P-1097. Efficacy of Rifaquizinone in a Murine Model of Prosthetic Joint Infection (PJI) with Fluoroquinolone-Sensitive and -Resistant <i>Staphylococcus aureus</i>

Open Forum Infectious Diseases · 2025-01-29

Abstract Background Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or acquired resistance to commonly used antibiotics and those associated with medical devices. RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. Current studies sought to evaluate the therapeutic efficacy of RFQ following intraperitoneal (IP) administration for 7- to14-day treatment in a murine model of S. aureus prosthetic joint infection (PJI). Methods K-wire was implanted in right hindlimb femurs of C57/BL6 mice followed by infection with 6.5-6.9 log10 CFU of a fluoroquinolone-sensitive (UNT005-4) or -resistant (UNT002-3) S. aureus strain. Doses of RFQ, ciprofloxacin, vancomycin, and vehicle were IP administered BID for 7 or 14 consecutive days starting 7 or 21 days after infection. Infected wires and femurs were collected and processed for CFU counts from untreated groups at the start of treatment and treated/vehicle groups within 18 hours of the final administered dose. Results In the 7 day UNT005-4 infection study, mean wire and femur counts for the infection group were 4.77 log10 CFU and 7.89 log10 CFU on Day 7 and for vehicle treatment were 5.02 log10 CFU and 6.83 log10 CFU on Day 14. Comparatively, RFQ at doses of 10, 25, and 62.5 mg/kg for 7 days treatment significantly reduced mean wire and femur counts by &amp;gt; 2.40 and &amp;gt; 1.60 log10 CFU. In the 21 day UNT005-4 infection study, compared to the infection and vehicle treatment, the same doses of RFQ administered for 14 days significantly reduced mean counts by &amp;gt;1.02 log10 CFU for wires and &amp;gt; 0.88 log10 CFU for femurs. In the 21 day UNT002-3 infection study, RFQ administered for 14 days significantly reduced mean counts by &amp;gt; 1.50 log10 CFU for wire and &amp;gt; 0.9 log10 CFU for femur. As expected, reduction in mean counts following 7 or 14 days of ciprofloxacin and vancomycin treatments were less than RFQ. Conclusion RFQ IP administered doses significantly reduced wire- and femur-associated counts for both S. aureus strains, and despite UNT002-3 resistant to ciprofloxacin treatment, the RFQ remained efficacious in the murine PJI model. Disclosures Mark E Pulse, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Phung Nguyen, BS, TenNor Therapeutics (Suzhou) Ltd: Investigator David Valtierra, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Kelly Peterson, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee William J Weiss, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator

Modeling fluid absorption in layered anisotropic cement-based materials

Materials and Structures · 2025-08-01 · 2 citations

Abstract The absorption of fluid in cement-based materials is often related to their durability. Current approaches to predict fluid absorption often assume material isotropy, which may not be accurate for layered systems. This paper presents a moisture transport modeling approach to investigate fluid absorption in layered anisotropic cement-based systems. The model is first validated by predicting the moisture profiles obtained from absorption experiments of two mortar samples, at times between 0.5 and 5 h. The model is then used to simulate layered geometries representative of 3D-printed mortar structures, emphasizing heterogeneity between filament and interfacial regions. Simulation results for the validation example match the moisture profiles obtained in the absorption experiments, with a Root Mean Square Percentage Error (RMSPE) of less than 12% in all cases. Simulation results for the layered geometries illustrate the anisotropic nature of fluid absorption in these systems. A layer arrangement parallel to the absorption direction leads to higher fluid uptake than when the layers are perpendicular to the absorption direction, due to lateral fluid transport from interfacial regions to filament regions. The roles of porosity, pore connectivity, and pore size distribution (PSD) are also examined, providing insights into how the microstructure of the material layers may impact fluid ingress. Additionally, it may be possible for material defects in these systems to be designed to control fluid absorption.

