code proprietary or keep the core proprietary and make the extension open source. When making decisions related to different openness strategies, firms need to take into account the level of effort they are exerting toward the improvement of the quality of software, the level of engagement of the open source community, and pricing. Hence, the decisions related to a firm's openness strategy are not straightforward. While this is an important question for many firms, it has not been analyzed in the literature. In this research, we attempt to fill this important gap by analyzing different openness strategies in the context of resource allocation for fixing defects. Specifically, using a game-theoretic model, we explore when a firm should make its software fully open source or partially open source and when it should keep it proprietary. Our results show that when the baseline demand for the firm increases with the extent of openness, the firm should either make its software fully open or keep it proprietary and, importantly, should not rely on partial openness. Next, in scenarios where customers are highly sensitive to security risks, the demand loss to efficiency gain ratio has an important role in determining a firm's optimal openness strategies. These findings provide important insights to firms on how to effectively plan their openness strategies and also establish a basis for future research on the topic of partial openness. [ABSTRACT FROM AUTHOR]

Coronal fractures of the anterior teeth are common sequelae of dental trauma. In case of complex fractures, where the fractured segment is available and there is close approximation of the segment to the remaining tooth, root canal treatment followed by reattachment of the fractured segment with fiber post reinforcement is a feasible option. The procedure is simple and economic and needs less chair-side time as compared to many conventional methods. In addition, the procedure provides good and long-lasting esthetics, because the original morphology, color, and surface texture are maintained. This paper reports three cases of complex coronal tooth fracture successfully managed using tooth fragment reattachment.

ObjectiveChronic pain due to osteoarthritis (OA) is a major clinical problem, and existing analgesics often have limited beneficial effects and/or adverse effects, necessitating the development of novel therapies. Epoxyeicosatrienoic acids (EETs) are endogenous antiinflammatory mediators, rapidly metabolized by soluble epoxide hydrolase (EH) to dihydroxyeicosatrienoic acids (DHETs). We undertook this study to assess whether soluble EH-driven metabolism of EETs to DHETs plays a critical role in chronic joint pain associated with OA and provides a new target for treatment.MethodsPotential associations of chronic knee pain with single-nucleotide polymorphisms (SNPs) in the gene-encoding soluble EH and with circulating levels of EETs and DHETs were investigated in human subjects. A surgically induced murine model of OA was used to determine the effects of both acute and chronic selective inhibition of soluble EH by N-[1-(1-oxopropy)-4-piperidinyl]-N'-(trifluoromethoxy)phenyl]-urea (TPPU) on weight-bearing asymmetry, hind paw withdrawal thresholds, joint histology, and circulating concentrations of EETs and DHETs.ResultsIn human subjects with chronic knee pain, 3 pain measures were associated with SNPs of the soluble EH gene EPHX2, and in 2 separate cohorts of subjects, circulating levels of EETs and DHETs were also associated with 3 pain measures. In the murine OA model, systemic administration of TPPU both acutely and chronically reversed established pain behaviors and decreased circulating levels of 8,9-DHET and 14,15-DHET. EET levels were unchanged by TPPU administration.ConclusionOur novel findings support a role of soluble EH in OA pain and suggest that inhibition of soluble EH and protection of endogenous EETs from catabolism represents a potential new therapeutic target for OA pain.