Exposure to the house dust mite Dermatophagoides pteronyssinus (D.p.) increases the risk for developing allergic diseases in humans and their best friends, the dogs. Here, we explored whether this allergenic mite...
http://ift.tt/2sALzcM
Medicine by Alexandros G.Sfakianakis,Anapafseos 5 Agios Nikolaos,Crete 72100,Greece,tel :00302841026182 & 00306932607174
Δευτέρα 3 Ιουλίου 2017
Innate function of house dust mite allergens: robust enzymatic degradation of extracellular matrix at elevated pH
Flow cytometry-based diagnosis of primary immunodeficiency diseases
Publication date: Available online 3 July 2017
Source:Allergology International
Author(s): Hirokazu Kanegane, Akihiro Hoshino, Tsubasa Okano, Takahiro Yasumi, Taizo Wada, Hidetoshi Takada, Satoshi Okada, Motoi Yamashita, Tzu-wen Yeh, Ryuta Nishikomori, Masatoshi Takagi, Kohsuke Imai, Hans D. Ochs, Tomohiro Morio
Primary immunodeficiencies (PIDs) are a heterogeneous group of inherited diseases of the immune system. The definite diagnosis of PID is ascertained by genetic analysis; however, this takes time and is costly. Flow cytometry provides a rapid and highly sensitive tool for diagnosis of PIDs.Flow cytometry can evaluate specific cell populations and subpopulations, cell surface, intracellular and intranuclear proteins, biologic effects associated with specific immune defects, and certain functional immune characteristics, each being useful for the diagnosis and evaluation of PIDs. Flow cytometry effectively identifies major forms of PIDs, including severe combined immunodeficiency, X-linked agammaglobulinemia, hyper IgM syndromes, Wiskott-Aldrich syndrome, X-linked lymphoproliferative syndrome, familial hemophagocytic lymphohistiocytosis, autoimmune lymphoproliferative syndrome, IPEX syndrome, CTLA 4 haploinsufficiency and LRBA deficiency, IRAK4 and MyD88 deficiencies, Mendelian susceptibility to mycobacterial disease, chronic mucocuneous candidiasis, and chronic granulomatous disease. While genetic analysis is the definitive approach to establish specific diagnoses of PIDs, flow cytometry provides a tool to effectively evaluate patients with PIDs at relatively low cost.
http://ift.tt/2skLeab
Population Pharmacokinetics and Dose Optimization of Teicoplanin during Venoarterial Extracorporeal Membrane Oxygenation [PublishAheadOfPrint]
Pharmacokinetics (PK) of drugs are known to be significantly altered in patients receiving extracorporeal membrane oxygenation (ECMO). However, clinical PK studies of drugs administered during ECMO are scarce and proper dosing adjustment is yet to be established. We developed a population PK model for teicoplanin, investigated covariates influencing teicoplanin exposure, and suggested an optimal dosing regimen for ECMO patients. PK samples were collected from ten adult patients, and a population PK analysis as well as simulations were performed to identify an optimal teicoplanin dose needed to provide a >50% probability of target attainment at 72 hours using a trough concentration target of >10 μg/mL for mild to moderate infections and of >15 μg/mL for severe infections. Teicoplanin was well described by a two-compartment PK model with first-order elimination. Presence of ECMO was associated with a lower central volume of distribution, and continuous renal replacement therapy (CRRT) with a higher peripheral volume of distribution. For mild to moderate infections, an optimal dose was a loading dose (LD) 600 mg and a maintenance dose (MD) 400 mg for ECMO patients not receiving CRRT; and a LD 800 mg and a MD 600 mg for those receiving CRRT. For severe infections, an optimal dose was a LD 1000 mg and a MD 800 mg for ECMO patients not receiving CRRT; and a LD 1200 mg and a MD 1000 mg for those receiving CRRT. In conclusion, higher than the standard doses are needed to achieve fast and appropriate teicoplanin exposure during ECMO.
http://ift.tt/2uEh0zy
In Vivo Emergence of Resistance to Novel Cephalosporin-{beta}-lactamase Inhibitor Combinations Through the Duplication of the Amino Acid D149 from OXA-2 {beta}-lactamase (OXA-539) in ST235 Pseudomonas aeruginosa [PublishAheadOfPrint]
Resistance development to novel cephalosporin-β-lactamase inhibitor combinations during ceftazidime treatment of a surgical infection by Pseudomonas aeruginosa was investigated. Both, initial (97C2) and final (98G1) isolates, belonged to the high-risk clone ST235 and were resistant to carbapenems (oprD-), fluoroquinolones (GyrA-T83I, ParC-S87L) and aminoglycosides (aacA7/aacA8/aadA6). 98G1 additionally showed resistance to ceftazidime, ceftazidime-avibactam and ceftolozane-tazobactam. Sequencing identified blaOXA-2 in 97C2, but 98G1 contained a 3-bp insertion leading to the duplication of the key residue D149 (designated OXA-539). Evaluation of PAO1 transformants producing cloned OXA-2 or OXA-539 confirmed that D149 duplication was the cause of resistance. Active surveillance of the emergence of resistance to these new valuable agents is warranted.
http://ift.tt/2tG7bny
Assessment of clinical pharmacokinetic drug-drug interaction of antimalarial drugs {alpha}/{beta}-arteether and sulfadoxine-pyrimethamine [PublishAheadOfPrint]
The antimalarial drugs combination therapy is now being widely used for treatment of uncomplicated malaria. The objective of the present study was to investigate the effects of co-administration of intramuscular α/β-arteether (AE) and oral sulfadoxine-pyrimethamine (SP) on the pharmacokinetic properties of each drug as a drug–drug interaction study to support developing the fixed-dose combination therapy. Single-dose, open-label, crossover clinical trial was conducted in healthy adult Indian male volunteers (18–45 years, n=13), received single dose of AE, SP and combination dose of AE and SP. Blood samples were collected upto 21 days post administration and concentrations of α-arteether, β-arteether, sulfadoxine and pyrimethamine were determined by using validated liquid chromatography–tandem mass spectrometry method. Pharmacokinetic parameters were calculated and statistically analyzed to calculate geometric mean ratio and confidence interval. Following single dose co-administration of intramuscular AE and oral SP, the pharmacokinetic properties of α/β-arteether were not significantly affected, and α/β-arteether had no significant effect on the pharmacokinetic properties of SP in these selected groups of healthy volunteers. However, more investigations would be needed to explore this further.
http://ift.tt/2uEpQxa
A novel 6-benzyl ether benzoxaborole is active against Mycobacterium tuberculosis in vitro [PublishAheadOfPrint]
We identified a novel 6-benzyl ether benzoxaborole with potent activity against Mycobacterium tuberculosis. The compound had a minimum inhibitory concentration of 2 μM in liquid medium. The compound was also able to prevent growth on solid medium at 0.8 μM and was active against intracellular bacteria (IC50 = 3.6 μM) without cytotoxicity against eukaryotic cells (IC50 >100 μM). We isolated resistant mutants (MIC ≥100 μM), which had mutations in Rv1683, Rv3068c and Rv0047c.
http://ift.tt/2tGAK8p
OXA-244-producing Escherichia coli isolates: a challenge for clinical microbiology laboratories [PublishAheadOfPrint]
OXA-244 is a single point mutant derivative of OXA-48 displaying reduced carbapenemase activity. Here, we report microbiological features of 7 OXA-244-producing E. coli isolates. Only one isolate grew on the ChromID® CARBA SMART medium (bioMérieux), but 6/7 grew on ChromID® ESBL medium (bioMérieux), as they co-produced either an extended spectrum β-lactamase and or a plasmid-encoded cephalosporinase. The production of a carbapenemase was detected in 57.1%, 71.4%, 71.4%, and 100% of the E. coli isolates using the Carba NP test, the RAPIDEC® CARBA NP (bioMérieux), a MALDI-TOF MS hydrolysis assay (Bruker), and OXA-48 K-SeT® (Coris bioconcept), respectively. Our results indicate that OXA-244-producing E. coli isolates are difficult to detect, which may lead to their silent spread.
http://ift.tt/2tG4YIC
In vitro susceptibility of the relapsing fever spirochete Borrelia miyamotoi to antimicrobial agents. [PublishAheadOfPrint]
Hard tick-borne relapsing fever (HTBRF) is an emerging infectious disease throughout the temperate zone caused by the relapsing fever spirochete Borrelia miyamotoi. Antibiotic treatment of HTBRF is empirically based on the treatment of Lyme borreliosis, however antibiotic susceptibility of B. miyamotoi has not been studied to date. Thus, we set out to determine the in vitro antimicrobial susceptibility of B. miyamotoi.
A microdilution method with 96-well microtiter plates was used to determine antibiotic susceptibility of two B. miyamotoi strains isolated on two different continents (Asia and North America), two Borrelia burgdorferi sensu lato (s.l.) strains and one Borrelia hermsii isolate for comparison. The MIC and MBC were determined by both microscopy and colorimetric assays.
