Epidemiological and clinical characteristics of nosocomial candidiasis in university hospitals in Cuiaba - Mato Grosso, Brazil

Background: Fungal infections are emerging as an important cause of human disease, especially among hospitalized patients with serious underlying disease and several risk factors. Aims: To evaluate epidemiological and clinical characteristics of patients with nosocomial candidiasis in university hospitals in Cuiaba - MT, Brazil. Methods: A descriptive study of 91 patients admitted to university hospitals in Cuiaba - MT, with clinical and laboratory diagnosis of nosocomial candidiasis, over a 20-month period. Results: A rate for nosocomial infections by Candida spp. of 5 per 1000 admissions, proportional mortality of 14.4% and lethality of 53.8% were determined. The patient age ranged from 29 days to 82 years-old, among which, 74.7% were adults and 25.3% children. The intensive care units contributed with the highest number of cases of infection by Candida spp. (69.2%). The most important underlying disease was gastrointestinal tract disease (11%). Prematurity and low birth weight were the most important risk factors among newborns. The use of antibiotics, invasive procedures, H-2 blockers, multiple blood transfusions and stay length of >= 21 days were the most frequent risk factors among adults. Candida albicans was the most common species in all cases. Conclusions: In this study, C. albicans was the most frequently detected species in candidiasis and risk factors increased the susceptibility of hospitalized patients to acquiring a nosocomial infection by Candida spp. (C) 2011 Revista Iberoamericana de Micologia. Published by Elsevier Espana, S.L. All rights reserved.

Cold-Nuclear-Matter Effects on Heavy-Quark Production in d+Au Collisions at root S-NN=200 GeV

The PHENIX experiment has measured electrons and positrons at midrapidity from the decays of hadrons containing charm and bottom quarks produced in d + Au and p + p collisions at root S-NN = 200 GeV in the transverse-momentum range 0.85 <= p(T)(e) <= 8.5 GeV/c. In central d + Au collisions, the nuclear modification factor R-dA at 1.5 < p(T) < 5 GeV/c displays evidence of enhancement of these electrons, relative to those produced in p + p collisions, and shows that the mass-dependent Cronin enhancement observed at the Relativistic Heavy Ion Collider extends to the heavy D meson family. A comparison with the neutral-pion data suggests that the difference in cold-nuclear-matter effects on light- and heavy-flavor mesons could contribute to the observed differences between the pi(0) and heavy-flavor-electron nuclear modification factors R-AA. DOI: 10.1103/PhysRevLett.109.242301

Deviation from quark number scaling of the anisotropy parameter v(2) of pions, kaons, and protons in Au+Au collisions at root s(NN)=200 GeV

Measurements of the anisotropy parameter v(2) of identified hadrons (pions, kaons, and protons) as a function of centrality, transverse momentum p(T), and transverse kinetic energy KET at midrapidity (vertical bar eta vertical bar < 0.35) in Au + Au collisions at root s(N N) = 200 GeV are presented. Pions and protons are identified up to p(T) = 6 GeV/c, and kaons up to p(T) = 4 GeV/c, by combining information from time-of-flight and aerogel Cerenkov detectors in the PHENIX Experiment. The scaling of v(2) with the number of valence quarks (n(q)) has been studied in different centrality bins as a function of transverse momentum and transverse kinetic energy. A deviation from previously observed quark-number scaling is observed at large values of KET/n(q) in noncentral Au + Au collisions (20-60%), but this scaling remains valid in central collisions (0-10%).

