Use and fit of filtering facepiece respirators in a department of anaesthesiology

A research report submitted to the Faculty of Health Sciences, University of the Witwatersrand, in partial fulfilment of the requirements for the degree of Master of Medicine in the branch of Anaesthesiology. Johannesburg, November 2016.Background: Reliable protection against nosocomial tuberculosis transmission in theatre depends on the appropriate use of filtering facepiece respirators (FFRs) with an N95 filter, as recommended by the Centers for Disease Control and Prevention. Aim: To describe anaesthetist compliance and comfort with the use of FFRs, followed by donning technique and fit tests outcomes. Design: Prospective, contextual, descriptive, two part study. Setting: Part 1 was done in a university affiliated department of anaesthesiology. Part 2 was a pilot study in the theatre complex of a 1200-bed tertiary-level academic hospital. Participants: Part 1 – anaesthetists in the department selected by convenience sampling (n=140). Part 2 – anaesthetists selected by stratified random sampling (10 male and 10 female). Methods: In Part 1 a self-administered questionnaire was distributed. In Part 2 the donning technique was directly observed, corrected, then followed by qualitative fit testing with the single model and size FFR available. Results: Part 1 -Compliance with the use of the FFR was inadequate with a compliance score of 14.5 (SD 5.0) out of 25. FFRs are deemed to be uncomfortable (discomfort score of 9.9 (SD 4.0) out of 21.) Part 2 - Of the 20 anaesthetists, six (30%), five males and one female, passed the fit test. Conclusions: Compliance with FFR use was poor and anaesthetists at the research institution found the FFRs uncomfortable. FFR donning technique was observed to be lacking. Research with a larger study group is required. Poor fit test results were most likely due to the availability of only one size and model of FFR.LG201

Extragalactic database. VII Reduction of astrophysical parameters

The Lyon-Meudon Extragalactic database (LEDA) gives a free access to the main astrophysical parameters for more than 100,000 galaxies. The most common names are compiled allowing users to recover quickly any galaxy. All these measured astrophysical parameters are first reduced to a common system according to well defined reduction formulae leading to mean homogeneized parameters. Further, these parameters are also transformed into corrected parameters from widely accepted models. For instance, raw 21-cm line widths are transformed into mean standard widths after correction for instrumental effect and then into maximum velocity rotation properly corrected for inclination and non-circular velocity. This paper presents the reduction formulae for each parameter: coordinates, morphological type and luminosity class, diameter and axis ratio, apparent magnitude (UBV, IR, HI) and colors, maximum velocity rotation and central velocity dispersion, radial velocity, mean surface brightness, distance modulus and absolute magnitude, and group membership. For each of these parameters intermediate quantities are given: galactic extinction, inclination, K-correction etc.. All these parameters are available from direct connexion to LEDA (telnet lmc.univ-lyon1.fr, login: leda, no passwd OR http://www-obs.univ-lyon1.fr/leda ) and distributed on a standard CD-ROM (PGC-ROM 1996) by the Observatoire de Lyon via the CNRS (mail to [email protected]).Comment: 13 pages, 12 figures. The CDROM of the extragalactic database LEDA is available by mailing to: [email protected]

Ankyrin-G mediates targeting of both Na+ and K-ATP channels to the rat cardiac intercalated disc

We investigated targeting mechanisms of Na+ and KATP channels to the intercalated disk (ICD) of cardiomyocytes. Patch clamp and surface biotinylation data show reciprocal downregulation of each other’s surface density. Mutagenesis of the Kir6.2 ankyrin binding site disrupts this functional coupling. Duplex patch clamping and Angle SICM recordings show that INa and IKATP functionally co-localize at the rat ICD, but not at the lateral membrane. Quantitative STORM imaging show that Na+ and KATP channels are localized close to each other and to AnkG, but not to AnkB, at the ICD. Peptides corresponding to Nav1.5 and Kir6.2 ankyrin binding sites dysregulate targeting of both Na+ and KATP channels to the ICD, but not to lateral membranes. Finally, a clinically relevant gene variant that disrupts KATP channel trafficking also regulates Na+ channel surface expression. The functional coupling between these two channels need to be considered when assessing clinical variants and therapeutics

MODULATION DU PHENOTYPE TYPIQUE DE MULTICHIMIORESISTANCE (MDR) DES CELLULES CANCEREUSES HUMAINES PAR DES LEURRES TRANSCRIPTIONNELS ET ETUDE DE LA REGULATION TRANSCRIPTIONNELLE DU GENE MDRI AU NIVEAU DE LA REGION MED-1

LYON1-BU.Sciences (692662101) / SudocSudocFranceF

Modulation of the typical multidrug resistance phenotype by targeting the MED-1 region of human MDR1 promoter.

