5,712 research outputs found
Endoscopic laser-ablation for the treatment of orthotopic and ectopic ureteroceles in dogs: 13 cases (2008-2017).
BACKGROUND: Ureteroceles are a rare condition in dogs in which conventional treatments can result in substantial morbidity. Cystoscopic and fluoroscopic-guided laser ablation (CLA) of ureteroceles can successfully relieve obstruction.
OBJECTIVES: To describe the technique and outcomes of attempting CLA for treatment of ureteroceles in dogs.
ANIMALS: Thirteen client-owned dogs that underwent CLA for treatment of ureteroceles.
METHODS: Retrospective multicentered study. Medical records were reviewed in all dogs that underwent CLA for ureterocele(s). A laser was used to extend the opening of the ureteral orifice (UO) unless surgical conversion was necessary. Data collected included signalment, clinicopathologic data, imaging, procedural findings, complications, and short- and long-term outcome.
RESULTS: Thirteen dogs with 13 ureteroceles associated with 14 UOs resulting in ureteral obstruction were included. One ureterocele extended bilaterally. Treatment was initiated via retrograde cystoscopy (7 females), percutaneous perineal urethrocystoscopy (4 males), or percutaneous antegrade cystoscopy (2 males). Surgical conversion was necessary in 2 males. Ten of 14 (71%) UOs associated with the ureteroceles were ectopic. Thirteen of 14 had stenotic or imperforate UOs. No postoperative complications were noted. Preoperative incontinence or pollakiuria was present in 9 of 13 and 3 of 13 dogs and resolved in 8 of 9 and 3 of 3 dogs, respectively. Follow-up imaging showed resolution of all ureteroceles and improved ureteral/renal pelvic dilatation. Median follow-up time was 27âmonths (range, 3-96âmonths).
CONCLUSIONS AND CLINICAL IMPORTANCE: Cystoscopic-guided laser ablation was effective for the treatment of ureteroceles(s) in 11 of 13 dogs
Relationship between plasma fibroblast growth factor-23 concentration and survival time in cats with chronic kidney disease
BACKGROUND: Fibroblast growth factorâ23 (FGFâ23) and parathyroid hormone (PTH) are commonly increased in cats with azotemic chronic kidney disease (CKD). Both are predictors of survival time in human patients, but these relationships have not previously been examined in the cat. OBJECTIVES: To investigate the relationship between plasma FGFâ23 and PTH concentrations at diagnosis of CKD in cats with survival time and with disease progression over 12 months. ANIMALS: 214 azotemic, clientâowned cats (â„9 years). METHODS: Retrospective study: Biochemical and urinary variables at diagnosis of azotemic CKD, including plasma FGFâ23 and PTH concentrations were assessed as predictors of survival time (allâcause mortality) using Cox regression, and as predictors of CKD progression over 12 months using logistic regression. RESULTS: In the final multivariable Cox regression model, survival was negatively associated with plasma creatinine (P = .002) and FGFâ23 concentrations (P = .014), urine proteinâtoâcreatinine ratio (P < .001) and age (P < .001). Survival was positively associated with PCV (P = .004). In the final multivariable logistic regression model, independent predictors of CKD progression included logFGFâ23 and age. Neither plasma phosphate nor PTH was found to be an independent predictor of survival time or of CKD progression. CONCLUSIONS AND CLINICAL IMPORTANCE: Plasma FGFâ23 concentration is a novel prognostic indicator in cats with CKD, independent of other factors including plasma creatinine and phosphate concentrations. Further work is required to assess if FGFâ23 contributes directly to CKD progression, but regardless these findings may make FGFâ23 a useful biomarker for predicting poorer outcomes in cats with CKD
Evidence for a core-shell structure of hydrothermal carbon
Hydrothermal carbonisation (HTC) has been demonstrated to be a sustainable thermochemical process, capable of producing functionalised carbon materials for a wide range of applications. In order to better apply such materials, the local chemistry and reaction pathways governing hydrothermal carbon growth must be understood. We report the use of scanning transmission X-ray microscopy (STXM) to observe chemical changes in the functionality of carbon between the interface and bulk regions of HTC. Spatially-resolved, element-specific X-ray photo-absorption spectra show the presence of differing local carbon chemistry between bulk âcoreâ and interface âshellâ regions of a glucose-derived hydrothermal carbon spherule. STXM provides direct evidence to suggest that mechanistic pathways differ between the core and shell of the hydrothermal carbon. In the shell region, at the water-carbon interface, more aldehyde and/or carboxylic species are suspected to provide a reactive interface for bridging reactions to occur with local furan-based monomers. In contrast, condensation reactions appear to dominate in the core, removing aryl-linking units between polyfuranic domains. The application of STXM to HTC presents opportunities for a more comprehensive understanding of the spatial distribution of carbon species within hydrothermal carbon, especially at the solvent-carbon interface
