The cardio-renal axis. Non ST-segment elevation myocardial infarction risk stratification according to renal dysfunction

Background: Chronic kidney disease (CKD) is one of the strongest risk factor for myocardial infarction (MI) and mortality. The aim of this study was to assess the association between renal dysfunction severity, short-term outcomes and the use of in-hospital evidence-based therapies among patients with non–ST-segment elevation myocardial infarction (NSTEMI). Methods: We examined data on 320 patients presenting with NSTEMI to Maggiore’s Emergency Department from 1st Jan 2010 to 31st December 2011. The study patients were classified into two groups according to their baseline glomerular filtration rate (GFR): renal dysfunction (RD) (GFR<60) and non-RD (GFR≥60 ml/min). Patients were then classified into four groups according to their CKD stage (GFR≥60, GFR 59-30, GFR 29-15, GFR <15). Results: Of the 320 patients, 155 (48,4%) had a GFR<60 ml/min at baseline. Compared with patients with a GFR≥60 ml/min, this group was, more likely to be female, to have hypertension, a previous myocardial infarction, stroke or TIA, had higher levels of uric acid and C-reactive protein. They were less likely to receive immediate (first 24 hours) evidence-based therapies. The GFR of RD patients treated appropriately increases on average by 5.5 ml/min/1.73 m2. The length of stay (mean, SD) increased with increasing CKD stage, respectively 5,3 (4,1), 7.0 (6.1), 7.8 (7.0), 9.2 (5.8) (global p <.0001). Females had on average a longer hospitalization than males, regardless of RD. In hospital mortality was higher in RD group (3,25%). Conclusions: The in-hospital mortality not was statically difference among the patients with a GFR value ≥60 ml/min, and patients with a GFR value <60 ml/min. The length of stay increased with increasing CKD stages. Despite patients with RD have more comorbidities then without RD less frequently receive guideline –recommended therapy. The GFR of RD patients treated appropriately improves during hospitalization, but not a level as we expected.

Plasmons as sensors

“Plasmon” is a synonym for collective oscillations of the conduction electrons in a metal nanoparticle (excited by an incoming light wave), which cause strong optical responses like efficient light scattering. The scattering cross-section with respect to the light wavelength depends not only on material, size and shape of the nanoparticle, but also on the refractive index of the embedding medium. For this reason, plasmonic nanoparticles are interesting candidates for sensing applications. Here, two novel setups for rapid spectral investigations of single nanoparticles and different sensing experiments are presented.rnrnPrecisely, the novel setups are based on an optical microscope operated in darkfield modus. For the fast single particle spectroscopy (fastSPS) setup, the entrance pinhole of a coupled spectrometer is replaced by a liquid crystal device (LCD) acting as spatially addressable electronic shutter. This improvement allows the automatic and continuous investigation of several particles in parallel for the first time. The second novel setup (RotPOL) usesrna rotating wedge-shaped polarizer and encodes the full polarization information of each particle within one image, which reveals the symmetry of the particles and their plasmon modes. Both setups are used to observe nanoparticle growth in situ on a single-particle level to extract quantitative data on nanoparticle growth.rnrnUsing the fastSPS setup, I investigate the membrane coating of gold nanorods in aqueous solution and show unequivocally the subsequent detection of protein binding to the membrane. This binding process leads to a spectral shift of the particles resonance due to the higher refractive index of the protein compared to water. Hence, the nanosized addressable sensor platform allows for local analysis of protein interactions with biological membranes as a function of the lateral composition of phase separated membranes.rnrnThe sensitivity on changes in the environmental refractive index depends on the particles’ aspect ratio. On the basis of simulations and experiments, I could present the existence of an optimal aspect ratio range between 3 and 4 for gold nanorods for sensing applications. A further sensitivity increase can only be reached by chemical modifications of the gold nanorods. This can be achieved by synthesizing an additional porous gold cage around the nanorods, resulting in a plasmon sensitivity raise of up to 50 % for those “nanorattles” compared to gold nanorods with the same resonance wavelength. Another possibility isrnto coat the gold nanorods with a thin silver shell. This reduces the single particle’s resonance spectral linewidth about 30 %, which enlarges the resolution of the observable shift. rnrnThis silver coating evokes the interesting effect of reducing the ensemble plasmon linewidth by changing the relation connecting particle shape and plasmon resonance wavelength. This change, I term plasmonic focusing, leads to less variation of resonance wavelengths for the same particle size distribution, which I show experimentally and theoretically.rnrnIn a system of two coupled nanoparticles, the plasmon modes of the transversal and longitudinal axis depend on the refractive index of the environmental solution, but only the latter one is influenced by the interparticle distance. I show that monitoring both modes provides a self-calibrating system, where interparticle distance variations and changes of the environmental refractive index can be determined with high precision.