P-1111. Efficacy of Intra-Articular Administration of Rifaquizinone in Rodent Models of Implant Infection Associated with <i>Staphylococcus aureus</i>

Open Forum Infectious Diseases · 2025-01-29

Abstract Background Rifaquizinone (RFQ, TNP-2092) is a novel multitargeting drug conjugate in development for the treatment of serious or life-threatening bacterial infections including those caused by gram-positive pathogens that have developed or acquired resistance to commonly used antibiotics and those associated with medical devices. RFQ exerts its antibacterial activity by inhibiting RNA polymerase, DNA gyrase, and topoisomerase IV. The current studies were conducted to evaluate the therapeutic efficacy of RFQ following intra-articular (IA) administration in two rodent prosthetic joint infections models with S. aureus. Methods Female C57BL/6 mice and male Wistar rats were used. Following surgical insertion of a metal wire into the femoral canal, the surgical site was inoculated with approximately 7 log10 CFU of an S. aureus strain. RFQ and control drugs were IA administered into mice and rats starting 7 days post-surgery once daily for 7 and 14 days, respectively. At 24 hours after the last dose, the wire and femur were aseptically removed and processed for bacterial titers. Results In the mice, mean wire and femur counts for the untreated controls at the end of the study were 4.77 and 6.88 log10 CFU, respectively. IA delivered RFQ resulted in mean wire and femur counts that were 2.50-2.72 log10 CFU and 1.71-3.42 log10 CFU lower than the untreated controls, respectively (p ≤ 0.0001). In the rats, mean wire and femur counts for the untreated controls at the end of the study were 6.02 and 5.06 log10 CFU, respectively. RFQ resulted in mean wire and femur counts that were 3.32-5.02 log10 CFU and 1.21-1.96 log10 CFU lower than the untreated controls, respectively (p ≤ 0.01). RFQ administration in the rats resulted in reduced knee swelling and expression of systemic inflammatory markers, a decrease in signs of femoral osteomyelitis and decreased biofilm formation. Doses of RFQ in both species were statistically more effective than vancomycin in reducing the bacterial burden. Conclusion The results of these studies indicate that IA injection of RFQ is effective in treating infections related to orthopedic implants. The studies serve as a basis for the use of RFQ in orthopedic practice and the treatment of serious implant-associated infections. Disclosures William J Weiss, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Mark E Pulse, MS, TenNor Therapeutics (Suzhou) Ltd: Investigator Phung Nguyen, BS, TenNor Therapeutics (Suzhou) Ltd: Investigator David Valtierra, Master, TenNor Therapeutics (Suzhou) Ltd: Investigator Kelly Peterson, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Adaeze Ogbonna, Bachelor, TenNor Therapeutics (Suzhou) Ltd: Investigator Lane Beeman, Bachelor, TenNor Therapeutics (Suzhou) Ltd: Investigator Tianyu Dai, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Liaobin Chen, PhD, TenNor Therapeutics (Suzhou) Ltd: Investigator Huan Wang, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee Zhenkun Ma, PhD, TenNor Therapeutics (Suzhou) Ltd: Employee

Concrete Conductivity/Resistivity with Conductive Aggregate

2025-09-27

The electrical properties of concrete (formation factor) are often used as a surrogate test method to assess fluid transport in concrete primarily because resistivity (or conductivity) can be measured rapidly and economically. While electrical properties have been measured for nearly a century, the recent rise in handheld, battery-operated testing tools coupled with the desire to quantify the transport performance of concrete has caused a sudden spike in interest in electrical property measurements as a quality control or quality acceptance tool. Standards have been developed (AASHTO T 358, AASHTO T 402, ASTM C1876) with an emphasis on the role of sample conditioning. Some users have reported that the use of certain aggregates tends to reduce the resistivity values (increase the conductivity) when compared with concrete made using the same matrix but different aggregates. This paper examines a fundamental assumption of the electrical testing, i.e., that the aggregate is resistive or non-conductive. It explores the implications if the aggregate is conductive using both an analytical and finite element approach to determining the impact of aggregate with a lower resistivity and discusses a procedure to account for aggregate conductivity.