We were able to show that both B. miyamotoi strains and B. hermsii demonstrated greater susceptibility to doxycycline and azithromycin, equal susceptibility to ceftriaxone and proved to be resistant to amoxicillin in vitro as compared to the B. burgdorferi s.l. isolates. The MIC and MBC of amoxicillin for B. miyamotoi evaluated by microscopy were 16-32 mg/L and 32-128 mg/L, respectively. Since B. miyamotoi is susceptible to doxycycline, azithromycin and ceftriaxone in vitro, our data suggests that these antibiotics can be used for treatment of HTBRF. Oral amoxicillin is currently used as an alternative for the treatment of HTBRF, however since we found antimicrobial resistance of the tested B. miyamotoi strains to amoxicillin in vitro, this warrants further study.
http://ift.tt/2uEwUKa
Mitochondrial toxicity of linezolid in blood cells and skin nerve fibers: influence of mitochondrial genetics [PublishAheadOfPrint]
Background: The antibiotic linezolid is a ribosomal inhibitor with excellent efficacy. Despite reduction in the administration period to 28 days, side effects usually of hematologic or neuropathic origin are still reported due to secondary inhibition of mitochondrial protein synthesis. Susceptibility to linezolid toxicity remains unknown.
Objective: To understand clinical heterogenicity in response to identical linezolid exposition through the exhaustive examination of the molecular basis of tissue-dependent mitotoxicity, derived cell dysfunction and mitochondrial genetic association to adverse effects of linezolid under the recommended period of administration.
Methods: Peripheral blood mononuclear cells (PBMC) and skin nerve fibers from 19 and 6 patients, respectively, were evaluated before and after 28-day linezolid treatment to assess mitochondrial and cell toxic consequences. Mitochondrial DNA haplotypes and SNPs in ribosomal sequences where linezolid binds to mitochondrial ribosome were additionally analyzed to investigate genetic contribution.
Results: Linezolid reduced mitochondrial protein levels, complex IV activity and mitochondrial mass in PBMC and trended to increase apoptosis. In skin tissue, mitochondrial amount increased within nerve fiber accompanied by subclinical axonal swelling. Mitochondrial U haplogroup, mutations in 12SrRNA and polymorphisms m.2706A>G, m.3197T>C and m.3010G>A in 16SrRNA trended to be associated to increased mitochondrial and clinical adverse effects.
Conclusions: Even with a shorter administration, adverse effects of linezolid are reported by 63% of patients. Linezolid exerts correlated tissue-dependent mitotoxicity responsible for downstream cellular consequences (blood cell death and nerve fiber swelling) leading to adverse hematologic and peripheral nervous side effects. Multicentric studies should confirm genetic susceptibility in bigger cohorts.
http://ift.tt/2tGtYPX
First report of Klebsiella oxytoca strain simultaneously producing NDM-1, IMP-4 and KPC-2 carbapenemases [PublishAheadOfPrint]
The nucleotide sequences of 5 plasmids from one Klebsiella oxytoca isolate were determined using the PacBio RS II system. Plasmid analysis revealed that blaNDM-1 was carried on an IncX3 plasmid. The blaIMP-4 and blaKPC-2 were located on an IncN and an IncP-6 plasmid, respectively. Comparative sequence analysis highlighted the successful spread of carbapenemase-harbouring plasmids among different enterobacterial species. It reports for the first time coproducing NDM-1, KPC-2 and IMP-4 carbapenemases on a K. oxytoca isolate.
http://ift.tt/2uEi3zm
Plasmids of diverse Inc groups disseminate the fosfomycin resistance gene fosA3 among Escherichia coli from pigs, chickens and dairy cows in Northeast China [PublishAheadOfPrint]
Thirty-nine fosfomycin-resistant E. coli isolates carrying fosA3 were obtained from pigs, chickens, dairy cows and staff in four Northeastern provinces of China during 06/2015-04/2016. The fosA3 was co-located with blaCTX-M genes on conjugative plasmids of the incompatibility groups IncN (n=12), IncN-F33:A-:B- (n=2), IncF33:A-:B- (n=14), IncF14:A-:B- (n=2), and IncI1/ST136 (n=9). Four different genetic contexts of fosA3 were detected among the 39 E. coli isolates. Three potential epidemic plasmids circulated among E. coli strains from this region.
http://ift.tt/2tGot45
Digital PCR for detection and quantification of fluoroquinolone resistance in Legionella pneumophila. [PublishAheadOfPrint]
The emergence of fluoroquinolone (FQ)-resistant mutants of Legionella pneumophila in infected humans has been previously reported using a next-generation DNA sequencing (NGS) approach. This finding could explain part of the therapeutic failures observed in legionellosis patients treated with these antibiotics. The aim of this study was to develop digital PCR (dPCR) assays allowing rapid and accurate detection and quantification of these resistant mutants in respiratory samples, especially when the proportion of mutants in a wild-type background is low. We designed three dPCRgyrA assays to detect and differentiate the wild-type and one of the three gyrA mutations previously described as associated with FQ resistance in L. pneumophila: 248C>T (T83I), 259G>A (D87N), and 259G>C (D87H). To assess the performance of these assays, mixtures of FQ-resistant and -susceptible strains of L. pneumophila were analyzed, and the results were compared with those obtained with Sanger DNA sequencing and real-time quantitative PCR (qPCR) technologies. The dPCRgyrA assays were able to detect mutated gyrA sequences in the presence of wild-type sequences up to 1:1000 resistant:susceptible allele ratios. In comparison, Sanger DNA sequencing and qPCR were less sensitive, allowing detection of gyrA mutants up to 1:1 and 1:10 ratios, respectively. When testing 38 respiratory samples from 23 legionellosis patients (69.6% treated with a FQ), dPCRgyrA detected small amounts of gyrA mutants in four (10.5%) samples from three (13.0%) patients. These results demonstrate that dPCR is a highly sensitive alternative to quantify FQ resistance in L. pneumophila, and it could be used in clinical practice to detect patients that could be at higher risk of therapeutic failure.
http://ift.tt/2uErtex
Characterization of a large antibiotic resistance plasmid found in enteropathogenic Escherichia coli strain B171 and its relatedness to plasmids of diverse E. coli and Shigella [PublishAheadOfPrint]
Enteropathogenic Escherichia coli (EPEC) are a leading cause of severe infantile diarrhea in developing countries. Previous research has focused on the diversity of the EPEC virulence plasmid, whereas less is known regarding the genetic content and distribution of antibiotic resistance plasmids carried by EPEC. A previous study demonstrated that in addition to the virulence plasmid, reference EPEC strain B171 harbors a second, larger plasmid that confers antibiotic resistance. To further understand the genetic diversity and dissemination of antibiotic resistance plasmids among EPEC, we describe the complete sequence of an antibiotic resistance plasmid from EPEC strain B171. The resistance plasmid, pB171_90, has a completed sequence length of 90,229 bp, a GC content of 54.55%, and carries protein-encoding genes involved in conjugative transfer, resistance to tetracycline (tetA), sulfonamides (sulI), and mercury, as well as several virulence-associated genes including the transcriptional regulator hha, and the putative calcium sequestration inhibitor (csi). In silico detection of the pB171_90 genes among 4,798 publicly-available E. coli genome assemblies indicates the unique genes of pB171_90 (csi and traI) are primarily restricted to genomes identified as EPEC and enterotoxigenic E. coli. However, conserved regions of the pB171_90 plasmid containing genes involved in replication, stability, and antibiotic resistance were identified among diverse E. coli pathotypes. Interestingly, pB171_90 also exhibited significant similarity with a sequenced plasmid from S. dysenteriae type I. Our findings demonstrate the mosaic nature of EPEC antibiotic resistance plasmids, and highlight the need for additional sequence-based characterization of antibiotic resistance plasmids harbored by pathogenic E. coli.
http://ift.tt/2tGxbzi
Identification and mode of action of a plant natural product targeting human fungal pathogens [PublishAheadOfPrint]
Candida albicans is a major cause of fungal diseases in humans and its resistance to available drugs is of concern. In an attempt to identify novel antifungal agents, we initiated a small scale screening of a 199 natural plant compounds (NPs) library. In vitro susceptibility profiling experiments identified 33 NPs with activity against C. albicans (MIC50 ≤ 32 μg/ml). Among the selected NPs, the sterol alkaloid tomatidine was further investigated. Tomatidine originates from Solanum lycopersicum (tomato) and exhibited high fungistatic activity against Candida species (MIC50 ≤ 1 μg/ml) but no cytotoxicity against mammalian cells. Genome-wide transcriptional analysis of C. albicans tomatidine-treated cells revealed a major alteration (upregulation) of ergosterol genes suggesting that the ergosterol pathway was targeted by this NP. Consistent with this transcriptional response, sterol content analysis of tomatidine-treated cells showed not only inhibition of Erg6 (C-24 sterol methyltransferase) but also of Erg4 (C-24 sterol reductase) activity. A forward genetic approach in Saccharomyces cerevisiae coupled with whole genome sequencing identified 2 non-synonymous mutations in ERG6 (amino acids: D249G and G132D) responsible for tomatidine resistance. Our results therefore identified unambiguously Erg6, a sterol C-24 methyltransferase absent in mammals, as the main direct target of tomatidine. We tested the in vivo efficacy of tomatidine in a mouse model of C. albicans systemic infection. Treatment with a nano-crystal pharmacological formulation successfully decreased the fungal burden in infected kidneys as compared to placebo and thus confirmed the potential of tomatidine as a therapeutic agent.
