Deactivation of Macrophages with Interleukin-4 Is the Key to the Isolation of Tropheryma whippelii

Whipple's disease is a systemic illness caused by a specific agent. Despite recognition of bacteria in lesions, efforts to isolate the causative agent remained futile. A novel strategy was devised to culture Whipple bacilli in deactivated mononuclear phagocytes. Infected tissue was inoculated into human phagocytes deactivated with interleukin (IL)-4, IL-10, and dexamethasone. Within 8-10 days, diastase-resistant periodic acid-Schiff-positive inclusions appeared, corresponding to intact and degenerating bacteria shown to be Tropheryma whippelii by electron microscopy and molecular analyses. T. whippelii was passaged several times in deactivated monocytes and a monoblastic cell line. Time-kinetics growth studies and comparative polymerase chain reaction analysis documented multiplication of T. whippelii in deactivated macrophages. Complementary studies showed that IL-4 rendered phagocytes permissive for T. whippelii, a strong indication that host factors contribute to the pathogenesis of Whipple's disease. The propagation of T. whippelii will permit microbiologic, immunologic, seroepidemiologic, and therapeutic studies of this pathoge

Neoadjuvant targeting of glioblastoma multiforme with radiolabeled DOTAGA-substance P—results from a phase I study

Complete surgical resection beyond tumor margins cannot be achieved in glioblastoma multiforme (GBM) because of infiltrative nature. In several cancers, neoadjuvant treatment has been implemented to reduce the risk of tumor cell spreading during resection. In GBM, the objective of a neoadjuvant approach is reduction of tumor cells within the main tumor mass and beyond in the infiltration zone. Such an approach can only be performed if elevated intracranial pressure can be medically controlled. In a previous study with recurrent gliomas, we showed that local intratumoral injection of radiolabeled DOTAGA-substance P substantially inhibited further growth and led to radionecrotic transformation of the tumor (CCR 2006). We have now examined this modality as neoadjuvant treatment for GBM, primarily assessing feasibility, toxicity, the extent of resection, and functional outcome. After diagnosis of GBM, 17 patients were included in a prospective phase I study. Repetitive intratumoral injections of radiolabeled DOTAGA-substance P were performed, followed by surgical resection. Chemical synthesis, radiolabeling, and local injection of the peptidic vector [90Yttrium]-DOTAGA-substance P were described previously. Neoadjuvant injection of [90Y]-DOTAGA-substance P was feasible without decompensation of intracranial pressure. Prolonged application of corticosteroids was identified as the main risk factor for side effects. Fifteen patients stabilized or improved their functional status. The mean extent of resection in subsequent surgery was 96%. Neoadjuvant therapy of GBM using locally injected radiolabeled DOTAGA-substance P was feasible and of low toxicity. The high extent of resection and concomitant irradiation of tumor cells in the infiltration zone may be prognostically relevan

Clinical and radiographic performance of late placed and early loaded dental implants with a conditioned hydrophilic surface in posterior mandible sites: A prospective case series with an 8.5‐ to 9.5‐year follow‐up

Objective: To assess the clinical outcomes by means of implant and prosthetic survival of late placed and early loaded implants with a hydrophilic, moderately rough surface for partially edentulous patients after a follow‐up of 8.5 to 9.5 years.Materials and methodsA prospective case series study involving 15 patients with single, late placed and early loaded implants in the posterior mandible was performed. Clinical and radiographical parameters, including biological and technical complications and patient satisfaction, were assessed.ResultsFrom an initial sample of 15 patients, 12 were included. A total of 16 implants were observed. After a mean follow‐up of 9 years and 7 months (SD ± 3.8 months), implant success and survival rate were 100%. The prosthetic survival rate was 100%, and the prosthetic success rate was 93.8% since a major chipping was observed. No biological complications were observed, and the mean modified plaque index was 0.03 (SD ± 0.09) with a mean probing pocket depth of 2.95 mm (SD ± 0.09). A mean marginal bone level (MBL) of 0.04 mm (SD ± 0.88) and a mean VAS of 9.42 (SD ± 0.90) for patient satisfaction were recorded.ConclusionLate placed and early loaded implants with a moderately rough endosseal surface are a reliable option for rehabilitating partially edentulous patients. An implant survival rate of 100% and a prosthodontic success rate of 93.8% were observed. Patient satisfaction scores were high and peri‐implant hard and soft tissues remained healthy. The study findings should be carefully interpreted because of the small sample

Individual particle handling in a microfluidic system based on parallel laser trapping

We present an optical trapping system combining individually addressable multiple laser traps with fluorescence spectroscopy. An in-line set of 64 near-IR laser diodes is used to create a line of individually addressable traps inside a microfluidic chip. This system is completed by an excitation/detection line for spectrally resolved fluorescence imaging of trapped particles. Highly parallel trapping in a constant flow (up to a few millimeters per second), fast particle handling rates (up to a few particles per second), and the possibility of recording fluorescence spectra of trapped objects lead to a performing bioanalytical platform, e. g., for highly parallel analysis and sorting. (C) 2011 Optical Society of Americ

Machine learning-led semi-automated medium optimization reveals salt as key for flaviolin production in Pseudomonas putida.

