The use of photodynamic agents in malignant cranial tumor surgery is quite common. For example five-aminolevulinic acid (5-ALA)-induced porphyrins in malignant gliomas are potent photosensitizers. ...Until today there is no comparable selective fluorescent substance available for meningiomas. Nevertheless, there is a demand for intraoperative fluorescent identification of e.g. invasive skull base meningiomas to increase radicality. This study was established to investigate fluorescent image-guided resection with somatostatin receptor labelled fluorescence dye for intracranial meningioma in the nude mice.
Primary meningioma cell culture samples were stereotactically implanted subdural into 20 nude mice. 90 days after inoculation of the cells, a cranial MRI with contrast agent revealed tumor growth. After detection of tumor mass in MRI, FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide was injected intravenously and tumor mass was hereafter resected under visualization via fluorescence microscope and endoscope. After attempted total resection, animal were sacrificed brain slices were obtained and histologically analysed to verify the resection extent.
In 18 mice tumor growth was detected in MRI after 90 days of inoculation. The tumor mass could be clearly identified with fluorescence microscope and endoscope after injecting FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide. The tumor margins could be better visualized. After fluorescence-guided resection no remaining tumor could be identified in histological analysis.
This study describes for the first time the use of FAM-TOC5,6-Carboxyfluoresceine-Tyr3-Octreotide and demonstrates its value of fluorescent identification of meningioma cells in vivo. Furthermore, the authors established a new experimental animal model for fluorescence meningioma surgery.
Abstract Recent discoveries of transiting giant exoplanets around M-dwarf stars (GEMS), aided by the all-sky coverage of TESS, are starting to stretch theories of planet formation through the ...core-accretion scenario. Recent upper limits on their occurrence suggest that they decrease with lower stellar masses, with fewer GEMS around lower-mass stars compared to solar-type. In this paper, we discuss existing GEMS both through confirmed planets, as well as protoplanetary disk observations, and a combination of tests to reconcile these with theoretical predictions. We then introduce the Searching for GEMS survey, where we utilize multidimensional nonparameteric statistics to simulate hypothetical survey scenarios to predict the required sample size of transiting GEMS with mass measurements to robustly compare their bulk-density with canonical hot Jupiters orbiting FGK stars. Our Monte Carlo simulations predict that a robust comparison requires about 40 transiting GEMS (compared to the existing sample of ∼15) with 5 σ mass measurements. Furthermore, we discuss the limitations of existing occurrence estimates for GEMS and provide a brief description of our planned systematic search to improve the occurrence rate estimates for GEMS.
A stereoselective synthesis of 2,3‐dihydro‐1H‐indoles with a RhII‐catalyzed C–H insertion is reported. The α‐diazo carbonyl intermediates can be obtained by a diazo‐transfer reaction of ...2‐aminophenylacetic acids. Optimization and kinetic studies were performed, which resulted to increased yields of the diazo transfer after mechanistic evaluation of the side‐product formation. trans‐2,3‐Dihydro‐1H‐indoles were obtained in high diasteromeric excesses (up to 94 % de) and enantiomeric excesses (up to 94 % ee).
Azides vs. Diazos: The competition between azide and diazo transfer was resolved, which allowed the development of a highly selective synthesis of trans‐indolines.
The biological role of RNA-binding proteins in the secretory pathway is not well established. Here, we describe that human HDLBP/Vigilin directly interacts with more than 80% of ER-localized mRNAs. ...PAR-CLIP analysis reveals that these transcripts represent high affinity HDLBP substrates and are specifically bound in their coding sequences (CDS), in contrast to CDS/3'UTR-bound cytosolic mRNAs. HDLBP crosslinks strongly to long CU-rich motifs, which frequently reside in CDS of ER-localized mRNAs and result in high affinity multivalent interactions. In addition to HDLBP-ncRNA interactome, quantification of HDLBP-proximal proteome confirms association with components of the translational apparatus and the signal recognition particle. Absence of HDLBP results in decreased translation efficiency of HDLBP target mRNAs, impaired protein synthesis and secretion in model cell lines, as well as decreased tumor growth in a lung cancer mouse model. These results highlight a general function for HDLBP in the translation of ER-localized mRNAs and its relevance for tumor progression.
As recommended by the WHO and many national healthcare authorities, health care institutions of most industrialised countries have employed a critical incident reporting system (CIRS). However, ...little is known about differences in critical incidents across clinical specialties, the use of CIRSs amongst different professional groups, the types, severity and risk of reoccurrence of critical incidents, their contributing factors and the preventive actions taken in response.
In this retrospective, descriptive study we critically reviewed all reports filed in the CIRS of our institution between 2013 and 2019 and analysed characteristics over time.
Of the 5493 analysed incidents, the main types were related to medications (32.8%), clinical procedures (32.6%) or behaviour of employees (23.3%). Only 21.6% of reports were made by physicians, 51.3% were rated at least "high risk". Major contributing factors were personal factors (44.0%), lack of training and knowledge (43.7%) and communication errors (36.1%). Most actions taken to prevent similar events aimed at improving communications (23.6%); in 46.3% no actions whatsoever were taken. Longitudinal analysis revealed that reporting increased in internal medicine and obstetrics but collapsed in laboratory medicine / microbiology. Steady increases in medication-type incidents as well as lack of training and knowledge as contributing factors were observed.
This study revealed that the efferent loop (feedback, preventive actions taken) was the weakest part of the CIRS in our institution, indicating that no learning may have resulted from a large number of reports. In particular, the actions taken appeared to not adequately address the major contributing factors. This highlights that special attention must be paid to the efferent loop of a CIRS to fulfil the purpose of such a reporting system and ultimately to improve patient safety.
