Metabolomic assays of amoxicillin, cephapirin and ceftiofur in chicken muscle. Application to treated chicken samples by liquid chromatography quadrupole time-of-flight mass spectrometry

The aim of this study was to identity metabolites and transformation products (TPs) in chicken muscle from amoxicillin (AMX), cephapirin (PIR) and ceftiofur (TIO), which are antibiotics of the β-lactam family. Liquid chromatography coupled to quadrupole time-of-flight (QqTOF) mass spectrometry was utilized due to its high resolution, high mass accuracy and MS/MS capacity for elemental composition determination and structural elucidation. Amoxicilloic acid (AMA) and amoxicillin diketopiperazine (DKP) were found as transformation products from AMX. Desacetylcephapirin (DAC) was detected as a metabolite of PIR. Desfuroylceftiofur (DFC) and its conjugated compound with cysteine (DFC-S-Cys) were detected as a result of TIO in contact with chicken muscle tissue. The metabolites and transformation products were also monitored during the in vivo AMX treatment and slaughtering period. It was found that two days were enough to eliminate AMX and associated metabolites/transformation products after the end of administration.

Optimization of OSEM parameters in myocardial perfusion imaging reconstruction as a function of body mass index: a clinical approach

AbstractObjective:The present study is aimed at contributing to identify the most appropriate OSEM parameters to generate myocardial perfusion imaging reconstructions with the best diagnostic quality, correlating them with patients' body mass index.Materials and Methods:The present study included 28 adult patients submitted to myocardial perfusion imaging in a public hospital. The OSEM method was utilized in the images reconstruction with six different combinations of iterations and subsets numbers. The images were analyzed by nuclear cardiology specialists taking their diagnostic value into consideration and indicating the most appropriate images in terms of diagnostic quality.Results:An overall scoring analysis demonstrated that the combination of four iterations and four subsets has generated the most appropriate images in terms of diagnostic quality for all the classes of body mass index; however, the role played by the combination of six iterations and four subsets is highlighted in relation to the higher body mass index classes.Conclusion:The use of optimized parameters seems to play a relevant role in the generation of images with better diagnostic quality, ensuring the diagnosis and consequential appropriate and effective treatment for the patient.

Effects of extra mass on the pelagic behavior of a seabird

Satellite transmitters and geographic-positioning-system devices often add substantial mass to birds to which they are attached. Studies on the effects of such instruments have focused on indirect measures, whereas the direct influence of extra mass on pelagic behavior is poorly known. We used 2.5-g geolocators to investigate the effect of extra mass on the pelagic behavior of Cory's Shearwaters (Calonectris diomedea) by comparing the traits of a single foraging trip among a group carrying 30-g weights, a group carrying 60-g weights, and a control group. The weights were attached to the birds' backs using typical techniques for attaching satellite transmitters to seabirds. The extra mass increased the duration of the birds' trips and decreased their foraging efficiency and mass gained at sea. These indirect effects may be related to foraging traits: weighted birds showed a greater search effort than control birds, traveled greater distances, covered a greater foraging area, and increased the maximum foraging range. Furthermore, the time spent on the sea surface at night was greater for weighted than for control groups, which showed that the extra mass also affected activity patterns. Our results underline the need to quantify the effects of monitoring equipment commonly used to study the pelagic behavior of seabirds. We suggest that geolocators can be used to obtain control data on foraging-trip movements and activity patterns.

Specificity and selectivity improvement in doping analysis using comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry

Comprehensive two-dimensional gas chromatography coupled with time-of-flight mass spectrometry was used for the identification of forty doping agents. The improvement in the specificity was remarkable, allowing the resolution of analytes that could not be done by one-dimensional chromatographic systems. The sensitivity observed for different classes of prohibited substances was clearly below the value required by the World Anti-Doping Agency. In addition time-of-flight mass spectrometry gives full spectrum for all analytes without any interference from the matrix, resulting in selectivity improvements. These results could support the implementation of an exhaustive monitoring approach for hundreds of doping agents in a single injection.