Thoughts on the Service Life of Internally Cured Concrete Considering ASR and FT

Proceedings of the International Conference on Concrete Pavements · 2025-01-22

Internal curing has been proven as a solution to reduce early-age shrinkage and related cracking in concrete. Internal curing can reduce the risk of built in stress, cracking, and curling in concrete pavements. However, the benefits of internal curing go beyond just shrinkage and cracking mitigation. Research by the author’s has shown the incorporation of fine lightweight aggregate-FLWA can significantly reduce the risk of deleterious alkali-silica reaction. When the FLWA replaces a reactive aggregate a dilution effect occurs, but other benefits also exist. The curing provided by internal curing can react a greater percentage of cementitious material allowing a reduction in cement and an increase in the amount of binder fillers thereby reducing the alkali loading of the mixture. Additionally, the internal curing was shown to reduce the pH of the internal concrete pore solution and led to a refinement of the interfacial transition zone, possibly due to a pozzolanic reaction. The FLWA provides a porous inclusion which appears to enable a reaction product, similar to ASR gel to form however with limited expansion.

Effect of Surface Evaporation and Slab Thickness on the Scaling Resistance of Concrete Containing Fly Ash

Proceedings of the International Conference on Concrete Pavements · 2025-01-17 · 2 citations

Laboratory tests (conducted in accordance with ASTM C672) frequently indicate that concrete containing fly ash may be susceptible to scaling. Based on this concern, a few northern USA states restrict the use of fly ash during the late-fall pavement construction season. However, a survey of twelve northern states revealed that scaling is rarely observed in actual pavements. In an attempt to develop a more clear understanding of the potential reasons for the apparent discrepancy between the scaling resistance of laboratory concretes and field concretes, scaling studies were conducted on concrete containing 20 percent of a Class C fly ash. The main variables in the study were the surface water evaporation rate (water loss was ranged from 0 to 4.5 kg/m2) and the thickness of the slab specimen (55 mm to 245 mm). The selected ranges of test variables were intended to represent moisture and temperature conditions that are likely to be encountered in the field. In addition to monitoring the mass of material lost from the surface due to scaling, the temperature gradient that developed inside the specimen during freezing was measured. In addition, scanning electron microscopy was performed to assess differences in porosity of the near surface concrete. The results indicate that ASTM C 672 is too severe when compared to the environmental conditions that are likely to be encountered in the field.

Experience with the Use of Interactive Classroom Technologies for the Implementation of Problem-Based, Peer-Interaction Learning Environment in Civil Engineering Materials

2025-02-18

Are you a faculty member who is curious if the class is following what you are presenting?Have you ever been curious to know what the student in the third row is thinking while you are talking?Do you spend many sleepless nights wondering how you will increase class participation?This paper describes the implementation of an interactive classroom technology that was designed to address each of these questions, and to improve your students experience in the classroom.This paper describes the experience of incorporating an interactive classroom response system in a required sophomore/junior course on Civil Engineering Materials.This course deals with cement, concrete, asphalt, and wood.Since this course is a required class with typically 70 to 100 students, it is often difficult to develop the type of personal interactions that you would expect from a smaller class.To overcome some of the limitations associated with the lack of participation that is typical in a large class, this course made use of a remote response (i.e., remote control) technology that enabled every student to participate and interact throughout the course of the lecture.In addition to encouraging nearly 100% participation and enabling nearly instant grading and attendance, the methodology developed enabled problem-based, peerinteractive learning during the large lecture format.This format enabled the students to work on practical problems by teaching one another, thereby reinforcing important class concepts.This paper will describe: 1) the background of civil engineering materials classes at Purdue, 2) the motivation for investigating how to improve the learning experience in the materials courses, 3) the background of interactive classroom technology, 4) methods to incorporate the personal response devices in class, and 5) plans for future developments.

