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Cancer invasion and metastasis are known to be potentiated by the expression of aquaporins (AQPs). Likewise, the expression levels of AQPs have been shown to be prognostic for survival in patients and have a role in tumor growth, edema, angiogenesis, and tumor cell migration. Thus, AQPs are key players in cancer biology and potential targets for drug development. Here, we present the single-particle cryo-EM structure of human AQP7 at 3.2-Å resolution in complex with the specific inhibitor compound Z433927330. The structure in combination with MD simulations shows that the inhibitor binds to the endofacial side of AQP7. In addition, cancer cells treated with Z433927330 show reduced proliferation. The data presented here serve as a framework for the development of AQP inhibitors., Competing Interests: Competing interests statement:The authors declare no competing interest.

Background: Given the serious nature of many neurosurgical pathologies, it is common for hospitalized patients to elect comfort care (CC) over aggressive treatment. Few studies have evaluated the incidence and risk factors of CC trends in patients admitted for neurosurgical emergencies., Objectives: To analyze all neurosurgical patients admitted to a tertiary care academic referral center via the emergency department (ED) to determine incidence and characteristics of those who initiated CC measures during their initial hospital admission., Methods: We performed a prospective, cohort analysis of all consecutive adult patients admitted to the neurosurgical service via the ED between October 2018 and May 2019. The primary outcome was the initiation of CC measures during the patient's hospital admission. CC was defined as cessation of life-sustaining measures and a shift in focus to maintaining the comfort and dignity of the patient., Results: Of the 428 patients admitted during the 7-month period, 29 (6.8%) initiated CC measures within 4.0 ± 4.0 days of admission. Patients who entered CC were significantly more likely to have a medical history of cerebrovascular disease (58.6% vs. 33.3%, p = 0.006), dementia (17.2% vs. 1.5%, p = 0.0004), or cancer with metastatic disease (24.1% vs. 7.0%, p = 0.001). Patients with a presenting pathology associated with cerebrovascular disease were significantly more likely to initiate CC (62.1% vs. 35.3, p = 0.04). Patients who underwent emergent surgery were significantly more likely to enter CC compared with those who had elective surgery (80.0% vs. 42.7%, p = 0.02). Only 10 of the 29 (34.5%) patients who initiated CC underwent a neurosurgical operation (p = 0.002). Twenty of the 29 (69.0%) patients died within 0.8 ± 0.8 days after the initiation of CC measures., Conclusion: CC measures were initiated in 6.8% of patients admitted to the neurosurgical service via the ED, with the majority of patients entering CC before an operation and presenting with a cerebrovascular pathology.

The assembly of heterometallic complexes capable of activating dioxygen is synthetically challenging. Here, we report two different approaches for the preparation of heterometallic superoxide complexes [ Ph L 2 Cr III -η 1 -O 2 ][MX] 2 ( Ph L = - OPh 2 SiOSiPh 2 O - , MX + = [CoCl] + , [ZnBr] + , [ZnCl] + ) starting from the Cr II precursor complex [ Ph L 2 Cr II ]Li 2 (THF) 4 . The first strategy proceeds via the exchange of Li + by [MX] + through the addition of MX 2 to [ Ph L 2 Cr II ]Li 2 (THF) 4 before the reaction with dioxygen, whereas in the second approach a salt metathesis reaction is undertaken after O 2 activation by adding MX 2 to [ Ph L 2 Cr III -η 1 -O 2 ]Li 2 (THF) 4 . The first strategy is not applicable in the case of redox-active metal ions, such as Fe 2+ or Co 2+ , as it leads to the oxidation of the central chromium ion, as exemplified with the isolation of [ Ph L 2 Cr III Cl][CoCl] 2 (THF) 3 . However, it provided access to the hetero-bimetallic complexes [ Ph L 2 Cr III -η 1 -O 2 ][MX] 2 ([MX] + = [ZnBr] + , [ZnCl] + ) with redox-inactive flanking metals incorporated. The second strategy can be applied not only for redox-inactive but also for redox-active metal ions and led to the formation of chromium(III) superoxide complexes [ Ph L 2 Cr III -η 1 -O 2 ][MX] 2 (MX + = [ZnCl] + , [ZnBr] + , [CoCl] + ). The results of stability and reactivity studies (employing TEMPO-H and phenols as substrates) as well as a comparison with the alkali metal series (M + = Li + , Na + , K + ) confirmed that although the stability is dependent on the Lewis acidity of the counterions M and the number of solvent molecules coordinated to those, the reactivity is strongly dependent on the accessibility of the superoxide moiety. Consequently, replacement of Li + by XZn + in the superoxides leads to more stable complexes, which at the same time behave more reactive toward O-H groups. Hence, the approaches presented here broaden the scope of accessible heterometallic O 2 activating compounds and provide the basis for further tuning of the reactivity of [ R L 2 Cr III -η 1 -O 2 ]M 2 complexes.

