Retrospective analysis of the use of tranexamic acid in critically ill dogs and cats (2018-2019): 266 dogs and 28 cats.

OBJECTIVE: To describe the signalment, dosing, adverse events, and patient diagnosis for dogs and cats admitted to the critical care unit (CCU) receiving tranexamic acid (TXA). DESIGN: Case series from 2018 to 2019. SETTING: Private referral and primary care veterinary hospital. ANIMALS: Two hundred and sixty-six dogs and 28 cats. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: Records of dogs and cats admitted to the CCU that received TXA were evaluated. A diagnosis was assigned to each patient based on the International Statistical Classification of Diseases system. "Neoplasia" ([most frequently] hemangiosarcoma) (89/226 [39%]) and "diseases of the blood and blood forming organs" (idiopathic hemoabdomen, pericardial effusion) (78/226 [34%]) were the most common disease processes for which dogs received TXA. In cats, "diseases of the blood and blood forming organs" (idiopathic hemoabdomen) (9/28 [32%]), "neoplasia" (hemangiosarcoma, mast cell tumor, carcinoma) (7/28 [25%]), and "injury, poisoning, or certain other consequences of external causes" (high-rise syndrome) (5/28 [17%]) were most common. One hundred and forty-eight dogs (65%) and 13 cats (46%) underwent an invasive procedure during hospitalization. Thirty percent (70/226) of dogs received a packed RBC (pRBC) transfusion. Administration of TXA before or after pRBC transfusion did not significantly affect median dose of pRBC administered (P = 0.808). The median IV dose of TXA was similar for dogs and cats at 10 mg/kg. One cat received a 10 times overdose of TXA and did not suffer any appreciable adverse effects. Adverse events were reported in 1.7% (4/226) of dogs including hypersalivation (3/226) and seizure (1/226) in a dog that received a cumulative dose of 280 mg/kg of TXA. Hypersalivation was the only adverse event reported in 3% (1/28) of cats. CONCLUSION: TXA is primarily utilized in critically ill dogs and cats diagnosed with neoplasia, bleeding disorders, and trauma at this institution. Adverse events were infrequent and largely mild.

Medical complications of obesity: heightened importance in a COVID era.

BACKGROUND: Obesity is a major public health problem associated with significant medical complications. MAIN BODY: This review examines 8 primary diseases: type 2 diabetes, hypertension, dementia, non-alcoholic fatty liver disease, polycystic ovarian syndrome, dyslipidemia, cancer, and their manifestations in obese patients. A total of 39 articles were used for this review. The authors conducted limited review, searching PubMed and Google Scholar databases using a combination of key words "COVID-19" or "SARS-COV2", "type 2 diabetes", "hypertension", "dementia", "non-alcoholic fatty liver disease", "polycystic ovarian syndrome", "dyslipidemia", "cancer", and "obesity". No specific date limitation was used. Obesity exacerbates many medical conditions and has recently been identified as an independent risk factor for COVID-19 severity. This sets obesity at the pinnacle of all disease complications. The long-term impact of obesity ranges from financial burden on the health system, lower life expectancy, and reduced survival rates. CONCLUSION: Obesity is an important modifiable risk factor. There is the need for healthcare providers to understand the medical complications associated with obesity to optimize patient care.

δ and φ back-donation in AnIV metallacycles.

In all known examples of metal-ligand (M-L) δ and φ bonds, the metal orbitals are aligned to the ligand orbitals in a "head-to-head" or "side-to-head" fashion. Here, we report two fundamentally new types of M-L δ and φ interactions; "head-to-side" δ and "side-to-side" φ back-bonding, found in complexes of metallacyclopropenes and metallacyclocumulenes of actinides (Pa-Pu) that makes them distinct from their corresponding Group 4 analogues. In addition to the known Th and U complexes, our calculations include complexes of Pa, Np, and Pu. In contrast with conventional An-C bond decreasing, due to the actinide contraction, the An-C distance increases from Pa to Pu. We demonstrate that the direct L-An σ and π donations combined with the An-L δ or φ back-donations are crucial in explaining this non-classical trend of the An-L bond lengths in both series, underscoring the significance of these δ/φ back-donation interactions, and their importance for complexes of Pa and U in particular.

Process Control and Energy Efficiency.

We review the impact of control systems and strategies on the energy efficiency of chemical processes. We show that, in many ways, good control performance is a necessary but not sufficient condition for energy efficiency. The direct effect of process control on energy efficiency is manyfold: Reducing output variability allows for operating chemical plants closer to their limits, where the energy/economic optima typically lie. Further, good control enables novel, transient operating strategies, such as conversion smoothing and demand response. Indirectly, control systems are key to the implementation and operation of more energy-efficient plant designs, as dictated by the process integration and intensification paradigms. These conclusions are supported with references to numerous examples from the literature.

Revisiting complexation thermodynamics of transplutonium elements up to einsteinium.