http://ift.tt/2uEq6wo
Effects of Isavuconazole on the Plasma Concentrations of Tacrolimus among Solid Organ Transplant Patients [PublishAheadOfPrint]
We evaluated the interaction between isavuconazole and tacrolimus among 55 organ transplant recipients. After isavuconazole discontinuation, tacrolimus concentration/dose normalized by weight (C/D) was reduced by 16%. Liver transplant recipients experienced the largest C/D reduction. A 1.3-fold decrease in tacrolimus daily dose was required to maintain desired tacrolimus levels. There was considerable inter-patient variability in the magnitude of the drug interaction. Tacrolimus doses should not be adjusted uniformly, but rather guided by therapeutic drug monitoring.
http://ift.tt/2tGx9aE
Subinhibitory concentrations of trimethoprim and sulfamethoxazole prevent biofilm formation by Acinetobacter baumannii through inhibition of Csu pili expression [PublishAheadOfPrint]
Acinetobacter baumannii is emerging as a multi-drug resistant nosocomial pathogen of increasing threat to human health worldwide. Pili are important bacterial virulence factors, playing a role in attachment to host cells and biofilm formation. The Csu pilus, assembled via the chaperone-usher secretion system, has been studied in A. baumannii ATCC 19606. Here we show that, in opposition to previous reports, the common lab strain ATCC 17978 produces Csu pili. We found that, although ATCC 17978 is resistant to sulfamethoxazole (Smx) and trimethoprim (Tmp), subinhibitory concentrations of these antibiotics abolish the expression of Csu and consequently a dramatic reduction in biofilm formation in ATCC 17978. Smx and Tmp act synergistically inhibiting the enzymatic systems involved in the bacterial synthesis of tetrahydrofolate (THF), which is required for the synthesis of nucleotides. The effect of these antibiotics was partially relieved by exogenous addition of THF, indicating that Smx and Tmp turn off Csu assembly by inducing folate stress. We propose that, for Acinetobacter, nanomolar concentrations of Smx and Tmp represent a "danger signal". In response to this signal, Csu expression is repressed, allowing biofilm dispersal and escape from potentially inhibitory concentrations of antibiotics. The roles of antibiotics as signalling molecules start to be increasingly acknowledged, which have clear implications for both, the treatment of bacterial diseases, and the understanding of the complex microbial interactions in the environment.
http://ift.tt/2uEzG1Y
Clinical Features of Breakthrough Acinetobacter Bacteremia during Carbapenem Therapy: A Multicenter Study [PublishAheadOfPrint]
Breakthrough Acinetobacter bacteremia during carbapenem therapy is not uncommon and creates therapeutic dilemmas for clinicians. This study was conducted to evaluate the clinical and microbiological characteristics of breakthrough Acinetobacter bacteremia during carbapenem therapy and to assess the efficacy of various antimicrobial therapies. We analyzed 100 adults who developed breakthrough Acinetobacter bacteremia during carbapenem therapy at 4 medical centers over a 6-year period. Their 30-day mortality rate was 57.0% and the carbapenem resistance rate of their isolates was 87.0%. Among patients with carbapenem-resistant Acinetobacter bacteremia, breakthrough bacteremia during carbapenem therapy was associated with a significant higher 14-day mortality (51.7% versus 37.4%, P = 0.025 by bivariate analysis) and a higher 30-day mortality (P = 0.037 by log-rank test of survival analysis) than in the non-breakthrough group. For treatment of breakthrough Acinetobacter bacteremia during carbapenem therapy, tigecycline-based therapy was associated with a significantly higher 30-day mortality (80.0%) than continued carbapenem therapy (52.5%) and colistin-based therapy (57.9%) by survival analysis (P = 0.047 and 0.045 by log-rank test, respectively). Cox regression controlling for confounders, including severity of illness indices, demonstrated that patients treated with tigecycline-based therapy for breakthrough Acinetobacter bacteremia was an independent predictor of 30-day mortality (hazard ratio, 3.659; 95% confidence interval, 1.794-7.465; P < 0.001). Patients with breakthrough Acinetobacter bacteremia during carbapenem therapy posed a poor outcome. Tigecycline should be used cautiously for treatment of breakthrough Acinetobacter bacteremia that develops during carbapenem therapy.
http://ift.tt/2tGp9qa
Repurposing thiram and disulfiram as antibacterial agents for multi-drug resistant Staphylococcus aureus infections [PublishAheadOfPrint]
Thiram and disulfiram were evaluated as antibacterial agents against multidrug resistant Staphylococcus aureus. Against a 30 member panel comprised of vancomycin-susceptible (VSSA), vancomycin-intermediate (VISA) and vancomycin-resistant (VRSA) strains, the MIC90 values of the respective test agents were 4 and 16 μg/mL. Additional analyses revealed that thiram and disulfiram are rapid-acting bacteriostatic agents with narrow, Gram-positive bacteria spectrum activity. Synergy studies further determined that disulfiram increases the vancomycin susceptibility of three clinical VRSA strains in vitro, thus establishing a potential use in combination therapy.
http://ift.tt/2uExxU9
In Vitro Antibiotic Susceptibilities of Francisella tularensis by Broth Micro-Dilution Following CLSI Methods. [PublishAheadOfPrint]
In vitro susceptibilities for 47 antibiotics were determined in 30 genetic diverse strains of Francisella tularensis by the broth micro-dilution method following Clinical Laboratory Standards Institute (CLSI) methods. The F. tularensis strains demonstrated susceptibility to aminoglycosides, fluoroquinolones and tetracyclines. There was a distinct difference in macrolide susceptibility between "A" and "B" type strains as has been noted previously. Establishing and comparing antibiotic susceptibilities of a diverse but specific set of F. tularensis strains by standardized methods and establishment of population ranges and MIC50/90 values provides reference information for assessing new antibiotic agents, and provides a baseline to monitor any future emergence of resistance, natural or intentional.
http://ift.tt/2tGtVnf
In Vitro Activity of Ceftolozane-Tazobactam and Other Antimicrobial Agents Against Burkholderia cepacia Complex and Burkholderia gladioli [PublishAheadOfPrint]
We tested the activity of ceftolozane-tazobactam and 13 other antimicrobial agents against 221 strains of Burkholderia cepacia complex and Burkholderia gladioli. Most strains (82%) were cultured from persons with cystic fibrosis, and most (85%) were recovered since 2011. The ceftolozane-tazobactam MIC was ≤ 8 μg/ml for 77% of the strains. However, the MIC range was broad (≤0.5 to >64 μg/ml; MIC50/90, 2/32 μg/ml). Significant differences in susceptibility to some antimicrobial agents were observed between species.
http://ift.tt/2uEq6MU
Screening the MMV Pathogen Box across multiple pathogens reclassifies starting points for open source drug discovery. [PublishAheadOfPrint]
Open access drug discovery provides a substantial resource for diseases primarily affecting the poor and disadvantaged. The open access Pathogen Box is comprised of a collection of compounds with demonstrated biological activity against specific pathogenic organisms. The supply of this resource by the Medicines for Malaria Venture has the potential to provide new chemical starting points for a number of tropical and neglected diseases, through repurposing of these compounds for use in drug discovery campaigns for these additional pathogens. Here we have tested the Pathogen Box against kinetoplastid parasites and malaria life cycle stages in vitro. Consequently, chemical starting points for malaria, human African trypanosomiasis, Chagas disease and leishmaniasis drug discovery efforts have been identified. Inclusive of this in vitro biological evaluation, outcomes from extensive literature reviews and database searches are provided. This information encompasses commercial availability, literature reference citations, other aliases and ChEMBL number with associated biological activity, where available. The release of this new data for the Pathogen Box collection into the public domain will aid the open source model of drug discovery. Importantly, this will provide novel chemical starting points for drug discovery and target identification in tropical disease research.
http://ift.tt/2tGcSBQ
Activities of LCB01-0371, a novel oxazolidinone, against Mycobacterium abscessus [PublishAheadOfPrint]
Mycobacterium abscessus is a highly pathogenic, drug-resistant, rapidly growing mycobacterium. In this study, we evaluated the in vitro, intracellular, and in vivo activities of LCB01-0371, a novel and safe oxazolidinone derivative, for the treatment of M. abscessus infection and compared its resistance to that of other oxazolidinone drugs. LCB01-0371 was effective against several M. abscessus strains in vitro and in a macrophage model of infection. In the murine model, a similar efficacy to linezolid was achieved, especially in the lungs. We induced laboratory-generated resistance to LCB01-0371; sequencing analysis revealed mutations of rplC T424C and G419A and nucleotide insertion at the 503 position. Furthermore, LCB01-0371 inhibited the growth of amikacin-, cefoxitin-, and clarithromycin-resistant strains. Collectively, our data indicated that LCB01-0371 might represent a promising new class of oxazolidinones with improved safety, which may replace linezolid for the treatment of M. abscessus.
http://ift.tt/2uEaN6Q
Absence of Relationship between Mitochondrial DNA Haplogroups and Cisplatin-Induced Hearing Loss
Background. Many drugs used for cancer chemotherapy produce reactive oxygen species, thus leading to various complications including nephrotoxicity, cardiotoxicity, and ototoxicity. Objective. We have provided a haplogroup analysis of a cohort of cancer patients treated with chemotherapy and compared factors associated with associated hearing loss. Study Design and Methods. This observational cohort study includes a pure-tone audiometry of the patients who underwent chemotherapeutic treatment. Medical history, presence of risk factors for hearing loss, toxic habits, and association with haplogroups have been determined. Results. 40% of patients developed hearing loss after administration of cisplatin, which was bilateral and symmetrical and of high frequencies. The most frequent haplogroup was H with a slight overexpression of groups V and K and a low frequency of groups J and T. No association of the haplogroup types with the hearing loss has been found; however age was revealed as an important determining factor. Conclusions. Ototoxicity caused by cisplatin is manifested as bilateral, symmetrical, and predominantly high frequency hearing loss. Although we did not find a strong correlation of haplogroups with ototoxicity, our results revealed the existence of a risk group of elderly patients over 60, which are more susceptible to hearing loss induced by cisplatin, than young adults, regardless of preexisting hearing loss.