On hypercharge flux and exotics in F-theory GUTs
We study SU(5) Grand Unified Theories within a local framework in F-theory
with multiple extra U(1) symmetries arising from a small monodromy group. The
use of hypercharge flux for doublet-triplet splitting implies massless exotics
in the spectrum that are protected from obtaining a mass by the U(1)
symmetries. We find that lifting the exotics by giving vacuum expectation
values to some GUT singlets spontaneously breaks all the U(1) symmetries which
implies that proton decay operators are induced. If we impose an additional
R-parity symmetry by hand we find all the exotics can be lifted while proton
decay operators are still forbidden. These models can retain the gauge coupling
unification accuracy of the MSSM at 1-loop. For models where the generations
are distributed across multiple curves we also present a motivation for the
quark-lepton mass splittings at the GUT scale based on a Froggatt-Nielsen
approach to flavour.Comment: 38 pages; v2: emphasised possibility of avoiding exotics in models
without a global E8 structure, added ref, journal versio
Wavefunctions and the Point of E8 in F-theory
In F-theory GUTs interactions between fields are typically localised at
points of enhanced symmetry in the internal dimensions implying that the
coefficient of the associated operator can be studied using a local
wavefunctions overlap calculation. Some F-theory SU(5) GUT theories may exhibit
a maximum symmetry enhancement at a point to E8, and in this case all the
operators of the theory can be associated to the same point. We take initial
steps towards the study of operators in such theories. We calculate
wavefunctions and their overlaps around a general point of enhancement and
establish constraints on the local form of the fluxes. We then apply the
general results to a simple model at a point of E8 enhancement and calculate
some example operators such as Yukawa couplings and dimension-five couplings
that can lead to proton decay.Comment: 46 page
Lifshitz black holes in string theory
We provide the first black hole solutions with Lifshitz asymptotics found in
string theory. These are expected to be dual to models enjoying anisotropic
scale invariance with dynamical exponent z=2 at finite temperature. We employ a
consistent truncation of type IIB supergravity to four dimensions with an
arbitrary 5-dimensional Einstein manifold times a circle as internal geometry.
New interesting features are found that significantly differ from previous
results in phenomenological models. In particular, small black holes are shown
to be thermodynamically unstable, analogously to the usual AdS-Schwarzschild
black holes, and extremality is never reached. This signals a possible
Hawking-Page like phase transition at low temperatures.Comment: 19 pages, 7 figures. v2 references adde
Ex vivo characterization of neuroinflammatory and neuroreceptor changes during epileptogenesis using candidate positron emission tomography biomarkers
Objective:
Identification of patients at risk of developing epilepsy before the first spontaneous seizure may promote the development of preventive treatment providing opportunity to stop or slow down the disease. //
Methods:
As development of novel radiotracers and onâsite setup of existing radiotracers is highly timeâconsuming and expensive, we used dualâcentre in vitro autoradiography as an approach to characterize the potential of innovative radiotracers in the context of epilepsy development. Using brain slices from the same group of rats, we aimed to characterise the evolution of neuroinflammation and expression of inhibitory and excitatory neuroreceptors during epileptogenesis using translational positron emission tomography (PET) tracers; 18Fâflumazenil (18FâFMZ; GABAA receptor), 18FâFPEB (metabotropic glutamate receptor 5; mGluR5), 18Fâflutriciclamide (translocator protein; TSPO, microglia activation) and 18Fâdeprenyl (monoamine oxidase B, astroglia activation). Autoradiography images from selected time points after pilocarpineâinduced status epilepticus (SE; baseline, 24 and 48 hours, 5, 10 and 15 days and 6 and 12â14 weeks after SE) were normalized to a calibration curve, coâregistered to an MRIâbased 2D regionâofâinterest atlas, and activity concentration (Bq/mm2) was calculated. //
Results:
