Randomized phase III trial of piroxicam in combination with mitoxantrone or carboplatin for first-line treatment of urogenital tract transitional cell carcinoma in dogs.

BackgroundReported response rates of transitional cell carcinoma (TCC) in dogs to piroxicam in combination with either mitoxantrone or carboplatin are similar; however, it is unknown whether either drug might provide superior duration of response.Hypothesis/objectivesTo determine if the progression-free interval (PFI) of dogs with TCC treated with mitoxantrone and piroxicam was different than that of dogs receiving carboplatin and piroxicam. The hypothesis was that the efficacy of mitoxantrone is no different from carboplatin.AnimalsFifty dogs with TCC without azotemia.MethodsProspective open-label phase III randomized study. Either mitoxantrone or carboplatin was administered every 3 weeks concurrently with piroxicam with restaging at 6-week intervals. Twenty-four dogs received carboplatin and 26 received mitoxantrone.ResultsResponse was not different between groups (P = .56). None of the dogs showed complete response. In the mitoxantrone group, there were 2 (8%) partial responses (PR) and 18 (69%) dogs with stable disease (SD). In the carboplatin group, there were 3 PR (13%) and 13 (54%) dogs with SD. The PFI was not significantly different between groups (mitoxantrone = 106 days; carboplatin = 73.5 days; P = .62; hazard ratio 0.86; 95% confidence interval 0.47-1.56). Dogs with prostatic involvement experienced a shorter survival (median, 109 days) compared to dogs with urethral, trigonal, or apically located tumors; this difference was significant (median 300, 190, and 645 days, respectively; P = .005).Conclusions and clinical importanceThis study did not detect a different in outcome in dogs with TCC treated with either mitoxantrone or carboplatin in combination with piroxicam

Frequency and Severity of Neutropenia Associated with Food and Drug Administration Approved and Compounded Formulations of Lomustine in Dogs with Cancer.

BackgroundCompounded lomustine is used commonly in veterinary patients. However, the potential variability in these formulations is unknown and concern exists that compounded formulations of drugs may differ in potency from Food and Drug Administration (FDA)-approved products.Hypothesis/objectivesThe initial objective of this study was to evaluate the frequency and severity of neutropenia in dogs treated with compounded or FDA-approved formulations of lomustine. Subsequent analyses aimed to determine the potency of lomustine obtained from several compounding pharmacies.AnimalsThirty-seven dogs treated with FDA-approved or compounded lomustine.MethodsDogs that received compounded or FDA-approved lomustine and had pretreatment and nadir CBCs performed were eligible for inclusion. Variables assessed included lomustine dose, neutrophil counts, and severity of neutropenia. Lomustine 5 mg capsules from 5 compounding sources were tested for potency using high-pressure liquid chromatography (HPLC) with ultraviolet (UV) detection.ResultsTwenty-one dogs received FDA-approved lomustine and 16 dogs were treated with lomustine prescribed from a single compounding pharmacy. All dogs treated with FDA-approved lomustine were neutropenic after treatment; 15 dogs (71%) developed grade 3 or higher neutropenia. Four dogs (25%) given compounded lomustine became neutropenic, with 2 dogs (12.5%) developing grade 3 neutropenia. The potency of lomustine from 5 compounding pharmacies ranged from 50 to 115% of the labeled concentration, with 1 sample within ±10% of the labeled concentration.Conclusions and clinical importanceThese data support broader investigation into the potency and consistency of compounded chemotherapy drugs and highlight the potential need for greater oversight of these products

Bacterial urinary tract infections associated with transitional cell carcinoma in dogs.

BackgroundUrinary tract infections (UTI) are believed to be common in dogs with transitional cell carcinoma (TCC), but incidence and contributing factors have not been reported.ObjectivesTo determine the frequency and bacterial agents associated with UTI in dogs with TCC and define contributing factors.AnimalsEighty-five dogs with a history of urogenital TCC undergoing treatment with chemotherapy that had at least 1 urine culture performed.MethodsMedical records and culture results were retrospectively reviewed and ultrasound images were reviewed when available. Clinical factors were evaluated statistically for association with positive culture.ResultsFifty-five percent (47/85) of dogs had at least 1 positive culture during the course of treatment. Female dogs (80%, 40/50) were more likely than male dogs (29%, 10/35) to have at least 1 positive culture. Ultrasound examination determined that female dogs were more likely to have urethral (74%, 31/42) or trigonal tumor involvement (71%, 30/42) compared to male dogs (32%, 9/28 and 43%, 12/28, respectively). The most commonly isolated organisms were Staphylococcus spp. (23.9%, 29/121) and Escherichia coli (19.8%, 24/121). Dogs with urethral involvement of TCC were significantly more likely to have at least 1 positive culture than dogs without urethral involvement (75%, 30/40 versus 30%, 9/30).ConclusionsUrinary tract infection is common in dogs with TCC highlighting the importance of regular monitoring for bacterial cystitis in dogs with TCC. In addition, clinical factors such as tumor location and sex may be predictive of positive culture and can help clinicians assess the risk of UTI

