Prospective evaluation of three point of care devices for glycemia measurement in a neonatal intensive care unit.

Hypoglycemia, if recurrent, may have severe consequences on cognitive and psychomotor development of neonates. Therefore, screening for hypoglycemia is a daily routine in every facility taking care of newborn infants. Point-of-care-testing (POCT) devices are interesting for neonatal use, as their handling is easy, measurements can be performed at bedside, demanded blood volume is small and results are readily available. However, such whole blood measurements are challenged by a wide variation of hematocrit in neonates and a spectrum of normal glucose concentration at the lower end of the test range. We conducted a prospective trial to check precision and accuracy of the best suitable POCT device for neonatal use from three leading companies in Europe. Of the three devices tested (Precision Xceed, Abbott; Elite XL, Bayer; Aviva Nano, Roche), Aviva Nano exhibited the best precision. None completely fulfilled the ISO-accuracy-criteria 15197: 2003 or 2011. Aviva Nano fulfilled these criteria in 92% of cases while the others were <87%. Precision Xceed reached the 95% limit of the 2003 ISO-criteria for values ≤4.2 mmol/L, but not for the higher range (71%). Although validated for adults, new POCT devices need to be specifically evaluated on newborn infants before adopting their routine use in neonatology.

Functional analysis of the post-transcriptional regulator RsmA reveals a novel RNA-binding site.

The RsmA family of RNA-binding proteins are global post-transcriptional regulators that mediate extensive changes in gene expression in bacteria. They bind to, and affect the translation rate of target mRNAs, a function that is further modulated by one or more, small, untranslated competitive regulatory RNAs. To gain new insights into the nature of this protein/RNA interaction, we used X-ray crystallography to solve the structure of the Yersinia enterocolitica RsmA homologue. RsmA consists of a dimeric beta barrel from which two alpha helices are projected. From structure-based alignments of the RsmA protein family from diverse bacteria, we identified key amino acid residues likely to be involved in RNA-binding. Site-specific mutagenesis revealed that arginine at position 44, located at the N terminus of the alpha helix is essential for biological activity in vivo and RNA-binding in vitro. Mutation of this site affects swarming motility, exoenzyme and secondary metabolite production in the human pathogen Pseudomonas aeruginosa, carbon metabolism in Escherichia coli, and hydrogen cyanide production in the plant beneficial strain Pseudomonas fluorescens CHA0. R44A mutants are also unable to interact with the small untranslated RNA, RsmZ. Thus, although possessing a motif similar to the KH domain of some eukaryotic RNA-binding proteins, RsmA differs substantially and incorporates a novel class of RNA-binding site.

In vitro susceptibility characteristics of Cryptococcus neoformans varieties from AIDS patients in Goiânia, Brazil

Sixty clinical isolates of Cryptococcus neoformans from AIDS from Goiânia, state of Goiás, Brazil, were characterized according to varieties, serotypes and tested for antifungal susceptibility. To differentiate the two varieties was used L-canavanine-glycine-bromothymol blue medium and to separate the serotypes was used slide agglutination test with Crypto Check Iatron. The Minimal Inhibitory Concentration (MIC) of fluconazole, itraconazole, and amphotericin B were determined by the National Committee for Clinical Laboratory Standards macrodilution method. Our results identified 56 isolates as C. neoformans var. neoformans serotype A and 4 isolates as C. neoformans var. gattii serotype B. MIC values for C. neoformans var. gattii were higher than C. neoformans var. neoformans. We verified that none isolate was resistant to itraconazole and to amphotericin B, but one C. neoformans var. neoformans and three C. neoformans var. gattii isolates were resistant to fluconazole. The presence of C. neoformans var. gattii fluconazole resistant indicates the importance of determining not only the variety of C. neoformans infecting the patients but also measuring the MIC of the isolate in order to properly orient treatment.

Antimicrobial activity of Hyptis ovalifolia towards dermatophytes

The essential oil and the aqueous, hexane and methanolic fractions from Hyptis ovalifolia leaves were evaluated for their antifungal activity in vitro against 60 strains of dermatophytes: 10 strains of Microsporum canis, 10 of M. gypseum, 20 of Trichophyton rubrum and 20 of T. mentagrophytes. The extracts inhibited growth of the dermatophytes tested at different concentrations. The most biologically active was the essential oil from the leaves which inhibited 57 isolates (95%) at a concentration of £ 500 µg/ml.