Search for the MSSM Neutral Higgs Boson in the mu+mu- final state with the CMS experiment at LHC

In this thesis, my work in the Compact Muon Solenoid (CMS) experiment on the search for the neutral Minimal Supersymmetric Standard Model (MSSM) Higgs decaying into two muons is presented. The search is performed on the full data collected during the years 2011 and 2012 by CMS in proton-proton collisions at CERN Large Hadron Collider (LHC). The MSSM is explored within the most conservative benchmark scenario, m_h^{max}, and within its modified versions, m_h^{mod +} and m_h^{mod -}. The search is sensitive to MSSM Higgs boson production in association with a b\bar{b} quark pair and to the gluon-gluon fusion process. In the m_h^{max} scenario, the results exclude values of tanB larger than 15 in the m_A range 115-200 GeV, and values of tanB greater than 30 in the m_A range up to 300 GeV. There are no significant differences in the results obtained within the three different scenarios considered. Comparisons with other neutral MSSM Higgs searches are shown.

Hair: a tool to evaluate the HPA axis activity

Hair cortisol is a novel marker to measure long-term secretion cortisol free from many methodological caveats associated with other matrices such as plasma, saliva, urine, milk and faeces. For decades hair analysis has been successfully used in forensic science and toxicology to evaluate the exposure to exogenous substances and assess endogenous steroid hormones. Evaluation of cortisol in hair matrix began about a decade ago and have over the past five years had a remarkable development by advancing knowledge and affirming this method as a new and efficient way to study the hypothalamic-pituitary-adrenal (HPA) axis activity over a long time period. In farm animals, certain environmental or management conditions can potentially activate the HPA axis. Given the importance of cortisol in monitoring the HPA axis activity, a first approach has involved the study on the distribution of hair cortisol concentrations (HCC) in healthy dairy cows showing a physiological range of variation of this hormone. Moreover, HCC have been significantly influenced also by changes in environmental conditions and a significant positive correlation was detected between HCC and cows clinically or physiologically compromised suggesting that these cows were subjected to repeated HPA axis activation. Additionally, Crossbreed F1 heifers showed significantly lower HCC compared to pure animals and a breed influence has been seen also on the HPA axis activity stimulated by an environmental change showing thus a higher level of resilience and a better adaptability to the environment of certain genotypes. Hair proved to be an excellent matrix also in the study of the activation of the HPA axis during the perinatal period. The use of hair analysis in research holds great promise to significantly enhance current understanding on the role of HPA axis over a long period of time.

Studio del comportamento catalitico nella reazione di Water Gas Shift a media ed alta temperatura

Per massimizzare la quantità di H2 nel gas di sintesi ottenuto dal processo di Steam Reforming (SR) si utilizza la reazione di Water Gas Shift (WGS): CO + H2O ⇆ CO2 + H2 ∆H0298 = - 41,2 KJ/mol Sulla base di sistemi catalitici Cu/Zn/Al si è cercato di modificarne la composizione per ottenere catalizzatori attivi e stabili in un intervallo di temperatura tra 350-450 °C, (High Temperature Shift o HTS), al fine di sostituire i tradizionali sistemi a base di Fe/Cr, in relazione alle limitazioni ambientali all’utilizzo del Cr e per poter operare con valori inferiori del rapporto S/DG. Si sono inoltre studiate le caratteristiche dei catalizzatori e le condizioni di reazione che favoriscono la produzione di metilammine ed alcoli nel processo a temperature intermedie, tra 300-350 °C (Middle Temperature Shift o MTS), in relazione alla disattivazione che questi composti comportano nel processo di SR a seguito del riciclo della fase acquosa dal reattore di WGS.