http://ift.tt/2sxeFtB
Characterization of gliomas: from morphology to molecules
Abstract
This article reviews the histologic and molecular characterization of gliomas, including the new "integrated diagnoses" of the World Health Organization Classification, 2016 edition. The entities reviewed within include diffuse gliomas (astrocytoma, oligodendroglioma, glioblastoma), as well as circumscribed and low-grade gliomas (angiocentric glioma, pilocytic astrocytoma, subependymal giant cell astrocytoma, pleomorphic xanthoastrocytoma, pilomyxoid astrocytoma, ependymoma, myxopapillary ependymoma, and subependymoma). Diagnostic, prognostic, and predictive biomarkers are discussed for each entity. We review how molecular testing for IDH1 and ATRX and detection of chromosome 1p/19q codeletion can be used to categorize glioblastomas as IDH-wildtype or IDH-mutant, and lower grade diffuse gliomas into three molecular groups that correlate better with patient outcomes than histologic subtyping. Pediatric diffuse gliomas are highlighted, including diffuse midline glioma, H3 K27M-mutant, and inherited germline mutations that predispose to pediatric gliomas. The utility of genomic profiling of certain gliomas is discussed, including identifying candidates for experimental therapies. This review is meant to be a concise summary of glioma characterization for the practicing pathologist.
http://ift.tt/2tKDq5X
Unusual metallic penile foreign body
Kulothungan Gunasekaran<br />Mar 27, 2017; 2017:bcr2017219377-bcr2017219377<br />case-report
http://ift.tt/2sA23BT
Laryngeal lipoma: a rare cause of acute intermittent airway obstruction
Peter George Deutsch<br />Apr 22, 2016; 2016:bcr2016215506-bcr2016215506<br />case-report
http://ift.tt/2tjHxCW
Case of pneumatosis intestinalis and hepatic portal venous gas following a laparoscopic right hemicolectomy
Edit Elisa Castren<br />Mar 21, 2016; 2016:bcr2016214431-bcr2016214431<br />case-report
http://ift.tt/2sAmO0j
An unusual case of KBG syndrome with unique oral findings
Abdul Hafiz<br />Jul 17, 2015; 2015:bcr2015210352-bcr2015210352<br />case-report
http://ift.tt/2tkbyTf
Access to essential paediatric eye surgery in the developing world: a case of congenital cataracts left untreated
Marilyn L Vinluan<br />Apr 22, 2015; 2015:bcr2014208197-bcr2014208197<br />case-report
http://ift.tt/2sAmKO7
Pulmonary co-infection with Nocardia and Aspergillus in a patient with adult-onset Still's disease receiving steroids and tacrolimus
Durga Prasanna Misra<br />Nov 14, 2014; 2014:bcr2014207335-bcr2014207335<br />case-report
http://ift.tt/2sA44OP
A rare presentation of multiple dens invaginatus in maxillary dentition
Jigar M Purani<br />Aug 1, 2014; 2014:bcr2013200389-bcr2013200389<br />case-report
http://ift.tt/2tk3YYs
Thoracic vertebral osteomyelitis: an unusual complication of Crohn's disease
Olushola Ajayi<br />Jun 10, 2014; 2014:bcr2013202150-bcr2013202150<br />case-report
http://ift.tt/2sAgBSc
Endodontic retreatment of a mandibular first molar with five root canal systems: an important clinical lesson
Muhammad Hasan<br />Mar 20, 2014; 2014:bcr2013201402-bcr2013201402<br />case-report
http://ift.tt/2tjXadz
Cold finger: urban frostbite in the UK
Stephen Mulgrew<br />Aug 29, 2013; 2013:bcr1120115167-bcr1120115167<br />case-report
http://ift.tt/2sA0hkv
Central nervous system infection with Acanthamoeba in a malnourished child
Sumeeta Khurana<br />Oct 24, 2012; 2012:bcr2012007449-bcr2012007449<br />case-report
http://ift.tt/2tk7lPo
Correction for Koch et al., Genetic rescue models refute nonautonomous rod cell death in retinitis pigmentosa [Correction]
NEUROSCIENCE Correction for "Genetic rescue models refute nonautonomous rod cell death in retinitis pigmentosa," by Susanne F. Koch, Jimmy K. Duong, Chun-Wei Hsu, Yi-Ting Tsai, Chyuan-Sheng Lin, Christian A. Wahl-Schott, and Stephen H. Tsang, which appeared in issue 20, May 16, 2017, of Proc Natl Acad Sci USA (114:5259–5264; first...
http://ift.tt/2uiWiWF
Correction for Lan et al., Long-read sequencing uncovers the adaptive topography of a carnivorous plant genome [Correction]
EVOLUTION Correction for "Long-read sequencing uncovers the adaptive topography of a carnivorous plant genome," by Tianying Lan, Tanya Renner, Enrique Ibarra-Laclette, Kimberly M. Farr, Tien-Hao Chang, Sergio Alan Cervantes-Pérez, Chunfang Zheng, David Sankoff, Haibao Tang, Rikky W. Purbojati, Alexander Putra, Daniela I. Drautz-Moses, Stephan C. Schuster, Luis Herrera-Estrella, and Victor...
http://ift.tt/2tJLgN4
Correction for Mattei et al., Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning [Correction]
PHYSIOLOGY Correction for "Integrated 3D view of postmating responses by the Drosophila melanogaster female reproductive tract, obtained by micro-computed tomography scanning," by Alexandra L. Mattei, Mark L. Riccio, Frank W. Avila, and Mariana F. Wolfner, which appeared in issue 27, July 7, 2015, of Proc Natl Acad Sci USA (112:8475–8480;...
http://ift.tt/2tJzbHE
Sex-specific early survival drives adult sex ratio bias in snowy plovers and impacts mating system and population growth [Population Biology]
Adult sex ratio (ASR) is a central concept in population biology and a key factor in sexual selection, but why do most demographic models ignore sex biases? Vital rates often vary between the sexes and across life history, but their relative contributions to ASR variation remain poorly understood—an essential step...
http://ift.tt/2tJRkVS
Hypocretin (orexin) is critical in sustaining theta/gamma-rich waking behaviors that drive sleep need [Neuroscience]
Hcrt gene inactivation in mice leads to behavioral state instability, abnormal transitions to paradoxical sleep, and cataplexy, hallmarks of narcolepsy. Sleep homeostasis is, however, considered unimpaired in patients and narcoleptic mice. We find that whereas Hcrtko/ko mice respond to 6-h sleep deprivation (SD) with a slow-wave sleep (SWS) EEG δ...
http://ift.tt/2uiRi4s
Boosting CNS axon regeneration by harnessing antagonistic effects of GSK3 activity [Neuroscience]
Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3S/A knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in...
http://ift.tt/2tKeawt
Virus-induced inflammasome activation is suppressed by prostaglandin D2/DP1 signaling [Microbiology]
Prostaglandin D2 (PGD2), an eicosanoid with both pro- and anti-inflammatory properties, is the most abundantly expressed prostaglandin in the brain. Here we show that PGD2 signaling through the D-prostanoid receptor 1 (DP1) receptor is necessary for optimal microglia/macrophage activation and IFN expression after infection with a neurotropic coronavirus. Genome-wide expression...
http://ift.tt/2sFHZJx
Multiple layers of heterogeneity and subset diversity in human MAIT cell responses to distinct microorganisms and to innate cytokines [Immunology and Inflammation]
Mucosa-associated invariant T (MAIT) cells are a large innate-like T-cell subset in humans defined by invariant TCR Vα7.2 use and expression of CD161. MAIT cells recognize microbial riboflavin metabolites of bacterial or fungal origin presented by the monomorphic MR1 molecule. The extraordinary level of evolutionary conservation of MR1 and the...
http://ift.tt/2tKe8Vn
Evolutionary radiation of lanthipeptides in marine cyanobacteria [Evolution]
Lanthipeptides are ribosomally derived peptide secondary metabolites that undergo extensive posttranslational modification. Prochlorosins are a group of lanthipeptides produced by certain strains of the ubiquitous marine picocyanobacteria Prochlorococcus and Synechococcus. Unlike other lanthipeptide-producing bacteria, picocyanobacteria use an unprecedented mechanism of substrate promiscuity for the production of numerous and diverse lanthipeptides...
http://ift.tt/2tJRmwY
A null model for microbial diversification [Evolution]
Whether prokaryotes (Bacteria and Archaea) are naturally organized into phenotypically and genetically cohesive units comparable to animal or plant species remains contested, frustrating attempts to estimate how many such units there might be, or to identify the ecological roles they play. Analyses of gene sequences in various closely related prokaryotic...
http://ift.tt/2tK7nTs
Structural complexity and molecular heterogeneity of a butterfly ejaculate reflect a complex history of selection [Evolution]
Male ejaculates are often structurally complex, and this complexity is likely to influence key reproductive interactions between males and females. However, despite its potential evolutionary significance, the molecular underpinnings of ejaculate structural complexity have received little empirical attention. To address this knowledge gap, we sought to understand the biochemical and...