Bicc1 links the regulation of cAMP signaling in polycystic kidneys to microRNA-induced gene silencing.

Genetic defects in autosomal-dominant polycystic kidney disease (ADPKD) promote cystic growth of renal tubules, at least in part by stimulating the accumulation of cAMP. How renal cAMP levels are regulated is incompletely understood. We show that cAMP and the expression of its synthetic enzyme adenylate cyclase-6 (AC6) are up-regulated in cystic kidneys of Bicc1(-)(/-) knockout mice. Bicc1, a protein comprising three K homology (KH) domains and a sterile alpha motif (SAM), is expressed in proximal tubules. The KH domains independently bind AC6 mRNA and recruit the miR-125a from Dicer, whereas the SAM domain enables silencing by Argonaute and TNRC6A/GW182. Bicc1 similarly induces silencing of the protein kinase inhibitor PKIα by miR-27a. Thus, Bicc1 is needed on these target mRNAs for silencing by specific miRNAs. The repression of AC6 by Bicc1 might explain why cysts in ADPKD patients preferentially arise from distal tubules.

Nanopartikel am Arbeitsplatz

Nanopartikel sind sehr kleine Partikel, die gezielt so hergestellt sind, dass ihr Durchmesser kleiner als etwa 100 nm ist. Sie werden in der Industrie eingesetzt, weil Materialien mit solch kleinen Dimensionen oft neue Eigenschaften aufweisen, die sie vom Ursprungsmaterial unterscheidet. Das Potenzial für mögliche Gesundheits- und Umwelteffekte von Nanomaterialien wird zurzeit intensiv diskutiert, denn die möglichen Effekte der neuen Eigenschaften auf Umwelt und Gesundheit sind erst unvollständig geklärt. Für die Abklärung der Risiken ist es wichtig, Informationen über die möglichen Expositionen und mögliche Freisetzungen in die Umwelt zu haben. Bisher wurden aber Daten über eingesetzte Stoffmengen und Materialarten selten systematisch erhoben. Wir haben in der Schweiz eine repräsentative Studie durchgeführt, um den Einsatz von Nanopartikeln im gesamten Industriesektor abschätzen zu können. Diese Studie ist unseres Wissens weltweit die erste solche Studie. Sie verwendete die Definition von Nanopartikeln, welche Nanofasern und Agglomerate von Nanopartikeln mit einschließt. Geschätzte 1.300 Arbeiter in 600 Firmen sind direkt an einer Nanopartikelanwendung beteiligt und könnten somit exponiert werden. Dies sind etwa 0,6% der Firmen und etwa 0,08% der Arbeiter des Schweizer Produktionssektors. Um nun zu bestimmen, ob solche Arbeiter mit Nanopartikel in Kontakt kommen oder nicht, stehen verschiedene Messmethoden zur Verfügung. Die aktuelle Technik erlaubt eine quantitative Messung der Anzahl der Partikel in der Luft, deren Masse oder auch Oberfläche. Diese Messgrößen allein geben zwar Hinweise auf die Präsenz von Nanopartikeln, die möglichen Gesundheitseffekte einer Exposition sind aber erst unvollständig abgeklärt und erlauben keine abschließende Risikoanalyse für den Arbeitsplatz. Mehrere Aktionspläne für die Entwicklung eines sicheren und nachhaltigen Umgangs mit Nanomaterialien wurden in den letzten Jahren gestartet (EU, Schweiz). Internationale und nationale Organisationen entwickelten Guidelines und Empfehlungen für industrielle Anwendungen (Internationale Organisation für Normung - ISO, Schweizerische Unfallversicherungsanstalt - SUVA, Bundesanstalt für Arbeitsschutz und Arbeitsmedizin - BAuA, zusammen mit dem Verband der Chemischen Industrie - VCI). Diese generellen Informationen müssen nun in die Industrie transferiert und an die spezifischen Bedürfnisse der betroffenen Unternehmen angepasst werden. Die aufgezeigte, relativ geringe Verbreitung von Nanopartikelanwendungen in der Industrie weist darauf hin, dass heute Schutzmaßnahmen noch proaktiv und kostengünstig entwickelt und eingeführt werden können. Aber sollte die vorhergesagte "Nano-Revolution" wirklich eintreten, ist die Zeit gekommen, jetzt aktiv zu werden. [Autoren]