Computer simulations of colloidal fluids in confinement

Computer-Simulationen von Kolloidalen Fluiden in Beschränkten Geometrien Kolloidale Suspensionen, die einen Phasenübergang aufweisen, zeigen eine Vielfalt an interessanten Effekten, sobald sie auf eine bestimmte Geometrie beschränkt werden, wie zum Beispiel auf zylindrische Poren, sphärische Hohlräume oder auf einen Spalt mit ebenen Wänden. Der Einfluss dieser verschiedenen Geometrietypen sowohl auf das Phasenverhalten als auch auf die Dynamik von Kolloid-Polymer-Mischungen wird mit Hilfe von Computer-Simulationen unter Verwendung des Asakura-Oosawa- Modells, für welches auf Grund der “Depletion”-Kräfte ein Phasenübergang existiert, untersucht. Im Fall von zylindrischen Poren sieht man ein interessantes Phasenverhalten, welches vom eindimensionalen Charakter des Systems hervorgerufen wird. In einer kurzen Pore findet man im Bereich des Phasendiagramms, in dem das System typischerweise entmischt, entweder eine polymerreiche oder eine kolloidreiche Phase vor. Sobald aber die Länge der zylindrischen Pore die typische Korrelationslänge entlang der Zylinderachse überschreitet, bilden sich mehrere quasi-eindimensionale Bereiche der polymerreichen und der kolloidreichen Phase, welche von nun an koexistieren. Diese Untersuchungen helfen das Verhalten von Adsorptionshysteresekurven in entsprechenden Experimenten zu erklären. Wenn das Kolloid-Polymer-Modellsystem auf einen sphärischen Hohlraum eingeschränkt wird, verschiebt sich der Punkt des Phasenübergangs von der polymerreichen zur kolloidreichen Phase. Es wird gezeigt, dass diese Verschiebung direkt von den Benetzungseigenschaften des Systems abhängt, was die Beobachtung von zwei verschiedenen Morphologien bei Phasenkoexistenz ermöglicht – Schalenstrukturen und Strukturen des Janustyps. Im Rahmen der Untersuchung von heterogener Keimbildung von Kristallen innerhalb einer Flüssigkeit wird eine neue Simulationsmethode zur Berechnung von Freien Energien der Grenzfläche zwischen Kristall- bzw. Flüssigkeitsphase undWand präsentiert. Die Resultate für ein System von harten Kugeln und ein System einer Kolloid- Polymer-Mischung werden anschließend zur Bestimmung von Kontaktwinkeln von Kristallkeimen an Wänden verwendet. Die Dynamik der Phasenseparation eines quasi-zweidimensionalen Systems, welche sich nach einem Quench des Systems aus dem homogenen Zustand in den entmischten Zustand ausbildet, wird mit Hilfe von einer mesoskaligen Simulationsmethode (“Multi Particle Collision Dynamics”) untersucht, die sich für eine detaillierte Untersuchung des Einflusses der hydrodynamischen Wechselwirkung eignet. Die Exponenten universeller Potenzgesetze, die das Wachstum der mittleren Domänengröße beschreiben, welche für rein zwei- bzw. dreidimensionale Systeme bekannt sind, können für bestimmte Parameterbereiche nachgewiesen werden. Die unterschiedliche Dynamik senkrecht bzw. parallel zu den Wänden sowie der Einfluss der Randbedingungen für das Lösungsmittel werden untersucht. Es wird gezeigt, dass die daraus resultierende Abschirmung der hydrodynamischen Wechselwirkungsreichweite starke Auswirkungen auf das Wachstum der mittleren Domänengröße hat.