Validity and reliability of the multidimensional health locus of control scale for college students

<p>Abstract</p> <p>Background</p> <p>The purpose of the present study was to assess the validity and reliability of Form A of Multidimensional Health Locus of Control scales in Iran. Health locus of control is one of the most widely measured parameters of health belief for the planning of health education programs.</p> <p>Methods</p> <p>496 university students participated in this study. The reliability coefficients were calculated in three different methods: test-retest, parallel forms and Cronbach alpha. In order to survey validity of the scale we used three methods including content validity, concurrent validity and construct validity.</p> <p>Results</p> <p>We established the content validity of the Persian translation by translating (and then back-translating) each item from the English version into the Persian version. The concurrent validity of the questionnaire, as measured by Levenson's IPC scale was .57 (P < .001), .49 (P < .01) and .53 (P < .001) for IPC, respectively. Exploratory principal components analysis supported a three-factor structure that items loading adequately on each factor. Moreover, the approximate orthogonal of the dimensions were obtained through correlation analyses. In addition, the reliability results were acceptable, too.</p> <p>Conclusion</p> <p>The results showed that the reliability and validity of Persian Form A of MHLC was acceptable and respectable and is suggested as an applicable criterion for similar studies in Iran.</p

High-Temperature Transport Properties of Yb4−xSmxSb3

Polycrystalline L4Sb3 (L = La, Ce, Sm, and Yb) and Yb4−x Sm x Sb3, which crystallizes in the anti-Th3P4 structure type (I-43d no. 220), were synthesized via high-temperature reaction. Structural and chemical characterization were performed by x-ray diffraction and electronic microscopy with energy-dispersive x-ray analysis. Pucks were densified by spark plasma sintering. Transport property measurements showed that these compounds are n-type with low Seebeck coefficients, except for Yb4Sb3, which shows semimetallic behavior with hole conduction above 523 K. By partially substituting Yb by a trivalent rare earth we successfully improved the thermoelectric figure of merit of Yb4Sb3 up to 0.7 at 1273 K

Developmentally Restricted Genetic Determinants of Human Arsenic Metabolism: Association between Urinary Methylated Arsenic and CYT19 Polymorphisms in Children

We report the results of a screen for genetic association with urinary arsenic metabolite levels in three arsenic metabolism candidate genes, PNP, GSTO, and CYT19, in 135 arsenic-exposed subjects from the Yaqui Valley in Sonora, Mexico, who were exposed to drinking water concentrations ranging from 5.5 to 43.3 ppb. We chose 23 polymorphic sites to test in the arsenic-exposed population. Initial phenotypes evaluated included the ratio of urinary inorganic arsenic(III) to inorganic arsenic(V) and the ratio of urinary dimethylarsenic(V) to monomethylarsenic(V) (D:M). In the initial association screening, three polymorphic sites in the CYT19 gene were significantly associated with D:M ratios in the total population. Subsequent analysis of this association revealed that the association signal for the entire population was actually caused by an extremely strong association in only the children (7–11 years of age) between CYT19 genotype and D:M levels. With children removed from the analysis, no significant genetic association was observed in adults (18–79 years). The existence of a strong, developmentally regulated genetic association between CYT19 and arsenic metabolism carries import for both arsenic pharmacogenetics and arsenic toxicology, as well as for public health and governmental regulatory officials

Defective extracellular matrix remodeling in brown adipose tissue is associated with fibro-inflammation and reduced diet-induced thermogenesis.

The relevance of extracellular matrix (ECM) remodeling is reported in white adipose tissue (AT) and obesity-related dysfunctions, but little is known about the importance of ECM remodeling in brown AT (BAT) function. Here, we show that a time course of high-fat diet (HFD) feeding progressively impairs diet-induced thermogenesis concomitantly with the development of fibro-inflammation in BAT. Higher markers of fibro-inflammation are associated with lower cold-induced BAT activity in humans. Similarly, when mice are housed at thermoneutrality, inactivated BAT features fibro-inflammation. We validate the pathophysiological relevance of BAT ECM remodeling in response to temperature challenges and HFD using a model of a primary defect in the collagen turnover mediated by partial ablation of the Pepd prolidase. Pepd-heterozygous mice display exacerbated dysfunction and BAT fibro-inflammation at thermoneutrality and in HFD. Our findings show the relevance of ECM remodeling in BAT activation and provide a mechanism for BAT dysfunction in obesity