International audienceMultidrug resistance of cancer (MDR) is the major cause of failure of chemotherapy. The typical MDR phenotype is due to the overexpression of membrane proteins among which the main representative is P-glycoprotein (Pgp) encoded by the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been unsuccessful in human therapy due to their intrinsic toxic effects. In an effort to modulate the MDR phenotype efficiently we designed an antisense and a transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter. The choice of the start point of transcription in a multiple start site window is related to an upstream MED-1 cis-element, the sequence and configuration of which are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A 12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both containing the MED-1 sequence, were designed and efficiently vectorized into the nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP) and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP cells decreased, and thus its production, and viability of CEM/VLB0.45 cells decreased by 63% in the presence of vinblastine, revealing that their resistance to the anticancer drug was reversed. These results open new insights into transcriptional decoy and anti-gene therapies of MDR cancers that overproduce Pgp. Gene Therapy (2000) 7, 1224-1233.Multidrug resistance of cancer (MDR) is the major cause of failure of chemotherapy. The typical MDR phenotype is due to the overexpression of membrane proteins among which the main representative is P-glycoprotein (Pgp) encoded by the MDR1 gene. Many attempts to modulate MDR by chemosensitizers have been unsuccessful in human therapy due to their intrinsic toxic effects. In an effort to modulate the MDR phenotype efficiently we designed an antisense and a transcriptional decoy strategy targeting the TATA-less human MDR1 gene promoter. The choice of the start point of transcription in a multiple start site window is related to an upstream MED-1 cis-element, the sequence and configuration of which are specific to human MDR1 gene expressed in Pgp-overproducing cancer cells. A 12mer antisense oligodeoxynucleotide (ODN) and a 12mer double-stranded ODN, both containing the MED-1 sequence, were designed and efficiently vectorized into the nucleus with the chimerical MPG peptide. A synthetic cellular model (NIH-EGFP) and highly resistant human CEM/VLB0.45 leukemia cells, significantly responded to transfection with the ODN/MPG complex. The level of EGFP fluorescence in NIH-EGFP cells decreased, and thus its production, and viability of CEM/VLB0.45 cells decreased by 63% in the presence of vinblastine, revealing that their resistance to the anticancer drug was reversed. These results open new insights into transcriptional decoy and anti-gene therapies of MDR cancers that overproduce Pgp. Gene Therapy (2000) 7, 1224-1233

Pax6 Regulates the Proglucagon Processing Enzyme PC2 and Its Chaperone 7B2▿ †

Pax6 is important in the development of the pancreas and was previously shown to regulate pancreatic endocrine differentiation, as well as the insulin, glucagon, and somatostatin genes. Prohormone convertase 2 (PC2) is the main processing enzyme in pancreatic α cells, where it processes proglucagon to produce glucagon under the spatial and temporal control of 7B2, which functions as a molecular chaperone. To investigate the role of Pax6 in glucagon biosynthesis, we studied potential target genes in InR1G9 α cells transfected with Pax6 small interfering RNA and in InR1G9 clones expressing a dominant-negative form of Pax6. We now report that Pax6 controls the expression of the PC2 and 7B2 genes. By binding and transactivation studies, we found that Pax6 indirectly regulates PC2 gene transcription through cMaf and Beta2/NeuroD1 while it activates the 7B2 gene both directly and indirectly through the same transcription factors, cMaf and Beta2/NeuroD1. We conclude that Pax6 is critical for glucagon biosynthesis and processing by directly and indirectly activating the glucagon gene through cMaf and Beta2/NeuroD1, as well as the PC2 and 7B2 genes

Transcriptional regulation of the human MDR1 gene at the level of the inverted MED-1 promoter region.

International audienceThe typical multidrug resistance phenotype (MDR), the major cause of failure of cancer chemotherapy, is the result of the overexpression of the human MDR1 gene, the regulation of which is still incompletely understood. Using several EMSA experiments, we have identified a new regulatory sequence located from -103 to -98 bp relative to the +1 start site in the MDR1 promoter region. This sequence, which we called inverted MED-1, acts as a cis-activator for this gene. In transient transfection experiments of highly resistant human lymphoblastic CEM/VLB5 cells, its deletion from the promoter region is responsible for 60% inhibition of the MDR1 transcriptional activity. This sequence specifically binds a nuclear protein of about 150-160 kDa. We showed that its binding capacity is related to the chemoresistance level of the studied cell lines and may reflect the increased transcriptional activity of the MDR1 gene in multidrug-resistant cells

Transcriptional regulators of the human multidrug resistance 1 gene: recent views.

International audienceThe multidrug resistance (MDR) phenotype is the major cause of failure of cancer chemotherapy. This phenotype is mainly due to the overexpression of the human MDR1 (hMDR1) gene. Several studies have shown that transcriptional regulation of this gene is unexpectedly complex and is far from being completely understood. Current work is aimed mainly at defining unclear and new control regions in the hMDR1 gene promoter as well as clarifying corresponding signaling pathways. Such studies provide new insights into the mechanisms by which xenobiotic molecules might modify the physiological hMDR1 expression as well as the possible role of oncogenes in the pathological dysregulation of the gene. Here we report recent findings on the regulation of hMDR1 which may help define specific targets aimed at modulating its transcription

An image database. II. Catalogue between

A preliminary list of 68.040 galaxies was built from extraction of 35.841 digitized images of the Palomar Sky Survey (Paper I). For each galaxy, the basic parameters are obtained: coordinates, diameter, axis ratio, total magnitude, position angle. On this preliminary list, we apply severe selection rules to get a catalog of 28.000 galaxies, well identified and well documented. For each parameter, a comparison is made with standard measurements. The accuracy of the raw photometric parameters is quite good despite of the simplicity of the method. Without any local correction, the standard error on the total magnitude is about 0.5 magnitude up to a total magnitude of BT=17. Significant secondary effects are detected concerning the magnitudes: distance to plate center effect and air-mass effect