Thermodynamic Two-Site Surface Reaction Model for Predicting Munition Constituent Reduction Kinetics with Iron (Oxyhydr)oxides.

Iron (oxyhydr)oxides comprise a significant portion of the redox-active fraction of soils and are key reductants for remediation of sites contaminated with munition constituents (MCs). Previous studies of MC reduction kinetics with iron oxides have focused on the concentration of sorbed Fe(II) as a key parameter. To build a reaction kinetic model, it is necessary to predict the concentration of sorbed Fe(II) as a function of system conditions and the redox state. A thermodynamic framework is formulated that includes a generalized double-layer model that utilizes surface acidity and surface complexation reactions to predict sorbed Fe(II) concentrations that are used for fitting MC reduction kinetics. Monodentate- and bidentate Fe(II)-binding sites are used with individual oxide sorption characteristics determined through data fitting. Results with four oxides (goethite, hematite, lepidocrocite, and ferrihydrite) and four nitro compounds (NB, CN-NB, Cl-NB, and NTO) from six separate studies have shown good agreement when comparing observed and predicted surface area-normalized rate constants. While both site types are required to reproduce the experimental redox titration, only the monodentate site concentration controls the MC reaction kinetics. This model represents a significant step toward predicting the timescales of MC degradation in the subsurface.

Linear Free Energy Relationship for Predicting the Rate Constants of Munition Compound Reduction by the Fe(II)-Hematite and Fe(II)-Goethite Redox Couples.

Abiotic reduction by iron minerals is arguably the most important fate process for munition compounds (MCs) in subsurface environments. No model currently exists that can predict the abiotic reduction rates of structurally diverse MCs by iron (oxyhydr)oxides. We performed batch experiments to measure the rate constants for the reduction of three classes of MCs (poly-nitroaromatics, nitramines, and azoles) by hematite or goethite in the presence of aqueous Fe2+. The surface area-normalized reduction rate constant (kSA) depended on the aqueous-phase one-electron reduction potential (EH1) of the MC and the thermodynamic state (i.e., pe and pH) of the iron oxide-Feaq2+ system. A linear free energy relationship (LFER), similar to that reported previously for nitrobenzene, successfully captures all MC reduction rate constants that span 6 orders of magnitude: log(kSA)=(1.12±0.04)[0.53EH159mV-(pH+pe)]+(5.52±0.23). The finding that the rate constants of all the different classes of MCs can be described by a single LFER suggests that these structurally diverse nitro compounds are reduced by iron oxide-Feaq2+ couples through a common mechanism up to the rate-limiting step. Multiple mechanistic implications of the results are discussed. This study expands the applicability of the LFER model for predicting the reduction rates of legacy and emerging MCs and potentially other nitro compounds.

Electron Transfer Energy and Hydrogen Atom Transfer Energy-Based Linear Free Energy Relationships for Predicting the Rate Constants of Munition Constituent Reduction by Hydroquinones.

No single linear free energy relationship (LFER) exists that can predict reduction rate constants of all munition constituents (MCs). To address this knowledge gap, we measured the reduction rates of MCs and their surrogates including nitroaromatics [NACs; 2,4,6-trinitrotoluene (TNT), 2,4-dinitroanisole (DNAN), 2-amino-4,6-dinitrotoluene (2-A-DNT), 4-amino-2,6-dinitrotoluene (4-A-DNT), and 2,4-dinitrotoluene (DNT)], nitramines [hexahydro-1,3,5-trinitro-1,3,5-triazine (RDX) and nitroguanidine (NQ)], and azoles [3-nitro-1,2,4-triazol-5-one (NTO) and 3,4-dinitropyrazole (DNP)] by three dithionite-reduced quinones (lawsone, AQDS, and AQS). All MCs/NACs were reduced by the hydroquinones except NQ. Hydroquinone and MC speciations were varied by controlling pH, permitting the application of a speciation model to determine second-order rate constants (k) from observed pseudo-first-order rate constants. The intrinsic reactivity of MCs (oxidants) decreased upon deprotonation, while the opposite was true for hydroquinones (reductants). The rate constants spanned ∼6 orders of magnitude in the order NTO ≈ TNT > DNP > DNT ≈ DNAN ≈ 2-A-DNT > DNP- > 4-A-DNT > NTO- > RDX. LFERs developed using density functional theory-calculated electron transfer and hydrogen atom transfer energies and reported one-electron reduction potentials successfully predicted k, suggesting that these structurally diverse MCs/NACs are all reduced by hydroquinones through the same mechanism and rate-limiting step. These results increase the applicability of LFER models for predicting the fate and half-lives of MCs and related nitro compounds in reducing environments.

Modeling the Reduction Kinetics of Munition Compounds by Humic Acids.