Multimetallic complexes have recently seen increased attention as next-generation charge carriers for nonaqueous redox flow batteries. Herein, we report the electrochemical performance of a molecular iron-molybdenum oxido complex, {[(Me 3 TACN)Fe][μ-(MoO 4 κ 3 O,O',O")]} 4 (Fe 4 Mo 4 O 16 ). In symmetric battery charging schematics, Fe 4 Mo 4 O 16 facilitates reversible two-electron storage with coulombic efficiencies >99 % over 100 cycles (5 days) with no molecular decomposition and minimal capacity fade. Energy efficiency throughout cycling remained high (∼82 %), as a result of the rapid electron-transfer kinetics observed for each of the complex's four redox events. We also report the synthesis of the analogous synthetic frameworks featuring tungstate vertices or bridging-sulfide moieties, revealing key observations relevant to structure-function relationships and design criteria for these types of heterometallic ensembles., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

O 2 activation at a chromium(II) siloxide complex in propionitrile leads to a chromium(III) complex with an end-on bound superoxide ligand, while the reaction in tetrahydrofuran leads to a side-on peroxo chromium(IV) compound. The superoxide reacts faster with (2,2,6,6-tetramethylpiperidin-1-yl)oxyl hydroxylamine while the peroxide, unlike the superoxide, proved capable of deformylating aldehydes. The system was found to represent a unique case, where even a switching between the two structures can be achieved via the solvent; its ability to coordinate at the position  trans to the O 2 ligand is decisive, as supported by density functional theory studies. Altogether, the results show that subtle changes can determine for an initially formed metal-dioxygen adduct, whether it exists as a superoxide or a peroxide, which thus merits consideration in discussions on mechanisms and possible reaction routes.