Measurement of the forward-backward asymmetry of Z boson decays in electron-positron pairs with the ATLAS detector in proton-proton collisions at root out s = 7TeV at the LHC

In this thesis the measurement of the effective weak mixing angle wma in proton-proton collisions is described. The results are extracted from the forward-backward asymmetry (AFB) in electron-positron final states at the ATLAS experiment at the LHC. The AFB is defined upon the distribution of the polar angle between the incoming quark and outgoing lepton. The signal process used in this study is the reaction pp to zgamma + X to ee + X taking a total integrated luminosity of 4.8\,fb^(-1) of data into account. The data was recorded at a proton-proton center-of-mass energy of sqrt(s)=7TeV. The weak mixing angle is a central parameter of the electroweak theory of the Standard Model (SM) and relates the neutral current interactions of electromagnetism and weak force. The higher order corrections on wma are related to other SM parameters like the mass of the Higgs boson.rnrnBecause of the symmetric initial state constellation of colliding protons, there is no favoured forward or backward direction in the experimental setup. The reference axis used in the definition of the polar angle is therefore chosen with respect to the longitudinal boost of the electron-positron final state. This leads to events with low absolute rapidity have a higher chance of being assigned to the opposite direction of the reference axis. This effect called dilution is reduced when events at higher rapidities are used. It can be studied including electrons and positrons in the forward regions of the ATLAS calorimeters. Electrons and positrons are further referred to as electrons. To include the electrons from the forward region, the energy calibration for the forward calorimeters had to be redone. This calibration is performed by inter-calibrating the forward electron energy scale using pairs of a central and a forward electron and the previously derived central electron energy calibration. The uncertainty is shown to be dominated by the systematic variations.rnrnThe extraction of wma is performed using chi^2 tests, comparing the measured distribution of AFB in data to a set of template distributions with varied values of wma. The templates are built in a forward folding technique using modified generator level samples and the official fully simulated signal sample with full detector simulation and particle reconstruction and identification. The analysis is performed in two different channels: pairs of central electrons or one central and one forward electron. The results of the two channels are in good agreement and are the first measurements of wma at the Z resonance using electron final states at proton-proton collisions at sqrt(s)=7TeV. The precision of the measurement is already systematically limited mostly by the uncertainties resulting from the knowledge of the parton distribution functions (PDF) and the systematic uncertainties of the energy calibration.rnrnThe extracted results of wma are combined and yield a value of wma_comb = 0.2288 +- 0.0004 (stat.) +- 0.0009 (syst.) = 0.2288 +- 0.0010 (tot.). The measurements are compared to the results of previous measurements at the Z boson resonance. The deviation with respect to the combined result provided by the LEP and SLC experiments is up to 2.7 standard deviations.

Phosphonate ligands in extended inorganic hybrids and as radical units in complexes

