Interpersonal and Communication Skills (ICS) and Professionalism milestones are challenging to evaluate during medical training. Paucity in proficiency, direction and validity evidence of assessment ...tools of these milestones warrants further research. We validated the reliability of the previously-piloted Instrument for Communication skills and Professionalism Assessment (InCoPrA) in medical learners.
This validity approach was guided by the rigorous Kane's Framework. Faculty-raters and standardized patients (SPs) used their respective InCoPrA sub-component to assess distinctive domains pertinent to ICS and Professionalism through multiple expert-built simulated-scenarios comparable to usual care. Evaluations included; inter-rater reliability of the faculty total score; the correlation between the total score by the SPs; and the average of the total score by two-faculty members. Participants were surveyed regarding acceptability, realism, and applicability of this experience.
Eighty trainees and 25 faculty-raters from five medical residency training sites participated. ICC of the total score between faculty-raters was generally moderate (ICC range 0.44-0.58). There was on average a moderate linear relationship between the SPs and faculty total scores (Pearson correlations range 0.23-0.44). Majority of participants ascertained receiving a meaningful, immediate, and comprehensive patient-faculty feedback.
This work substantiated that InCoPrA was a reliable, standardized, evidence-based, and user-friendly assessment tool for ICS and Professionalism milestones. Validating InCoPrA showed generally-moderate agreeability and high acceptability. Using InCoPrA also promoted engaging all stakeholders in medical education and training-faculty, learners, and SPs-using simulation-media as pathway for comprehensive feedback of milestones growth.
Synthetic biology provides insight into natural gene-network dynamics and enables assembly of engineered transcription circuitries for production of difficult-to-access therapeutic molecules. In ...Mycobacterium tuberculosis EthR binds to a specific operator (OethR) thereby repressing ethA and preventing EthA-catalyzed conversion of the prodrug ethionamide, which increases the resistance of the pathogen to this last-line-of-defense treatment. We have designed a synthetic mammalian gene circuit that senses the EthR-OethR interaction in human cells and produces a quantitative reporter gene expression readout. Challenging of the synthetic network with compounds of a rationally designed chemical library revealed 2-phenylethyl-butyrate as a nontoxic substance that abolished EthR's repressor function inside human cells, in mice, and within M. tuberculosis where it triggered derepression of ethA and increased the sensitivity of this pathogen to ethionamide. The discovery of antituberculosis compounds by using synthetic mammalian gene circuits may establish a new line of defense against multidrug-resistant M. tuberculosis.
Preprolipopoprotein diacylglyceryl transferase (Lgt) is the gating enzyme of lipoprotein biosynthesis, and it attaches a lipid structure to the N-terminal part of preprolipoproteins. Using Lgt from ...Escherichia coli in a BLASTp search, we identified the corresponding Lgt homologue in Mycobacterium tuberculosis and two homologous (MSMEG_3222 and MSMEG_5408) Lgt in Mycobacterium smegmatis. M. tuberculosis lgt was shown to be essential, but an M. smegmatis ΔMSMEG_3222 mutant could be generated. Using Triton X-114 phase separation and 14Cpalmitic acid incorporation, we demonstrate that MSMEG_3222 is the major Lgt in M. smegmatis. Recombinant M. tuberculosis lipoproteins Mpt83 and LppX are shown to be localized in the cell envelope of parental M. smegmatis but were absent from the cell membrane and cell wall in the M. smegmatis ΔMSMEG_3222 strain. In a proteomic study, 106 proteins were identified and quantified in the secretome of wild-type M. smegmatis, including 20 lipoproteins. All lipoproteins were secreted at higher levels in the ΔMSMEG_3222 mutant. We identify the major Lgt in M. smegmatis, show that lipoproteins lacking the lipid anchor are secreted into the culture filtrate, and demonstrate that M. tuberculosis lgt is essential and thus a validated drug target.
Maribo-A new CM fall from Denmark HAACK, Henning; GRAU, Thomas; BISCHOFF, Addi ...