In epileptogenesisâassociated brain regions, 18FâFMZ and 18FâFPEB showed an early decrease after SE. 18FâFMZ decrease was maintained in the latent phase and further reduced in the chronic epileptic animals, while 18FâFPEB signal recovered from day 10, reaching baseline levels in chronic epilepsy. 18Fâflutriciclamide showed an increase of activated microglia at 24 hours after SE, peaking at 5â15 days and decreasing during the chronic phase. On the other hand, 18Fâdeprenyl autoradiography showed late astrogliosis, peaking in the chronic phase. //
Significance:
Autoradiography revealed different evolution of the selected targets during epileptogenesis. Our results suggest an advantage of combined imaging of interârelated targets like glutamate and GABAA receptors, or microglia and astrocyte activation, in order to identify important interactions, especially when using PET imaging for the evaluation of novel treatments
Molecular Variation at a Candidate Gene Implicated in the Regulation of Fire Ant Social Behavior
The fire ant Solenopsis invicta and its close relatives display an important social polymorphism involving differences in colony queen number. Colonies are headed by either a single reproductive queen (monogyne form) or multiple queens (polygyne form). This variation in social organization is associated with variation at the gene Gp-9, with monogyne colonies harboring only B-like allelic variants and polygyne colonies always containing b-like variants as well. We describe naturally occurring variation at Gp-9 in fire ants based on 185 full-length sequences, 136 of which were obtained from S. invicta collected over much of its native range. While there is little overall differentiation between most of the numerous alleles observed, a surprising amount is found in the coding regions of the gene, with such substitutions usually causing amino acid replacements. This elevated coding-region variation may result from a lack of negative selection acting to constrain amino acid replacements over much of the protein, different mutation rates or biases in coding and non-coding sequences, negative selection acting with greater strength on non-coding than coding regions, and/or positive selection acting on the protein. Formal selection analyses provide evidence that the latter force played an important role in the basal b-like lineages coincident with the emergence of polygyny. While our data set reveals considerable paraphyly and polyphyly of S. invicta sequences with respect to those of other fire ant species, the b-like alleles of the socially polymorphic species are monophyletic. An expanded analysis of colonies containing alleles of this clade confirmed the invariant link between their presence and expression of polygyny. Finally, our discovery of several unique alleles bearing various combinations of b-like and B-like codons allows us to conclude that no single b-like residue is completely predictive of polygyne behavior and, thus, potentially causally involved in its expression. Rather, all three typical b-like residues appear to be necessary
mRNA profiling of the cancer degradome in oesophago-gastric adenocarcinoma.
BACKGROUND: Degradation of the extracellular matrix is fundamental to tumour development, invasion and metastasis. Several protease families have been implicated in the development of a broad range of tumour types, including oesophago-gastric (OG) adenocarcinoma. The aim of this study was to analyse the expression levels of all core members of the cancer degradome in OG adenocarcinoma and to investigate the relationship between expression levels and tumour/patient variables associated with poor prognosis. METHODS: Comprehensive expression profiling of the protease families (matrix metalloproteinases (MMPs), members of the ADAM metalloproteinase-disintegrin family (ADAMs)), their inhibitors (tissue inhibitors of metalloproteinase), and molecules involved in the c-Met signalling pathway, was performed using quantitative real-time reverse transcription polymerase chain reaction in a cohort of matched malignant and benign peri-tumoural OG tissue (n=25 patients). Data were analysed with respect to clinico-pathological variables (tumour stage and grade, age, sex and pre-operative plasma C-reactive protein level). RESULTS: Gene expression of MMP1, 3, 7, 9, 10, 11, 12, 16 and 24 was upregulated by factors >4-fold in OG adenocarcinoma samples compared with matched benign tissue (P<0.01). Expression of ADAM8 and ADAM15 correlated significantly with tumour stage (P=0.048 and P=0.044), and ADAM12 expression correlated with tumour grade (P=0.011). CONCLUSION: This study represents the first comprehensive quantitative analysis of the expression of proteases and their inhibitors in human OG adenocarcinoma. These findings implicate elevated ADAM8, 12 and 15 mRNA expression as potential prognostic molecular markers
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