Methods for construction and analysis of computational models in systems biology : applications to the modelling of the heat shock response and the self-assembly of intermediate filaments

Systems biology is a new, emerging and rapidly developing, multidisciplinary research field that aims to study biochemical and biological systems from a holistic perspective, with the goal of providing a comprehensive, system- level understanding of cellular behaviour. In this way, it addresses one of the greatest challenges faced by contemporary biology, which is to compre- hend the function of complex biological systems. Systems biology combines various methods that originate from scientific disciplines such as molecu- lar biology, chemistry, engineering sciences, mathematics, computer science and systems theory. Systems biology, unlike “traditional” biology, focuses on high-level concepts such as: network, component, robustness, efficiency, control, regulation, hierarchical design, synchronization, concurrency, and many others. The very terminology of systems biology is “foreign” to “tra- ditional” biology, marks its drastic shift in the research paradigm and it indicates close linkage of systems biology to computer science. One of the basic tools utilized in systems biology is the mathematical modelling of life processes tightly linked to experimental practice. The stud- ies contained in this thesis revolve around a number of challenges commonly encountered in the computational modelling in systems biology. The re- search comprises of the development and application of a broad range of methods originating in the fields of computer science and mathematics for construction and analysis of computational models in systems biology. In particular, the performed research is setup in the context of two biolog- ical phenomena chosen as modelling case studies: 1) the eukaryotic heat shock response and 2) the in vitro self-assembly of intermediate filaments, one of the main constituents of the cytoskeleton. The range of presented approaches spans from heuristic, through numerical and statistical to ana- lytical methods applied in the effort to formally describe and analyse the two biological processes. We notice however, that although applied to cer- tain case studies, the presented methods are not limited to them and can be utilized in the analysis of other biological mechanisms as well as com- plex systems in general. The full range of developed and applied modelling techniques as well as model analysis methodologies constitutes a rich mod- elling framework. Moreover, the presentation of the developed methods, their application to the two case studies and the discussions concerning their potentials and limitations point to the difficulties and challenges one encounters in computational modelling of biological systems. The problems of model identifiability, model comparison, model refinement, model inte- gration and extension, choice of the proper modelling framework and level of abstraction, or the choice of the proper scope of the model run through this thesis.

Accumulation of dry mass and macronutrients by sourgrass plants

The experiment was carried out aiming to analyze the dry mass production and distribution and the content and accumulation of macronutrients in sourgrass (Digitaria insularis) plants cultivated under mineral nutrition standard conditions. Plants grew in 7-liter pots filled with sand substrate and daily irrigated with nutrient solution, being maintained under greenhouse conditions. Treatments consisted of times of evaluation (21, 35, 49, 63, 77, 91, 105, 119, and 133 days after emergence - DAE) and were arranged in a completely randomized design with four replicates. Sourgrass showed small accumulation of dry mass (0.3 g per plant) and macronutrients (3.7 mg of N per plant, 0.4 mg of P per plant, 5.6 mg of K per plant, 0.9 mg of Ca per plant, 0.7 mg of Mg per plant, and 0.3 mg of S per plant) at vegetative growth stage (< 49 DAE). Those accumulations increased mainly after 77 DAE, reaching the maximum theoretical value at 143, 135, 141, 129, 125, 120, and 128 DAE, for dry mass (12.4 g per plant), N (163.2 mg per plant), P (27.1 mg per plant), K (260.5 mg per plant), Ca (47.6 mg per plant), Mg (30.9 mg per plant), and S (13.7 mg per plant), respectively. K and N were found with higher rates and, as a consequence, they were required and accumulated in greater amounts in plant tissues of sourgrass.

Influence of body mass and environmental oxygen tension on the oxygen consumption rates of an enteropneust, Glossobalanus crozieri

The present study deals with a species of enteropneust, Glossobalanus crozieri, focusing on two aspects of its respiration: a) oxygen consumption and body mass, and b) the influence of environmental oxygen tension on the respiratory rate. Preliminarily, the body water content was shown to be 85% of the whole body weight. The regression coefficient of the oxygen consumption on the wet body mass (0.578) seems to agree with the view that in enteropneusts respiration is mainly cutaneous. The respiratory rate was significantly reduced at O2 tensions from 76 mmHg downwards, suggesting conformity rather than regulation

Association of body mass index with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis

