Αρχειοθήκη ιστολογίου

Σάββατο 30 Σεπτεμβρίου 2017

A Few of My Favorite Spaces: The 1-Dimensional Sphere

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There's more to the circle than meets the π

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Incidental late diagnosis of cystic fibrosis following AH1N1 influenza virus pneumonia: a case report

Cystic fibrosis is an autosomal recessive disorder characterized by chronic progressive multisystem involvement. AH1N1 virus infections caused classic influenza symptoms in the majority of cystic fibrosis pati...

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Coast Line: Dientes celebrates 25 years Thursday

Dientes Community Dental Care will commemorate its 25th Anniversary with an evening celebration 5:30-7:30 p.m. Thursday, 1830 Commercial Way. There will be a short program at 5:45 p.m. and tours of the main clinic as well as food, beverages and live music.



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Identification of keratin 19-positive cancer stem cells associating human hepatocellular carcinoma using CYFRA 21-1

Abstract

The current lack of an easily measurable surrogate marker of cancer stem cells (CSCs) prevents the clinical application of CSCs for hepatocellular carcinoma (HCC). We previously reported that keratin 19 (K19) is a novel HCC-CSC marker associated with transforming growth factor beta (TGFβ)/Smad signaling, and that K19+ HCC-CSCs could be a new therapeutic target of TGFβ receptor 1 inhibitor LY2157299. In this study, we examined whether K19+ HCC-CSCs can be tracked using cytokeratin 19 fragment CYFRA 21-1. In 147 HCC patients who underwent curative resection and evaluated K19 expression by immunohistochemistry, preoperative serum CYFRA 21-1 levels were significantly higher in K19+ patients than in K19 patients (< 0.01). Receiver operating characteristic analyses revealed that serum CYFRA 21-1 was the statistically significant and the most sensitive predictor of tumor K19 expression among preoperative laboratory test values (< 0.001). In HCC cells encoding with a K19 promoter-driven enhanced green fluorescent protein, fluorescence-activated cell sorting (FACS)-isolated K19+ cells displayed significantly higher levels of supernatant CYFRA 21-1 than K19 cells (< 0.01). Gain/loss of K19 function experiments confirmed that CYFRA 21-1 levels were regulated by K19 function in HCC cells. Furthermore, CYFRA 21-1 levels reflected the treatment efficacy of LY2157299 in K19+ cells. In conclusion, CYFRA 21-1 can be used to predict K19 expression in HCC, and should thereby aid in the development of novel therapeutic strategies targeting K19+ HCC-CSCs.

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Keratin 19 (K19) is known to be a cancer stem cells (CSCs) marker in hepatocellular carcinoma (HCC). However, easily-measurable surrogate marker of K19 +  HCC-CSCs has not been identified. This study showed that serum CYFRA 21-1 is the significant predictor of K19 expression in human HCC, and that CYFRA 21-1 levels reflect K19 function and TGFβ receptor 1 inhibitor treatment efficacy in HCC cells.



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Moyamoya

Moyamoya: A pattern of progressive obstructive and occlusive cerebral arteritis (inflammation of the cerebral arteries that obstructs and occludes them), predominantly in children and young adults. Symptoms include headaches, behavioral abnormalities, and recurrent attacks of paralysis. The radiology findings are helpful in the diagnosis.



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Analysis of molecular genetic study on the polymorphic C-159T locus of the CD14 gene in children with increased risk of recurrent episodes of acute obstructive bronchitis

Abstract

A molecular genetic study of the polymorphic C-159T locus of the CD14 gene has been carried out in 31 children with recurrent episodes of acute obstructive bronchitis as well as in a cohort of 50 randomly sampled subjects forming the control group. As a result of the study, no higher statistically significant frequency of the CC, CT, and TT genotypes has been recorded at the polymorphic C-159T locus of the CD14 gene among children of the main group compared with the control. However, there is a trend towards a more frequent observation of the TT genotype among children with recurrent episodes of acute obstructive bronchitis compared with the control group (32.25 vs. 22.0%).



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Association of FGFR2 (rs2981579) gene polymorphism with the risk of mesial occlusion

Abstract

The molecular-genetic testing of the polymorphic rs2981579 (C>T) locus of the FGFR2 gene as the marker of increased predisposition to the development of mesial occlusion was carried out in 110 patients with mesial occlusion and 103 general-population control subjects from Ukraine. It was shown that polymorphism rs2981579 in gene FGFR2 is associated with mesial occlusion (OR = 1.67, 95% CI = 1.14–2.45, p = 0.009). Compared to CC carriers, TT+CT carriers had a 3.21-fold higher risk of mesial occlusion (95% CI = 1.57–6.57, p = 0.001). We found the protective effect of the homozygous allele C on mesial occlusion development (OR = 0.31, p = 0.001). This is the first published data on FGFR2 polymorphisms rs2981579 (C>T) in patients with mesial occlusion.



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Genetic approaches in research on the role of trehalose in plants

Abstract

Data concerning the synthesis and functions of trehalose in plants have been analyzed and the contribution of trehalose to tolerance to different types of abiotic stress has been considered. Data on phenotypic changes and stress resistance (including drought resistance) in transgenic plants that expressed genes required for trehalose biosynthesis have been summarized.



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Epigenetic mechanisms regulating seed germination rate

Abstract

Changes in epigenetic polymorphism degree within wheat seedlings' population under radiation stimulating exposure of germination were investigated. Variations in seeds sample allocations by germination rate in both control and chronically exposed variants were estimated. Changes in DNA methylation patterns of seedlings from seeds with different germination rate were studied. Variations in epigenetic polymorphism–"distance" between DNA methylation patterns of "fast" and "slow" seedlings of different wheat varieties under radiation exposure were assessed. Indicated, that increased germination rate of seeds sample was associated with decreasing degree of epigenetic polymorphism. Issue concerning both role of epigenetic polymorphism in plant population stability and its decreasing degree that could initiate less effectiveness of production process was discussed.



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Erratum to: “Cytogenetic and molecular cytogenetic investigations in relapse of B-cell chronic lymphocytic leukemia”

Figure 3 should be:



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Inheritance of the traits of spike and grain color and morphometric parameters of the grain in F 1 and F 2 hybrids of Triticum spelta L. × Triticum aestivum L.

Abstract

The character of inheritance of the morphological traits of spike and grain color and morphometric parameters of the grain in simple and backcross F1 and F2 hybrids of spelt and soft wheat has been investigated. The experiments confirmed that single homologous genes determine the trait of grain width in different species of wheat. Incomplete dominance of the gene that determines the trait of grain length has been revealed. The increase of the dosage of genes from one wheat species in a backcross hybrid has been shown to increase the deviation from the other species and to bring the values of the quantitative parameters of the grain closer to the values for the saturating species. Splitting of the spike color trait in the F2 offspring has been shown to follow the 15: 1 dihybrid cross scheme and to be controlled by two dominant homologous genes.



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Cytogenetic characteristics of wheat lines with modified 1RS.1BL rye-wheat translocation

Abstract

The higher frequency (almost 90%) of inheritance through pollen of heterozygous hybrids has been shown for the modified 1RS.1BL translocation compared with the 1BL telocentric, and, as a result, the segregations at the Gli-B1 and Glu-B1 loci strongly deviated from the expected values. The distance between the Glu-B1 locus and the centromere was 15.7–24.4 cM. Products of the 1RSm.1BL translocation "misdivision" were observed at a frequency of 0.05%. Both the Pavon MA1 lines and the winter wheat line with the 1RSm.1BLal translocation have shown a significant decrease in the level of homologous chromosome pairing, causing aneuploidy. These lines did not contain any reciprocal translocations with respect to the Kuyal'nik cultivar. A "hybrid desynapsis" has been observed in F1 hybrids (Kuyal'nik × Pavon MA1) in contrast to analogous hybrids from a winter line by the 1RSm.1BLal type. No single case of the 21ClosedII formation has been observed among the studied 693 pollen mother cells (PMCs), which would have indicated the presence of pairing between the short arms of the 1RSm.1BL translocations and the intact chromosome 1B.



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First detection of cytomixis and its consequences in Thalictrum cultratum Wall. (Ranunculaceae)

Abstract

In current paper, we studied the meiotic chromosome number and details of cytomixis recorded for the first time in Thalictrum cultratum Wall. from the high altitude areas of northwest Himalaya (India). Cytomixis, the phenomenon of inter PMC (pollen mother cell) migration of chromatin material has been reported in many angiosperms and other groups of plants, but there is no published report in Thalictrum cultratum. All the presently studied accessions of the species existed at diploid level (x = 7). The present chromosome count of n = 14 has been reported for the first time from the study area. The cytological stability of any plant is an important consideration in view of its existence in nature. Meiotic disturbances can impose threat to the reproductive potential of plant. Current study reveals the occurrence of inter PMC migration of chromatin material. In present investigation, the phenomenon of cytomixis can be observed between 2 to 9 PMCs. Chromatin migration occurs through narrow and broad cytoplasmic channels or occasionally fused together during metaphase-I and anaphase-I. Cytomixis resulted in the formation of hypo- (n = 2, 2 + 1 small fragment, n = 3 + 3 small fragments, 4, 5 + extra mass of chromatin, 13) and hyperploid (n = 7 + 2 small fragments, 8 + 2 small fragments, 14, 14 + 2 small fragments, 15) PMCs, variable sized pollen grains and pollen sterility (20%). The current study reveals that cytomixis is responsible for formation of PMCs with variable chromosomes (hypoand hyperploid) and pollen grains of heterogeneous sizes and pollen sterility in T. cultratum. This is the first report of cytomixis in the species.



