γ-Catenin-Dependent Signals Maintain BCR-ABL1+ B Cell Acute Lymphoblastic Leukemia

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Field-Applicable Recombinase Polymerase Amplification Assay for Rapid Detection of Mycoplasma capricolum subsp. capripneumoniae

Contagious caprine pleuropneumonia (CCPP) is a highly contagious disease caused by Mycoplasma capricolum subsp. capripneumoniae that affects goats in Africa and Asia. Current available methods for the diagnosis of Mycoplasma infection, including cultivation, serological assays, and PCR, are time-consuming and require fully equipped stationary laboratories, which make them incompatible with testing in the resource-poor settings that are most relevant to this disease. We report a rapid, specific, and sensitive assay employing isothermal DNA amplification using recombinase polymerase amplification (RPA) for the detection of M. capricolum subsp. capripneumoniae. We developed the assay using a specific target sequence in M. capricolum subsp. capripneumoniae, as found in the genome sequence of the field strain ILRI181 and the type strain F38 and that was further evidenced in 10 field strains from different geographical regions. Detection limits corresponding to 5 × 10³ and 5 × 10⁴ cells/ml were obtained using genomic DNA and bacterial culture from M. capricolum subsp. capripneumoniae strain ILRI181, while no amplification was obtained from 71 related Mycoplasma isolates or from the Acholeplasma or the Pasteurella isolates, demonstrating a high degree of specificity. The assay produces a fluorescent signal within 15 to 20 min and worked well using pleural fluid obtained directly from CCPP-positive animals without prior DNA extraction. We demonstrate that the diagnosis of CCPP can be achieved, with a short sample preparation time and a simple read-out device that can be powered by a car battery, in <45 min in a simulated field setting.     

Arzneimittelprüfung an nicht einwilligungsfähigen Erwachsenen: Kritische Bewertung der neuen gesetzlichen Regelung durch medizinische Ethikkommissionen in Deutschland

Bundesgesundheitsblatt - Gesundheitsforschung - Gesundheitsschutz - In Deutschland wurde 2016 das 4.&nbsp;Arzneimittelrechtsänderungsgesetz (AMG) verabschiedet, welches auch die...     

Effects of ketamine and midazolam on resting state connectivity and comparison with ENIGMA connectivity deficit patterns in schizophrenia

Subanesthetic administration of ketamine is a pharmacological model to elicit positive and negative symptoms of psychosis in healthy volunteers. We used resting‐state pharmacological functional MRI (rsPhfMRI) to identify cerebral networks affected by ketamine and compared them to the functional connectivity (FC) in schizophrenia. Ketamine can produce sedation and we contrasted its effects with the effects of the anxiolytic drug midazolam. Thirty healthy male volunteers (age = 19–37 years) underwent a randomized, three‐way, cross‐over study consisting of three imaging sessions, with 48 hr between sessions. A session consisted of a control period followed by infusion of placebo or ketamine or midazolam. The ENIGMA rsfMRI pipeline was used to derive two long‐distance (seed‐based and dual‐regression) and one local (regional homogeneity, ReHo) FC measures. Ketamine induced significant reductions in the connectivity of the salience network (Cohen's d: 1.13 ± 0.28, p = 4.0 × 10^?3), auditory network (d: 0.67 ± 0.26, p = .04) and default mode network (DMN, d: 0.63 ± 0.26, p = .05). Midazolam significantly reduced connectivity in the DMN (d: 0.77 ± 0.27, p = .03). The effect sizes for ketamine for resting networks showed a positive correlation (r = .59, p = .07) with the effect sizes for schizophrenia‐related deficits derived from ENIGMA's study of 261 patients and 327 controls. Effect sizes for midazolam were not correlated with the schizophrenia pattern (r = ?.17, p = .65). The subtraction of ketamine and midazolam patterns showed a significant positive correlation with the pattern of schizophrenia deficits (r = .68, p = .03). RsPhfMRI reliably detected the shared and divergent pharmacological actions of ketamine and midazolam on cerebral networks. The pattern of disconnectivity produced by ketamine was positively correlated with the pattern of connectivity deficits observed in schizophrenia, suggesting a brain functional basis for previously poorly understood effects of the drug.     

Small‐Angle X‐Ray Scattering Measurements on Amphiphilic Polymer Conetworks Swollen in Orthogonal Solvents

Amphiphilic polymer conetworks (APCNs), which combine two different polymer nanophases, have a broad range of applications that involve their unique potential to separately swell one of these nanophases in a selective solvent. Little is known about the structural changes of such APCNs upon swelling in dependence on the topology. Here, conetworks composed of poly(2‐ethylhexyl acrylate) crosslinked by poly(2‐methyl‐2‐oxazoline) (PMOx) are investigated with small‐angle X‐ray scattering in dry and swollen state using the orthogonal solvents water and toluene. The data clearly show that the structural changes induced by swelling are strongly dependent on the topology of the APCNs. While water leads to fusion of PMOx phases resulting in larger structures than found in the dry APCN, toluene is only swelling the hydrophobic phases without structural changes.     

Evaluation of Glass Delamination Risk in Pharmaceutical 10 mL/10R Vials

Glass delamination is characterized by the dissociation of glass flakes from the glass surface. Since glass delamination is time dependent, 5 vial types were investigated to assess delamination under accelerated stress conditions published as quick tests in literature and compared to stress testing recommended per United States Pharmacopoeia <1660>. A broad panel of analytical techniques was employed to test the solution for visible/subvisible particles and leachables and characterize topography and composition of the surface. The vial types showed significant differences in surface durability when applying the same stress conditions. An increase in glass leachables and change in topography were shown for uncoated vials. An indication for an elevated delamination risk was confirmed for Expansion 33 vials only by the compiled analytical data set including particle assessment and change in elemental composition of the near glass surface investigated by dynamic secondary ion mass spectrometry. The delamination test protocols differ in test solution, handling, and time. Before choosing the most appropriate protocol to predict delamination propensity and mimic real-time conditions, long-term storage data are needed. A combination of analytical techniques to study the risk for long-term corrosion of glass is highly recommended covering the 3 aspects: visible/subvisible particle assessment, solution analysis, and surface characterization.     

Er:YAG laser osteotomy directed by sensor controlled systems

BACKGROUND: Great efforts have been taken in the past to develop laser systems suitable for bone cutting. Laser systems emitting light in the infrared spectrum (2.9, 3.0 microm) have been found to be ideal for efficient bone ablation with very little carbonization. AIM: To evaluate a new laser bone cutting system enabling the automatic detection of different tissue qualities by an integrated sensor to avoid damage to sensitive structures such as blood vessels or nerves. MATERIAL: An Erbium:YAG laser containing an integrated closed-loop control system, was constructed and tested on dissected bone. Process emissions such as resonance changes caused by the interaction of laser light and various tissue structures can be used for a controlled system. Sensor signals from a photodiode and a piezo-electric accelerometer were received and processed to guide the laser osteotomy. METHODS: Tests were performed on dissected bone specimens from rabbit femur (14) and minipig jaw (6). After laser application, the bone specimens were evaluated macroscopically and histologically. RESULTS: The specimens were evaluated histomorphometrically for the depth of cortical bone ablation when the closed-loop control system switched off the laser. Mean courses of 97.45% (pig) and 97.83% (rabbit) showed that the systems work with precision. CONCLUSION: After penetrating the cortical bone layer, the laser beam was promptly interrupted due to extreme changes of the signal character received by the sensor system. The in vitro tests of this new laser closed-loop control system were successful.