In recent years, it has become clear that the presence of redox-inactive Lewis acidic metal ions can decisively influence the reactivity of metal-dioxygen moieties that are formed in the course of O 2 activation, in molecular complexes, and metalloenzymes. Superoxide species are often formed as the primary intermediates but they are mostly too unstable for a thorough investigation. We report here a series of chromium(III) superoxide complexes [L 2 Cr]M 2 O 2 (THF) y (L= - OSiPh 2 OSiPh 2 O - , M + =Li + , Na + , K + and y=4, 5), which could be accessed, studied spectroscopically and partly crystallized at low temperatures. They only differ in the two incorporated Lewis acidic alkali metal counterions (M + ) and it could thus be shown that the nature of M + determines considerably its interaction with the superoxide ligand. This interaction, in turn, has a significant influence on the stability and reactivity of these complexes towards substrates with OH groups. Furthermore, we show that stability and reactivity are also highly solvent dependent (THF versus nitriles), as donor solvents coordinate to the alkali metal ions and thus also influence their interaction with the superoxide moiety. Altogether, these results provide a comprehensive and detailed picture concerning the correlation between spectroscopic properties, structure, and behavior of such superoxides, that may be exemplary for other systems., (© 2019 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Dialkyl phthalates are plasticizers used in household products made from polyvinyl chloride (PVC). Diisononyl phthalate (DINP) is the principal phthalate in soft plastic toys. Because DINP is not tightly bound to PVC, it may be released when children mouth PVC products. The potential chronic health risks of phthalate exposure to infants have been under scrutiny by regulatory agencies in Europe, Canada, Japan, and the U.S. This report describes a risk assessment of DINP exposure from children's products, by the U.S. Consumer Product Safety Commission (CPSC) staff. This report includes the findings of a CPSC Chronic Hazard Advisory Panel (CHAP) which: (1) concluded that DINP is unlikely to present a human cancer hazard and (2) recommended an acceptable daily intake (ADI) level of 120 microg/kg-d, based on spongiosis hepatis in rats. The risk assessment incorporates new measurements of DINP migration rates from 24 toys and a new observational study of children's mouthing activities, with a detailed characterization of the objects mouthed. Probabilistic methods were used to estimate exposure. Mouthing behavior and, thus, exposure depend on the child's age. Approximately 42% of tested soft plastic toys contained DINP. Estimated DINP exposures for soft plastic toys were greatest among children 12-23 months old. The mean exposure for this age group was 0.08 (95% confidence interval 0.04-0.14) microg/kg-d, with a 99th percentile of 2.4 (1.3-3.2) microg/kg-d. The authors conclude that oral exposure to DINP from mouthing soft plastic toys is not likely to present a health hazard to children. The opinions expressed by the authors have not been reviewed or approved by, and do not necessarily reflect the views of, the U.S. Consumer Product Safety Commission. Because this material was prepared by the authors in their official capacity, it is in the public domain and may be freely copied or reprinted.

N-Nitrosamines and precursors are present in rubber products in which the accelerators and stabilizers used in the vulcanization process were derived from dialkylamines. Research was performed to develop data concerning the presence of N-nitrosamines and precursors so that the health significance of the exposure problem related to infant ingestion of these chemicals could be properly assessed. Volatile N-nitrosamines were determined in cut-up pacifier nipples by extraction with dichloromethane followed by concentration in a Kuderna-Danish evaporator, high-temperature mineral oil purge and trap, and analysis by gas chromatography--thermal energy analysis (GC-TEA). N-nitrosodibutylamine (NDBA) was the principal N-nitrosamine found, with concentrations up to 427 ppb. N-Nitrosamines and precursors in cut-up and intact nipples were determined by GC-TEA after a single extraction with artificial saliva. NDBA was the principal nitrosamine found, at levels up to 1040 ppb, while dibutylamine (DBA) was the principal precursor found, at levels up to 3890 ppb. The persistence of these compounds in intact nipples was determined by multiple artificial saliva extractions. Amounts of NDBA and DBA found after 15 artificial saliva extractions of intact pacifier nipples totalled 824 ppb and 15.6 ppm, respectively. N-Nitrosamine levels generally showed a gradual decrease in concentration with each extraction, whereas no consistent trend could be determined for concentrations of precursors.

Volatile N-nitrosamines in infant latex rubber pacifiers were determined using a modification of a previously described dichloromethane extraction procedure, followed by gas chromatography/thermal energy analysis. Under an interagency agreement between the National Center for Toxicological Research and the Consumer Product Safety Commission (CPSC), data were obtained on the baseline and compliance concentrations of volatile N-nitrosamines in infant pacifiers sold in the United States. Pacifiers made by 18 different manufacturers before and after the January 1, 1984 action level of 60 ppb was set by the CPSC were analyzed for volatile N-nitrosamines. N-Nitrosodibutylamine was the principal N-nitrosamine found, along with trace amounts of N-nitrosodimethylamine, N-nitrosodiethylamine, and N-nitrosopiperidine. Mean total volatile N-nitrosamine levels for baseline and compliance samples were 63.9 and 21.2 ppb, respectively. The pacifier lots sampled after January 1, 1984 showed a significant decrease in contamination levels, indicating that at least 98% of the market share is in compliance with the CPSC enforcement policy for N-nitrosamines in infant pacifiers sold in the United States.