Dissolved organic matter (DOM) comprises a sizeable portion of the redox-active constituents in the environment and is an important reductant for the abiotic transformation of nitroaromatic compounds and munition constituents (NACs/MCs). Building a predictive kinetic model for these reactions would require the energies associated with both the reduction of the NACs/MCs and the oxidation of the DOM. The heterogeneous and unknown structure of DOM, however, has prohibited reliable determination of its oxidation energies. To overcome this limitation, humic acids (HAs) were used as model DOM, and their redox moieties were modeled as a collection of quinones of different redox potentials. The reduction and oxidation energies of the NACs/MCs and hydroquinones, respectively, via hydrogen atom transfer (HAT) reactions were then calculated quantum chemically. HAT energies have been used successfully in a linear free energy relationship (LFER) to predict second-order rate constants for NAC reduction by hydroquinones. Furthermore, a linear relationship between the HAT energies and the reduction potentials of quinones was established, which allows estimation of hydroquinone reactivity (i.e., rate constants) from HA redox titration data. A training set of three HAs and two NACs/MCs was used to generate a mean HA redox profile that successfully predicted reduction kinetics in multiple HA/MC systems.

A Unified Linear Free Energy Relationship for Abiotic Reduction Rate of Nitroaromatics and Hydroquinones Using Quantum Chemically Estimated Energies.

Determining the fate of nitroaromatic compounds (NACs) in the environment requires the use of predictive models for compounds and conditions for which experimental data are insufficient. Previous studies have developed linear free energy relationships (LFERs) that relate the thermodynamic energy of NAC reduction to its corresponding rate constant. We present a comprehensive LFER that incorporates both the reduction and oxidation half-reactions through quantum chemically calculated energies. Environ Toxicol Chem 2020;39:2389-2395. © 2020 SETAC.

Hydrogen Atom Transfer Reaction Free Energy as a Predictor of Abiotic Nitroaromatic Reduction Rate Constants: A Comprehensive Analysis.

A linear free energy model is presented that predicts the second-order rate constant for the abiotic reduction of nitroaromatic compounds (NACs). Previously presented models use the one-electron reduction potential EH1(ArNO2) of the NAC reaction ArNO2+e-→ArNO2•- . If EH1(ArNO2) is not available, it has been proposed that EH1(ArNO2) be computed directly or estimated from the gas-phase electron affinity (EA). The model proposed uses the Gibbs free energy of the hydrogen atom transfer (HAT) reaction ArNO2+H•→ArNOOH• as the parameter in the linear free energy model. Both models employ quantum chemical computations for the required thermodynamic energies. The available and proposed models are compared using experimentally determined second-order rate constants from 5 investigations from the literature in which a variety of NACs were exposed to a variety of reductants. A comprehensive analysis utilizing all the NACs and reductants demonstrate that the HAT energy model and the experimental one-electron reduction potential model have similar root mean square errors and residual error probability distributions. In contrast, the model using the computed EA has a more variable residual error distribution with a significant number of outliers. The results suggest that a linear free energy model utilizing computed HAT reaction free energy produces a more reliable prediction of the NAC abiotic reduction second-order rate constant than previously available methods. The advantages of the proposed HAT energy model and its mechanistic implications are discussed as well. Environ Toxicol Chem 2020;39:1678-1684. © 2020 SETAC.

Effectiveness of cold coagulation in treating high-grade cervical intraepithelial neoplasia: the human papillomavirus evidence of cure.

We retrospectively analysed post-treatment human papillomavirus (HPV) results in women treated for cervical intraepithelial neoplasia (CIN) to establish if 'virological cure' rates achieved by cold coagulation matched those for large-loop excision of the transformation zone (LLETZ) in the treatment of CIN. The main outcome measure was the rate of non-detection of HPV at 6- and 18-month follow-up. HPV was not detected in 82.0% and 86.0% of women at 6- and 18-month follow-up, respectively. In women with high-grade CIN (CIN 2 or worse), there was no difference in HPV non-detection rates among the two treatment methods at six-month (81.8% for cold coagulation vs. 84.0% for LLETZ, χ2=0.23, p value=.632), and 18-month follow-up (83.3% for cold coagulation vs. 89.2% for LLETZ, χ2=1.46, p value=.227). Cervical cold coagulation provides a high 'virological cure' rate for all grades of CIN, equivalent to that seen with LLETZ. Impact Statement What is already known on this subject? It is well established that CIN cure rates after treatment with cold coagulation are comparable to those of excisional methods and are over 90% on cytological follow-up post-treatment. Furthermore, there are no demonstrable adverse effects on fertility and delivery in pregnancies conceived after cold coagulation according to long-term follow-up studies. In contrast, there is a positive correlation between treatment with LLETZ and the risk of subsequent subfertility and adverse pregnancy outcomes. What the results of this study add? This study provides evidence that cold coagulation achieves similar cure rates to that of LLETZ not only in cytology but also in HPV test of cure. This finding is significant as we are moving to a primary HPV cervical screening programme. What the implications are of these findings for clinical practice and/or further research? A negative high-risk HPV test provides a greater reassurance of a low risk of CIN 3 or cancer than a negative cytology result. Therefore, given parity to LLETZ in 'virological cure' rate and having no known adverse effects on fertility and pregnancy, cold coagulation should be used to treat most cases of CIN, especially in women of reproductive age.