Literature casts einsteinium as a departure from earlier transplutonium actinides, with a decrease in stability constants with aminopolycarboxylate ligands. This report studies transplutonium chemistry - including Am, Bk, Cf, and Es - with aminopolycarboxylate ligands. Es complexation follows similar thermodynamic and structural trends established by the earlier actinides, consistent with first-principle calculations.

Competitive Interactions Within Cm(III) Solvation in Binary Water/Methanol Solutions.

Competitive forces exist in multicomponent solutions, and within electrolytes they consist of both ion-solvent and solvent-solvent interactions. These can influence a myriad of processes, including ligand complexation. In the case of water/alcohol solutions, recent work revealed an interesting dilemma regarding the overall solution dynamics and organization as compared to solute-solvent interactions. This is particularly true for highly charged ions in solution, whose ion-solvent interactions were demonstrated to be highly sensitive to the composition of the immediate solvation environment. Faster solvent exchange should be observed about the ion, considering that second-order Møller-Plesset perturbation theory predicts an average decrease in ion-solvent dissociation energy when methanol enters the first solvation shell of Cm3+(aq). Yet the addition of methanol to water causes the dynamic features of the hydrogen-bond network of the entire solution to slow. The apparent competition between these contrary forces was examined using a combination of electronic structure calculations with both ab initio and classical molecular dynamics simulations, using binary water/methanol solutions and Cm3+ as a representative solute. This combination of theoretical methods predicts that, among the competitive effects of the solvent-solvent and ion-solvent interactions, the solution-phase dynamics imparted by the addition of methanol to water kinetically restricts the solvation exchange rates about Cm3+ in these binary solutions.

Bond Covalency and Oxidation State of Actinide Ions Complexed with Therapeutic Chelating Agent 3,4,3-LI(1,2-HOPO).

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) is a promising agent for biological decorporation of radionuclides, and allows spectroscopic detection of many lanthanide (Ln) and actinide (An) species via sensitized luminescence. Despite the manifest uses of this ligand, the structural and thermodynamic properties of its complexes across the An series remain understudied. Theoretical investigations of the binding of An(III) and An(IV) ions, from actinium to einsteinium, by the 3,4,3-LI(1,2-HOPO) ligand, as well as experimental extended X-ray absorption fine structure (EXAFS) studies on the trivalent americium, curium, and californium complexes were employed to address the resulting structures, thermodynamic parameters, redox properties, and corresponding electronic configurations. An(IV) ions were found to form much stronger complexes than An(III) ions, consistent with experimental measurements. Complexation of both An(III) and An(IV) ions generally becomes more favorable for heavier actinides, reflecting increased energy degeneracy driven covalency and concomitant orbital mixing between the 5f orbitals of the An ions and the π orbitals of the ligand. Notably, the ability of this ligand to either accept or donate electron density as needed from its pyridine rings is found to be key to its extraordinary stability across the actinide series.

Spectroscopic and Computational Characterization of Diethylenetriaminepentaacetic Acid/Transplutonium Chelates: Evidencing Heterogeneity in the Heavy Actinide(III) Series.

The chemistry of trivalent transplutonium ions (Am3+ , Cm3+ , Bk3+ , Cf3+ , Es3+ …) is usually perceived as monotonic and paralleling that of the trivalent lanthanide series. Herein, we present the first extended X-ray absorption fine structure (EXAFS) study performed on a series of aqueous heavy actinide chelates, extending past Cm. The results obtained on diethylenetriaminepentaacetic acid (DTPA) complexes of trivalent Am, Cm, Bk, and Cf show a break to much shorter metal-oxygen nearest-neighbor bond lengths in the case of Cf3+ . Corroborating those results, density functional theory calculations, extended to Es3+ , suggest that the shorter Cf-O and Es-O bonds could arise from the departure of the coordinated water molecule and contraction of the ligand around the metal relative to the other [MIII DTPA(H2 O)]2- (M=Am, Cm, Bk) complexes. Taken together, these experimental and theoretical results demonstrate inhomogeneity within the trivalent transplutonium series that has been insinuated and debated in recent years, and that may also be leveraged for future nuclear waste reprocessing technologies.

Acceleration of metal-ligand complexation kinetics by electrospray ionization.

Electrospray ionization mass spectrometry (ESI-MS) is a valuable and frequently used analytical technique across nearly all branches of chemistry, and has recently seen increasing use in the study of metal-ligand solution equilibria. Despite its prevalence, the method by which ESI produces gas-phase ions from solutions containing metal-ligand complexes is not fully understood, with recent reports showing significant changes to solution equilibria during ESI analysis. This study examines perturbations to the formation kinetics of metal-ligand complexes during the ESI process, showing how quickly new equilibria - reflective of the ionization process and not solution - can be established. Electrospray ionization mass spectrometry (ESI-MS) and ion mobility spectrometry (IMS) are used to examine the well studied Lu-DOTA (1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetic acid) complexation reaction, with collision cross section modeling based on density functional theory (DFT) optimized structures used to aid in the interpretation of the ion mobility results. The electrospray process was found to significantly accelerate the formation kinetics, increasing the formation rate constant by more than an order of magnitude over its previously determined solution-phase value.