Brain network analysis of patients with Temporal Lobe Epilepsy

Patients with Temporal Lobe Epilepsy (TLE) suffer from widespread subtle white matter abnormalities and abnormal functional connectivity extending beyond the affected lobe, as revealed by Diffusion Tensor MR Imaging, volumetric and functional MRI studies. Diffusion Spectrum Imaging (DSI) is a diffusion imaging technique with high angular resolution for improving the mapping of white matter pathways. In this study, we used DSI, connectivity matrices and topological measures to investigate how the alteration in structural connectivity influences whole brain structural networks. Eleven patients with right-sided TLE and hippocampal sclerosis and 18 controls underwent our DSI protocol at 3T. The cortical and subcortical grey matters were parcellated into 86 regions of interest and the connectivity between every region pair was estimated using global tractography and a connectivity matrix (the adjacency matrix of the structural network). We then compared the networks of patients and controls using topological measures. In patients, we found a higher characteristic path length and a lower clustering coefficient compared to controls. Local measures at node level of the clustering and efficiency showed a significant difference after a multiple comparison correction (Bonferroni). These significant nodes were located within as well outside the temporal lobe, and the localisation of most of them was consistent with regions known to be part of epileptic networks in TLE. Our results show altered connectivity patterns that are concordant with the mapping of functional epileptic networks in patients with TLE. Further studies are needed to establish the relevance of these findings for the propagation of epileptic activity, cognitive deficits in medial TLE and outcome of epilepsy surgery in individual patients.

Nanoparticle usage and protection measures in the manufacturing industry : a representative survey

Addressing the risks of nanoparticles requires knowledge about release into the environment and occupational exposure. However, such information currently is not systematically collected; therefore, this risk assessment lacks quantitative data. The goal was to evaluate the current level of nanoparticle usage in Swiss industry as well as health, safety, and environmental measures, and the number of potentially exposed workers. A representative, stratified mail survey was conducted among 1626 clients of the Swiss National Accident Insurance Fund (SUVA), which insures 80,000 manufacturing firms, representing 84% of all Swiss manufacturing companies (947 companies answered the survey for a 58.3% response rate). The extrapolation to all Swiss manufacturing companies results in 1309 workers (95% confidence interval [CI]: 1073 to 1545) potentially exposed to nanoparticles in 586 companies (95% CI: 145 to 1027). This corresponds to 0.08% of workers (95% CI: 0.06% to 0.09%) and to 0.6% of companies (95% CI: 0.2% to 1.1%). The industrial chemistry sector showed the highest percentage of companies using nanoparticles (21.2%). Other important sectors also reported nanoparticles. Personal protection equipment was the predominant protection strategy. Only a few applied specific environmental protection measures. This is the first nationwide representative study on nanoparticle use in the manufacturing sector. The information gained can be used for quantitative risk assessment. It can also help policymakers design strategies to support companies developing a safer use of nanomaterial. Notingthe current low use of nanoparticles, there is still time to proactively introduce protective methods. If the predicted "nano-revolution" comes true, now is the time to take action. [Supplementary materials are available for this article. Go to the publisher's online edition of Journal of occupational and Environmental Hygiene for the following free supplemental resource: a pdf file containing a detailed description of the approach to statistical analyses, English translation of the questionnaire, additional information for Figure 1, and additional information for the SUVA-code.] [Authors]

How Can Nanotechnology Help to Repair the Body? Advances in Cardiac, Skin, Bone, Cartilage and Nerve Tissue Regeneration

Nanotechnologists have become involved in regenerative medicine via creation of biomaterials and nanostructures with potential clinical implications. Their aim is to develop systems that can mimic, reinforce or even create in vivo tissue repair strategies. In fact, in the last decade, important advances in the field of tissue engineering, cell therapy and cell delivery have already been achieved. In this review, we will delve into the latest research advances and discuss whether cell and/or tissue repair devices are a possibility. Focusing on the application of nanotechnology in tissue engineering research, this review highlights recent advances in the application of nano-engineered scaffolds designed to replace or restore the followed tissues: (i) skin; (ii) cartilage; (iii) bone; (iv) nerve; and (v) cardiac.