Fenofibrate metabolism in the cynomolgus monkey using ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry-based metabolomics

Fenofibrate, widely used for the treatment of dyslipidemia, activates the nuclear receptor, peroxisome proliferator-activated receptor alpha. However, liver toxicity, including liver cancer, occurs in rodents treated with fibrate drugs. Marked species differences occur in response to fibrate drugs, especially between rodents and humans, the latter of which are resistant to fibrate-induced cancer. Fenofibrate metabolism, which also shows species differences, has not been fully determined in humans and surrogate primates. In the present study, the metabolism of fenofibrate was investigated in cynomolgus monkeys by ultraperformance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOFMS)-based metabolomics. Urine samples were collected before and after oral doses of fenofibrate. The samples were analyzed in both positive-ion and negative-ion modes by UPLC-QTOFMS, and after data deconvolution, the resulting data matrices were subjected to multivariate data analysis. Pattern recognition was performed on the retention time, mass/charge ratio, and other metabolite-related variables. Synthesized or purchased authentic compounds were used for metabolite identification and structure elucidation by liquid chromatographytandem mass spectrometry. Several metabolites were identified, including fenofibric acid, reduced fenofibric acid, fenofibric acid ester glucuronide, reduced fenofibric acid ester glucuronide, and compound X. Another two metabolites (compound B and compound AR), not previously reported in other species, were characterized in cynomolgus monkeys. More importantly, previously unknown metabolites, fenofibric acid taurine conjugate and reduced fenofibric acid taurine conjugate were identified, revealing a previously unrecognized conjugation pathway for fenofibrate.

In vitro comparison of laser fluorescence performance with visual examination for detection of occlusal caries in permanent and primary molars

The aim of this study was to compare the performance of the DIAGNOdent 2095 with visual examination for occlusal caries detection in permanent and primary molars. The sample comprised 148 permanent human molars and 179 primary human molars. The samples were measured and visually examined three times by two examiners. After measurement, the teeth were histologically prepared and assessed for caries extension. Sensitivity, specificity, accuracy and area under the receiver operating characteristics (ROC) curve were calculated. Intra-class correlation (ICC), unweighted kappa and the Bland and Altman method were used to assess inter- and intra-examiner reproducibility. DIAGNOdent showed higher specificity and lower sensitivity than did visual examination. The ICC values indicated an excellent agreement between the examinations. Kappa values varied from good to excellent for DIAGNOdent but from poor to good for visual examination. In conclusion, the DIAGNOdent may be a useful adjunct to conventional methods for occlusal caries detection.

Tn6198, a novel transposon containing the trimethoprim resistance gene dfrG embedded into a Tn916 element in Listeria monocytogenes

OBJECTIVES: To characterize Tn6198, a novel conjugative transposon from the clinical Listeria monocytogenes strain TTH-2007, which contains the tetracycline and trimethoprim resistance genes tet(M) and dfrG, respectively, and to assess its transferability in vitro and in situ. METHODS: The complete sequence of Tn6198 was determined using a primer walking strategy. Horizontal gene transfer studies were performed by filter matings, as well as on the surface of smear-ripened cheese and smoked salmon. The presence of Tn916-like circular intermediates was determined by PCR. Antibiotic resistance was determined by the broth microdilution method and microarray hybridization. RESULTS: Sequencing of Tn6198 revealed that a 3.3 kb fragment containing dfrG was integrated between open reading frames 23 and 24 of Tn916. Furthermore, an additional copy of Tn916 was present in L. monocytogenes TTH-2007. Both elements were transferred simultaneously and separately in vitro to recipients L. monocytogenes 10403S and Enterococcus faecalis JH2-2 by conjugation, resulting in either tetracycline- and trimethoprim-resistant or solely tetracycline-resistant transconjugants. On the surface of cheese and salmon, only L. monocytogenes 10403S transconjugants were detected. CONCLUSIONS: This study reports the first Tn916-like element associated with a trimethoprim resistance gene, as well as the first fully characterized transposon conferring multidrug resistance in L. monocytogenes. This is of concern, as trimethoprim is administered to listeriosis patients with β-lactam allergy and as Tn6198 has a large potential for dissemination, indicated by both intra-species and inter-genus transfer.

Does normalized signal intensity of cervical discs on T2 weighted MRI images change in whiplash patients?

PURPOSE We tested the hypothesis that whiplash trauma leads to changes of the signal intensity of cervical discs in T2-weighted images. METHODS AND MATERIALS 50 whiplash patients (18-65 years) were examined within 48h after motor vehicle accident, and again after 3 and 6 months and compared to 50 age- and sex-matched controls. Signal intensity in ROI's of the discs at the levels C2/3 to C7/T1 and the adjacent vertebral bodies were measured on sagittal T2 weighted MR images and normalized using the average of ROI's in fat tissue. The contrast between discs and both adjacent vertebrae was calculated and disc degeneration was graded by the Pfirrmann-grading system. RESULTS Whiplash trauma did not have a significant effect on the normalized signals from discs and vertebrae, on the contrast between discs and adjacent vertebrae, or on the Pfirrmann grading. However, the contrast between discs and adjacent vertebrae and the Pfirrmann grading showed a strong correlation. In healthy volunteers, the contrast between discs and adjacent vertebrae and Pfirrmann grading increased with age and was dependent on the disc level. CONCLUSION We could not find any trauma related changes of cervical disc signal intensities. Normalized signals of discs and Pfirrmann grading changed with age and varied between disc levels with the used MR sequence.