Inverse size exclusion chromatography (ISEC)

In this work, an improved protocol for inverse size-exclusion chromatography (ISEC) was established to assess important pore structural data of porous silicas as stationary phases in packed chromatographic columns. After the validity of the values generated by ISEC was checked by comparison with data obtained from traditional methods like nitrogen sorption at 77 K (Study A), the method could be successfully employed as valuable tool at the development of bonded poly(methacrylate)-coated silicas, while traditional methods generate partially incorrect pore structural information (Study B). Study A: Different mesoporous silicas were converted by a pseudomorphical transition into ordered MCM-41-type silica while maintaining the particle-size and -shape. The essential parameters like specific surface area, average pore diameter and specific pore volume, the pore connectivity from ISEC remained nearly the same which was reflected by the same course of the theoretical plate height vs. linear velocity curves. Study B: In the development of bonded poly(methacrylate)-coated silicas for the reversed phase separation of biopolymers, ISEC was the only method to generate valid pore structural information of the polymer-coated materials. Synthesis procedures were developed to obtain reproducibly covalently bonded poly(methacrylate) coatings with good thermal stability on different base materials, employing as well particulate and monolithic materials.

NMR spectroscopy and imaging of hyperpolarized gases

Since the discovery of the nuclear magnetic resonance (NMR) phenomenon, countless NMR techniques have been developed that are today indispensable tools in physics, chemistry, biology, and medicine. As one of the main obstacles in NMR is its notorious lack of sensitivity, different hyperpolarization (HP) methods have been established to increase signals up to several orders of magnitude. In this work, different aspects of magnetic resonance, using HP noble gases, are studied, hereby combining different disciplines of research. The first part examines new fundamental effects in NMR of HP gases, in theory and experiment. The spin echo phenomenon, which provides the basis of numerous modern experiments, is studied in detail in the gas phase. The changes of the echo signal in terms of amplitude, shape, and position, due to the fast translational motion, are described by an extension of the existing theory and computer simulations. With this knowledge as a prerequisite, the detection of intermolecular double-quantum coherences was accomplished for the first time in the gas phase. The second part of this thesis focuses on the development of a practical method to enhance the dissolution process of HP 129Xe, without loss of polarization or shortening of T1. Two different setups for application in NMR spectroscopy and magnetic resonance imaging (MRI) are presented. The continuous operation allows biological and multidimensional spectroscopy in solutions. Also, first in vitro MRI images with dissolved HP 129Xe as contrast agent were obtained at a clinical scanner.

Analisi Convessa in Spazi Vettoriali Topologici e Ottimizzazione

Questa tesi presenta alcuni aspetti dell'analisi convessa, in spazi vettoriali topologici, indirizzati allo studio di problemi generali di minimizzazione. Dai risultati geometrici dei teoremi di Hahn-Banach, attraverso la descrizione di proprietà fondamentali delle funzioni convesse e del sottodifferenziale, viene descritta la dualità di Fenchel-Moreau, e poi applicata a problemi generali di Ottimizzazione convessa, sotto forma prima di problema primale-duale, e poi come rapporto tra i punti di sella della Lagrangiana e le soluzioni della funzione da minimizzare.

Einfluss des Treg-Aktivierungsmarkers GARP auf die Differenzierung und Funktion von T-Zellen