Although synthetic biology can produce valuable chemicals in a renewable manner, its progress is still hindered by a lack of predictive capabilities. Media optimization is a critical, and often overlooked, process which is essential to obtain the titers, rates and yields needed for commercial viability. Here, we present a molecule- and host-agnostic active learning process for media optimization that is enabled by a fast and highly repeatable semi-automated pipeline. Its application yielded 60% and 70% increases in titer, and 350% increase in process yield in three different campaigns for flaviolin production in Pseudomonas putida KT2440. Explainable Artificial Intelligence techniques pinpointed that, surprisingly, common salt (NaCl) is the most important component influencing production. The optimal salt concentration is very high, comparable to seawater and close to the limits that P. putida can tolerate. The availability of fast Design-Build-Test-Learn (DBTL) cycles allowed us to show that performance improvements for active learning are rarely monotonous. This work illustrates how machine learning and automation can change the paradigm of current synthetic biology research to make it more effective and informative, and suggests a cost-effective and underexploited strategy to facilitate the high titers, rates and yields essential for commercial viability

Renal uptake of different radiolabelled peptides is mediated by megalin: SPECT and biodistribution studies in megalin-deficient mice

Contains fulltext : 98302.pdf (publisher's version ) (Closed access)PURPOSE: Radiolabelled peptides used for peptide receptor radionuclide therapy are excreted mainly via the kidneys and are partly reabsorbed and retained in the proximal tubular cells. The resulting high renal radiation dose can cause nephrotoxicity, limiting the maximum activity dose and the effectiveness of peptide receptor radionuclide therapy. The mechanisms of kidney reabsorption of these peptides are incompletely understood, but the scavenger receptor megalin has been shown to play a role in the reabsorption of (111)In-octreotide. In this study, the role of megalin in the renal reabsorption of various relevant radiolabelled peptides was investigated. METHODS: Groups of kidney-specific megalin-deficient mice and wild-type mice were injected with (111)In-labelled somatostatin, exendin, neurotensin or minigastrin analogues. Single photon emission computed tomographic (SPECT) images of the kidneys were acquired and analysed quantitatively, or the animals were killed 3 h after injection and the activity concentration in the kidneys was measured. RESULTS: Megalin-deficient mice showed significantly lower uptake of all studied radiolabelled peptides in the kidneys, ranging from 22% ((111)In-octreotide) to 65% ((111)In-exendin) of uptake in wild-type kidneys. Quantitative analysis of renal uptake by SPECT and ex vivo measurements showed a very good correlation. CONCLUSION: Megalin is involved in the renal reabsorption of radiolabelled octreotide, octreotate, exendin, neurotensin and minigastrin. This knowledge may help in the design of strategies to reduce this reabsorption and the resulting nephrotoxicity in peptide receptor radionuclide therapy, enabling more effective therapy. Small-animal SPECT is an accurate tool, allowing in vivo quantification of renal uptake and serial measurements in individual mice

Konsum von Energy-Drinks im Sekundarschulalter und die Auswirkung auf die Konzentrationsleistung

Die Wirkung von Energy-Drinks und deren Inhaltsstoffen auf den menschlichen Kör-per wurde bereits ausgiebig untersucht. Bisherige Befunde weisen jedoch weder po-sitive noch negative Auswirkungen auf den Organismus aus, vorausgesetzt der Kon-sum ist nicht chronisch (Konsum an 4-5 Tagen der Woche) und überschreitet die Menge von ungefähr einem Liter pro Woche nicht. In der vorliegenden Arbeit wird der Konsum von Energy-Drinks und die damit ver-bundene Auswirkung auf die Konzentrationsleistung von Kindern und Jugendlichen näher betrachtet und anhand der Hypothese, dass der Konsum von Energy-Drinks die schulische Konzentrationsleistung von Kindern und Jugendlichen im Sekundar-schulalter negativ beeinflusst, geprüft. Durch eine Studie mit einer Stichprobengrösse von n=21 wird der Konsum von Ener-gy-Drinks und die damit verbundene Auswirkung auf die Konzentrationsleistung in drei Klassen der Oberstufe untersucht. Dafür wird der Test d2-R zu zwei unterschied-lichen Zeitpunkten durchgeführt, einmal mit dem Konsum 30 Minuten vor dem Test, einmal mit dem Konsum eines neutralen Ersatzgetränkes (Coca-Cola Zero koffein-frei). Dabei wurden Daten zur Konzentrationsleistung in Abhängigkeit zum Konsum von Energy-Drinks gesammelt. Die Ergebnisse der Testpersonen, welche vor dem Test einen Energy-Drink konsumiert haben, weisen darauf hin, dass sowohl im ers-ten, wie auch im zweiten Testdurchgang unter Einfluss der Wirkstoffe von 2.5dl Energy-Drink tiefere Konzentrationsleistungen erreicht wurden. Mit einem Wert von t(16)=0.352 für den ersten Testdurchgang und t(13)= 0.068 für den zweiten wurden jedoch knapp keine signifikanten Werte erreicht, die Hypothese muss somit diesbe-züglich verworfen werden. Lediglich wenn die Ergebnisse aus den beiden Testdurchgängen je Getränkegruppe addiert werden, ergeben sich signifikante Unterschiede mit einem Wert von t(17)= 0.0033*. Dabei sind die Unterschiede auf die hohen Konzentrationen der einzelnen Inhaltsstoffe (Koffein, Taurin und Zucker), der damit verbundene rasante Anstieg und Zerfall des Blutzuckerspiegels und den Übungseffekt zurückzuführen. Der Übungsef-fekt kann trotz der Tatsache, dass er wohl bei beiden Testgruppen im 2. Durchgang ungefähr den gleichen Einfluss auf die erbrachten Resultate genommen hat, nicht vernachlässigt werden. Die Ergebnisse sind somit mit Vorsicht zu geniessen und aufgrund der kleinen Stichprobengrösse nicht repräsentativ