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Induced autotetraploidy in Trachyspermum ammi (L.) Sprague (Apiaceae)

Abstract

Polyploidization is an event that developed in plants during evolutionary path which confer them better survivorship than diploids towards the harsh environmental conditions. Regarding this approach polyploids acquire most of appealing facts in it which are the special concern of biologists. Present study is an attempt to induce autotetraploids in an important medicinal plant, Trachyspermum ammi (L.) Sprague through colchicine. The seedlings of Trachyspermum ammi (L.) Sprague were treated with 3 different concentrations of colchicine (0.2, 0.4 and 0.5%, w/v) for 3 different durations. The autotetraploidy in plants have been confirmed on the basis of cytological, morphological and palynological observations. Total six autotetraploid plants (4n = 36) were induced. On the basis of the number of induced autotetraploids, 36 hours duration of 0.2% concentration of colchicine was found to be more effective. The morphological parameters such as increased flower size, reproductive organs, stomata size, pollen length and diameter, plant height, leaf length and width, number of umbel/plant, number of umbellate/umbel and stomatal frequency etc. were considered for the detection of autotetraploids. Various chromosomal configurations have been observed during meiotic analysis. Pollen fertility was decreased in autotetraploids than diploids.



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The effects of polymorphisms in growth hormone and growth hormone receptor genes on production and reproduction traits in Aberdeen-Angus cattle ( Bos taurus L., 1758)

Abstract

The study was aimed to analyze the relation between individual genotypes and allelic variants of SNPs g.2141C>G of growth hormone gene, g.914T>A and g.257A>G of growth hormone receptor gene with growth and reproduction traits and to evaluate the populationgenetic structure in Aberdeen-Angus cattle (Bos taurus L., 1758) sample of Eastern Ukraine according SNPs studied. Allele C of SNP g.2141C>G has a positive correlation with birth weight, body stature, bigger rump, udder and total exterior evaluation score, shorter calving interval and better calve birth weight and negative correlation with calve average daily gain. Allele T of SNP g.914T>A has positive correlation with the muscle and udder size; live weight in each age, average daily gain, weight and average daily gain of calves born conform to the principle AA>TTTA. SNP g.257A>G showed a positive correlation for G allele with muscle size. The population is in equilibrium for SNPs g.2141C>G and g.257A>G, and in disequilibrium for SNP g.914T>A. The analysis showed no linkage disequilibrium between SNPs g.914T>A and g.257A>G. Inbreeding coefficient FST in Aberdeen-Angus group studied was 16.1%.



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Transformation and evaluation of different transgenic lines for Glyphosate tolerance and cane borer resistance genes in sugarcane ( Saccharum officinarum L.)

Abstract

The aim of this study was to ensure the systematic protein expression of two genes (GTG and Cry1Ac) under the influence of two different constitutive promoters i.e. Ubiquitin-1 and CaMV 35S promoters in different sugarcane lines. PCR amplification of GTG and Cry1Ac was achieved from putative transgenic plants through gene specific primers. Qualitative comparisons of GTG and Cry1Ac genes expression under two different promoters were obtained through protein dot blot and dipstick assay. The appearance of comparatively dark color dots in dot blot and dark color bands on dipstick with Ubiquitin as compared to light color bands with CaMV35S promoter, qualitatively confirmed high protein expression of two genes under Ubiquitin promoter. In quantitative gene expression comparisons maximum optical density (OD) at 450 nm of UV-light was obtained for GTG (3.7 OD) and Cry1Ac (3 OD) under Ubiquitin promoter, while for GTG (1.6 OD) and Cry1Ac (2.5 OD) with CaMV 35S promoter. The results indicated higher expression of two genes under Ubiquitin-1 promoter in sugarcane was found as compared to CaMV 35S promoter. This study provides a guide for stable and high expression of transgenes with reference to Ubiquitin-1 promoter which can be utilize in sugarcane as well as in other monocots.



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Formation of adaptive reactions in Arabidopsis thaliana wild-type and mutant jin1 plants under action of abscisic acid and salt stress

Abstract

To elucidate the possible role of the transcription factor (TRF) JIN1/MYC2 in implementation of stress-protective effects of abscisic acid (ABA), the effect of exogenous ABA on the state of stomata and the activity of antioxidant enzymes and proline content under salt stress conditions in Arabidopsis thaliana plants of wild type (Col-0) and jin1 mutants with impaired jasmonate signaling was investigated. Treatment of leaves' epidermis with ABA (10 or 100 μM) caused the closing of stomata in Col-0 plants but has hardly any influence on stomatal aperture in jin1 mutants. Salt stress (200 mM NaCl exposure for 24 h) caused a reduction of the water content in the plant leaves of both genotypes. Addition of 10 μM ABA into the growing medium contributed to a maintaining of normal hydration in wild-type but not in jin1 plants under salt stress. ABA treatment caused an almost twofold increase in proline content in the leaves of plants of both genotypes under normal conditions. Pretreatment with phytohormone contributed to enhancing the proline content in wild-type plants at salt stress and had a less significant effect on its amount in jin1 plants. Treatment with ABA under physiologically normal conditions increased the catalase activity in wild-type plants. Both genotypes under ABA influence showed increased activity of superoxide dismutase (SOD). Under salt stress conditions, higher activity of SOD, catalase, and guaiacol peroxidase was observed in ABA-treated wild-type plants but not in jin1 mutants. A conclusion about the participation of TRF JIN1/MYC2 in the formation of certain ABA-induced physiological responses of Arabidopsis plants was made.



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Clinical Thyroidology for the Public – Highlighted Article

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From Clinical Thyroidology for the Public: In 2016, the encapsulated follicular variant of papillary thyroid cancer with no evidence of spread into the thyroid capsule or into the blood vessels seen under the microscope was renamed as noninvasive follicular thyroid neoplasm with papillary-like nuclear features (NIFTP), and was suggested that it was a non-cancer diagnosis. Read More….

We welcome your feedback and suggestions. Let us know what you want to see in this publication.

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The post Clinical Thyroidology for the Public – Highlighted Article appeared first on American Thyroid Association.



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IJMS, Vol. 18, Pages 2082: Experimental and Kinetic Study on Lignin Depolymerization in Water/Formic Acid System

IJMS, Vol. 18, Pages 2082: Experimental and Kinetic Study on Lignin Depolymerization in Water/Formic Acid System

International Journal of Molecular Sciences doi: 10.3390/ijms18102082

Authors: Qi Wang Sipian Guan Dekui Shen

Microwave-assisted depolymerization of black-liquor lignin in formic acid was studied, concentrating on the yield of liquid fractions as bio-oil 1 (mainly aromatic monomers) and bio-oil 2 (mainly aromatic oligomers) and the distribution of the specific compositions. Bio-oil 1 (9.69%) and bio-oil 2 (54.39%) achieved their maximum yields under 160 °C with the reaction time of 30 min. The chemical compositions of bio-oil 1 and bio-oil 2 were respectively identified by means of Gas Chromatography-Mass Spectrometer (GC-MS) and Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS). Ethanone, 1-(4-hydroxy-3-methoxyphenyl) and Ethanone, 1-(4-hydrox-3,5-dimethoxyphenyl) were evidenced to be the two prominent compounds in bio-oil 1. Production of aromatic oligomers with the molecular weight of 328, 342, 358, 378, 394, 424 and 454 identified by MALDI-TOF MS was substantially tuned with the reaction temperature. A two-separate-stage kinetic model was proposed to describe the acidic solvolysis of lignin assisted by microwave heating, where the first stage is dominated by the depolyerization of lignin to monomers and oligomers with the activation energy of 40.27 kJ·mol−1, and the second stage with the activation energy of 49.18 kJ·mol−1 is mainly ascribed to the repolymerization of first-stage produced compounds.



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Clausena anisata and Dysphania ambrosioides essential oils: from ethno-medicine to modern uses as effective insecticides

Abstract

Dysphania ambrosioides (L.) Mosyakin & Clemants (Amaranthaceae) and Clausena anisata (Willd.) Hook. f. ex Benth. (Rutaceae) are two aromatic species traditionally used in Cameroon to repel and kill insects. The present work was carried out to substantiate this traditional use and to evaluate the possible incorporation in commercial botanical insecticides of their essential oils (EOs). The EOs were distilled from leaves of C. anisata and aerial parts of D. ambrosioides and analyzed by gas chromatography-mass spectrometry (GC-MS). The insecticidal activity of both EOs was investigated against the filariasis vector, Culex quinquefasciatus, and the housefly, Musca domestica. As possible mode of action, the inhibition of acetylcholinesterase (AChE) by the two EOs was investigated as well. The D. ambrosioides EO was characterized by the monoterpene peroxide ascaridole (61.4%) and the aromatic p-cymene (29.0%), whereas the C. anisata EO was dominated by the phenylpropanoids (E)-anethole (64.6%) and (E)-methyl isoeugenol (16.1%). The C. anisata EO proved to be very toxic to third instar larvae of C. quinquefasciatus showing LC50 of 29.3 μl/l, whereas D. ambrosioides EO was more toxic to adults of M. domestica showing a LD50 of 51.7 μg/adult. The mixture of both EOs showed a significant synergistic effect against mosquito larvae with LC50 estimated as 19.3 μl/l, whereas this phenomenon was not observed upon application to M. domestica adults (LD50 = 75.9 μg/adult). Of the two EOs, the D. ambrosioides one provided a good inhibition of AChE (IC50 = 77 μg/ml), whereas C. anisata oil was not effective. These findings provide new evidences supporting the ethno-botanical use of these two Cameroonian plants, and their possible application even in synergistic binary blends, to develop new eco-friendly, safe and effective herbal insecticides.