CD4+CD25+FoxP3+ regulatorische T-Zellen (Treg) spielen eine essentielle Rolle bei der Unterdrückung von schädlichen Immunreaktionen. Da aktivierte CD4+ T-Helferzellen auch CD25 und FoxP3 exprimieren, können diese nicht als spezifische Marker zur Identifikation von Treg verwendet werden. Die Analyse der Membranproteinexpression beider Populationen führte zur Identifikation von GARP (glycoprotein A repetitions predominant) als spezifischer Marker auf aktivierten Treg. GARP bindet LAP und TGF-beta, welches für die Unterdrückung von entzündlichen T-Zellantworten von Bedeutung ist. Um die Funktion von GARP unabhängig von Treg zu untersuchen, wurde ein lösliches GARP Protein (sGARP) synthetisiert und sein Effekt auf die Aktivierung und Differenzierung von humanen T-Zellen untersucht. Die Ergebnisse zeigen, dass sGARP die Proliferation von naiven CD4+ T-Zellen supprimiert und zu einer Phosphorylierung von SMAD2/3 sowie zu der Induktion von FoxP3 führt. Zusätzlich inhibiert sGARP die Produktion von Effektorzytokinen wie IL-2 und IFN-gamma. Die Stimulation von naiven CD4+ T-Zellen mit sGARP induziert die Differenzierung zu Treg, welche in Kokultur die Aktivierung von T-Effektorzellen supprimieren. Die Wirkung war vergleichbar in naiven CD4+ und ruhenden CD4+CD45RA+ T-Zellen, konnte aber in differenzierten CD4+CD45RO+ T-Zellen nicht nachgewiesen werden. Die Induktion von FoxP3 und die Phosphorylierung von SMAD2/3 konnte durch eine Blockade des TGF-beta-Signalweges inhibiert werden. Dies lässt vermuten, dass die Funktion von sGARP zumindest teilweise von TGF-beta abhängig ist. Zusätzlich zu seiner passiven Rolle als TGF-beta-Transporter, induzierte sGARP die TGF-beta-Produktion in naiven T-Zellen und trägt so zum Mechanismus der infektiösen Toleranz bei. Des Weiteren fördert die Stimulation von sGARP in Anwesenheit von IL-6 und IL-23 die Differenzierung zu Th17 Zellen. rnNeben dem Einfluss von sGARP auf die Differenzierung von CD4+ T-Zellen, supprimiert sGARP die Proliferation und Granzyme B-Expression in CD8+ T-Zellen. rnFür die Analyse der immunmodulatorischen Funktion von sGARP in vivo wurde ein Modell einer xenogenen GvHD (graft-versus-host disease) verwendet. Der Transfer von humanen PBMC in neugeborene, immundefiziente Rag2-/-gamma-chain-/--Mäuse führt zu einer letalen GvHD, welche durch die Applikation von humanen Treg dosisabhängig unterdrückt werden kann. In diesem Modell konnte die repetitive Gabe von sGARP, ohne zusätzliche Zugabe von Treg, ebenfalls die GvHD unterdrücken. Dies lässt auf einen synergistischen Effekt von sGARP und Treg bei der Suppression inflammatorischer T-Zellantworten schließen. rnZusammengefasst lassen die Ergebnisse auf eine entscheidende Rolle von GARP in der Modulation der peripheren Toleranz folgern und zeigen sGARP als potentes Biological für die Behandlung von unerwünschten inflammatorischen Immunantworten.

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G presenting as childhood-onset severe myopathy: threshold determination through segregation study

Mitochondrial tRNA(Leu(UUR)) mutation m.3302A > G is associated with respiratory chain complex I deficiency and has been described as a rare cause of mostly adult-onset slowly progressive myopathy. Five families with 11 patients have been described so far; 5 of them died young due to cardiorespiratory failure. Here, we report on a segregation study in a family with an index patient who already presented at the age of 18 months with proximal muscular hypotonia, abnormal fatigability, and lactic acidosis. This early-onset myopathy was rapidly progressive. At 8 years, the patient is wheel-chair bound, requires nocturnal assisted ventilation, and suffers from recurrent respiratory infections. Severe complex I deficiency and nearly homoplasmy for m.3302A > G were found in muscle. We collected blood, hair, buccal swabs and muscle biopsies from asymptomatic adults in this pedigree and determined heteroplasmy levels in these tissues as well as OXPHOS activities in muscle. All participating asymptomatic adults had normal OXPHOS activities. In contrast to earlier reports, we found surprisingly little variation of heteroplasmy levels in different tissues of the same individual. Up to 45% mutation load in muscle and up to 38% mutation load in other tissues were found in non-affected adults. The phenotypic spectrum of tRNA(Leu(UUR)) m.3302A > G mutation seems to be wider than previously described. A threshold of more than 45% heteroplasmy in muscle seems to be necessary to alter complex I activity leading to clinical manifestation. The presented data may be helpful for prognostic considerations and counseling in affected families.

