Gas-phase H/D exchange reactions of polyamine complexes: (M + H)+, (M + alkali metal+), and (M + 2H)2+

AbstractGas-phase hydrogen/deuterium exchange reactions between noncovalent polyamine complexes and D2O, CH3OD, or ND3 are undertaken in a quadrupole ion trap mass spectrometer. Structural features of the protonated polyamines can be differentiated by the rates and overall extent of exchange, specifically the presence of propylene units and/or a cyclic structure noticeably decreases exchange compared to the exchange observed for acyclic polyamines with only ethylene bridges between amino groups. Significant differences are observed for singly protonated vs. doubly protonated complexes, where the doubly protonated complexes undergo more efficient exchange at a higher rate than the analogous singly protonated complexes. Molecular modeling calculations suggest that more diffuse conformations may exist for the higher charge states, thus facilitating H/D exchange. In addition, H/D exchange reactions between the alkali metal cationized complexes and ND3 are nearly quenched, compared to the significant exchange seen for singly protonated complexes. A conformational change or the loss of a low energy reaction pathway may explain the limited exchange reactions seen when a bulky cation replaces a proton in the complex

Gas-phase complexation of polyethers with halide ions

AbstractGas-phase complexes of halide anions with a variety of crown ethers and acyclic analogs are formed by ion-molecule reactions in the chemical ionization source of a triple-quadrupole mass spectrometer. The ether complexes of iodide, bromide, and chloride dissociate on collisional activation by cleavage of the halide-ether electrostatic hydrogen bonds, resulting in the formation of bare halide anions. By contrast, the fluoride complexes dissociate by loss of HF, which may occur in conjunction or sequentially with losses of ethylene oxide units. This dissociation of behavior is similar to that observed for collisionally activated dissociation of [M — H]− ions of the crown ethers and suggests that the fluoride ion is capable of promoting an intramolecular proton abstraction within the [M + F]− complex. This type of dissociation chemistry is only observed for the fluoride ion complexes, and the fluoride ion is the most basic of all the halides. The kinetic method was used to establish orders of relative halide binding strengths, and the trends for the chloride and bromide affinities were 12-crown-4 < triethylene glycol dimethyl ether < 15-crown-5 < tetraethylene glycol dimethyl ether < 18-crown-6 < 21-crown-7 < tetraethylene glycol < pentaethylene glycol < 1,4,7,10,13-pentathiacyclopentadecane

Effects of functional group interactions on the bimolecular and dissociation reactions of diols

AbstractThe influence of functional group interactions on the bimolecular and dissociation reactions of diols were examined in a quadrupole ion trap mass spectrometer. Reactions of dimethyl ether ions with diols resulted in formation of (M + H)+ ions and (M + 13)+ ions (by net methyne additin). The product distribution depended on the relative separation of the hydroxyl groups within each diol, with the more proximate diols producing the greatest abundance of (M + 13)+ ions compared to (M + H)+ ions. The enhancement of the formation of (M + 13)+ ions is attributed to the capability for electrostatic interactions between the hydroxyl groups and the electropositive methylene group of the methoxymethylene reagent ion. The enhancement is most significant for diols that can adopt five- or to a lesser extent six-membered ring transition states (i.e., any 1,2 or 1,3 diol). Collision-activated dissociation (CAD) techniques, including both sequential activation experiments (MSn) and comparison of CAD spectra for model compounds, suggest that the (M + 13)+ ions are protonated cyclic diethers

Threshold dissociation and molecular modeling of transition metal complexes of flavonoids

The relative threshold dissociation energies of a series of flavonoid/transition metal/auxiliary ligand complexes of the type [MII (flavonoid − H) auxiliary ligand]+ formed by electrospray ionization (ESI) were measured by energy-variable collisionally activated dissociation (CAD) in a quadrupole ion trap (QIT). For each of the isomeric flavonoid diglycoside pairs, the rutinoside (with a 1–6 inter-saccharide linkage) requires a greater CAD energy and thus has a higher dissociation threshold than its neohesperidoside (with a 1–2 inter-saccharide linkage) isomer. Likewise, the threshold energies of complexes containing flavones are higher than those containing flavanones. The monoglycoside isomers also have characteristic threshold energies. The flavonoids that are glycosylated at the 3-O- position tend to have lower threshold energies than those glycosylated at the 7-O- or 4′-O- position, and those that are C- bonded have lower threshold energies than the O- bonded isomers. The structural features that substantially influence the threshold energies include the aglycon type (flavanone versus flavone), the type of disaccharide (rutinose versus neohesperidose), and the linkage type (O- bonded versus C- bonded). Various computational means were applied to probe the structures and conformations of the complexes and to rationalize the differences in threshold energies of isomeric flavonoids. The most favorable coordination geometry of the complexes has a plane-angle of about 62°, which means that the deprotonated flavonoid and 2,2′-bipyridine within a complex do not reside on the same plane. Stable conformations of five cobalt complexes and five deprotonated flavonoids were identified. The conformations were combined with the point charges and helium accessible surface areas to explain qualitatively the differences in threshold energies for isomeric flavonoids