Phosphonatliganden in erweiterten anorganischen Hybridmaterialien undrnals Radikalträgern in KomplexenrnrnAnorganisch-organische Hybridmaterialien sind in der Regel extrem vielseitig. Die systematische Darstellung von niederdimensionalen Materialien (eindimensionale Kettenverbindungen oder zweidimensionalen Schichtverbindungen) mit einer Kontrolle über die Art der Verbindung,rnbietet neue Möglichkeiten im Bereich des molekularen Magnetismus. Hier im Fall von Metall-Phosphonat Verbindungen in erweiterten anorganischen Hybriden wurde der pH - Wert während der Reaktion eingestellt, wodurch der Grad der Protonierung des Phosphonatliganden kontrolliert wurde. Aufgrund der Tatsache, dass alle erhaltenen Metall Phosphonatverbindungen neutral waren, konnte das Ligand zu Metallverhältnis erstmals vorhergesagt werden. So wurden mehrere neue Metall–Phosphonat Verbindungen im Bereich von Null-dimensionalen (I0O0, Co-Kristallisation von M(H2O)6 mitrndeprotonierten Phosphonatligand), über eindimensionalen (I1O0, Kettenstrukturen) bis hin zu zweidimensionalen (I2O0, Schichtstrukturen) ausführlich diskutiert in Bezug auf ihr magnetisches Verhalten. Im Allgemeinen sind die erwarteten Austauschwechselwirkungen in einem erweiterten anorganischen Hybridmaterial stark, weil oft ein Superaustausch durch ein einzelnes Sauerstoffatom möglich ist. Hier waren oft mehrere konkurrierende Austauschwechselwirkungen vorhanden, so dass kompliziertere magnetische Verhalten beobachtet wurden.rnrnDarüber hinaus wurden drei neue Beispiele von Nitronyl-Nitroxidradikale dargestellt, in denen eine zusätzliche saure Funktionalität eingeführt war. Die Auswirkungen des sauren Charakters der zusätzlich eingeführten Sulfonsäure oder Phosphonsäure-Gruppe auf das Nitronyl-Nitroxidradikal wurden im Detail zum ersten Mal untersucht. Die mit der Phosphonsäure-Gruppe versehenen Nitronyl-Nitroxidradikale sind perfekte Proben für die Untersuchung einer Spin-Verschiebung in Nitronyl-Nitroxidradikale durch EPR-Spektroskopie, aufgrund des eingeführten Phosphors. Auch der Protonierungsgrad der zusätzlich eingeführten Phosphonsäure-Gruppe wurde berücksichtigt. In dieser Arbeit wurden die ersten Metallkomplexe der neuen substituierten sauren Nitronyl-Nitroxidradikale vorgestellt. Die Koordination von Nickel(II) Metallionen an die saure, zweite funktionelle Gruppe des Nitronyl–Nitroxid Radikal wurde beschrieben. Die magnetische Austauschwechselwirkung der Metallionen untereinander und die Metall-Radikal-Austauschwechselwirkungen wurden untersucht. rnrnIm Allgemeinen können interessante molekulare magnetische Materialien dadurch dargestellt werden, dass die Dimension der Metall-Phosphonat-Verbindungen als Beispiele für die erweiterten anorganischen Hybridmaterialien gesteuert werden kann. Mit Nitronyl-Nitroxidradikale als organische Liganden können in Zukunft noch mehr Spin-Träger in anorganisch-organischen Gerüstmaterialien integriert werden um die magnetischen Eigenschaften zu verbesseren.rn

Catalizzatori per la reazione di Water Gas Shift a media ed alta temperatura

L’H2 è un vettore energetico di elevato interesse, utilizzato nell’industria chimica per la produzione di NH3 e CH3OH, oltre che per le reazioni di idrogenazione ed HDS. Un importante processo nella produzione di H2 è la reazione di Water Gas Shift (WGS), usata nel trattamento delle correnti uscenti dal reattore di Steam Reforming (SR) del metano: CO + H2O  CO2 + H2 ∆H0298K = -41,2 KJ/mol. Sulla base di precedenti lavori, sono stati sviluppati nuovi catalizzatori per la reazione WGS ad alta temperatura (HTS), alternativi ai tradizionali sistemi a base di Fe/Cr, in considerazione dei vincoli economici (elevati valori del rapporto vapore/gas secco o S/DG) ed ambientali (formazione di CrVI) di questi sistemi. Partendo da sistemi Cu/Zn/Al con un basso contenuto di rame, ottenuti da precursori tipo idrotalcite (HT), stato studiato l’effetto dell’aggiunta di piccole quantità di alcuni promotori sull’attività e stabilità dei catalizzatori ottenuti, osservando un effetto positivo sulle caratteristiche fisiche, come l’aumento dell’area superficiale e della dispersione della fase attiva. I campioni contenenti i promotori erano inoltre caratterizzati da una maggiore stabilità termica e, in alcuni casi, da un’attività catalitica superiore a quella del catalizzatore di riferimento privo di promotori. L’aggiunta di piccole quantità di alcali alla formulazione con la migliore attività portava ad un ulteriore aumento di attività e di stabilità, attribuibile ad una minore formazione di coke sulla superficie. I sistemi più interessanti potevano operare anche a bassi valori del rapporto S/DG, interessanti dal punto di vista industriale. Lo studio dell’adsorbimento di CO mediante FT-IR ha permesso di ipotizzare la possibile natura della fase attiva nei sistemi. Infine, lo studio è stato esteso a sistemi per la reazione di WGS a media temperatura (MTS), osservando anche in questo caso un positivo effetto legato all’aggiunta di promotori, con un aumento dell’attività catalitica e della stabilità con il tempo di reazione.