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Removal of industrial dyes and heavy metals by Beauveria bassiana : FTIR, SEM, TEM and AFM investigations with Pb(II)

Abstract

Presence of industrial dyes and heavy metal as a contaminant in environment poses a great risk to human health. In order to develop a potential technology for remediation of dyes (Reactive remazol red, Yellow 3RS, Indanthrene blue and Vat novatic grey) and heavy metal [Cu(II), Ni(II), Cd(II), Zn(II), Cr(VI) and Pb(II)] contamination, present study was performed with entomopathogenic fungi, Beauveria bassiana (MTCC no. 4580). High dye removal (88–97%) was observed during the growth of B. bassiana while removal percentage for heavy metals ranged from 58 to 75%. Further, detailed investigations were performed with Pb(II) in terms of growth kinetics, effect of process parameters and mechanism of removal. Growth rate decreased from 0.118 h−1 (control) to 0.031 h−1, showing 28% reduction in biomass at 30 mg L−1 Pb(II) with 58.4% metal removal. Maximum Pb(II) removal was observed at 30 °C, neutral pH and 30 mg L−1 initial metal concentration. FTIR analysis indicated the changes induced by Pb(II) in functional groups on biomass surface. Further, microscopic analysis (SEM and atomic force microscopy (AFM)) was performed to understand the changes in cell surface morphology of the fungal cell. SEM micrograph showed a clear deformation of fungal hyphae, whereas AFM studies proved the increase in surface roughness (RSM) in comparison to control cell. Homogenous bioaccumulation of Pb(II) inside the fungal cell was clearly depicted by TEM-high-angle annular dark field coupled with EDX. Present study provides an insight into the mechanism of Pb(II) bioremediation and strengthens the significance of using entomopathogenic fungus such as B. bassiana for metal and dye removal.



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Hyliion and Its Hybrid 18-Wheelers Raise $21 Million in Series A Funding

This month, a start-up company called Hyliion that is looking to hybridize Class 8 trucks around the world raised $21 million in Series A funding.

-- Read more on ScientificAmerican.com

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J. Intell., Vol. 5, Pages 33: Overemphasized “g”

J. Intell., Vol. 5, Pages 33: Overemphasized "g"

Journal of Intelligence doi: 10.3390/jintelligence5040033

Authors: Lazar Stankov

In this paper I argue that the emphasis on "g" has become a hindrance to the study of broadly defined human cognitive abilities. Abilities captured by the first- and second-stratum factors in the Cattel-Horn-Carroll (CHC) theory have been neglected. The focus has been on a narrow range of cognitive processes that excludes those common to some sensory modalities and a host of new tasks and constructs that have become available through recent conceptual analyses and technological developments. These new areas have emerged from psychology itself (complex problem solving tasks and emotional intelligence) and from disciplines related to psychology like education and economics (economic games and cognitive biases in decision-making).



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Editorial Board



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Medication errors in pediatric inpatients: a study based on a national mandatory reporting system

Abstract

The aim was to describe medication errors (MEs) in hospitalized children reported to the national mandatory reporting and learning system, the Danish Patient Safety Database (DPSD). MEs were extracted from DPSD from the 5-year period of 2010–2014. We included reports from public hospitals on patients aged 0–17 years and categorized by reporters as medication-related. Reports from psychiatric wards and outpatient clinics were excluded. A ME was defined as any medication-related error occurring in the medication process whether harmful or not. MEs were categorized as harmful if they resulted in actual harm or interventions to prevent harm. MEs were further categorized according to occurrence in the medication process, type of error, and the medicines involved. A total of 2071 MEs including 487 harmful MEs were identified. Most MEs occurred during prescribing (40.8%), followed by dispensing (38.7%). Harmful MEs occurred mainly during dispensing (40.3%). Dosing errors were the most reported type of error, 47.7% of all MEs and 45.4% of harmful MEs. Antibiotics and analgesics were the most frequently reported medication classes. Common medicines associated with MEs included morphine, paracetamol, and gentamicin. MEs caused no harm (74.9%), mild (11.7%), moderate (10.5%), or severe harm (1.3%), but none were lethal.

Conclusion: MEs in hospitalized children occur in all medication processes and mainly involve dosing errors. Strategies should be developed to prevent MEs as these still threaten medication safety in pediatric inpatients.

What is known:
• Hospitalized children are more likely to experience medication errors than adults.
• Voluntary national and local reporting and learning systems have previously been used to describe the nature and types of medication errors.
What is new:
• Medication errors in hospitalized children occur in all steps of the medication process, most frequently involving dosing errors and most commonly involving morphine, paracetamol, and gentamicin.
• Of the medication errors, 1.3% cause severe harm, but no fatal errors were reported.


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How Much Does Carpooling Matter? A Lot.

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The end of a policy to support carpooling in Jakarta, Indonesia led to an 87% increase in evening rush-hour traffic, according to a study published this summer in Science.

-- Read more on ScientificAmerican.com
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'I was screaming': Patients testify against dentist accused of health, safety violations

The fate of a Lewiston dentist accused of putting the health and safety of his patients in jeopardy likely won't be known for several months. On Friday, the Maine Board of Dental Practice held its first hearing to determine whether Dr. Jan Kippax should be further disciplined after his license was temporarily suspended in February.



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Le partage des données au service de l’éthique, de la transparence et de la reproductibilité de la science médicale

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Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): O. Laccourreye, P. Bonfils, R. Garrel, R. Jankowski, A. Karkas, N. Leboulanger, M. Makeieff, C. Righini, C. Vincent, C. Martin




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Chirurgie de l’hyperparathyroïdie primaire en ambulatoire : à propos d’une série de 67 cas

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): D. Culié, B. Pescetto, O. Dassonville, N. Guevara, D. Benisvy, J. Santini
IntroductionLa chirurgie de l'hyperparathyroïdie primaire, ciblée par l'imagerie morphologique et fonctionnelle, remplit les conditions théoriques d'une réalisation ambulatoire. L'objectif de notre étude était de valider ce type de prise en charge sur une série homogène de patients.Patients et méthodesL'ensemble des patients chez qui a été réalisée une chirurgie d'hyperparathyroïdie primaire en ambulatoire dans notre institution entre janvier 2013 et avril 2015 a été inclus dans cette étude rétrospective. Les critères habituels d'évaluation de la chirurgie ambulatoire ont été étudiés.RésultatsDurant la période étudiée, 144 patients ont été opérés d'une hyperparathyroïdie primaire. Dans 67 cas une chirurgie ambulatoire a pu être réalisée, avec un diagnostic préopératoire d'adénome parathyroïdien en imagerie. La recherche de la glande pathologique a été réalisée par une échographie chez tous les patients, et chez 66 d'entre eux par une scintigraphie. Cela a permis une chirurgie unilatérale, ciblée, dans 98,5 % des cas. Deux patients ont dû être hospitalisés pour la nuit en lien avec des complications mineures.ConclusionLa chirurgie de l'adénome parathyroïdien peut, dans une population de patients bien sélectionnée, être réalisée sur des durées opératoires courtes et avec un minimum de complications permettant ainsi sa réalisation en ambulatoire.



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Connaissances concernant le syndrome d’apnées-hypopnées obstructives du sommeil par la population générale de Lorraine

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): F. Arous, J.-M. Boivin, A. Chaouat, C. Rumeau, R. Jankowski, D.T. Nguyen
ObjectifLe syndrome d'apnées-hypopnées obstructives du sommeil (SAHOS) semble être sous-diagnostiqué. L'objectif de cette étude était d'évaluer les connaissances du SAHOS par la population générale de Lorraine.MéthodesUne enquête à l'aide d'un questionnaire anonyme portant sur les connaissances des symptômes et des complications du SAHOS a été menée de juillet 2015 à novembre 2015, en région Lorraine. Le questionnaire a également été diffusé sur Internet à l'aide de réseaux sociaux. Les critères d'exclusion étaient les personnes de moins de 18 ans, le refus de remplir le questionnaire et la barrière linguistique.RésultatsAu total, 1307 personnes ont répondu à l'enquête : 1020 sous format papier et 287 via Internet. La plupart des symptômes étaient connus par environ deux tiers de la population. Les complications notamment cardiovasculaires et neurologiques étaient en revanche mal connues. Être atteint du SAHOS, avoir fait des études supérieures et avoir moins de 40 ans étaient des facteurs associés à une meilleure connaissance de la maladie. Les répondeurs sur Internet connaissaient aussi mieux cette pathologie.ConclusionMalgré des résultats concernant les symptômes du SAHOS plutôt encourageants, les connaissances du grand public concernant ses complications sont limitées. De nouvelles campagnes d'informations auprès des médecins ainsi qu'auprès du grand public devraient être réalisées afin d'informer la population de cette pathologie et de la sensibiliser sur ses complications.