http://ift.tt/2tJZJZw
Correction for Saito et al., Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography [Correction]
APPLIED BIOLOGICAL SCIENCES, ENGINEERING Correction for "Investigation of hindwing folding in ladybird beetles by artificial elytron transplantation and microcomputed tomography," by Kazuya Saito, Shuhei Nomura, Shuhei Yamamoto, Ryuma Niyama, and Yoji Okabe, which appeared in issue 22, May 30, 2017, of Proc Natl Acad Sci USA (114:5624–5628; first published May...
http://ift.tt/2uiP0SQ
Enhancing T1 magnetic resonance imaging contrast with internalized gadolinium(III) in a multilayer nanoparticle [Chemistry]
Multifunctional nanoparticles for biomedical applications have shown extraordinary potential as contrast agents in various bioimaging modalities, near-IR photothermal therapy, and for light-triggered therapeutic release processes. Over the past several years, numerous studies have been performed to synthesize and enhance MRI contrast with nanoparticles. However, understanding the MRI enhancement mechanism in...
http://ift.tt/2uiRbG4
Subunit-specific role for the amino-terminal domain of AMPA receptors in synaptic targeting [Neuroscience]
The amino-terminal domain (ATD) of AMPA receptors (AMPARs) accounts for approximately 50% of the protein, yet its functional role, if any, remains a mystery. We have discovered that the translocation of surface GluA1, but not GluA2, AMPAR subunits to the synapse requires the ATD. GluA1A2 heteromers in which the ATD...
http://ift.tt/2uDCGMo
Application of metabolic controls for the maximization of lipid production in semicontinuous fermentation [Applied Biological Sciences]
Acetic acid can be generated through syngas fermentation, lignocellulosic biomass degradation, and organic waste anaerobic digestion. Microbial conversion of acetate into triacylglycerols for biofuel production has many advantages, including low-cost or even negative-cost feedstock and environmental benefits. The main issue stems from the dilute nature of acetate produced in such...
http://ift.tt/2tJI9op
G9a drives hypoxia-mediated gene repression for breast cancer cell survival and tumorigenesis [Genetics]
G9a is an epigenetic regulator that methylates H3K9, generally causing repression of gene expression, and participates in diverse cellular functions. G9a is genetically deregulated in a variety of tumor types and can silence tumor suppressor genes and, therefore, is important for carcinogenesis. Although hypoxia is recognized to be an adverse...
http://ift.tt/2uiNyzH
Tetrahydrobiopterin regulates monoamine neurotransmitter sulfonation [Biochemistry]
Monoamine neurotransmitters are among the hundreds of signaling small molecules whose target interactions are switched "on" and "off" via transfer of the sulfuryl-moiety (–SO3) from PAPS (3′-phosphoadenosine 5′-phosphosulfate) to the hydroxyls and amines of their scaffolds. These transfer reactions are catalyzed by a small family of broad-specificity enzymes—the human cytosolic...
http://ift.tt/2tJZFce
Distinguishing attosecond electron-electron scattering and screening in transition metals [Physics]
Electron–electron interactions are the fastest processes in materials, occurring on femtosecond to attosecond timescales, depending on the electronic band structure of the material and the excitation energy. Such interactions can play a dominant role in light-induced processes such as nano-enhanced plasmonics and catalysis, light harvesting, or phase transitions. However, to...
http://ift.tt/2tK7zCv
Structure of human Fe-S assembly subcomplex reveals unexpected cysteine desulfurase architecture and acyl-ACP-ISD11 interactions [Biochemistry]
In eukaryotes, sulfur is mobilized for incorporation into multiple biosynthetic pathways by a cysteine desulfurase complex that consists of a catalytic subunit (NFS1), LYR protein (ISD11), and acyl carrier protein (ACP). This NFS1–ISD11–ACP (SDA) complex forms the core of the iron–sulfur (Fe–S) assembly complex and associates with assembly proteins ISCU2,...
http://ift.tt/2uiywKr
Inner Workings: How saving some of the Southeast’s oldest trees might help scientists monitor climate change [Environmental Sciences]
In the swampy floodplains of North Carolina's Black River stand ancient trees with a story to tell. Many of these bald cypress (Taxodium distichum) were well over a millennium old when Columbus discovered the Western Hemisphere. As it turns out, their locale has greatly promoted their longevity: by being relatively...
http://ift.tt/2skd3iG
Health Related Quality of Life among schoolchildren aged 12–13 years in relation to food hypersensitivity phenotypes: a population-based study
While Health Related Quality of Life has been investigated among children with IgE-mediated food allergy, less is known about quality of life among children with other types of hypersensitivity to food. The ai...
http://ift.tt/2szpdIM
Prenatal diagnosis and prevention of toxoplasmosis in pregnant women in Northern Vietnam: study protocol
Background: In Vietnam, no systematic prenatal toxoplasmosis screening is in place, and only few studies have assessed the prevalence and importance of this zoonotic parasite infection. In addition, no studies have been conducted to assess the risk factors associated with toxoplasmosis. This study protocol was developed to determine the seroprevalence of toxoplasmosis in pregnant women in Hanoi and Thai Binh, Northern Vietnam, and to evaluate the association with risk factors and congenital toxoplasmosis. The protocol was developed in a way that it could potentially evolve into a countrywide prenatal diagnosis and prevention program, with the main focus on primary prevention. Methods: The collaborating gynaecologists will invite eligible pregnant women attending antenatal care for the first time to participate in the study. At first consult, information about toxoplasmosis and its prevention will be provided. All participants will be asked to fill in a questionnaire, which is designed to analyse socio-demographic and biologically plausible risk factors associated with toxoplasmosis, and blood samples will be collected to determine the seroprevalence of toxoplasmosis in pregnant women. In case there is suspicion of a primary infection during pregnancy, the concerned women will be followed-up by the gynaecologists according to a predefined protocol. Every participant will be informed on her serological status, risk factors and prevention measures and is offered appropriate medical information and medical follow-up if required. Discussion: The hypothesis is that congenital toxoplasmosis is an important but currently under-diagnosed public health problem in Vietnam. This study can strengthen sustainable control of toxoplasmosis in Vietnam, provide a protocol for prenatal diagnosis, boost overall awareness, improve the knowledge about toxoplasmosis prevention and can be essential for evidence-based health policy.
http://ift.tt/2uisx8t
Packing The Hospital Bag
Have you ever played the game, "What's in my bag?" We're playing the pregnancy version on Belly to Baby! Learn what items need to go to the hospital, what can stay behind … and which things should be in the car at all times.
The post Packing The Hospital Bag appeared first on ChildrensMD.
http://ift.tt/2sjCvVq
A genome-wide association study suggested that the mitogen-activated protein kinase 14 gene (MAPK14) is associated with diabetic foot ulcer
Summary
Background
Diabetic foot ulcer (DFU) is a devastating complication of diabetes.
Objectives
We aimed to identify genetic contributors of DFU based on a genome-wide association study approach using a Scottish diabetic cohort.
Methods
A genome-wide association approach was applied. A case was defined as a diabetic patient (type 1 or type 2) who had ever been recorded in the linked e-health records as having a foot ulcer (current or previous) in at least one foot as well as a positive result of the monofilament test in the longitudinal e-health records. A control in this study was defined as a diabetic individual (type 1 or type 2) who has never been recorded as having a foot ulcer in either foot in the linked e-health records and the monofilament test results of any foot was once recorded to be positive in the longitudinal e-health records.
Results
We have 699 DFU cases and 2,695 controls in the Genetics of Diabetes Audit and Research in Tayside Scotland (GoDARTS) dataset. The lowest P value of rs80028505 (Chr6p21.31) in the MAPK14 gene was 2.45x10-8. The narrow-sense heritability of this phenotype is 0.06.
Conclusions
We suggest that the MAPK14 gene is associated with DFU.
This article is protected by copyright. All rights reserved.
http://ift.tt/2tCmEW8
Recovery position significantly associated with a reduced admission rate of children with loss of consciousness
Background Loss of consciousness (LOC) is often seen in children. The response of caregivers to a child with LOC has been poorly investigated. Potential caregivers (parents, teachers) seem to have a poor knowledge of the recovery position (RP)-that is, the position into which an unconscious child should be placed in order to protect the airway. Objectives To report the management and diagnoses of LOC in childhood, and to evaluate variables associated with an increased hospital admission rate. Methods We conducted a prospective cohort study of consecutive children aged between 0 and 18 years diagnosed with LOC at 11 paediatric emergency departments (PEDs) of 6 European countries. The enrolment period was 3 months. Data were obtained from parental interviews, PED reports and clinical examination. Results 553 children were enrolled. The most frequent final diagnoses causing LOC were seizures (n= 278, 50.3%), and vasovagal syncope (n= 124, 22.4%). Caregivers put the child in the RP in 145 cases (26.2%). The RP was independently associated with a significant decrease in the admission rate (aOR= 0.28; 95% CI 0.17 to 0.48; p< 0.0001). Conclusions Our study demonstrates for the first time that the RP may reduce the admission rate of infants with LOC. Caregivers often perform inadequate manoeuvres when a child becomes unconscious. Campaigns aiming at increasing knowledge of the RP should be promoted.