Meteoritics & planetary science,
01/2012, Letnik:
47, Številka:
1
Journal Article
Recenzirano
– Maribo is a new Danish CM chondrite, which fell on January 17, 2009, at 19:08:28 CET. The fall was observed by many eye witnesses and recorded by a surveillance camera, an all sky camera, a few ...seismic stations, and by meteor radar observatories in Germany. A single fragment of Maribo with a dry weight of 25.8 g was found on March 4, 2009. The coarse‐grained components in Maribo include chondrules, fine‐grained olivine aggregates, large isolated lithic clasts, metals, and mineral fragments (often olivine), and rare Ca,Al‐rich inclusions. The components are typically rimmed by fine‐grained dust mantles. The matrix includes abundant dust rimmed fragments of tochilinite with a layered, fishbone‐like texture, tochilinite–cronstedtite intergrowths, sulfides, metals, and carbonates often intergrown with tochilinite. The oxygen isotopic composition: (δ17O = −1.27‰; δ18O = 4.96‰; Δ17O = −3.85‰) plots at the edge of the CM field, close to the CCAM line. The very low Δ17O and the presence of unaltered components suggest that Maribo is among the least altered CM chondrites. The bulk chemistry of Maribo is typical of CM chondrites. Trapped noble gases are similar in abundance and isotopic composition to other CM chondrites, stepwise heating data indicating the presence of gas components hosted by presolar diamond and silicon carbide. The organics in Maribo include components also seen in Murchison as well as nitrogen‐rich components unique to Maribo.
Lipoproteins of Gram-negative and Gram-positive bacteria carry a thioether-bound diacylglycerol but differ by a fatty acid amide bound to the α-amino group of the universally conserved cysteine. In ...Escherichia coli the N-terminal acylation is catalyzed by the N-acyltransferase Lnt. Using E. coli Lnt as a query in a BLASTp search, we identified putative lnt genes also in Gram-positive mycobacteria. The Mycobacterium tuberculosis lipoprotein LppX, heterologously expressed in Mycobacterium smegmatis, was N-acylated at the N-terminal cysteine, whereas LppX expressed in a M. smegmatis lnt::aph knock-out mutant was accessible for N-terminal sequencing. Western blot analyses of a truncated and tagged form of LppX indicated a smaller size of about 0.3 kDa in the lnt::aph mutant compared with the parental strain. Matrix-assisted laser desorption ionization time-of-flight/time-of-flight analyses of a trypsin digest of LppX proved the presence of the diacylglycerol modification in both strains, the parental strain and lnt::aph mutant. N-Acylation was found exclusively in the M. smegmatis parental strain. Complementation of the lnt::aph mutant with M. tuberculosis ppm1 restored N-acylation. The substrate for N-acylation is a C16 fatty acid, whereas the two fatty acids of the diacylglycerol residue were identified as C16 and C19:0 fatty acid, the latter most likely tuberculostearic acid. We demonstrate that mycobacterial lipoproteins are triacylated. For the first time to our knowledge, we identify Lnt activity in Gram-positive bacteria and assigned the responsible genes. In M. smegmatis and M. tuberculosis the open reading frames are annotated as MSMEG_3860 and M. tuberculosis ppm1, respectively.
BACKGROUND AND OBJECTIVEFor cannulation of the internal jugular vein (IJV), ultrasound increases the number of first pass successes and reduces the rate of mechanical complications. A frequent ...complication of IJV access is the accidental injury of the common carotid artery (CCA), which can be dangerous in some circumstances. Landmarks and palpation of the CCA are used when ultrasound is not available. These conventional methods are based on the lateral position of the IJV to the CCA, and physicians traditionally employ head rotation to increase the success rates of IJV cannulation. Ultrasound scanning strictly from the anterior to posterior is not possible for this process because the probe must be adequately coupled to compensate for the curvature of the neck. Scans have been performed from different angles lateral to the neck, but misleadingly depict the relationship of the IJV to the CCA. In this study, the authors examined the effect of scanning at a 45° angle at the level of the cricoid on the depiction of the IJV in relation to the CCA. Furthermore, the influence of 30° head rotation to the contralateral side was also investigated.
METHODThe relationship of the IJV to the CCA was recorded using ultrasound in 600 patients. Patients were placed in a supine position and the probe was coupled at the level of the cricoid, scanning at an angle of 45° from the lateral side of the neck. Based on the ultrasound images, the position of the IJV in relation to the CCA was recorded using a segmented grid. The centre of the vein (cross-section of the vertical and longitudinal diameter) determined the segment classification, in which the top of the ultrasound image was defined as the anterior. Additionally, in 300 patients, the head was rotated to the contralateral side at 30° to examine the impact of head rotation on the position of the IJV.
RESULTSThe IJV was found in the lateral segment in only 3.0–3.3% of the patients. It was found in the anteromedial segment more frequently on the left side compared to the right side (P < 0.005). On the right side, the IJV was shown more frequently in the anterolateral position (P < 0.0001). Head rotation at 30° in 300 of the 600 patients caused a significant change of the IJV position in the left anteromedial segment, in that it frequently placed the IJV towards the anterior and anterolateral segment (P < 0.05). There was no significant impact of head rotation on the IJV representation on the right side. Atypical positions of the IJV (posterior, medial or thrombosis) were found in some cases.