A study of the turbulence of the neutral medium in two nearby spiral galaxies

The width of the 21 cm line (HI) emitted by spiral galaxies depends on the physical processes that release energy in the Interstellar Medium (ISM). This quantity is called velocity dispersion (σ) and it is proportional first of all to the thermal kinetic energy of the gas. The accepted theoretical picture predicts that the neutral hydrogen component (HI) exists in the ISM in two stable phases: a cold one (CNM, with σ~0.8 km/s) and a warm one (WNM, with σ~8 km/s). However, this is called into question by the observation that the HI gas has usually larger velocity dispersions. This suggests the presence of turbulence in the ISM, although the energy sources remain unknown. In this thesis we want to shed new light on this topic. We have studied the HI line emission of two nearby galaxies: NGC6946 and M101. For the latter we used new deep observations obtained with the Westerbork radio interferometer. Through a gaussian fitting procedure, we produced dispersion maps of the two galaxies. For both of them, we compared the σ values measured in the spiral arms with those in the interarms. In NGC6946 we found that, in both arms and interarms, σ grows with the column density, while we obtained the opposite for M 101. Using a statistical analysis we did not find a significant difference between arm and interarm dispersion distributions. Producing star formation rate density maps (SFRD) of the galaxies, we studied their global and local relations with the HI kinetic energy, as inferred from the measured dispersions. For NGC6946 we obtained a good log-log correlation, in agreement with a simple model of supernova feedback driven turbulence. This shows that in this galaxy turbulent motions are mainly induced by the stellar activity. For M 101 we did not find an analogous correlation, since the gas kinetic energy appears constant with the SFRD. We think that this may indicate that in this galaxy turbulence is driven also by accretion of extragalactic material.

Sviluppo di un sistema integrato innovativo per la contemporanea produzione e separazione di H2 ultrapuro, attraverso oxy-reforming, water-gas shift e membrane al Pd

Il presente lavoro di tesi si è focalizzato sullo studio e sulla ottimizzazione di un sistema integrato, che utilizzi la reazione di oxy-reforming del metano al fine di produrre syngas che venga trattato attraverso la water-gas shift al fine di abbattere il contenuto di CO e al tempo stesso aumentare la resa in H2. Con l’obiettivo di ottenere H2 ad elevata purezza (>99%) da poter essere inviato direttamente a celle a combustible ed in impianti di piccola taglia con possibile delocalizzazione della produzione industriale di energia elettrica e termica “pulita”, la miscela reale uscente dal processo di oxy-reforming è stata processata tramite successiva water-gas shift direttamente all’interno di una membrana ceramica al Pd selettiva nella separazione di H2. L’innovativià di questo progetto di studio è data da diversi parametri quali: 1) l’impiego dell’oxy-reforming in alternativa al normale steam-reforming del CH4, che permette di condurre il processo a temperature decisamente inferiori (700-750°C), utilizzando un minor quantitativo di vapore (S/C = 0.7); 2) l’utilizzo di due nuove formulazioni di catalizzatore di WGS per alte temperature, capace di operare in un unico stadio conversioni di CO ottenibili industrialmente solo attraverso i convenzionali due due stadi di reazione (e due diverse formulazioni di catalizzatori a base di Fe/Cr e Cu); 3) l’utilizzo di supporti ceramici con membrana a base di Pd, capaci di ospitare al loro interno un catalizzatore eterogeneo per la reazione di WGS a 400°C, rendendo quindi possibile la produzione e contemporanea separazione di H2 con un ulteriore effetto positivo poiché la membrana rimuovendo H2 dalla zona di reazione favorisce il superamento dell’equilibrio termodinamico per la conversione del CO, abbassandone il contenuto nel flusso uscente dei gas reazione e rendendo non più necessari sistemi aggiuntivi di separazione quali PSA o PROXY.