http://ift.tt/2tiCIJX
Possible gasoline-induced chronic liver injury due to occupational malpractice in a motor mechanic: a case report
Hydrocarbon-induced occupational liver injury is a well-known clinical entity among petroleum industry workers. There are many types of hydrocarbon exposure, with inhalation being the most common. Hydrocarbon-...
http://ift.tt/2uhSvch
Applied Cultural and Social Studies are Needed for a Sustainable Reduction of Genetic Disease Incidence
While clinical and basic biomedical research focus on diagnoses and cures for common and rare genetic diseases, they are unable to address one of the largest underlying causes for genetic disease: mating within families or other small genetically isolated sub-populations. This interdisciplinary literature study investigates theoretical, moral and practical aspects to solve this major cause for genetic disease from an alternative angle: through cultural change and encouragement of an outbreeding reproductive behavior. Understanding why some communities persist with choosing consanguineous reproductive partners when the modern society has eliminated the economic rationale to do so, and to develop strategies to encourage a cultural change in those communities, is critical for a sustainable long-term solution to reduce the number of new cases of genetic disease and undiagnosed (sub-clinical) but detrimental genetic abnormalities in vulnerable and marginalized groups in modern Western societies.
http://ift.tt/2tEAjvj
Immune biomarkers for chronic inflammation related complications in non-cancerous and cancerous diseases
Abstract
Chronic inflammation arising in a diverse range of non-cancerous and cancerous diseases, dysregulates immunity and exposes patients to a variety of complications. These include immunosuppression, tissue damage, cardiovascular diseases and more. In cancer, chronic inflammation and related immunosuppression can directly support tumor growth and dramatically reduce the efficacies of traditional treatments, as well as novel immune-based therapies, which require a functional immune system. Nowadays, none of the immune biomarkers, regularly used by clinicians can sense a developing chronic inflammation, thus complications can only be detected upon their appearance. This review focuses on the necessity for such immune status biomarkers, which could predict complications prior to their appearance. Herein we bring examples for the use of cellular and molecular biomarkers in diagnosis, prognosis and follow-up of patients suffering from various cancers, for prediction of response to immune-based anti-cancer therapy and for prediction of cardiovascular disease in type 2 diabetes patients. Monitoring such biomarkers is expected to have a major clinical impact in addition to unraveling of the entangled complexity underlying dysregulated immunity in chronic inflammation. Thus, newly discovered biomarkers and those that are under investigation are projected to open a new era towards combating the silent damage induced by chronic inflammation.
http://ift.tt/2uhAf2q
DAS 28 correlated poorly with the objective evidence of inflammation as detected by ultrasound examination of hands and feet in patients with rheumatoid arthritis
Brown, G; Cotton, A; Guinto, J; Ciurtin, C; (2016) DAS 28 correlated poorly with the objective evidence of inflammation as detected by ultrasound examination of hands and feet in patients with rheumatoid arthritis. Presented at: Rheumatology 2016, Birmingham, UK.
http://ift.tt/2siWgg3
The computer ate my personality
Olhede, S; Rodrigues, R; (2017) The computer ate my personality. Significance , 14 (3) pp. 6-7. 10.1111/j.1740-9713.2017.01030.x .
http://ift.tt/2tBYlYo
Intertext and postmodern space in the work of Pier Vittorio Tondelli
Massaccesi, C; (2007) Intertext and postmodern space in the work of Pier Vittorio Tondelli. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2sja22e
Associations between Mobility, Cognition, and Brain Structure in Healthy Older Adults
Demnitz, N; Zsoldos, E; Mahmood, A; Mackay, CE; Kivimäki, M; Singh-Manoux, A; Dawes, H; Demnitz, N; Zsoldos, E; Mahmood, A; Mackay, CE; Kivimäki, M; Singh-Manoux, A; Dawes, H; Johansen-Berg, H; Ebmeier, KP; Sexton, CE; - view fewer (2017) Associations between Mobility, Cognition, and Brain Structure in Healthy Older Adults. Frontiers in Aging Neuroscience , 9 , Article 155. 10.3389/fnagi.2017.00155 . Green open access
http://ift.tt/2tBzdB6
Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains
Nachshon, A; Atamni, HJA-T; Steuerman, Y; Sheikh-Hamed, R; Dorman, A; Mott, R; Dohm, JC; Nachshon, A; Atamni, HJA-T; Steuerman, Y; Sheikh-Hamed, R; Dorman, A; Mott, R; Dohm, JC; Lehrach, H; Sultan, M; Shamir, R; Sauer, S; Himmelbauer, H; Iraqi, FA; Gat-Viks, I; - view fewer (2016) Dissecting the Effect of Genetic Variation on the Hepatic Expression of Drug Disposition Genes across the Collaborative Cross Mouse Strains. Frontiers in Genetics , 7 , Article 172. 10.3389/fgene.2016.00172 . Green open access
http://ift.tt/2siAdGk
Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data
Brigadoi, S; Phan, P; Highton, D; Powell, S; Cooper, RJ; Hebden, J; Smith, M; Brigadoi, S; Phan, P; Highton, D; Powell, S; Cooper, RJ; Hebden, J; Smith, M; Tachtsidis, I; Elwell, CE; Gibson, AP; - view fewer (2017) Image reconstruction of oxidized cerebral cytochrome C oxidase changes from broadband near-infrared spectroscopy data. Neurophotonics , 4 (2) , Article 021105. 10.1117/1.NPh.4.2.021105 . Green open access
http://ift.tt/2tBzbJu
“As a Parent You Become a Tiger”: Parents Talking about Bullying at School
Hale, R; Fox, CL; Murray, M; (2017) "As a Parent You Become a Tiger": Parents Talking about Bullying at School. Journal of Child and Family Studies , 26 (7) pp. 2000-2015. 10.1007/s10826-017-0710-z . Green open access
http://ift.tt/2siWdRp
In vitro expansion of donor-derived CMV-specific T lymphocytes for adoptive cellular therapy: Optimisation of antigen presentation by dendritic cells, characterisation of the culture output, and adaptation of culture conditions to CMV-NA donors
Verfueth, S; (2006) In vitro expansion of donor-derived CMV-specific T lymphocytes for adoptive cellular therapy: Optimisation of antigen presentation by dendritic cells, characterisation of the culture output, and adaptation of culture conditions to CMV-NA donors. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2tBKOQm
Structure-function Studies in Mouse Embryonic Stem Cells Using Recombinase-mediated Cassette Exchange
Gene engineering in mouse embryos or embryonic stem cells (mESCs) allows for the study of the function of a given protein. Proteins are the workhorses of the cell and often consist of multiple functional domains, which can be influenced by posttranslational modifications. The depletion of the entire protein in conditional or constitutive knock-out (KO) mice does not take into account this functional diversity and regulation. An mESC line and a derived mouse model, in which a docking site for FLPe recombination-mediated cassette exchange (RMCE) was inserted within the ROSA26 (R26) locus, was previously reported. Here, we report on a structure-function approach that allows for molecular dissection of the different functionalities of a multidomain protein. To this end, RMCE-compatible mice must be crossed with KO mice and then RMCE-compatible KO mESCs must be isolated. Next, a panel of putative rescue constructs can be introduced into the R26 locus via RMCE targeting. The candidate rescue cDNAs can be easily inserted between RMCE sites of the targeting vector using recombination cloning. Next, KO mESCs are transfected with the targeting vector in combination with an FLPe recombinase expression plasmid. RMCE reactivates the promoter-less neomycin-resistance gene in the ROSA26 docking sites and allows for the selection of the correct targeting event. In this way, high targeting efficiencies close to 100% are obtained, allowing for insertion of multiple putative rescue constructs in a semi-high throughput manner. Finally, a multitude of R26-driven rescue constructs can be tested for their ability to rescue the phenotype that was observed in parental KO mESCs. We present a proof-of-principle structure-function study in p120 catenin (p120ctn) KO mESCs using endoderm differentiation in embryoid bodies (EBs) as the phenotypic readout. This approach enables the identification of important domains, putative downstream pathways, and disease-relevant point mutations that underlie KO phenotypes for a given protein.
http://ift.tt/2t9kJXO
Clinical and economic value of in-hospital clinical pharmacy activities form a health care perspective
Economic evaluations have become increasingly important in health care systems. Scarce resources necessitate to consider both outcomes and costs to guide decision-making. This dissertation explores the return on investment of pharmaceutical recommendations in a hospital setting ('a clinical pharmacy service'). Subsequently the clinical added value of clinical pharmacy, the methodology to evaluate a clinical pharmacy program and the studied cost benefit are presented. In a last part this work explores the role of information technology in reducing the pharmacist workload.
http://ift.tt/2sEoSzE
Transcriptomic responses of the olive fruit fly Bactrocera oleae and its symbiont Candidatus Erwinia dacicola to olive feeding
The olive fruit fly, Bactrocera oleae, is the most destructive pest of olive orchards worldwide. The monophagous larva has the unique capability of feeding on olive mesocarp, coping with high levels of phenolic compounds and utilizing non-hydrolyzed proteins present, particularly in the unripe, green olives. On the molecular level, the interaction between B. oleae and olives has not been investigated as yet. Nevertheless, it has been associated with the gut obligate symbiotic bacterium Candidatus Erwinia dacicola. Here, we used a B. oleae microarray to analyze the gene expression of larvae during their development in artificial diet, unripe (green) and ripe (black) olives. The expression profiles of Ca. E. dacicola were analyzed in parallel, using the Illumina platform. Several genes were found overexpressed in the olive fly larvae when feeding in green olives. Among these, a number of genes encoding detoxification and digestive enzymes, indicating a potential association with the ability of B. oleae to cope with green olives. In addition, a number of biological processes seem to be activated in Ca. E. dacicola during the development of larvae in olives, with the most notable being the activation of amino-acid metabolism.