The multidrug resistance gene MDR1 encodes for an efflux transporter called P-glycoprotein (P-gp). In the canine Mdr1 gene, a nonsense mutation was identified in certain dog breeds causing increased ...drug sensitivity to various P-gp substrates such as antiparasitic macrocyclic lactones. Symptoms of neurologic toxicity include ataxia, depression, salivation, tremor, apparent blindness, and mydriasis. In the current report, a Thuringian goat developed similar neurological signs after treatment with doramectin, a compound from the macrocyclic lactone class. Therefore, Mdr1 might be defective in this individual goat. For diagnostic purposes, sequencing of the complete mRNA transcript coding for caprine Mdr1 was performed to investigate a potential missense mutation. The Mdr1 transcripts of two related goats without drug sensitivity were also sequenced to allow differential diagnosis and were compared to the suspected drug-sensitive goat. The only position where the Mdr1 sequence from the suspected drug-sensitive goat differed was in the 3′-untranslated region, being a heterozygous single nucleotide polymorphism c.3875C>A. It can be suspected that this variant affects the expression level, stability, or translation efficiency of the Mdr1 mRNA transcript and therefore might be associated with the suspected drug sensitivity. To clarify this, further studies are needed, particularly investigating the Mdr1 mRNA and protein expression levels from brain material of affected goats. In conclusion, Mdr1 variants may exist not only in dogs, but also in individual goats. The current report provides the first Mdr1 mRNA transcript sequence of a goat and therefore represents the basis for more detailed Mdr1 sequence and expression analyses.
The increased relevance of large-volume metrology (LVM) in industrial applications entails certain challenges: measurements must be cost-efficient and the technologies must be easy to use while ...ensuring accuracy and reliability. Portable photogrammetry shows great potential to overcome such challenges, but industrial users do not yet rely on its accuracy for large scenarios (3 to 64 m), especially when mass-market cameras are not conceived of as industrial metrology instruments. Furthermore, the measurement results might also depend on the operator’s skills and knowledge of the key process variables. In this work, a methodology was designed so that the measurement uncertainty of portable photogrammetry can be evaluated under controlled conditions for LVM. To do so, PTB’s reference wall, which was designed to assess laser-based methods applied to large volumes, was used as a reference artefact to study the measurement performance under different conditions, enabling an analysis of the relative influence of two process variables: the spatial arrangement of the optical instruments on the scene, and the relative camera poses for an accurate triangulation. According to these variables, different measuring conditions were designed (Monte Carlo analysis), and experimentally evaluated and reported (LME, length measuring errors), analysing the performance figures expected from both unskilled and expert users.
The last 6000
years are of particular interest to the understanding of the Earth System because the boundary conditions of the climate system did not change dramatically (in comparison to larger ...glacial–interglacial changes), and because abundant, detailed regional palaeoclimatic proxy records cover this period. We use selected proxy-based reconstructions of different climate variables, together with state-of-the-art time series of natural forcings (orbital variations, solar activity variations, large tropical volcanic eruptions, land cover and greenhouse gases), underpinned by results from General Circulation Models (GCMs) and Earth System Models of Intermediate Complexity (EMICs), to establish a comprehensive explanatory framework for climate changes from the Mid-Holocene (MH) to pre-industrial time. The redistribution of solar energy, due to orbital forcing on a millennial timescale, was the cause of a progressive southward shift of the Northern Hemisphere (NH) summer position of the Intertropical Convergence Zone (ITCZ). This was accompanied by a pronounced weakening of the monsoon systems in Africa and Asia and increasing dryness and desertification on both continents. The associated summertime cooling of the NH, combined with changing temperature gradients in the world oceans, likely led to an increasing amplitude of the El Niño Southern Oscillation (ENSO) and, possibly, increasingly negative North Atlantic Oscillation (NAO) indices up to the beginning of the last millennium. On decadal to multi-century timescales, a worldwide coincidence between solar irradiance minima, tropical volcanic eruptions and decadal to multi-century scale cooling events was not found. However, reconstructions show that widespread decadal to multi-century scale cooling events, accompanied by advances of mountain glaciers, occurred in the NH (e.g., in Scandinavia and the European Alps). This occurred namely during the Little Ice Age (LIA) between AD ∼1350 and 1850, when the lower summer insolation in the NH, due to orbital forcing, coincided with solar activity minima and several strong tropical volcanic eruptions. The role of orbital forcing in the NH cooling, the southward ITCZ shift and the desertification of the Sahara are supported by numerous model simulations. Other simulations have suggested that the fingerprint of solar activity variations should be strongest in the tropics, but there is also evidence that changes in the ocean heat transport took place during the LIA at high northern latitudes, with possible additional implications for climates of the Southern Hemisphere (SH).
MEX3A belongs to the MEX3 (Muscle EXcess) protein family consisting of four members (MEX3A-D) in humans. Characteristic for MEX3 proteins is their domain structure with 2 HNRNPK homology (KH) domains ...mediating RNA binding and a C-terminal really interesting new gene (RING) domain that harbors E3 ligase function. In agreement with their domain composition, MEX3 proteins were reported to modulate both RNA fate and protein ubiquitination. MEX3 paralogs exhibit an oncofetal expression pattern, they are severely downregulated postnatally, and re-expression is observed in various malignancies. Enforced expression of MEX3 proteins in various cancers correlates with poor prognosis, emphasizing their oncogenic potential. The latter is supported by MEX3A's impact on proliferation, self-renewal as well as migration of tumor cells in vitro and tumor growth in xenograft studies.
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