The objective of this observational, multicenter study was to evaluate the association of body mass index (BMI) with disease severity and prognosis in patients with non-cystic fibrosis bronchiectasis. A total of 339 patients (197 females, 142 males) diagnosed with non-cystic fibrosis bronchiectasis by high-resolution computed tomography were classified into four groups: underweight (BMI<18.5 kg/m2), normal weight (18.5≤BMI<25.0 kg/m2), overweight (25.0≤BMI<30.0 kg/m2), and obese (BMI≥30.0 kg/m2). Clinical variables expressing disease severity were recorded, and acute exacerbations, hospitalizations, and survival rates were estimated during the follow-up period. The mean BMI was 21.90 kg/m2. The underweight group comprised 28.61% of all patients. BMI was negatively correlated with acute exacerbations, C-reactive protein, erythrocyte sedimentation rate, radiographic extent of bronchiectasis, and chronic colonization by P. aeruginosa and positively correlated with pulmonary function indices. BMI was a significant predictor of hospitalization risk independent of relevant covariates. The 1-, 2-, 3-, and 4-year cumulative survival rates were 94%, 86%, 81%, and 73%, respectively. Survival rates decreased with decreasing BMI (χ2=35.16, P<0.001). The arterial carbon dioxide partial pressure, inspiratory capacity, age, BMI, and predicted percentage of forced expiratory volume in 1 s independently predicted survival in the Cox proportional hazard model. In conclusion, an underweight status was highly prevalent among patients with non-cystic fibrosis bronchiectasis. Patients with a lower BMI were prone to developing more acute exacerbations, worse pulmonary function, amplified systemic inflammation, and chronic colonization by P. aeruginosa. BMI was a major determinant of hospitalization and death risks. BMI should be considered in the routine assessment of patients with non-cystic fibrosis bronchiectasis.

By Laws of the Corporation of the Town of Welland, 1878 [fragment]

The fragment appears to be part of a larger group of bylaws for the Town of Welland, 1878. The fragment includes bylaws Cap. I and Cap. II. Cap. I is a bylaw appointing auditors for the town for the year 1878. Due to paper loss only a portion of the title of the Cap. II bylaw is extent but appears to be a bylaw appointing a Hey…….trustee for the town. Welland was incorporated in 1858 as a town and became a city in 1917.

Developmental trajectories of body mass index in early childhood : an 8-year longitudinal study

Trajectoires développementales de l’IMC durant l’enfance: Une étude longitudinale sur 8 ans. Introduction : L’obésité infantile, origine de nombreux problèmes de santé, représente un grand défi en santé publique. Récemment, l’importance d’étudier l’évolution du surpoids durant l’enfance ainsi que les facteurs de risques précoces pour l’obésité a été reconnue. Les trajectoires développementales d’indice de masse corporelle (IMC) chez les jeunes représentent une approche innovatrice qui nous permet de mieux comprendre cette problématique importante. Objectifs: 1) Identifier des trajectoires développementales distinctes de groupes d’enfants selon leur IMC durant l’enfance, et 2) Explorer les facteurs de risques précoces qui prédisent l’appartenance de l’enfant à la trajectoire d’IMC le plus élevé Hypothèses: 1) On s’attend à retrouver un groupe d’enfants qui suit une trajectoire d’IMC élevée durant l’enfance. 2) On s’attend à ce que certaines caractéristiques de la mère (ex : tabac pendant la grossesse et IMC élevé), soient associées à l’appartenance de l’enfant au groupe ayant la trajectoire «IMC élevé ». Méthodes: Estimation des trajectoires développementales d’IMC d’enfants, dans un échantillon populationnel (n=1957) au Québec (ELDEQ). Les IMC ont été calculés à partir de données fournies par les mères des enfants et recueillis chaque année sur une durée de 8 ans. Des données propres à l’enfant sa mère, ainsi que socioéconomiques, ont étés recueillies. Une régression logistique multinomiale a été utilisée pour distinguer les enfants avec un IMC élevé des autres enfants, selon les facteurs de risques précoces. Les programmes PROC TRAJ (extension de SAS), SPSS (version 16), et SAS (version 9.1.3) ont été utilisés pour ces analyses. Résultats: Trois trajectoires d’IMC ont étés identifiées : IMC « bas-stable » (54,5%), IMC « modéré » (41,0%) et IMC « élevé et en hausse » (4,5%). Le groupe « élevé et en hausse » incluait des enfants pour qui l’IMC à 8 ans dépassait la valeur limite pour l’obésité. Les analyses de régression logistique ont révélé que deux facteurs de risques maternels étaient significativement associés avec la trajectoire “en hausse” par rapport aux deux autres groupes : le tabac durant la grossesse et le surpoids maternel. Conclusions: Des risques d’obésité infantile peuvent êtres identifiés dès la grossesse. Des études d’intervention sont requises pour identifier la possibilité de réduire le risque d’obésité chez l’enfant en ciblant le tabac et le surpoids maternelle durant la grossesse. Mots clés: Indice de masse corporelle (IMC), obésité infantile, trajectoires développementales de groupe, facteurs de risque précoce, étude populationnelle, tabac pendant la grossesse, obésité maternelle.