Carbonation Potential for Concrete Using Thermodynamic Modeling for Concrete Sustainability Calculations

Transportation Research Record Journal of the Transportation Research Board · 2025-05-21 · 2 citations

The design of concrete is transitioning from mixtures that are predominately clinker based to mixtures that have less clinker with a substantial replacement with fillers and supplementary cementitious materials (SCMs). There is a growing interest in accounting for the CO 2 sequestered by concrete mixtures via carbonation. This paper discusses some nuances of how material composition and mixture design are affected as industry drives toward zero carbon emission goals. This paper begins by discussing the current life-cycle assessment (LCA) approaches and outlines the complexity of determining at which step in the LCA process carbonation should be considered, a particularly important point as current environmental product declarations focus on the A1 to A3 (cradle to gate) stages and therefore “favor” forced carbonation approaches. Specifically, it highlights how upfront minimization of CO 2 is generally preferable to forced or natural carbonation. It also discusses the need for clarification on carbonation in the LCA process. The paper uses thermodynamic modeling to determine similar paste performance and indicates that the potential CO 2 sequestered varies from mixture to mixture. From a carbon emissions perspective, calculations show that moderately reactive SCMs might be preferable to highly reactive ones as the former allow higher clinker replacements while maintaining required concrete performance. The work illustrates how this would be affected by the paste volume of the concrete—higher paste volumes should be avoided. Carbonation potential of structures with large and exposed surfaces, such as pavements, might help reduce the global warming potential of concrete.

Predicting sorption isotherms from thermodynamic calculations

Cement · 2025-01-18 · 1 citations

Accurate sorption/desorption isotherms for cementitious materials are important in predicting drying shrinkage, moisture transport, ionic transport, freezable water content, and the service life of concrete. This paper develops a framework for constructing water sorption isotherms for hydrated cementitious pastes from the outputs of thermodynamic modeling and a pore partitioning model (PPM). Thermodynamic modeling helps quantify the solid phases and pore space in the hydrated matrix. The PPM provides the volume of evaporable water in crystalline hydrates, the total volume of gel water, the volume of capillary water, and volume of pores due to chemical shrinkage. The sorption isotherm is constructed from information on the evaporable water present in individual phases at each RH, water adsorbed on C-S-H, water in pores with kelvin radius of 2–5 nm, capillary water, and water in pores due to chemical shrinkage and air voids. The Brunauer-Skalny-Bodor (BSB) model is used to calculate the water adsorbed on the C-S-H. This model predicts the sorption isotherms from the literature to within an error of 2–19 %. The areas for future work and the challenges in predicting the desorption isotherms are discussed.

Examining the influence of colloidal silica admixtures on salt ingress and reaction in mortar

Oregon State University · 2025-08-29

This report examines the influence of commercially available colloidal silica admixtures on salt ingress and reaction in mortar. The admixtures have been designed to aid contractors in placing and finishing concrete on-site. A series of mixtures was tested using isothermal calorimetry (IC), thermogravimetric analysis (TGA), low temperature differential scanning calorimetry (LTDSC), evaporation rate measurements, and chloride profiling. Thermodynamic modeling was used to support the experiments. IC showed that the heat of hydration was slightly higher (2-3%) than the reference mixture when the admixtures were used. TGA indicated up to 18% reduction in calcium hydroxide at relatively low admixture concentrations (4-12 oz/cwt), which was greater than what would be expected based on pozzolanic reactions alone. At higher dosages, similar or higher calcium hydroxide contents were measured due to similar or increased hydration reactions, as assessed using non-evaporable water content. LTDSC results showed up to 30% reduction in calcium oxychloride formation potential, which was related to the reduced calcium hydroxide content. The rate of water evaporation was slightly slower from the admixture than water. The admixtures also stabilized at masses that are greater than their solid content during drying, which implies that they retain a portion of their water content, even at relative humidities much lower than those encountered during cement paste hydration. Admixtures did not affect chloride ingress profiles significantly (with the exception of the water repellent). Thermodynamic calculations show that even though the admixtures provide some reactive silica that acts pozzolanically, this amount is relatively small in the studied admixture dosages, as indicated by the small decrease in the CH content. Overall, the results are consistent with a limited pozzolanic activity associated with low silica contents introduced (0.08 to 1.35% of cement mass for the dosage considered). Keywords: colloidal silica, deicing salts, hydration, pozzolanic reaction