Epidemiology of diabetes mellitus among 193,435 cats attending primary-care veterinary practices in England

BACKGROUND: Diabetes mellitus (DM) is a common endocrine disease of cats. The prevalence of DM in cats in England is not well‐defined. HYPOTHESIS/OBJECTIVES: To estimate the prevalence and identify risk factors for DM in a large population of cats attending primary‐care practices. ANIMALS: A cohort of 193,563 cats in the VetCompass Programme attending 118 primary‐care practices in England. METHODS: Cross‐sectional analysis of cohort clinical data. Data were extracted covering September 1st 2009 and August 31st 2014. Period prevalence of DM was calculated. Associations between risk factors and DM were assessed using logistic regression modelling. RESULTS: Of 1,128 DM cases were identified among 194,563 cats (period prevalence 0.58%; 95% confidence interval [CI] 0.54–0.61). Multivariable modelling indicated that Tonkinese (OR 4.1; 95% CI 1.8–9.6; P = .001), Norwegian Forest (odds ratio [OR] 3.5; 95% CI 1.3–9.6; P = .001) and Burmese (OR 3.0; 95% CI 2.0–4.4; P < .001) cats had increased odds of DM compared with crossbred cats. DM odds increased as bodyweight categories increased above 4 kg (P < .001), as cats aged beyond 6 years old (P < .001) and in insured cats (OR 2.0; 95% CI 1.6–2.4; P < .001) but sex was not significantly associated with DM. CONCLUSIONS AND CLINICAL IMPORTANCE: Diabetes mellitus is an important component of the primary‐care practice caseload with 1‐in‐200 cats affected. An increased risk of DM in certain cat breeds supports a genetic predisposition. These results can guide future research and preventative healthcare

Prevalence and risk factors for mast cell tumours in dogs in England

BACKGROUND: Mast cell tumour (MCT) appears to be a frequent tumour type in dogs, though there is little published in relation to its frequency in dogs in the UK. The current study aimed to investigate prevalence and risk factors for MCTs in dogs attending English primary-care veterinary practices. METHODS: Electronic patient records from practices participating in the VetCompass animal surveillance project between July 2007 and June 2013 were searched for MCT diagnosis. Various search terms and standard diagnostic terms (VeNom codes) identified records containing MCT diagnoses, which were evaluated against clinical criteria for inclusion to the study. MCT prevalence for the entire dataset and specific breed types were calculated. Descriptive statistics characterised MCT cases and multivariable logistic regression methods evaluated risk factors for association with MCT (P < 0.05). RESULTS: Within a population of 168,636 dogs, 453 had MCT, yielding a prevalence of 0.27% (95% confidence interval (CI) 0.24% - 0.29%). The highest breed type specific prevalences were for the Boxer at 1.95% (95% CI 1.40% - 2.51%), Golden Retriever at 1.39% (0.98% - 1.81%) and Weimaraner at 0.85% (95% CI 0.17% to 1.53%). Age, insurance status, neuter status, weight and breed type were associated with MCT diagnosis. Of dogs of specific breed type, the Boxer, Pug and Staffordshire Bull Terrier showed greater odds of MCT diagnosis compared with crossbred dogs. Conversely, the German Shepherd Dog, Border Collie, West Highland White Terrier, Springer Spaniel and Cocker Spaniel had reduced odds of MCT diagnosis compared with crossbred dogs. No association was found between MCT diagnosis and sex. CLINICAL SIGNIFICANCE: This study highlights a clinically significant prevalence of MCT and identifies specific breed types with predisposition to MCT, potentially aiding veterinarian awareness and facilitating diagnosis

Epidemiology of recurrent seizure disorders and epilepsy in cats under primary veterinary care in the United Kingdom