Control of Steroid 21-oic Acid Synthesis by Peroxisome Proliferator-activated Receptor and Role of the Hypothalamic-Pituitary-Adrenal Axis

A previous study identified the peroxisome proliferator-activated receptor alpha (PPARalpha) activation biomarkers 21-steroid carboxylic acids 11beta-hydroxy-3,20-dioxopregn-4-en-21-oic acid (HDOPA) and 11beta,20-dihydroxy-3-oxo-pregn-4-en-21-oic acid (DHOPA). In the present study, the molecular mechanism and the metabolic pathway of their production were determined. The PPARalpha-specific time-dependent increases in HDOPA and 20alpha-DHOPA paralleled the development of adrenal cortex hyperplasia, hypercortisolism, and spleen atrophy, which was attenuated in adrenalectomized mice. Wy-14,643 activation of PPARalpha induced hepatic FGF21, which caused increased neuropeptide Y and agouti-related protein mRNAs in the hypothalamus, stimulation of the agouti-related protein/neuropeptide Y neurons, and activation of the hypothalamic-pituitary-adrenal (HPA) axis, resulting in increased adrenal cortex hyperplasia and corticosterone production, revealing a link between PPARalpha and the HPA axis in controlling energy homeostasis and immune regulation. Corticosterone was demonstrated as the precursor of 21-carboxylic acids both in vivo and in vitro. Under PPARalpha activation, the classic reductive metabolic pathway of corticosterone was suppressed, whereas an alternative oxidative pathway was uncovered that leads to the sequential oxidation on carbon 21 resulting in HDOPA. The latter was then reduced to the end product 20alpha-DHOPA. Hepatic cytochromes P450, aldehyde dehydrogenase (ALDH3A2), and 21-hydroxysteroid dehydrogenase (AKR1C18) were found to be involved in this pathway. Activation of PPARalpha resulted in the induction of Aldh3a2 and Akr1c18, both of which were confirmed as target genes through introduction of promoter luciferase reporter constructs into mouse livers in vivo. This study underscores the power of mass spectrometry-based metabolomics combined with genomic and physiologic analyses in identifying downstream metabolic biomarkers and the corresponding upstream molecular mechanisms.

Education of tobacco use prevention and cessation for dental professionals--a paradigm shift

The use of tobacco continues to be a substantial risk factor in the development and progression of oral cancer, periodontitis, implant failure and poor wound healing. Dental and dental hygiene education providers have made great advances towards the incorporation of tobacco education into their curricula in recent years. Unfortunately, however, both medical and dental education research has consistently reported schools providing only basic knowledge-based curricula that rarely incorporate more effective, behaviourally-based components affecting long-term change. The limited training of oral healthcare students, at least in part, is reflected in practising dental professionals continuing to report offering incomplete tobacco interventions. In order to prepare the next generation of oral healthcare providers, this paper proposes a paradigm shift in how tobacco use prevention and cessation (TUPAC) may be incorporated into existing curricula. It is suggested that schools should carefully consider: to what level of competency should TUPAC be trained in dental and dental hygiene schools; the importance of establishing rapport through good communication skills; the core knowledge level for TUPAC; suggested instructional and assessment strategies; the importance of continuing professional education for the enhancement of TUPAC.