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Résultats fonctionnels de la chirurgie endoscopique du diverticule de Zenker

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): A. Dissard, L. Gilain, R. Pastourel, T. Mom, N. Saroul
But du travailL'objectif principal de cette étude rétrospective était l'évaluation des résultats fonctionnels de la chirurgie endoscopique du diverticule de Zenker. Les objectifs secondaires étaient d'évaluer la sécurité de la procédure, d'identifier les facteurs de risque de récidive et d'en déterminer leur conduite en cas de récidive.Patients et méthodesDe 2000 à 2014, 50 patients ont bénéficié d'une chirurgie endoscopique avec marsupialisation d'un diverticule de Zenker. Les symptômes de régurgitations et de dysphagie ont été évalués par l'échelle FOIS avant et après chirurgie. Le taux de récidives et le taux de complications ont été déterminés de manière rétrospective avec un suivi minimal de 18 mois.RésultatsLes régurgitations et la dysphagie ont été améliorées respectivement chez 96 % et 86 % des patients. Le taux de complications était de 12 %, complications le plus souvent mineures. Les temps moyens d'hospitalisation et de reprise alimentaire orale étaient respectivement de 2,0 et 1,3jours. Neuf patients (18 %) ont présenté une récidive de leur symptomatologie initiale et ont nécessité une reprise chirurgicale dans un délai moyen de 2,7 années. Elle a pu être réalisée dans la majorité des cas par voie endoscopique. Un seul facteur de risque de récidive a été identifié : la petite taille du diverticule.ConclusionLa chirurgie endoscopique du diverticule de Zenker permet une amélioration fonctionnelle dans la majorité de cas. Associant sécurité et efficacité, elle est actuellement la procédure de choix dans le traitement du diverticule de Zenker.



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Données étiologiques des sous-maxillites aiguës et prise en charge étiologique

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): C. Bignet, J. Carvalho, E. Lemaire, A. Charpiot
ButL'objectif de notre étude est de vérifier l'hypothèse que les sous-maxillites aiguës sont liées à un obstacle sur les voies salivaires. Notre étude évalue les caractéristiques de ces obstacles et leurs prises en charge.Matériel et méthodesOnt été inclus de façon rétrospective les patients ayant fait un épisode de sous-maxillite aiguë entre 2009 et 2015. Tous les patients ont bénéficié d'une exploration des voies salivaires par imagerie et/ou par sialendoscopie, et un examen anatomopathologique en cas d'ablation de la glande pour le diagnostic étiologique. Concernant le traitement étiologique : si la lésion causale n'était pas traitable par sialendoscopie uniquement, l'opérateur pouvait avoir recours à une voie combinée aidée par sialendoscope. En cas d'échec de ces procédures, l'indication d'une sous-maxillectomie était posée.RésultatsVingt-neuf patients ont été inclus dans l'étude et 28 patients présentaient une anomalie des voies salivaires. Au moins un calcul était retrouvé chez 27 patients, ceux-ci étaient majoritairement uniques (n=20), dans le tiers moyen (n=21) et volumineux (7,7mm de moyenne). Une sténose était retrouvée chez 10 patients et pour 9 patients, associée à un calcul salivaire. Vingt-cinq patients avec un obstacle ont bénéficié d'une sialendoscopie. La prise en charge par sialendoscopie uniquement a été possible dans 5 cas et par voie combinée dans 13 cas.ConclusionUn épisode de sous-maxillite impose un examen des voies salivaires par sialendoscopie pour une prise en charge précoce en raison de la fréquence de calculs associés et du taux élevé de traitement conservateur guidé par sialendoscopie.



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Editorial Board

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Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5





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Carcinome indifférencié de type nasopharyngé chez l’enfant : particularités cliniques et évolutives

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): W.S. Zrafi, S. Tebra, S. Tbessi, S. Ouni, M. Jebsi, N. Bouaouina
ObjectifsParticularités épidémiologiques, cliniques et thérapeutiques du carcinome indifférencié de type nasopharyngé chez l'enfant.Matériel et méthodesÉtude rétrospective d'une série de 40 patients d'âge inférieur à 17 ans suivis pour un carcinome indifférencié du nasopharynx, dans les deux centres d'oncologie radiothérapie du centre tunisien entre 1995 et 2012.RésultatsL'âge médian était 14 ans, le sex-ratio 1,3. Le délai moyen de consultation était de 5 mois, la circonstance de découverte était l'apparition d'adénopathies cervicales dans 90 % des cas. Sur le plan thérapeutique, 37 patients ont reçu un traitement à visée curative. Le schéma thérapeutique était séquentiel dans 85 % des cas, commençant par une chimiothérapie puis une radiothérapie du cavum et des aires ganglionnaires cervicales. La dose médiane au niveau du cavum était de 70,4Gy. L'évolution a été marquée par la survenue de deux récidives locales, cinq rechutes métastatiques, toutes osseuses. Après un recul moyen de 80,5 mois (1–180), 29 patients (72,5 %) étaient en rémission complète, huit sont décédés et trois perdus de vue. La survie globale à 5 ans était de 77,7 %.ConclusionLe carcinome indifférencié du nasopharynx de l'enfant représente dans notre région 6 % des cas d'UCNT pris en charge dans nos institutions. Il est souvent découvert à un stade évolué. L'association séquentielle de chimiothérapie et de radiothérapie a permis un excellent taux de contrôle local.



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Exploration électrophysiologique de l’audition

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): D. Bakhos, M. Marx, A. Villeneuve, E. Lescanne, S. Kim, A. Robier
Les examens audiométriques électrophysiologiques se sont développés depuis les années 1960 avec comme objectif la détermination objective des seuils auditifs. Ils sont maintenant utilisés pour le dépistage de la surdité néonatale. Si ces tests permettent de préciser les seuils auditifs, leur interprétation ne peut se faire qu'en complémentarité de l'audiométrie subjective que représente l'audiométrie tonale et vocale. En effet, si les tests objectifs permettent de préciser les seuils auditifs, ils ne peuvent généralement pas déterminer le type de surdité en cause. Chaque examen teste une région anatomique différente permettant l'exploration du système auditif de l'organe de Corti au cortex auditif. Ainsi, les examens d'audiométrie objective sont complémentaires.



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Le nez brûlé : une analyse en 4 dimensions

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): J. Bouguila, C. Ho Quoc, R. Viard, A. Brun, D. Voulliaume, J.-P. Comparin, J.L. Foyatier
De part sa position et sa projection, le nez est exposé aux diverses agressions comme les brûlures. Ce type de lésion peut concerner le nez de façon isolée ou entrer dans un contexte plus large constituant les brûlures nasofaciales. La reconstruction du nez constitue un défi, car cette entité anatomique est formée d'un ensemble tridimensionnel complexe, auquel s'ajoute même une « quatrième dimension » : la fonction. La prise en charge du nez brûlé constitue un défi esthétique et fonctionnel. Le traitement des séquelles doit s'adapter au degré d'atteinte du nez et aux impératifs esthétiques et fonctionnels de cette structure anatomique. Ce n'est qu'au terme de multiples interventions chirurgicales et de longs mois de rééducation que le patient brûlé retrouvera une vie sociale satisfaisante.



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Thérapie cellulaire et cordes vocales cicatricielles

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): A. Mattei, J. Magalon, B. Bertrand, C. Philandrianos, J. Veran, A. Giovanni
La microstructure des cordes vocales est complexe et peut être altérée par une microchirurgie laryngée. On peut alors observer un état cicatriciel n'autorisant plus le découplage mécanique entre épithélium et muscle, responsable de difficultés vibratoires à l'origine d'une dysphonie invalidante. Les possibilités thérapeutiques actuelles sont réduites et souvent inefficaces sur la vibration : elles n'apportent qu'un effet volumateur limitant la fuite glottique. L'objectif de cette revue de la littérature était double : i) décrire l'état actuel de la littérature quant à l'intérêt de la thérapie cellulaire dans la prise en charge des cordes vocales cicatricielles ; ii) analyser l'intérêt thérapeutique de la fraction vasculaire stromale d'origine adipeuse parmi l'arsenal thérapeutique préexistant. Notre recherche sur PubMed® en septembre 2016 a référencé les articles originaux de langue anglaise ou française traitant de l'usage des cellules souches dans la prise en charge des cordes vocales cicatricielles. Vingt-sept articles publiés entre 2003 et 2016 répondaient aux critères de sélection. Les cellules souches mésenchymateuses étaient les plus utilisées, majoritairement extraites de la moelle osseuse ou du tissu adipeux. Quatre études étaient réalisées in vitro sur fibroblastes et dix-huit in vivo chez l'animal. Les critères d'évaluation étaient : i) l'analyse de la cicatrisation (morphologie macroscopique et microscopique, propriétés viscoélastiques, matrice extracellulaire, fibroblastes) ; ii) l'évaluation de la survie et différenciation des cellules souches. Ces études démontrent l'action bénéfique des cellules souches mésenchymateuses, notamment d'origine adipeuse. Par ailleurs, la fraction vasculaire stromale possède des propriétés qui pourraient permettre d'améliorer ces résultats, en facilitant la logistique de production.



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La maladie de Kikuchi-Fujimoto, une cause rare d’adénopathie en Afrique. Description de la première observation au Sénégal et revue de la littérature

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): C.-A. Lame, B. Loum, A.-K. Fall, J. Cucherousset, A.-R. Ndiaye
IntroductionLa maladie de Kikuchi-Fujimoto est une lymphadénite histiocytaire nécrosante. Cette pathologie bénigne atteint le plus souvent le sujet féminin d'âge mûr. Elle se manifeste généralement par des adénopathies cervicales fébriles. Elle doit être évoquée dans notre contexte d'exercice dominé par la fréquence des adénopathies tuberculeuses et des hémopathies malignes.ObservationNous rapportons le cas d'une femme sénégalaise âgée de 33 ans qui a présenté des adénopathies cervicales subaiguës dans un contexte fébrile. Il existait un syndrome inflammatoire biologique. Les bilans sérologique et tuberculeux étaient négatifs. L'analyse histopathologique d'une biopsie ganglionnaire, après échec d'un traitement antibiotique non spécifique, concluait à une maladie de Kikuchi-Fujimoto. L'évolution était favorable sous corticothérapie.ConclusionEn Afrique noire, l'association de polyadénopathies et de syndrome fébrile doit faire penser et rechercher, après la tuberculose et les lymphomes à des pathologies rares comme la maladie de Kikuchi-Fujimoto.