Experimental Validation of Hydrogen Atom Transfer Gibbs Free Energy as a Predictor of Nitroaromatic Reduction Rate Constants.

Nitroaromatic compounds (NACs) are a class of prevalent contaminants. Abiotic reduction is an important fate process that initiates NAC degradation in the environment. Many linear free energy relationship (LFER) models have been developed to predict NAC reduction rates. Almost all LFERs to date utilize experimental aqueous-phase one-electron reduction potential ( EH1) of NAC as a predictor, and thus, their utility is limited by the availability of EH1 data. A promising new approach that utilizes computed hydrogen atom transfer (HAT) Gibbs free energy instead of EH1 as a predictor was recently proposed. In this study, we evaluated the feasibility of HAT energy for predicting NAC reduction rate constants. Using dithionite-reduced quinones, we measured the second-order rate constants for the reduction of seven NACs by three hydroquinones of different protonation states. We computed the gas-phase energies for HAT and electron affinity (EA) of NACs and established HAT- and EA-based LFERs for six hydroquinone species. The results suggest that HAT energy is a reliable predictor of NAC reduction rate constants and is superior to EA. This is the first independent, experimental validation of HAT-based LFER, a new approach that enables rate prediction for a broad range of structurally diverse NACs based solely on molecular structures.

Prophylactic Negative Pressure Dressing Use in Closed Laparotomy Wounds Following Abdominal Operations: A Randomized, Controlled, Open-label Trial: The P.I.C.O. Trial.

OBJECTIVE: A randomized controlled trial was undertaken to investigate the effect of prophylactic negative pressure dressings on postoperative surgical site infection (SSI) rates in closed laparotomy wounds. SUMMARY OF BACKGROUND DATA: Laparotomy wounds are associated with high rates of SSI. The effect of prophylactic negative pressure dressing of closed incisional wounds on SSI rate is unknown. METHODS: A randomized, controlled, open-label trial was conducted (clinicaltrials.gov registration number NCT02780453). Fifty patients undergoing open abdominal surgery were included, with 25 patients randomized to the negative pressure dressing group and 25 to the standard dressing group. The primary endpoint was SSI incidence at 30 days postoperatively. Secondary endpoints included SSI incidence at 4 days, length of stay, cosmetic outcome, and patient satisfaction. Statistical analysis was performed on a per-protocol basis using SPSS version 23.0. RESULTS: The incidence of SSI at 30 days postoperatively was significantly reduced in the treatment group compared with the control group [8.3% vs 32.0%, P = 0.043 (1-sided), P = 0.074 (2-sided)]. There was no difference in SSIs at 4 days postoperatively [4.1% vs 8.0%, P = 0.516 (1-sided), P = 1.0 (2-sided)]. Analysis of predictors of wound infection identified standard wound dressings as the only significant predictor of SSI development. Length of stay was significantly reduced in the negative pressure dressing group [6.1 vs 14.7 days, P = 0.019 (2-sided)]. Cosmetic outcome and patient satisfaction did not show any difference between the 2 groups. CONCLUSIONS: Prophylactic use of negative pressure dressings for closed laparotomy wounds significantly reduces the incidence of SSI at 30 days postoperatively.

Treatment of endometrial stromal sarcoma with a gonadotropin-releasing hormone analogue.

BACKGROUND: Endometrial stromal sarcoma can present management difficulties due to its lack of response to conventional chemotherapy and radiotherapy. Various hormonal therapies have been shown to reduce tumor volume in both primary and recurrent disease. CASE: A woman who underwent myomectomy was discovered to have a low-grade endometrial stromal sarcoma. Treatment with the gonadotropin-releasing hormone (GnRH) analogue triptorelin before surgery had produced reduction in uterine size. The woman developed tumor recurrence six months after definitive surgical treatment. The tumor enlarged rapidly during a 2-month period, with development of a right-sided hydronephrosis. Repeat administration of triptorelin was accompanied by resolution of the hydronephrosis and reduction in tumor volume. Biopsy results confirmed recurrent low-grade endometrial stromal sarcoma with moderate estrogen and progesterone receptor positivity. CONCLUSION: Control of progression of a recurrent endometrial stromal sarcoma was achieved with the GnRH analogue triptorelin. This is the first report in the English-language literature during a 30-year period of single-agent GnRH analogue being an effective treatment intervention in this context.