CONCLUSIONUltrasound images used for IJV access usually depict the vein as being anterior to the CCA and only to a minor extent in the lateral position. This positioning is important for needle processing in order to avoid accidental arterial puncture and to identify atypical positions of the IJV. To determine the ideal puncture site, images of the neck vessels along their entire pathway should be obtained when using ultrasound for vascular access.
– We report an analysis of instrumental observations of a very bright fireball which terminated with a meteorite fall near the town of Jesenice in Slovenia on April 9, 2009, at 0h59m46s UT. The ...fireball designated EN090409 was recorded photographically and photoelectrically by two southern stations of the Czech part of the European Fireball Network (EN). Simultaneously, a part of the luminous trajectory was also captured by two all‐sky CCD systems and one video camera of the Slovenian meteor network. In addition to these optical recordings, the sonic booms produced by the Jesenice fireball were detected at 16 seismic stations located within 150 km of the trajectory. From all these records, we reconstructed the fireball’s atmospheric trajectory, basic geophysical data, the possible impact area, and the original heliocentric orbit of the meteoroid. Using a detailed fireball light curve, we modeled the atmospheric fragmentation of the meteoroid. Both the atmospheric behavior and the heliocentric orbit proved to be quite normal in comparison with other observed meteorite falls. The Jesenice orbit is markedly different from the Příbram and Neuschwanstein orbital meteorite pair, which fell on similar dates (April 7, 1959, and April 6, 2002, respectively). Three meteorites with a total weight of 3.6 kg (until April 2010) were found in a high mountain area near the town of Jesenice. They are classified as L6 ordinary chondrites (Bischoff et al. 2010).
Study Objective:
To assess the clinical use of ultrasonographic localization of the epidural space, and to evaluate the clinical efficacy of ultrasound diagnostics in obstetric anesthesia.
Design:
...Randomized prospective study.
Setting:
University Clinic of Obstetrics and Gynecology.
Patients:
300 parturients, 85 of whom had conventional delivery and 65 who underwent cesarean section.
Interventions:
Patients underwent ultrasonography for the identification of the intervertebral structures. Puncture depth and angle were measured to improve the placement of the Tuohy needle.
Measurements:
In the ultrasound group, additional puncture data, optimized puncture point, expected puncture depth, and angle were used to optimize the puncture technique. To control for side effects, we compiled data on the number of puncture attempts and the number of necessary puncture levels, visual analog scale (VAS) scores, the rate of side effects, and the patient acceptance of the technique.
Main Results:
The two groups were similar regarding demographic data. Using ultrasound for structure detection, the rate of puncture attempts were significantly (p
< 0.013) reduced from 2.18 ± 1.07 to 1.35 ± 0.61. The mean rate of necessary puncture levels was 1.30 ± 0.55 and with ultrasound detection 1.136 ± 0.36 (p
< 0.029). Complete analgesia was achieved in 147 patients with ultrasound detection versus
138 patients in the Control group (p
< 0,03). The maximum VAS pain score in the control group was 1.3 ± 2.1 versus
0.8 ± 1.5 in the Ultrasound group (p
< 0.006). The rate of side effects were reduced significantly: 99 patients in the Control group had no side effects compared with 120 patients from the Ultrasound group who were free of side effects. Patient acceptance of the technique in the Ultrasound group was significantly higher than in the Control group.
Conclusion:
The clinical use of ultrasound for epidural catheter placement may improve regional anesthesia. The use of ultrasound resulted in superior quality in all measured endpoints.
The causative and infectious agent of the transmissible spongiform encephalopathies, e.g. bovine spongiform encephalopathy in cattle or variant Creutzfeldt–Jakob disease in humans, is a pathogenic ...form of the scrapie prion protein (PrP
Sc) generated by a conformational rearrangement in the normal cellular prion protein (PrP
C). Anti-PrP antibodies have been shown to exert a protective effect against infection with PrP
Sc. However, the generation of anti-PrP antibodies has proven quite difficult in wild-type animals, PrP being a notoriously poor immunogen. We developed a vaccine against PrP by mixing recombinant murine PrP 23–231 with DnaK, an Hsp70 homolog in
Escherichia coli, and cross-linking the two proteins by means of glutaraldehyde. After three injections of the vaccine into BALB/c mice at 6, 8 and 9 weeks of age, a low-titer immune response was detected with ELISA in all animals. The specificity of the antibodies for PrP was confirmed with Western blotting. The straightforward procedure might render active immunization against prion infection feasible.
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