Health-related quality of life in rural children living in four European countries: the GABRIEL study

OBJECTIVE Measuring children's health-related quality of life (HRQOL) is of growing importance given increasing chronic diseases. By integrating HRQOL questions into the European GABRIEL study, we assessed differences in HRQOL between rural farm and non-farm children from Germany, Austria, Switzerland and Poland to relate it to common childhood health problems and to compare it to a representative, mostly urban German population sample (KIGGS). METHODS The parents of 10,400 school-aged children answered comprehensive questionnaires including health-related questions and the KINDL-R questions assessing HRQOL. RESULTS Austrian children reported highest KINDL-R scores (mean: 80.9; 95 % CI [80.4, 81.4]) and Polish children the lowest (74.5; [73.9, 75.0]). Farm children reported higher KINDL-R scores than non-farm children (p = 0.002). Significantly lower scores were observed in children with allergic diseases (p < 0.001), with sleeping difficulties (p < 0.001) and in overweight children (p = 0.04). The German GABRIEL sample reported higher mean scores (age 7-10 years: 80.1, [79.9, 80.4]; age 11-13 years: 77.1, [74.9, 79.2]) compared to the urban KIGGS study (age 7-10 years: 79.0, [78.7-79.3]; age 11-13 years: 75.1 [74.6-75.6]). Socio-demographic or health-related factors could not explain differences in HRQOL between countries. CONCLUSIONS Future increases in chronic diseases may negatively impact children's HRQOL.

Mitteilungen der Antiquarischen Gesellschaft in Zürich

Die Antiquarische Gesellschaft in Zürich veröffentlicht seit 1837 jedes Jahr auf den Berchtoldstag (2. Januar) ein Neujahrsblatt. Das erste «Neujahrsstück» war neu entdeckten keltischen Gräber im Burghölzli und auf der Forch nahe Zürich gewidmet. Nach einer langen Serie von Monografien zu historischen, archäologischen und kunsthistorischen Themen mit Zürcher Bezug werden in den letzten Jahren auch häufig Sammelbände veröffentlicht, in denen Autorinnen und Autoren ein Thema aus verschiedenen Perspektiven beleuchten.

Reduplication in Mapuzungun: form and function

Mapuzungun has reduplicative structures based on elements other than verb stems that are of very limited productivity. With verb stems, however, several formal patterns can be distinguished, which consist of the repetition of the lexical verb stem plus the addition of an apparently grammaticalized version of one of three verb roots or a zero morpheme. The previous literature has attempted to identify form/function correlations for these more or less productive verbal reduplicative patterns, and the present paper contributes to the discussion by surveying older studies and exploring several cases that suggest that such form/function correspondences are substantially less straightforward than a casual observer might think.

Antibiotic resistance spread in food

Nutritive and therapeutic treatment of farm animals with antibiotics, amounting to half of the world's antibiotic output, has selected for resistant bacteria that may contaminate the food produced. Antibiotic-resistant enterococci and staphylococci from animals are found in food when they survive the production processes, as in raw cured sausages and raw milk cheeses1. The broad host ranges of some plasmids and the action of transposons in many bacteria allow antibiotic-resistance genes to be communicated by conjugation between different species and genera2,3. A multi-antibiotic resistance plasmid from a lactococcus found in cheese provides a historical record of such events.

Nominal compounds in Mapudungun

It is perhaps unsurprising that the rich agglutinative-polysynthetic verb morphology of Mapudungun has drawn most attention in linguistic studies. So far unnoticed in the literature are Mapudungun complex noun phrases, which show a puzzling distribution in terms of the internal structure they display. Some complex NPs are head-final (mapu-che ‘people of the land’). Others are head-initial, and of these a subset appears to be less lexicalized. In some cases, all three possibilities are found with the same components: mamüll-che ‘wood people’, che-mamüll ‘people made of wood’, and che mamüll ‘wood-like people’. The present paper reviews the comparatively modest literature on these phenomena, deals with them in an account based on semantic factors, and places them in a broader typological context.

Strange Relations. Cultural Translation of Noh Theatre in Ezra Pound’s Dance Poems and W. B. Yeats’s At the Hawk’s Well

Drawing on the reception of Noh drama by Ezra Pound and William Butler Yeats, the article analyses both the literary and cultural ‘translations’ of this form of Japanese theatre in their works, focusing on Yeats’s play At the Hawk’s Well (1917). I conceptualize ‘cultural translation’ as the staging of relations that mark a residual cultural difference. Referred to as ‘foreignizing’ in translation theory, this method enables what Erika Fischer-Lichte has termed a ‘liminal experience’ for the audience –– an effect Yeats intended for the performance of his play. It evokes situations in which opposites collapse and new ways of acting or new combinations of symbols can be tried out. Yeats’s play will be used to sketch how an analysis of relations could serve as a general model for the study of cultural transfer as cultural translation in general. Keywords: cultural translation, translation theory, performance, William Butler Yeats, Itō Michio, Ezra Pound, At the Hawk’s Well

Temperature terms in Mapudungun

Mapudungun (unclassified) is spoken in south-central Chile and southwestern Argentina at different altitudes in climates ranging from tundra and subalpine to Mediterranean. This paper surveys the basic semantics and morphosyntax of nine temperature terms, of which wütre ‘cold’, füshkü ‘cool’, eñum ‘warm’ and are ‘hot’ are probably the most frequently used ones. While these terms can be used for tactile, ambient, and personal-feeling temperatures, the other five are specialised for one or two of these kinds of evaluations. Notably, all terms can be used as main verbs in predications; most can also be used as adjectives in order to modify nouns, and only wütre and are are commonly used as nouns referring to ‘cold’ and ‘heat’ respectively.