Assessment of Tandem Mass Spectrometry and High Resolution Mass Spectrometry for the Analysis of Bupivacaine in Plasma

Triple quadrupole mass spectrometers coupled with high performance liquid chromatography are workhorses in quantitative bioanalyses. It provides substantial benefits including reproducibility, sensitivity and selectivity for trace analysis. Selected Reaction Monitoring allows targeted assay development but data sets generated contain very limited information. Data mining and analysis of non-targeted high-resolution mass spectrometry profiles of biological samples offer the opportunity to perform more exhaustive assessments, including quantitative and qualitative analysis. The objectives of this study was to test method precision and accuracy, statistically compare bupivacaine drug concentration in real study samples and verify if high resolution and accurate mass data collected in scan mode can actually permit retrospective data analysis, more specifically, extract metabolite related information. The precision and accuracy data presented using both instruments provided equivalent results. Overall, the accuracy was ranging from 106.2 to 113.2% and the precision observed was from 1.0 to 3.7%. Statistical comparisons using a linear regression between both methods reveal a coefficient of determination (R2) of 0.9996 and a slope of 1.02 demonstrating a very strong correlation between both methods. Individual sample comparison showed differences from -4.5% to 1.6% well within the accepted analytical error. Moreover, post acquisition extracted ion chromatograms at m/z 233.1648 ± 5 ppm (M-56) and m/z 305.2224 ± 5 ppm (M+16) revealed the presence of desbutyl-bupivacaine and three distinct hydroxylated bupivacaine metabolites. Post acquisition analysis allowed us to produce semiquantitative evaluations of the concentration-time profiles for bupicavaine metabolites.

Effects of tubers of the Jerusalem artichoke (Helianthus tuberosus) and potatoes (Solanum tuberosum) on the intestinal microbiota of pigs and evaluation of a procedure for quantification of microbial mass in pig faeces