Pregnancy and reproduction in autoimmune rheumatic diseases

Despite evidence for the important role of oestrogens in the aetiology and pathophysiology of chronic immune/inflammatory diseases, the previous view of an unequivocal beneficial effect of oestrogens on RA compared with a detrimental effect on SLE has to be reconsidered. Likewise, the long-held belief that RA remits in the majority of pregnant patients has been challenged, and shows that only half of the patients experience significant improvement when objective disease activity measurements are applied. Pregnancies in patients with SLE are mostly successful when well planned and monitored interdisciplinarily, whereas a small proportion of women with APS still have adverse pregnancy outcomes in spite of the standard treatment. New prospective studies indicate better outcomes for pregnancies in women with rare diseases such as SSc and vasculitis. Fertility problems are not uncommon in patients with rheumatic disease and need to be considered in both genders. Necessary therapy, shortly before or during the pregnancy, demands taking into account the health of both mother and fetus. Long-term effects of drugs on offspring exposed in utero or during lactation is a new area under study as well as late effects of maternal rheumatic disease on children.

Dynamic reorganization of flotillins in chemokine-stimulated human T-lymphocytes

Different types of membrane microdomains (rafts) have been postulated to be present in the rear and front of polarized migrating T-lymphocytes. Disruption of rafts by cholesterol sequestration prevents T-cell polarization and migration. Reggie/flotillin-1 and -2 are two highly homologous proteins that are thought to shape membrane microdomains. We have previously demonstrated the enrichment of flotillins in the uropod of human neutrophils. We have now investigated mechanisms involved in chemokine-induced flotillin reorganization in human T-lymphocytes, and possible roles of flotillins in lymphocyte polarization.

Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer

Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy.

Phosphatidylethanol (PEth) as a Biomarker of Alcohol Consumption in HIV-Positive Patients in Sub-Saharan Africa

Background:  Alcohol is heavily consumed in sub-Saharan Africa and affects HIV transmission and treatment and is difficult to measure. Our goal was to examine the test characteristics of a direct metabolite of alcohol consumption, phosphatidylethanol (PEth). Methods:  Persons infected with HIV were recruited from a large HIV clinic in southwestern Uganda. We conducted surveys and breath alcohol concentration (BRAC) testing at 21 daily home or drinking establishment visits, and blood was collected on day 21 (n = 77). PEth in whole blood was compared with prior 7-, 14-, and 21-day alcohol consumption. Results:  (i) The receiver operator characteristic area under the curve (ROC-AUC) was highest for PEth versus any consumption over the prior 21 days (0.92; 95% confidence interval [CI]: 0.86 to 0.97). The sensitivity for any detectable PEth was 88.0% (95% CI: 76.0 to 95.6) and the specificity was 88.5% (95% CI: 69.8 to 97.6). (ii) The ROC-AUC of PEth versus any 21-day alcohol consumption did not vary with age, body mass index, CD4 cell count, hepatitis B virus infection, and antiretroviral therapy status, but was higher for men compared with women (p = 0.03). (iii) PEth measurements were correlated with several measures of alcohol consumption, including number of drinking days in the prior 21 days (Spearman r = 0.74, p < 0.001) and BRAC (r = 0.75, p < 0.001). Conclusions:  The data add support to the body of evidence for PEth as a useful marker of alcohol consumption with high ROC-AUC, sensitivity, and specificity. Future studies should further address the period and level of alcohol consumption for which PEth is detectable.

Characterization of sialic acid index of plasma apolipoprotein J and phosphatidylethanol during alcohol detoxification--a pilot study

Apolipoprotein J (ApoJ) is a component of plasma high-density lipoproteins. Previous studies have shown progressive recovery of ApoJ sialic acid content with increased duration of alcohol abstinence. Therefore, the sialic acid index of plasma apolipoprotein J (SIJ) seems to be a promising alcohol biomarker. Phosphatidylethanol (PEth) is a direct ethanol metabolite and has recently attracted attention as a biomarker of prolonged intake of higher amounts of alcohol. The aim of the pilot study was to explore sensitivity, specificity, and normalization of SIJ and PEth in comparison with traditional and emerging biomarkers.