http://ift.tt/2t8sNIo
High mannose-specific lectin Msl mediates key interactions of the vaginal Lactobacillus plantarum isolate CMPG5300
To characterize the interaction potential of the human vaginal isolate Lactobacillus plantarum CMPG5300, its genome was mined for genes encoding lectin-like proteins. cmpg5300.05_29 was identified as the gene encoding a putative mannose-binding lectin. Phenotypic analysis of a gene knock-out mutant of cmpg5300.05_29 showed that expression of this gene is important for auto-aggregation, adhesion to the vaginal epithelial cells, biofilm formation and binding to mannosylated glycans. Purification of the predicted lectin domain of Cmpg5300.05_29 and characterization of its sugar binding capacity confirmed the specificity of the lectin for high-mannose glycans. Therefore, we renamed Cmpg5300.05_29 as a mannose-specific lectin (Msl). The purified lectin domain of Msl could efficiently bind to HIV-1 glycoprotein gp120 and Candida albicans, and showed an inhibitory activity against biofilm formation of uropathogenic Escherichia coli, Staphylococcus aureus and Salmonella Typhimurium. Thus, using a combination of molecular lectin characterization and functional assays, we could show that lectin-sugar interactions play a key role in host and pathogen interactions of a prototype isolate of the vaginal Lactobacillus microbiota.
http://ift.tt/2sE9Hqp
Acute Appendicitis: An Extracolonic Manifestation of Clostridium difficile Colitis
The current report is the case of a 30-year-old male patient who presented with symptomatology suggestive of appendicitis. However, careful history-taking and laboratory tests led to the diagnosis of Clostridium difficile colitis, resulting in successful nonsurgical management of this patient. Although both appendicitis and C. difficile colitis are common conditions, they are rarely diagnosed concurrently. This is reflected by paucity of literature describing this manifestation. Given this current presentation, the authors contend that the manifestation of extracolonic colitis within the appendix is possibly underdiagnosed or misdiagnosed as an acute appendicitis and thus potentially results in unnecessary surgical intervention. This report reminds physicians to consider the medical approach to managing acute appendicitis given the possibility of underlying C. difficile colitis as the causative factor.
http://ift.tt/2tB1YxR
Laryngeal surgical treatment in transgender women: A systematic review and meta-analysis
Objective
To identify the effects of laryngeal surgical treatment in the voice of transgender women, especially on the fundamental frequency (f0).
Study Design
We performed a systematic review in PubMed and Scopus in July 2016, covering the period between 2005 and 2016.
Methods
Inclusion criteria were studies in English or Portuguese about the laryngeal surgical treatment in transgender women, featuring experimental design, title, year of publication, country of origin, journal of publication, participants, intervention, results. For the meta-analysis, only studies that had control group were selected. Exclusion criteria were articles that mentioned the use of surgical techniques but did not use the procedure in research, animal studies, studies of revision, and postmortem studies.
Results
Four hundred and twenty-three articles were identified in the initial search; 94 were selected for analysis by two referees, independently. After applying all the selection criteria, five studies remained in the meta-analysis. The surgical procedures that were identified included laryngoplasty with or without thyrohyoid approximation, Wendler glottoplasty, cricothyroid approximation, laser glottoplasty reduction and the vocal fold shortening and retrodisplacement of anterior commissure. There was no significant difference between the experimental group and the control group in relation to f0.
Conclusion
No randomized clinical trials and prospective cohort studies are available, and a small number of retrospective cohort and case-control studies of surgical techniques reveal an increase in the f0. The evidence produced is not conclusive regarding which surgical technique would be better for vocal treatment of transgender women.
Level of Evidence
NA Laryngoscope, 2017
http://ift.tt/2tBsA1C
Osteonecrosis after intranasal injection with bevacizumab in treating hereditary hemorrhagic telangiectasia: A case report
Intranasal bevacizumab injections have been used in treating hereditary hemorrhagic telangiectasia (HHT)-related epistaxis since 2009. It is believed to be a safe and effective treatment for a selected group of HHT patients in reducing frequency and intensity of epistaxis, with few or none adverse effects. In this case report, however, we will describe a patient who developed bilateral osteonecrosis in the knees while undergoing regular intranasal submucosal bevacizumab injections. Although osteonecrosis previously has been documented in patients receiving bevacizumab intravenously in oncologic doses, thus far it has not been reported in patients treated with intranasal submucosal injections. Laryngoscope, 2017
http://ift.tt/2si3roM
Mandibular condylar hypoplasia in children with isolated unilateral congenital aural atresia
Objectives/Hypothesis
We hypothesized that children with isolated nonsyndromic unilateral congenital aural atresia have subclinical mandibular condylar hypoplasia ipsilateral to the atretic ear, and that the Jahrsdoerfer score is associated with the degree of condylar hypoplasia.
Study Design
Retrospective self-controlled case series.
Methods
We reviewed high-resolution computed tomography scans of the temporal bones of 68 children with isolated nonsyndromic unilateral congenital aural atresia. Images were viewed in the transverse (axial) plane perpendicular to the axis of the mandibular ramus and scanned from the mandibular notch to the condylar top. The slice where the condyle had the largest cross-sectional area was measured and checked for correlation with atresia status, age, and sex. The Jahrsdoerfer score of the atretic ear was calculated and correlated with condyle cross-sectional area, age, and sex.
Results
Cross-sectional area of the condyle ipsilateral to the atretic ear was, on average, 8.41 mm2 smaller than the contralateral condyle (P < .0001). The Jahrsdoerfer score was not associated with the condylar cross-sectional area, age, or sex.
Conclusion
Isolated nonsyndromic unilateral congenital aural atresia is associated with mild hypoplasia of the mandibular condyle ipsilateral to the atretic ear. This is consistent with the hypothesis that congenital aural atresia is a variant of craniofacial (hemifacial) microsomia.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2tAGmle
Impact of obstructive sleep apnea in transsphenoidal pituitary surgery: An analysis of inpatient data
Objectives/Hypothesis
Although previous studies have reported increased perioperative complications among obstructive sleep apnea (OSA) patients undergoing any surgery requiring general anesthesia, there is a paucity of literature addressing the impact of OSA on postoperative transsphenoidal surgery (TSS) complications. The aim of this study was to analyze postoperative outcomes in transsphenoidal pituitary surgery patients with OSA. Secondarily, we examined patient characteristics and comorbidities.
Study Design
Retrospective analysis.
Methods
The 2002 to 2013 National Inpatient Sample was queried for patients undergoing TSS for pituitary neoplasm. Patients with an additional diagnosis of OSA were identified, and compared to a non-OSA cohort.
Results
There were 17,777 patients identified; 5.0% (N = 889) had an additional diagnosis of OSA. The OSA cohort had more comorbidities including diabetes mellitus, congestive heart failure, chronic pulmonary disease, coagulopathy, hypertension, hypothyroidism, liver disease, obesity, peripheral vascular disease, renal failure, acromegaly, and Cushing's syndrome. Postoperatively, OSA was independently associated with increased risks of tracheostomy (P = .015) and hypoxemia (P < .001), and decreased risk of cardiac complications (P = .034). OSA patients did not have increased rates of cerebrospinal fluid rhinorrhea, diabetes insipidus, reintubation, aspiration pneumonia, infectious pneumonia, thromboembolic complications, or urinary/renal complications. In-hospital mortality rates did not vary between the two cohorts.
Conclusions
In patients who underwent transsphenoidal pituitary surgery, OSA was associated with higher rates of certain pulmonary and airway complications. OSA was not associated with increased non–pulmonary/airway complications or inpatient mortality, despite older average age and higher comorbidity rates.
Level of Evidence
2C Laryngoscope, 2017
http://ift.tt/2siE99O
Comparison of facility type outcomes for oral cavity cancer: Analysis of the national cancer database
Objective
Determine whether facility type effects overall survival in patients with oral cavity cancer.
Study Design
Retrospective cohort study.
Methods
Patients included in the National Cancer Database who were diagnosed with oral cavity cancer between 1998 and 2011 were included in the study. Data was stratified by facility where care was provided, including community cancer programs (CCP), comprehensive community cancer programs (CCCP), and academic centers (AC). Univariate analysis was performed using analysis of variance, chi squared, and log-rank test, whereas multivariate analysis was performed using Cox regression.
Results
A total of 32,510 patients were included in the study, with 7.58% of patients receiving care at CCPs (n = 2,553), 39.53% at CCCPs (n = 12,852), and 52.61% at ACs (n = 17,105). Between 1998 and 2011, there was a greater percentage of patients receiving care at ACs, and a greater percentage of patients receiving surgical therapy versus nonsurgical therapy. Patients treated at ACs had the best 5-year overall survival of 51.26%, with a significant difference across facility types (P < 0.01). After adjusting for confounders, receiving care at ACs was a positive predictor of survival (hazard ratio: 0.95 95% confidence interval [0.91,0.98])).
Conclusion
Patients treated at ACs are more likely to receive surgical treatment, and have a greater 5-year overall survival compared to those patients treated at CCPs and CCCPs. Therefore, we advocate referring patients with advanced oral cavity cancers to ACs.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2tBpryS
Laryngectomy and smoking: An analysis of postoperative risk
Objectives
To investigate the impact of smoking on complication rates following total laryngectomy.