Logopenic and nonfluent variants of primary progressive aphasia are differentiated by acoustic measures of speech production

Differentiation of logopenic (lvPPA) and nonfluent/agrammatic (nfvPPA) variants of Primary Progressive Aphasia is important yet remains challenging since it hinges on expert based evaluation of speech and language production. In this study acoustic measures of speech in conjunction with voxel-based morphometry were used to determine the success of the measures as an adjunct to diagnosis and to explore the neural basis of apraxia of speech in nfvPPA. Forty-one patients (21 lvPPA, 20 nfvPPA) were recruited from a consecutive sample with suspected frontotemporal dementia. Patients were diagnosed using the current gold-standard of expert perceptual judgment, based on presence/absence of particular speech features during speaking tasks. Seventeen healthy age-matched adults served as controls. MRI scans were available for 11 control and 37 PPA cases; 23 of the PPA cases underwent amyloid ligand PET imaging. Measures, corresponding to perceptual features of apraxia of speech, were periods of silence during reading and relative vowel duration and intensity in polysyllable word repetition. Discriminant function analyses revealed that a measure of relative vowel duration differentiated nfvPPA cases from both control and lvPPA cases (r2 = 0.47) with 88% agreement with expert judgment of presence of apraxia of speech in nfvPPA cases. VBM analysis showed that relative vowel duration covaried with grey matter intensity in areas critical for speech motor planning and programming: precentral gyrus, supplementary motor area and inferior frontal gyrus bilaterally, only affected in the nfvPPA group. This bilateral involvement of frontal speech networks in nfvPPA potentially affects access to compensatory mechanisms involving right hemisphere homologues. Measures of silences during reading also discriminated the PPA and control groups, but did not increase predictive accuracy. Findings suggest that a measure of relative vowel duration from of a polysyllable word repetition task may be sufficient for detecting most cases of apraxia of speech and distinguishing between nfvPPA and lvPPA

M5 spikes and operators in the HVZ membrane theory

In this note we study some aspects of the so-called dual ABJM theory introduced by Hanany, Vegh & Zaffaroni. We analyze the spectrum of chiral operators, and compare it with the spectrum of functions on the mesonic moduli space M=C^2\times C^2/Z_k, finding expected agreement for the coherent branch. A somewhat mysterious extra branch of dimension N^2 opens up at the orbifold fixed point. We also study BPS solutions which represent M2/M5 intersections. The mesonic moduli space suggests that there should be two versions of this spike: one where the M5 lives in the orbifolded C^2 and another where it lives in the unorbifolded one. While expectedly the first class turns out to be like the ABJM spike, the latter class looks like a collection of stacks of M5 branes with fuzzy S^3 profiles. This shows hints of the appearance of the global SO(4) at the non-abelian level which is otherwise not present in the bosonic potential. We also study the matching of SUGRA modes with operators in the coherent branch of the moduli space. As a byproduct, we present some formulae for the laplacian in conical CY_4 of the form C^n\times CY_{4-n}.Comment: 22 pages, 1 figure. Published version with corrected typos

Alternative tissue fixation for combined histopathological and molecular analysis in a clinically representative setting

Formalin is the principal tissue fixative used worldwide for clinical and research purposes. Despite optimal preservation of morphology, its preservation of DNA and RNA is poor. As clinical diagnostics increasingly incorporates molecular-based analysis, the requirement for maintaining nucleic acid quality is of increasing importance. Here we assess an alternative non-formalin-based tissue fixation method, PAXgene Tissue system, with the aim of better preserving nucleic acids, while maintaining the quality of the tissue to be used for vital existing diagnostic techniques. In this study, these criteria are assessed in a clinically representative setting. In total, 203 paired PAXgene Tissue and formalin-fixed samples were obtained. Blind-scored haematoxylin and eosin (H&E) sections showed comparable and acceptable staining. Immunohistochemistry (IHC) staining was suboptimal using existing protocols but improved with minor method adjustment and optimisation. Quality of DNA and RNA was significantly improved by PAXgene tissue fixation [RIN 2.8 versus 3.8 (p < 0.01), DIN 5.68 versus 6.77 (p < 0.001)], which translated into improved performance on qPCR assay. These results demonstrate the potential of PAXgene Tissue to be used routinely in place of formalin, maintaining adequate histological staining and significantly improving the preservation of biological molecules in the genomic era