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Fibrose angiocentrique à éosinophiles ethmoïdo-orbitaire droite

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): S. Gorostis, M. Bacha, S. Gravier, T. Raguin
IntroductionLa fibrose angiocentrique à éosinophiles (EAF) est une affection bénigne et lentement progressive, affectant la muqueuse des voies aériennes supérieures ou l'orbite plus rarement. Elle appartient au spectre de la maladie associée aux IgG4.Cas cliniqueNous rapportons le cas d'un homme de 61 ans présentant une atteinte orbitaire (baisse d'acuité visuelle, douleurs, exophtalmie, œdème palpébral), céphalées et obstruction nasale. L'imagerie révèle une masse ethmoïdo-orbitaire droite infiltrant la graisse périorbitaire et englobant le nerf optique. L'analyse anatomopathologique a posé le diagnostic d'EAF devant l'infiltration périvasculaire par des cellules inflammatoires – majoritairement des polynucléaires éosinophiles – et des zones de fibrose « en bulbe d'oignon ». L'immunohistochimie a permis d'apparenter les lésions aux maladies associées aux IgG4. La prise en charge initiale par corticothérapie, puis dapsone n'a pas suffi au contrôle des crises évolutives, avec une importante corticodépendance. Une ethmoïdectomie chirurgicale emportant la lame papyracée a été réalisée dans le but de permettre l'expansion du globe oculaire vers la fosse nasale en cas de nouvelle crise.DiscussionL'association du rituximab à la chirurgie a permis la régression durable des douleurs et de l'exophtalmie.



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Carcinome mucoépidermoïde sclérosant de la glande sublinguale

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): D.H. Lee, J.H. Kim, J.K. Lee, S.C. Lim
IntroductionLe carcinome mucoépidermoïde sclérosant de la glande salivaire est un sous-type rare de carcinome mucoépidermoïde. Les sites les plus touchés par le carcinome mucoépidermoïde sclérosant des glandes salivaires sont par ordre de fréquence la glande parotide, la glande sous-mandibulaire et les glandes salivaires accessoires.ObservationNous rapportons ici le premier cas de carcinome mucoépidermoïde sclérosant de la glande sublinguale.DiscussionLes cliniciens doivent évoquer le carcinome mucoépidermoïde sclérosant dans le diagnostic différentiel du néoplasme de la glande salivaire. L'exérèse chirurgicale avec marges saines est une option thérapeutique initiale qui semble suffisante pour le carcinome mucoépidermoïde sclérosant de la glande salivaire.



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Démarche diagnostique devant un œdème labial diffus isolé d’apparition soudaine

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): O. Laccourreye, F. Rubin, J. Delort, P. Bonfils
À partir d'un cas d'œdème labial diffus isolé de survenue soudaine, les auteurs précisent les points clefs de la démarche diagnostique ainsi que les principales données épidémiologiques et cliniques.



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Les corps étrangers nasaux chez les enfants dans un hôpital pédiatrique au Sénégal : une évaluation de 3 ans

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): P.E.J. Regonne, M. Ndiaye, A. Sy, Y. Diandy, A.D. Diop, B.K. Diallo
ObjectifsLes corps étrangers nasaux (CEN) sont un accident domestique fréquent chez les enfants. L'objectif de ce travail était de présenter les particularités des CEN chez les enfants dans un hôpital pédiatrique sénégalais et décrire notre attitude thérapeutique.Matériel et méthodesÉtude rétrospective descriptive au service d'oto-rhino-laryngologie du Centre hospitalier national pour enfants de Diamniadio du 1er janvier 2013 au 31 décembre 2015 incluant tous les enfants de moins de 15 ans reçus pour CEN. Les variables étudiées étaient l'âge, le sexe, la provenance, le motif de consultation, le délai de consultation, la nature du CEN, la méthode d'extraction et les complications.RésultatsCinquante-huit CEN avaient été recensés. L'âge moyen était de 3 ans 4 mois. Parmi les patients, 93 % avaient moins de 5 ans. Il y avait une prédominance féminine (53,45 %), soit un sex-ratio de 0,87. Les CEN étaient localisés chez 43 patients (74,1 %) à droite. Le premier motif de consultation était la rhinorrhée purulente retrouvée chez 51,7 % ; parmi les patients, 17,24 % étaient amenés en consultation dans les 24 premières heures. La mousse était le premier CEN (29,3 %), suivie des graines (20,7 %). L'extraction a été réalisée en consultation chez 84,5 % et chez 15,5 % au bloc opératoire. La morbidité était de 22,41 %. Il s'agissait dans 17,24 % d'une épistaxis et dans 5,17 % d'une infection nasale.ConclusionLes CEN sont des accidents fréquents chez l'enfant de moins de 5 ans. Notre contexte est marqué par un retard à la consultation.



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Tuméfaction inflammatoire basicervicale

Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): H. Benkhatar, F. Scotte, O. Laccourreye, C. Benoit




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Masse fluctuante cervicale : lettre à l’éditeur et revue de la littérature de phlébectasie de la veine jugulaire antérieure

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Publication date: October 2017
Source:Annales françaises d'Oto-rhino-laryngologie et de Pathologie Cervico-faciale, Volume 134, Issue 5
Author(s): M.Y. Abboud, A. de Lafontaine-Ruel, B. Riederer, D. Philippon




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Forum nazionale della Salute, Zagonel (Iov) sull'immunoncologia nel tumore colorettale

Forum nazionale della Salute, Zagonel (Iov) sull'immunoncologia nel tumore colorettale

Cinque anni fa l'immuno-oncologia sembrava essere "solo" una delle grandi speranze della ricerca sulle neoplasie: oggi si è ormai passati dalla fase delle speranze a quella delle...



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Molecular characterization of Cryptococcus neoformans isolated from the environment in Beijing, China

Abstract
The molecular type of environmental Cryptococcus neoformans in Beijing was not clear. Our study aims to reveal the molecular characterization of C. neoformans complex from environment in Beijing, China. A total of 435 samples of pigeon droppings from 11 different homes in Beijing were collected from August to November in 2015. Pigeon droppings were inoculated onto caffeic acid cornmeal agar (CACA) to screen C. neoformans complex. Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for species identification. Serotype and mating type was determined by specific primers. Restriction fragment length polymorphisms of URA5 (URA5-RFLP) were applied to genotype. Multi-locus sequence typing (MLST) was done for further identification and sequence type (ST) determination. Altogether, 81 isolates of C. neoformans AFLP1/VNI were recognized from 435 pigeon droppings in this study. The positive rate for C. neoformans AFLP1/VNI from pigeon droppings in different homes varied from 5.0% to 52.6%, the average was 20.2%. All of these cryptococcal strains were serotype A, MATα. They were genotyped as VNI by URA5-RFLP and were confirmed by MLST. No other molecular types of C. neoformans and Cryptococcus gattii isolates were isolated. Their STs were identified as ST 31 (n = 54, 66.7%), followed by ST 53 (n = 10), ST 191 (n = 8), ST 5 (n = 5), ST 57 (n = 3), and ST 38 (n = 1). We concluded that not only clinical but also environmental isolates of C. neoformans need to be investigated more deeply and more extensively. The virulence difference between ST 5 and ST 31 need to be explored in the future.

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Yeasts from Scarlet ibises ( Eudocimus ruber ): A focus on monitoring the antifungal susceptibility of Candida famata and closely related species

Abstract
This study aimed to identify yeasts from the gastrointestinal tract of scarlet ibises (Eudocimus ruber) and from plant material collected from the environment where they live. Then, the isolates phenotypically identified as Candida famata were submitted to molecular identification of their closely related species and evaluated for their antifungal susceptibility and possible resistance mechanisms to antifungal drugs. Cloacal swabs from 20 scarlet ibises kept in captivity at Mangal das Garças Park (Brazil), pooled stool samples (n = 20) and samples of trunks and hollow of trees (n = 20) obtained from their enclosures were collected. The samples were seeded on Sabouraud agar supplemented with chloramphenicol. The 48 recovered isolates were phenotypically identified as 15 Candida famata, 13 Candida catenulata, 2 Candida intermedia, 1 Candida lusitaniae, 2 Candida guilliermondii, 1 Candida kefyr, 1 Candida amapae, 1 Candida krusei, 8 Trichosporon spp., and 4 Rhodotorula spp. The C. famata isolates were further identified as 3 C. famata, 8 Debaryomyces nepalensis, and 4 C. palmioleophila. All C. famata and C. palmioleophila were susceptible to caspofungin and itraconazole, while one D. nepalensis was resistant to fluconazole and voriconazole. This same isolate and another D. nepalensis had lower amphotericin B susceptibility. The azole resistant strain had an increased efflux of rhodamine 6G and an alteration in the membrane sterol content, demonstrating multifactorial resistance mechanism. Finally, this research shows that scarlet ibises and their environment harbor C. famata and closely related species, including antifungal resistant isolates, emphasizing the need of monitoring the antifungal susceptibility of these yeast species.