Die Mikrobiota im Gastrointestinaltrakt (GIT) spielt eine bedeutende Rolle beim Fermentationsprozess im Bezug auf die Nährstoffversorgung sowie die Gesundheit des Darms und des gesamten Organismus. Inulin und resistente Stärke (RS) konnten als präbiotisch wirksame Substanzen identifiziert werden und sind jeweils auch in den Knollen der Topinamburpflanze (Helianthus tuberosus) und in Kartoffeln (Solanum tuberosum) enthalten. Da sie ebenfalls energiereiche Futtermittel für Schweine sind, war es das Ziel der ersten beiden Studien, die Auswirkungen der Aufnahme von Topinamburknollen und Kartoffeln auf die intestinale Mikrobiota und Parameter des Immunsystems bei Endmastschweinen zu bestimmen. In der dritten Studie wurde die mikrobielle Biomasse quantitativ mit einem Verfahren zur Isolation von Bakterien in einer Flüssigkeit durch Hochgeschwindigkeits-Zentrifugation erfasst und der bakteriell gebundene Stickstoff (MP-N) mit dem bakteriellen und endogenem Kotstickstoff (BEDN) verglichen. Im ersten Versuch wurden 72 Endmastschweine in einem Freilandhaltungssystem in eine Kontroll- (CT), die mit Kraftfutter entsprechend des Bedarfs der Tiere für ein Leistungsniveau von 700 g täglichem Lebendmassezuwachs versorgt wurde, und eine Versuchsvariante (ET) aufgeteilt. In der Versuchsvariante erhielten die Tiere nur 70% der Kraftfuttermenge der Kontrollvariante, hatten aber Zugang zu einer abgeteilten Fläche, auf der Topinamburknollen angebaut waren. Die freie Aufnahme von Topinamburknollen wurde auf 1•24 kg Trockenmasse (TM)/Tag bestimmt, entsprechend einer Inulinaufnahme von durchschnittlich 800 g/Tag. Während sich die Wachstumsleistung in der Kontrollvariante auf 0•642 ± 0•014 kg/Tag belief, war sie in der Versuchsvariante mit 0•765 ± 0•015 kg/Tag (P=0•000) höher. Die freie Verfügbarkeit von Inulin und Fructo-oligosacchariden (FOS) im GIT der Schweine erhöhte die Keimzahlen der anaeroben Bakterien (P=0•000), Laktobazillen (P=0•046) und Hefen (P=0•000) signifikant und verringerte das Vorkommen von Clostridium perfringens im Schweinekot erheblich von lg 5•24 ± 0•17 kolonie-bildende Einheiten pro g Frischmasse (KbE/ g FM) in der Kontrollvariante auf lg 0•96 ± 0•20 KbE/ g FM in der Versuchsvariante (P=0•000). C-reaktives Protein (CRP) und Antikörper gegen Lipopolysaccharide (LPS) von Escherichia coli J5 ließen keine Unterschiede zwischen den Fütterungsvarianten erkennen. In der zweiten Untersuchung wurden 58 Endmastschweine einer Kontrollvariante (CT), die bedarfsgerecht mit einer Kraftfuttermischung für ein Leistungsniveau von 700 g Tageszunahmen gefüttert wurde, und zwei Versuchsvarianten zugeteilt. Die Versuchsvarianten erhielten eine Menge von 1•2 kg TM gedämpften Kartoffeln (potato treatment, PT) oder gedämpften und einsilierten Kartoffeln (silage treatment, ST) pro Tag und nur 46% bzw. 43% der Menge des Kraftfutters der Kontrollvariante. Die Wachstumsleistung und Schlachtkörperzusammensetzung ließen keine signifikanten Unterschiede zwischen den Varianten erkennen. Im PT und ST waren gegenüber dem CT im Kot der pH-Wert sowie die Gehalte von TM, Neutral-Detergenz-Faser (NDF), unverdautem Futterstickstoff (UDN) und teilweise von Säure-Detergenz-Faser (ADF) signifikant niedriger (P=0•000) und die von Ammonium (NH4) und Ammoniumstickstoff (NH4-N) signifikant höher (P=0•000). Das hohe Angebot von hitzebehandelten Kartoffeln führte zu einer erheblichen Verringerung von E. coli (P=0•000), C. perfringens (P=0•000) und Immunoglobulin A gegen LPS von E. coli J5 (P=0•001). Darüber hinaus waren in der ersten Versuchsperiode im ST die aeroben und anaeroben Gesamtkeimzahlen sowie die Laktobazillen und Hefen gegenüber dem PT signifikant erhöht. Die Unterschiede in der Mikrobiota zwischen der Kontroll- und Versuchsvarianten weisen auf die positiven Auswirkungen von Topinamburknollen und hitzebehandelten Kartoffeln auf die Mikrobiota im hinteren Darmabschnitt hin. Das Ziel der dritten Untersuchung war die Modifizierung des Verfahrens zur Isolation von Bakterien in einer Flüssigkeit mittels verschiedener Zentrifugationsschritte, um ein mikrobielles Pellet (MP) zu erhalten, welches die quantitative Abtrennung und Erfassung der Bakterien in Schweinekot ermöglicht. Zusätzlich wurde der BEDN Anteil sowie die Gehalte der Aminozucker Galactosamin, Glucosamin, Mannosamin und Muraminsäure im Kot und im MP bestimmt. Die untersuchten Kotproben stammten von Schweinen eines Phosphor (P) Stoffwechselversuch. Zehn männlich-kastrierte Schweine mit einem durchschnittlichen Lebendgewicht von 51•1 ± 8•5 kg wurden einzeln in Stoffwechselkäfigen gehalten. Die Tiere wurden fünf Fütterungsvarianten zugeteilt, die dem Bedarf der Tiere für ein Leistungsniveau von 700 g Tageszunahmen entsprachen, in den Rationen 2 bis 5 jedoch eine P-Gehalt unter dem Tagesbedarf der Tiere aufwiesen und in den Rationen 3 bis 5 mit abgestuften Gehalten von 50, 100 sowie 200 mg/kg einer experimentellen Phytase ergänz waren. Die Absenkung des P Gehaltes im Futter verringerte den Asche- (P=0•024) und Trockenmassegehalt im Kot (P=0•017) sowie die P Konzentration im MP (P=0•000) signifikant. Die mikrobielle Biomasse im Kot wurde durch die Wiegung des MP auf durchschnittlich 467 g/kg TM bestimmt. Der Stickstoffgehalt im Kot betrug im Mittel 46•1 g/kg TM und der in die Bakterienmasse eingebaute Stickstoffanteil 27•1 g/kg TM bzw. 58% vom Gesamtstickstoffgehalt im Kot. Die BEDN Fraktion wurde auf 73% am Kotstickstoff bestimmt. Der P-Gehalt im Kot sowie der N Gehalt im MP mit durchschnittlichen 10•4 und 57•9 g/kg TM lagen im Bereich von Literaturangaben. Die P Gehalte im MP schwankten in Abhängigkeit von der Zugabe von Phytase signifikant (P=0•000) von 1•8 bis 4•8 g/kg TM. Die Aminozucker wiesen keine signifikanten unterschiede zwischen Fütterungsvarianten auf und lagen im Bereich von Werten von Rinderkot. Ergebnisse weisen darauf hin, dass die angewandte Methode zur direkten Quantifizierung der mikrobiellen Biomasse geeignet ist.