Background Little epidemiological evaluation of recurrent seizure disorders in cats currently exists in veterinary literature. Objectives To report the prevalence and risk factors for recurrent seizure disorders (RSD) and epilepsy in cats presented to primary care veterinary practices in the United Kingdom (UK). Animals A total of 285 547 cats under veterinary care during 2013 presenting to 282 primary care clinics in the UK. Methods Cohort study using multivariable logistic regression modeling for risk factor analysis. Results There were 458 confirmed RSD cases, giving a 1‐year period prevalence of 0.16% (95% confidence interval [CI], 0.15‐0.18). A subset of 114 (24.89%) cases was recorded as having epilepsy, giving a 1‐year period prevalence of 0.04% (95% CI, 0.03‐0.5). Increasing age was significantly associated with increasing odds of RSD. Breed, sex, neuter status, and body weight were not associated with RSD. Epilepsy was most frequently diagnosed in adult to middle‐aged cats. Cats aged 3.0 to <6.0 years had 3.32 times higher odds of epilepsy diagnosis compared to cats <3.0 years of age. Insured cats were more likely to be diagnosed with epilepsy compared to noninsured cats. Conclusions and Clinical Importance Although less common than in dogs, RSD and epilepsy still comprise an important disorder group in the UK cat population. Aging is a significant risk factor for these disorders in cats

Photodissociation of Non-Covalent Peptide-Crown Ether Complexes

Highly chromogenic 18-crown-6-dipyrrolylquinoxaline coordinates primary amines of peptides, forming non-covalent complexes that can be transferred to the gas-phase by electrospray ionization. The appended chromogenic crown ether facilitates efficient energy transfer to the peptide upon ultraviolet irradiation in the gas phase, resulting in diagnostic peptide fragmentation. Collisional-activated dissociation and infrared multiphoton dissociation of these non-covalent complexes result only in their disassembly with the charge retained on either the peptide or crown ether, yielding no sequence ions. Upon UV photon absorption the intermolecular energy transfer is facilitated by the fast activation timescale of ultraviolet photodissociation (<10 ns) and by the collectively strong hydrogen bonding between the crown ether and peptide, thus allowing effective transfer of energy to the peptide moiety before disruption of the intermolecular hydrogen bonds

VetCompass Australia: A National Big Data Collection System for Veterinary Science

VetCompass Australia is veterinary medical records-based research coordinated with the global VetCompass endeavor to maximize its quality and effectiveness for Australian companion animals (cats, dogs, and horses). Bringing together all seven Australian veterinary schools, it is the first nationwide surveillance system collating clinical records on companion-animal diseases and treatments. VetCompass data service collects and aggregates real-time, clinical records for researchers to interrogate, delivering sustainable and cost-effective access to data from hundreds of veterinary practitioners nationwide. Analysis of these clinical records will reveal geographical and temporal trends in the prevalence of inherited and acquired diseases, identify frequently prescribed treatments, revolutionize clinical auditing, help the veterinary profession to rank research priorities, and assure evidence-based companion-animal curricula in veterinary schools. VetCompass Australia will progress in three phases: (1) roll-out of the VetCompass platform to harvest Australian veterinary clinical record data; (2) development and enrichment of the coding (data-presentation) platform; and (3) creation of a world-first, real-time surveillance interface with natural language processing (NLP) technology. The first of these three phases is described in the current article. Advances in the collection and sharing of records from numerous practices will enable veterinary professionals to deliver a vastly improved level of care for companion animals that will improve their quality of life

Development and internal validation of a prediction tool to aid the diagnosis of Cushing's syndrome in dogs attending primary-care practice.

Novel methods to aid identification of dogs with spontaneous Cushing's syndrome are warranted to optimize case selection for diagnostics, avoid unnecessary testing, and ultimately aid decision-making for veterinarians. To develop and internally validate a prediction tool for dogs receiving a diagnosis of Cushing's syndrome using primary-care electronic health records. Three hundred and ninety-eight dogs diagnosed with Cushing's syndrome and 541 noncase dogs, tested for but not diagnosed with Cushing's syndrome, from a cohort of 905 544 dogs attending VetCompass participating practices. A cross-sectional study design was performed. A prediction model was developed using multivariable binary logistic regression taking the demography, presenting clinical signs and some routine laboratory results into consideration. Predictive performance of each model was assessed and internally validated through bootstrap resampling. A novel clinical prediction tool was developed from the final model. The final model included predictor variables sex, age, breed, polydipsia, vomiting, potbelly/hepatomegaly, alopecia, pruritus, alkaline phosphatase, and urine specific gravity. The model demonstrated good discrimination (area under the receiver operating curve [AUROC] = 0.78 [95% CI = 0.75-0.81]; optimism-adjusted AUROC = 0.76) and calibration (C-slope = 0.86). A tool was developed from the model which calculates the predicted likelihood of a dog having Cushing's syndrome from 0% (score = -13) to 96% (score = 10). A tool to predict a diagnosis of Cushing's syndrome at the point of first suspicion in dogs was developed, with good predictive performance. This tool can be used in practice to support decision-making and increase confidence in diagnosis. [Abstract copyright: © 2020 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.