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Effect of peritoneal dialysis fluids on activity of echinocandins against Candida spp. biofilm

Abstract
Peritoneal dialysis fluids (PDFs) impair microorganisms' growth, which may compromise effectivity of some antimicrobials. The purpose of this study was to investigate the effect of three different PDFs (lactate/bicarbonate-buffered Physioneal 40® with 2.2% glucose, lactate-buffered Nutrineal PD4® with 1.1% amino acid, and lactate-buffered Extraneal® with 7.5% icodextrin) on biofilm formation of four different Candida spp and antibiofilm effectiveness of anidulafungin, caspofungin and micafungin against Candida spp. biofilm in PDFs. All tested PDFs attained inhibitory effect on the biofilm formation but also reduced biofilm effectiveness of echinocandins against biofilm in PDFs was detected.

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Identification of a Novel Rhizopus -specific Antigen by Screening with a Signal Sequence Trap and Evaluation as a Possible Diagnostic Marker of Mucormycosis

Abstract
Mucormycosis is the second most common mould infection, often indistinguishable from other invasive mould infections such as aspergillosis. Although an appropriate antifungal therapy is effective at an early stage of the infection, there is no reliable diagnostic method for decision making. Thus, it is necessary to develop an efficient method that can detect mucormycosis rapidly and accurately. We searched for secreted or membrane-bound proteins of Rhizopus oryzae, which is the most common pathogen of mucormycosis, using the method of a signal sequence trap by retrovirus-mediated expression (SST-REX). Among the identified proteins, a Rhizopus-specific antigen was selected as a candidate, and efficacy of this specific antigen was evaluated using R. oryzae–infected mice. Of 302 clones obtained from the SST-REX library, a hypothetical protein (23 kDa, named "protein RSA") was selected as a candidate because of its highest prevalence of clones. Protein RSA was detected at significantly higher concentrations in serum and in lung homogenates of the infected mice as compared to those of uninfected mice. Our study indicates that protein RSA may be a promising biomarker of R. oryzae infection. SST-REX may be useful for comprehensive screening of prospective eukaryotic biomarkers of intractable mould infections.

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Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design

Abstract
Clioquinol is an 8-hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti-Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8-hydroxyquinoline derivatives (8-hydroxy-5-quinolinesulfonic acid and 8-hydroxy-7-iodo-5-quinolinesulfonic acid). Antifungal activity was tested by broth microdilution and the fungicidal or fungistatic effect was checked by a time-kill assay. Permeation and histopathological evaluation were performed in Franz diffusion cells with ear skin of pigs and examined under light microscopy. An HET-CAM test was used to determine the potential irritancy. The three compounds were active against all isolates showing anti-Candida and antidermatophyte activity, with MIC ranges of 0.031–2 μg/ml, 1–512 μg/ml, and 2–1024 μg/ml for clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid, respectively. All compounds showed fungistatic effect for Candida, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid showed a fungicidal effect for M. canis and T. mentagrophytes, and clioquinol showed a fungicidal effect only for T. mentagrophytes. Furthermore, they presented a fungicidal effect depending on the time and concentration. The absence of lesions was observed in histopathological evaluation and no compound was irritating. Moreover, clioquinol and 8-hydroxy-5-quinolinesulfonic acid accumulated in the epithelial tissue, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid had a high degree of permeation. In conclusion, 8-hydroxyquinoline derivatives showed antifungal activity and 8-hydroxy-5-quinolinesulfonic acid demonstrated the potential for antifungal drug design.

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Planktonic growth and biofilm formation profiles in Candida haemulonii species complex

Abstract
Candida haemulonii species complex have emerged as multidrug-resistant yeasts able to cause fungemia worldwide. However, very little is known regarding their physiology and virulence factors. In this context, planktonic growth and biofilm formation of Brazilian clinical isolates of Candida haemulonii (n = 5), Candida duobushaemulonii (n = 4), and Candida haemulonii var. vulnera (n = 3) were reported. Overall, the fungal planktonic growth curves in Sabouraud dextrose broth reached the exponential phase in 48 h at 37°C. All the clinical isolates formed biofilm on polystyrene in a time-dependent event, as judged by the parameters evaluated: biomass (crystal violet staining), metabolic activity (XTT reduction), and extracellular matrix (safranin incorporation). No statistically significant differences were observed when the average measurements among the three Candida species were compared regarding both planktonic and biofilm lifestyles; however, typical isolate-specific differences were clearly noticed in fungal growth kinetics.

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Is a biomarker-based diagnostic strategy for invasive aspergillosis cost effective in high-risk haematology patients?

Abstract
Empirical antifungal therapy is frequently used in hematology patients at high risk of invasive aspergillosis (IA), with substantial cost and toxicity. Biomarkers for IA aim for earlier and more accurate diagnosis and targeted treatment. However, data on the cost-effectiveness of a biomarker-based diagnostic strategy (BDS) are limited. We evaluated the cost effectiveness of BDS using results from a randomized controlled trial (RCT) and individual patient costing data. Data inputs derived from a published RCT were used to construct a decision-analytic model to compare BDS (Aspergillus galactomannan and PCR on blood) with standard diagnostic strategy (SDS) of culture and histology in terms of total costs, length of stay, IA incidence, mortality, and years of life saved. Costs were estimated for each patient using hospital costing data to day 180 and follow-up for survival was modeled to five years using a Gompertz survival model. Treatment costs were determined for 137 adults undergoing allogeneic hematopoietic stem cell transplant or receiving chemotherapy for acute leukemia in four Australian centers (2005–2009). Median total costs at 180 days were similar between groups (US$78,774 for SDS [IQR US$50,808–123,476] and US$81,279 for BDS [IQR US$59,221–123,242], P = .49). All-cause mortality was 14.7% (10/68) for SDS and 10.1% (7/69) for BDS, (P = .573). The costs per life-year saved were US$325,448, US$81,966, and US$3,670 at 180 days, one year and five years, respectively. BDS is not cost-sparing but is cost-effective if a survival benefit is maintained over several years. An individualized institutional approach to diagnostic strategies may maximize utility and cost-effectiveness.

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Report on novel environmental niches for Cryptococcus neoformans and Cryptococcus gattii in Colombia: Tabebuia guayacan and Roystonea regia

Abstract
Knowledge of the environmental distribution of C. neoformans/C. gattii is important in the epidemiology and ecology of the etiological agent, which causes cryptococcosis, a deadly disease worldwide. The aim of this report is to describe the presence of C. neoformans/C. gattii in new environmental niches in Colombia. A total of 837 environmental samples were collected from six different species of trees across four cities; molecular type was determined by PCR fingerprinting and RFLP. Molecular type VNI and VGIII were isolated from different species of trees, resulting in two novel niches for this pathogen: Tabebuia guayacan and Roystonea regia.

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Epidemiology of Trichophyton verrucosum infection in Rennes University Hospital, France: A 12-year retrospective study

Abstract
Trichophyton verrucosum is a zoophilic dermatophyte, known as a causative agent of inflammatory mycoses of the skin and the scalp in humans. In this study, we reviewed all cases of T. verrucosum infection diagnosed in our laboratory over a 12-year period, to determine epidemiological and clinical characteristics. Among 18,340 samples analyzed, 5,186 cultured positive with dermatophytes (2674 patients), of which 64 samples (41 patients) were positive for T. verrucosum. Our data show that there was a strong influence of age on the type of lesion, with children and adults presenting more frequently with tinea capitis and skin infections, respectively (P < .0001). Infection of children and adults resulted more frequently from indirect and direct exposure to cattle, respectively (P < .01). We observed a marked increase of cases over the last 4 years, with a correlation of the number of cases and the mean annual rainfall (P < .05), suggesting that increasing humidity favors cattle infection, and thereby, human infection. Whether this increase is the consequence of climate changes remains to be determined but should be considered.

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Study of differential expression of miRNAs in lung tissue of mice submitted to experimental infection by Paracoccidioides brasiliensis

Abstract
MicroRNAs (miRNAs) are small single stranded RNA sequences involved in post-transcriptional regulation of different biological and physiological processes. Paracoccidioidomycosis (PCM) is an infection caused by Paracoccidioides brasiliensis, and it is a major cause of mortality due to systemic mycoses in Brazil. To date, there have been few reports on the role of miRNAs in the immune response against fungi, especially PCM. The objective of this study was to evaluate the differential expression of miRNAs related to the inflammatory response associated with pulmonary infection by P. brasiliensis. For this purpose, lungs from BALB/c mice, intravenously infected with P. brasiliensis (2.7×107 yeast cells/ml, n = 12) and noninfected BALB/c mice (n = 8), were collected at the 28 and 56 day after infection. The lung parenchyma presented a great number of yeast cells, granulomas, and edema at 28 days and a framework of resolution of the inflammatory process after 56 days. The mRNAs gata-3, ror-γt, foxp3, and IL-6 were positively regulated at the moment at the 56 day, while the TGF-β1 mRNA was positively regulated at both moments. The miRNAs 126a-5p, 340–5p, 30b-5p, 19b-3p, 221–3p, 20a-5p, 130a-3p, and 301a-3p, 466k presented the greatest increase in expression levels 28 days after infection, and the miRNAs let-7f-5p, let-7a-5p, 5p-26b, let-7e-5p and 369-3p, 466k presented a greater increase in levels of expression 56 days after infection. This study shows a set of differentially expressed miRNAs possibly involved in the immune response in mice during pulmonary infection by P. brasiliensis.