On the Origin of Covalent Bonding in Heavy Actinides.

Recent reports have suggested the late actinides participate in more covalent interactions than the earlier actinides, yet the origin of this shift in chemistry is not understood. This report considers the chemistry of actinide dipicolinate complexes to identify why covalent interactions become more prominent for heavy actinides. A modest increase in measured actinide:dipicolinate stability constants is coincident with a significant increase in An 5f energy degeneracy with the dipicolinate molecular orbitals for Bk and Cf relative to Am and Cm. While the interactions in the actinide-dipicolinate complex are largely ionic, the decrease in 5f orbital energy across the series manifests in orbital-mixing and, hence, covalency driven by energy degeneracy. This observation suggests the origin of covalency in heavy actinide interactions stems from the degeneracy of 5f orbitals with ligand molecular orbitals rather than spatial orbital overlap. These findings suggest that the limiting radial extension of the 5f orbitals later in the actinide series could make the heavy actinides ideal elements to probe and tune effects of energy degeneracy driven covalency.

Structural and Thermodynamic Properties of the Cm(III) Ion Solvated by Water and Methanol.

The geometric and electronic structures of the 9-coordinate Cm(3+) ion solvated with both water and methanol are systematically investigated in the gas phase at each possible solvent-shell composition and configuration using density functional theory and second-order Møller-Plesset perturbation theory. Ab initio molecular dynamics simulations are employed to assess the effects of second and third solvent shells on the gas-phase structure. The ion-solvent dissociation energy for methanol is greater than that of water, potentially because of increased charge donation to the ion made possible by the electron-rich methyl group. Further, the ion-solvent dissociation energy and the ion-solvent distance are shown to be dependent on the solvent-shell composition. This has implications for solvent exchange, which is generally the rate-limiting step in complexation reactions utilized in the separation of curium from complex metal mixtures that derive from the advanced nuclear fuel cycle.

Structure and Dynamics of NaCl Ion Pairing in Solutions of Water and Methanol.

Ion pairing can have profound effects upon the ionic strength of electrolyte solutions but is poorly understood in solutions containing more than one solvent. Herein a combined density functional theory and molecular dynamics approach is used to examine the effect of both methanol concentration and interionic distance upon the structure and dynamics within successive solvation shells of Na(+) and Cl(-) in water/methanol binary solutions. The structure and dynamics of the first and second solvation shells were studied along a reaction coordinate associated with ion pair formation using potential of mean force simulations. The lifetimes of the solvent-solvent hydrogen bonds become perturbed when the second solvation shells of the ions begin to interact. In contrast, the structural properties within the first and second solvation shells of the ions were found to be largely independent of both methanol concentration and interionic distance until a contact ion pair is formed. Thus, as the ions are brought together, the effect of the opposing ion manifests itself in the solvation dynamics before any structural changes are observed. As anticipated based upon the decreased dielectric constant of the binary solution, ion pair formation becomes energetically more favorable as the concentration of methanol increases.

Adsorption and release of surfactant into and from multifunctional zwitterionic poly(NIPAm-co-DMAPMA-co-AAc) microgel particles.

We synthesize monodispersed zwitterionic microgel (ZI-MG) particles that undergo an extensive, reversible change in volume in response to environmental stimuli such as pH and temperature. These aqueous ZI-MG dispersions exhibit a minimum hydrodynamic diameter value at an adjustable isoelectric point (IEP). In addition, the study elucidates the controlled uptake and release of ionic and nonionic surfactants from these particle systems. The extent of surfactant loading and the ensuing relative swelling/deswelling behaviors within the colloidal polymer networks are explained in terms of their binding interactions.

137Cs activities and 135Cs/137Cs isotopic ratios from soils at Idaho National Laboratory: a case study for contaminant source attribution in the vicinity of nuclear facilities.

Radiometric and mass spectrometric analyses of Cs contamination in the environment can reveal the location of Cs emission sources, release mechanisms, modes of transport, prediction of future contamination migration, and attribution of contamination to specific generator(s) and/or process(es). The Subsurface Disposal Area (SDA) at Idaho National Laboratory (INL) represents a complicated case study for demonstrating the current capabilities and limitations to environmental Cs analyses. (137)Cs distribution patterns, (135)Cs/(137)Cs isotope ratios, known Cs chemistry at this site, and historical records enable narrowing the list of possible emission sources and release events to a single source and event, with the SDA identified as the emission source and flood transport of material from within Pit 9 and Trench 48 as the primary release event. These data combined allow refining the possible number of waste generators from dozens to a single generator, with INL on-site research and reactor programs identified as the most likely waste generator. A discussion on the ultimate limitations to the information that (135)Cs/(137)Cs ratios alone can provide is presented and includes (1) uncertainties in the exact date of the fission event and (2) possibility of mixing between different Cs source terms (including nuclear weapons fallout and a source of interest).