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Employment of methylene blue irradiated with laser light source in photodynamic inactivation of biofilm formed by Candida albicans strain resistant to fluconazole

Abstract
A promising approach for the eradication of biofilm formed by the yeast Candida albicans seems to be photodynamic inactivation (PDI). This work presents a use of methylene blue (MB, 1 mM) irradiated with a red laser (output power 190 mW/cm2, wavelength 660 nm) for the eradication of a biofilm formed by the fluconazole-resistant (FLC-resistant) strain C. albicans CY 1123 compared to the standard strain C. albicans SC5314. The periods of irradiation corresponded to the fluence of 15, 23 and 57 J/cm2. Effectiveness of PDI was evident with following percentage of survived biofilm cells: 24.57, 23.46, and 22.29% for SC5314 and 40.28, 17.91, and 5.89% for CY 1123, respectively, compared to the samples without irradiation. Light and confocal laser scanning microscopy confirmed the effectiveness of PDI. However, the morphological form of C. albicans seems to play an important role as well, since prolonged duration of irradiation did not increase efficiency of PDI on C. albicans SC5314. An experiment with the yeast-to-hyphae transition revealed that the FLC-resistant strain expressed a markedly reduced capacity to form hyphae compared to SC5314. We summarized that PDI was effective on biofilm formed by the FLC-resistant strain, but resistance most likely did not play significant role in PDI. Additionally, we observed differences in susceptibility to PDI between biofilms composed of the mycelia and only of the yeasts, and finally, the employment of a laser in PDI enabled a decreasing period of irradiation while maintaining the high effectiveness of PDI.

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Bone and joint infections caused by mucormycetes: A challenging osteoarticular mycosis of the twenty-first century

Abstract
Osteomyelitis and arthritis caused by mucormycetes are rare diseases that rank among the most challenging complications in orthopedic and trauma surgery. The aim of this work is to review the epidemiological, clinical, diagnostic, and therapeutic aspects of the osteoarticular mucormycosis with particular emphasis on high-risk patients. A systematic review of osteoarticular mucormycosis was performed using PUBMED and EMBASE databases from 1978 to 2014. Among 34 patients with median age 41 (0.5–73 years), 24 (71%) were males. While 12 (35%) were immunocompromised patients, 14 (41%) had prior surgery, and seven (21%) suffered trauma. Other underlying conditions included diabetes mellitus, hematological malignancies, transplantation, and corticosteroid therapy. The median diagnostic delay from onset of symptoms and signs was 60 (10–180) days. The principal mechanism of the infection was direct inoculation (n = 19; 56%), and in immunocompromised patients was usually hematogenous disseminated. The long bones were infected by trauma or surgery, while a wide variety of bones were involved by hematogenous dissemination. Combined surgery and amphotericin B treatment were implemented in 28 (82%) and eight (23%) had an unfavorable outcome. Osteoarticular mucormycosis occurs most frequently after trauma or surgical procedures. These infections are progressively destructive and more virulent in individuals with impaired immune systems. Early diagnosis, timely administration of amphotericin B, control of underlying conditions, and surgical debridement of infected tissue are critical for successful management of osteoarticular mucormycosis.

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Inhibition of dermatophytes by photodynamic treatment with curcumin

Abstract
Treatment of dermatophytoses with currently available antimycotic agents is often tedious and sometimes unsatisfactory. A search for better therapeutic methods—ideally with an immediate fungicidal effect—has, among others, lead to photodynamic procedures as a promising alternative, and recently curcumin was found to be a suitable agent for this application. In this study the effect of photodynamic treatment with curcumin on dermatophytes was tested in vitro. Wells of microtiter plates were filled with conidia of Trichophyton rubrum, Trichophyton interdigitale, Trichophyton terrestre, Microsporum canis, Microsporum gypseum and Epidermophyton floccosum in buffer. Then curcumin was added to the conidia and after 20 min the assays were irradiated one time only with visible light (peak wave length 367 nm, 5 J/cm2). Thereafter the wells were filled up with Sabouraud's glucose broth and in the following fungal growth was measured photometrically. The results showed that all dermatophytes were markedly inhibited depending on the concentration of curcumin. With 5.4 mg/l curcumin plus irradiation fungal growth was significantly suppressed over a period of 96 h (P < .001). Even after 96 h inhibition of T. rubrum was still complete and marked for all other species as well. M. gypseum was least susceptible. Our results are very encouraging to pursue the development of a photodynamic therapy of tinea with curcumin. The outstanding tolerance of curcumin and the innocuousness of the required light are favorable preconditions for this task.

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Cathelicidin (LL-37) level in the scalp hair of patients with tinea capitis

Abstract
Antimicrobial peptides (AMPs) are considered an important first line of defense against pathogens. Cathelicidin LL-37 was upregulated in response to fungal infection. In this work we aimed to evaluate cathelicidin LL-37 in the hair of tinea capitis and compare it to normal controls. Hair samples were collected from 30 children and 30 controls aged from 2 to10 years old, and the level of cathelicidin LL-37 in the hair was detected by quantitative real-time PCR. The 30 patients were further subdivided into three subgroups according to their clinical type. Ten patients were scaly type, 10 patients were black dots type, and 10 patients were kerion type. Cathelicidin level in patients ranged from 6.0 to 17.5 with mean ± SD (11.3 ± 2.3) and in control ranged from 1.02 to 6.2, with mean ± SD (2.8 ± 1.5). There was a significant difference between the patients and controls regarding the cathelicidin level; P value was 0. The mean cathelicidin level was lowest in the kerion type10.73 ± 2.6 and highest in the black dot type 12.05 ± 2.76. However, there was no significant difference between the cathelicidin level of the different clinical types of tinea capitis; P value was 0.58. In conclusion, the level of cathelicidin LL-37 in hair specimens of human tinea capitis was significantly higher than controls.

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Givinostat exhibits in vitro synergy with posaconazole against Aspergillus spp

Abstract
In vitro interactions of givinostat, a hydroxamate-derived histone deacetylase inhibitor, and antifungals including itraconazole, voriconazole, posaconazole, amphotericin B and caspofungin against Aspergillus spp. were assessed via broth microdilution checkerboard technique system. A total of 30 isolates of Aspergillus spp., including 20 strains of A. fumigatus and 10 strains of A. flavus were studied. The results revealed favorable synergistic effects between givinostat and posaconazole (83.3%) against Aspergillus isolates. Limited synergism was observed when givinostat was combined with itraconazole or voriconazole. No interaction was observed between givinostat and amphotericin B or caspofungin. No antagonism was observed in all combinations.

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Diagnostic utilities of a fully automated molecular test for toxigenic Clostridium difficile

Publication date: Available online 30 September 2017
Source:Journal of Infection and Chemotherapy
Author(s): Yoshitomo Morinaga, Norihiko Akamatsu, Junichi Matsuda, Hiroko Tateno, Takeshi Tomaru, Ai Tanaka, Sayuri Morita, Makoto Nakamura, Hideaki Kato, Megumi Annaka, Yoshishige Masuda, Yasutomo Itakura, Takashi Inamatsu, Katsunori Yanagihara
Laboratory underdiagnosis of toxigenic Clostridium difficile can lead to inappropriate management of C. difficile infection (CDI). A fully automated molecular test (FAMT), BD MAX, and enzyme immunoassays for C. difficile glutamate dehydrogenase (GDH) and for toxin A/B antigen test were evaluated using clinical specimens. Laboratory analysis of 231 fecal specimens from patients suspected with CDI, indicated that the sensitivity (Sn), specificity (Sp), positive predictive value (PPV), and negative predictive value (NPV) of FAMT was 98.1%, 98.9%, 96.3%, and 99.4%, while that of toxin A/B antigen was 52.8%, 100.0%, 100.0%, and 87.7%, respectively, compared to toxigenic culture. Sn, Sp, PPV, and NPV of GDH test compared to toxigenic culture was 92.5%, 94.4%, 83.1%, and 97.7%, respectively. FAMT can support the accurate laboratory diagnosis of toxigenic C. difficile and be an effective tool for appropriate treatment of CDI.



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Evaluating the toxic effects of three priority hazardous and noxious substances (HNS) to rotifer Brachionus plicatilis

Abstract

Hazardous and noxious substances (HNS) spill in the marine environment is an issue of growing concern, and it will mostly continue to do so in the future owing to the increase of high chemical traffic. Nevertheless, the effects of HNS spill on marine environment, especially on aquatic organisms are unclear. Consequently, it is emergent to provide valuable information for the toxicities to marine biota caused by HNS spill. Accordingly, the acute toxicity of three preferential HNS and sub-lethal effects of acrylonitrile on Brachionus plicatilis were evaluated. The median lethal concentration (LC50) at 24 h were 47.2 mg acrylonitrile L−1, 276.9 mg styrene L−1, and 488.3 mg p-xylene L−1, respectively. Sub-lethal toxicity effects of acrylonitrile on feeding behavior, development, and reproduction parameters of B. plicatilis were also evaluated. Results demonstrated that rates of filtration and ingestion were significantly reduced at 2.0, 4.0, and 8.0 mg L−1 of acrylonitrile. Additionally, reproductive period, fecundity, and life span were significantly decreased at high acrylonitrile concentrations. Conversely, juvenile period was significantly increased at the highest two doses and no effects were observed on embryonic development and post-reproductive period. Meanwhile, we found that ingestion rate decline could be a good predictor of reproduction toxicity in B. plicatilis and ecologically relevant endpoint for toxicity assessment. These data will be useful to assess and deal with marine HNS spillages.



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Chemical characteristics and source analysis on ionic composition of rainwater collected in the Carpathians “Cold Pole,” Ciuc basin, Eastern Carpathians, Romania

Abstract

A study of precipitation chemistry was conducted for 11 years (01 January 2006–31 December 2016) in the Ciuc basin, Eastern Carpathians, Romania. The studied area is an enclosed basin, also called "the Carpathians cold pole." All collected samples were analyzed for major cations and anions. HCO3 concentrations were calculated based on the empirical relationship between pH and HCO3. The multiannual arithmetic mean of pH values was found to be 6.57. The lowest and highest pH values were measured in 2009 and 2013, being 6.57% lower, respectively, 7.57% higher than the multiannual mean. Only 3.31% of the studied rainwater samples indicate acidic character. In descending order, the majority of the samples are as follows: NH4+ >Ca2+ >SO42− >Cl >HCO3 >NO3 >Na+ >K+ >Mg2+ >NO2 >H+. Principal component analysis (PCA) showed the NH4+, Ca2+, and Mg2+ contribution to the neutralization process and their sources. The anthropogenic origin of SO42− was supported by the high non-sea-salt fraction (NSSF) (~ 91%). The results of this study suggest that rainwater chemistry is strongly influenced by local natural and anthropogenic sources (agricultural activities) rather than marine sources. The pollutants in rainwater samples were mainly derived from calcareous and dolomitic soil dust and specific local climatic conditions, long-range transport, local industry, and traffic sources.



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Identification of groundwater redox process induced by landfill leachate based on sensitive factor method

Abstract

Landfill site is a significant source of groundwater pollution. To ensure that the groundwater contamination of landfills can be controlled and repaired scientifically, the identification of groundwater pollution process is needed. On the basis of biogeochemical process of leachate pollutants in the groundwater environment, a sensitive factor method for the identification of groundwater redox process from landfills was established in this research. The method encompasses four phases, including sensitive factors selection, redox zone characterization, weight calculation, and redox zone identification. In the sensitive factor index system employed here, five indicators involving dissolved oxygen (DO), nitrite, Fe2+, sulfide, and CO2 were selected. The boundary of each redox zones was determined by the quantitative method, and the weight of each indicator was calculated by combined weight method. This method was applied to a landfill site in the northeast of China. The result showed that there were five redox zones that appeared in pollution plume, including methanogenic zone (MGZ), sulfate reduction zone (SRZ), iron reduction zone (IRZ), nitrate reduction zone (NRZ), and oxygen reduction zone (ORZ). The results were consistent with the actual situation of the site. The sensitive factor method was scientific and effective to identify the groundwater redox process in landfill and can provide reference data related to investigation and remediation of groundwater pollution in landfill sites.



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Molecular characterization of Cryptococcus neoformans isolated from the environment in Beijing, China

Abstract
The molecular type of environmental Cryptococcus neoformans in Beijing was not clear. Our study aims to reveal the molecular characterization of C. neoformans complex from environment in Beijing, China. A total of 435 samples of pigeon droppings from 11 different homes in Beijing were collected from August to November in 2015. Pigeon droppings were inoculated onto caffeic acid cornmeal agar (CACA) to screen C. neoformans complex. Bruker Biotyper matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) was performed for species identification. Serotype and mating type was determined by specific primers. Restriction fragment length polymorphisms of URA5 (URA5-RFLP) were applied to genotype. Multi-locus sequence typing (MLST) was done for further identification and sequence type (ST) determination. Altogether, 81 isolates of C. neoformans AFLP1/VNI were recognized from 435 pigeon droppings in this study. The positive rate for C. neoformans AFLP1/VNI from pigeon droppings in different homes varied from 5.0% to 52.6%, the average was 20.2%. All of these cryptococcal strains were serotype A, MATα. They were genotyped as VNI by URA5-RFLP and were confirmed by MLST. No other molecular types of C. neoformans and Cryptococcus gattii isolates were isolated. Their STs were identified as ST 31 (n = 54, 66.7%), followed by ST 53 (n = 10), ST 191 (n = 8), ST 5 (n = 5), ST 57 (n = 3), and ST 38 (n = 1). We concluded that not only clinical but also environmental isolates of C. neoformans need to be investigated more deeply and more extensively. The virulence difference between ST 5 and ST 31 need to be explored in the future.

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Yeasts from Scarlet ibises ( Eudocimus ruber ): A focus on monitoring the antifungal susceptibility of Candida famata and closely related species

Abstract
This study aimed to identify yeasts from the gastrointestinal tract of scarlet ibises (Eudocimus ruber) and from plant material collected from the environment where they live. Then, the isolates phenotypically identified as Candida famata were submitted to molecular identification of their closely related species and evaluated for their antifungal susceptibility and possible resistance mechanisms to antifungal drugs. Cloacal swabs from 20 scarlet ibises kept in captivity at Mangal das Garças Park (Brazil), pooled stool samples (n = 20) and samples of trunks and hollow of trees (n = 20) obtained from their enclosures were collected. The samples were seeded on Sabouraud agar supplemented with chloramphenicol. The 48 recovered isolates were phenotypically identified as 15 Candida famata, 13 Candida catenulata, 2 Candida intermedia, 1 Candida lusitaniae, 2 Candida guilliermondii, 1 Candida kefyr, 1 Candida amapae, 1 Candida krusei, 8 Trichosporon spp., and 4 Rhodotorula spp. The C. famata isolates were further identified as 3 C. famata, 8 Debaryomyces nepalensis, and 4 C. palmioleophila. All C. famata and C. palmioleophila were susceptible to caspofungin and itraconazole, while one D. nepalensis was resistant to fluconazole and voriconazole. This same isolate and another D. nepalensis had lower amphotericin B susceptibility. The azole resistant strain had an increased efflux of rhodamine 6G and an alteration in the membrane sterol content, demonstrating multifactorial resistance mechanism. Finally, this research shows that scarlet ibises and their environment harbor C. famata and closely related species, including antifungal resistant isolates, emphasizing the need of monitoring the antifungal susceptibility of these yeast species.

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Effect of peritoneal dialysis fluids on activity of echinocandins against Candida spp. biofilm

Abstract
Peritoneal dialysis fluids (PDFs) impair microorganisms' growth, which may compromise effectivity of some antimicrobials. The purpose of this study was to investigate the effect of three different PDFs (lactate/bicarbonate-buffered Physioneal 40® with 2.2% glucose, lactate-buffered Nutrineal PD4® with 1.1% amino acid, and lactate-buffered Extraneal® with 7.5% icodextrin) on biofilm formation of four different Candida spp and antibiofilm effectiveness of anidulafungin, caspofungin and micafungin against Candida spp. biofilm in PDFs. All tested PDFs attained inhibitory effect on the biofilm formation but also reduced biofilm effectiveness of echinocandins against biofilm in PDFs was detected.

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Identification of a Novel Rhizopus -specific Antigen by Screening with a Signal Sequence Trap and Evaluation as a Possible Diagnostic Marker of Mucormycosis

Abstract
Mucormycosis is the second most common mould infection, often indistinguishable from other invasive mould infections such as aspergillosis. Although an appropriate antifungal therapy is effective at an early stage of the infection, there is no reliable diagnostic method for decision making. Thus, it is necessary to develop an efficient method that can detect mucormycosis rapidly and accurately. We searched for secreted or membrane-bound proteins of Rhizopus oryzae, which is the most common pathogen of mucormycosis, using the method of a signal sequence trap by retrovirus-mediated expression (SST-REX). Among the identified proteins, a Rhizopus-specific antigen was selected as a candidate, and efficacy of this specific antigen was evaluated using R. oryzae–infected mice. Of 302 clones obtained from the SST-REX library, a hypothetical protein (23 kDa, named "protein RSA") was selected as a candidate because of its highest prevalence of clones. Protein RSA was detected at significantly higher concentrations in serum and in lung homogenates of the infected mice as compared to those of uninfected mice. Our study indicates that protein RSA may be a promising biomarker of R. oryzae infection. SST-REX may be useful for comprehensive screening of prospective eukaryotic biomarkers of intractable mould infections.

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Evaluation of 8-Hydroxyquinoline Derivatives as Hits for Antifungal Drug Design

Abstract
Clioquinol is an 8-hydroxyquinoline derivative that was widely used from the 1950s to 1970s as an oral antiparasitic agent. In 1970, the oral forms were withdrawn from the market due to reports of toxicity, but topical formulations for antifungal treatment remained available. Thus, the purpose of this study was to evaluate the toxicity, anti-Candida and antidermatophyte activity and to determine pharmacodynamic characteristics of clioquinol and other 8-hydroxyquinoline derivatives (8-hydroxy-5-quinolinesulfonic acid and 8-hydroxy-7-iodo-5-quinolinesulfonic acid). Antifungal activity was tested by broth microdilution and the fungicidal or fungistatic effect was checked by a time-kill assay. Permeation and histopathological evaluation were performed in Franz diffusion cells with ear skin of pigs and examined under light microscopy. An HET-CAM test was used to determine the potential irritancy. The three compounds were active against all isolates showing anti-Candida and antidermatophyte activity, with MIC ranges of 0.031–2 μg/ml, 1–512 μg/ml, and 2–1024 μg/ml for clioquinol, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid, respectively. All compounds showed fungistatic effect for Candida, 8-hydroxy-5-quinolinesulfonic acid, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid showed a fungicidal effect for M. canis and T. mentagrophytes, and clioquinol showed a fungicidal effect only for T. mentagrophytes. Furthermore, they presented a fungicidal effect depending on the time and concentration. The absence of lesions was observed in histopathological evaluation and no compound was irritating. Moreover, clioquinol and 8-hydroxy-5-quinolinesulfonic acid accumulated in the epithelial tissue, and 8-hydroxy-7-iodo-5-quinolinesulfonic acid had a high degree of permeation. In conclusion, 8-hydroxyquinoline derivatives showed antifungal activity and 8-hydroxy-5-quinolinesulfonic acid demonstrated the potential for antifungal drug design.

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