Study Design and Methods
The National Surgical Quality Improvement Program database was queried for all total laryngectomies between 2005 and 2014. Patients were identified as smokers (n = 561) or nonsmokers (n = 513) and compared via univariate and multivariate analyses. A nearest-neighbor propensity score-generating algorithm was used to build a subpopulation (n = 714) of matched cases and evaluated in a similar manner. Additionally, pack-year data was available for select cases and analyzed appropriately.
Results
On multivariate analysis of the unmatched cohort accounting for demographics and confounders, no significant difference in overall medical complications was identified between groups (odds ratio = 0.799, P = 0.495). Propensity matching corrected for all significantly distributed comorbidities, except for alcohol, which remained associated with the smoking group (P = < 0.001). In the matched population, there were no significant differences in complication rates between the two groups. Pack-year data was available for 340 patients. These cases were subdivided into cohorts with < 50 (n = 204) and 51+ (n = 136) pack-years. Postoperative pneumonia, ventilation for more than 48 hours, sepsis, and overall medical complications were associated with > 50 pack-years of smoking. After multivariate regression, sepsis and overall medical complications remained significant for the 51+ pack-year smoking cohort.
Conclusion
After accounting for confounding comorbidities, smoking is found to play an insignificant role in the development of postoperative complications following total laryngectomy. However, those with 51+ pack-years are at an increased risk for postoperative sepsis and overall medical complications following these complex procedures.
Level of Evidence
4. Laryngoscope, 2017
http://ift.tt/2si5jxW
Impact of human immunodeficiency virus on hepatitis B-specific immune responses
Lascar, RM; (2006) Impact of human immunodeficiency virus on hepatitis B-specific immune responses. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2uh76o4
Replik auf Dews und ein Plädoyer für Schelling
Gardner, S; (2017) Replik auf Dews und ein Plädoyer für Schelling. Deutsche Zeitschrift für Philosophie , 65 (2) 10.1515/dzph-2017-0017 .
http://ift.tt/2tIcyn9
European boundaries in question?
Bellamy, R; Lacey, J; Nicolaïdis, K; (2017) European boundaries in question? Journal of European Integration pp. 1-16. 10.1080/07036337.2017.1333118 . (In press).
http://ift.tt/2uhi0Kr
Identification of genes regulating glucocorticoid-induced and antigen-mediated thymocyte apoptosis
Woodward, MJ; (2008) Identification of genes regulating glucocorticoid-induced and antigen-mediated thymocyte apoptosis. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2tIjD6W
Host thin films incorporating nanoparticles
Qureshi, U; (2007) Host thin films incorporating nanoparticles. Doctoral thesis, UCL (University College London). Green open access
http://ift.tt/2ugMnAJ
Silencing CHALCONE SYNTHASE in maize impedes the incorporation of tricin into lignin and increases lignin content
Lignin is a phenolic heteropolymer that is deposited in secondary-thickened cell walls, where it provides mechanical strength. A recent structural characterization of cell walls from monocot species showed that the flavone tricin is part of the native lignin polymer, where it is hypothesized to initiate lignin chains. In this study, we investigated the consequences of altered tricin levels on lignin structure and cell wall recalcitrance by phenolic profiling, nuclear magnetic resonance, and saccharification assays of the naturally silenced maize (Zea mays) C2-Idf (inhibitor diffuse) mutant, defective in the CHALCONE SYNTHASE Colorless2 (C2) gene. We show that the C2-Idf mutant produces highly reduced levels of apigenin-and tricin-related flavonoids, resulting in a strongly reduced incorporation of tricin into the lignin polymer. Moreover, the lignin was enriched in beta-beta and beta-5 units, lending support to the contention that tricin acts to initiate lignin chains and that, in the absence of tricin, more monolignol dimerization reactions occur. In addition, the C2-Idf mutation resulted in strikingly higher Klason lignin levels in the leaves. As a consequence, the leaves of C2-Idf mutants had significantly reduced saccharification efficiencies compared with those of control plants. These findings are instructive for lignin engineering strategies to improve biomass processing and biochemical production.
http://ift.tt/2thGbIG
Capacitive water release and internal leaf water relocation delay drought-induced cavitation in African Maesopsis eminii
The impact of drought on the hydraulic functioning of important African tree species, like Maesopsis eminii Engl., is poorly understood. To map the hydraulic response to drought-induced cavitation, sole reliance on the water potential at which 50% loss of xylem hydraulic conductivity (Psi(50)) occurs might be limiting and at times misleading as the value alone does not give a comprehensive overview of strategies evoked by M. eminii to cope with drought. This article therefore uses a methodological framework to study the different aspects of drought-induced cavitation and water relations in M. eminii. Hydraulic functioning of wholebranch segments was investigated during bench-top dehydration. Cumulative acoustic emissions and continuous weight measurements were used to quantify M. eminii's vulnerability to drought-induced cavitation and hydraulic capacitance. Wood structural traits, including wood density, vessel area, diameter and wall thickness, vessel grouping index, solitary vessel index and vessel wall reinforcement, were used to underpin observed physiological responses. On average, M. eminii's Psi 50 (+/- SE) was -1.9 +/- 0.1 MPa, portraying its xylem as drought vulnerable, just as one would expect for a common tropical pioneer. However, M. eminii additionally employed an interesting desiccation delay strategy, fuelled by internal relocation of leaf water, hydraulic capacitance and the presence of parenchyma around the xylem vessels. Our findings suggest that exclusive dependence on Psi 50 would have misdirected our assessments of M. eminii's drought stress vulnerability. Hydraulic capacitance linked to anatomy and leaf-water relocation behaviour was equally important to better understand M. eminii's drought survival strategies. Because our study was conducted on branches of 3-year-old greenhouse-grown M. eminii seedlings, the findings cannot be simply extrapolated to adult M. eminii trees or their mature wood, because structural and physiological plant properties change with age. The techniques and methodological framework used in this study are, however, transferable to other species regardless of age.
http://ift.tt/2tHLkg8
Early summer drought stress during the first growing year stimulates extra shoot growth in oak seedlings (Quercus petraea)
More severe summer droughts are predicted for mid-latitudes in Europe. To evaluate the impact on forest ecosystems and more specifically on forest regeneration, we studied the response to summer drought in oak seedlings (Quercus petraea). Acorns were collected from different mother trees in three stands in Belgium, sown in pots and grown in non-heated greenhouse conditions. We imposed drought on the seedlings in early summer by first watering the pots to saturation and then stopping any watering. Weight of the pots and stomatal conductance were regularly measured. Re-watering followed this drought period of 5 weeks. Height of the seedlings and apical bud development were observed. Stomatal resistance increased toward the end of the experiment in the drought-treated group and was restored after re-watering. The seedlings from the drought treatment displayed a higher probability to produce additional shoot growth after re-watering (p <= 0.05). A higher competition for water (two plants per pot) increased this chance. Although this chance was also higher for smaller seedlings, the actual length of the extra growth after re-watering was higher for larger seedlings (p <= 0.01). Both in the drought-treated and in the control group the autochthonous provenance growing on a xeric site produced less extra shoots compared to the two other provenances. Finally, stressed plants showed less developed apical buds compared to the control group after re-watering, suggesting a phenological effect on the growth cycle of oaks (p <= 0.0001). The higher chance for an extra shoot growth after the drought period can be considered as a compensation for the induced growth arrest during the drought period.
http://ift.tt/2tI2haD
Root xylem CO2 flux : an important but unaccounted-for component of root respiration
Root respiration has been considered a large component of forest soil CO2 efflux, but recent findings indicate that it may be even more important than previous measurements have shown because a substantial fraction of root-respired CO2 remains within the tree root system and moves internally with the transpiration stream. The high concentration of CO2 in roots appears to originate mainly within the root. It has been suggested that plants can take up dissolved inorganic carbon (DIC) from soil, but under most conditions uptake from soil is minimal due to the root-to-soil diffusion gradient, which suggests that most of the CO2 in root xylem is derived from root respiration. Estimates of the internal flux of CO2 through root xylem are based on combined measurements of sap flow and internal [CO2]. Results quantifying root xylem CO2 flux, obtained for a limited number of species, have raised important concerns regarding our understanding of tree respiration. Taken together, the results of these studies call into question the partitioning of ecosystem respiration into its above- and belowground components, and redefine the energetic costs of tree root metabolism and hence estimates of belowground carbon allocation. Expanding our observations of root xylem CO2 flux to more species and at longer time scales, as well as improving the techniques used to study this process, could be fruitful avenues for future research, with the potential to substantially revise our understanding of root respiration and forest carbon cycles.
http://ift.tt/2ugSXay
When the language bonus becomes an onus : a Belgian case study
Belgian public servants are entitled to a language bonus, ranging from €20 to €110 per month, when they need to use two official languages, mainly Dutch and French, in their jobs. Some of the employees (window clerks) of a state-owned, public service company (company X) receive this bonus, but only those who work in Brussels, because it is an official bilingual area (French/Dutch). To get an insight into the language practices and beliefs of their Flemish colleagues, we analysed the answers of a survey study of 129 participants working in the monolingual area (Dutch). The language bonus is a source of dissatisfaction for clerks working in monolingual regions, such as Antwerp, because they also need to be multilingual to perform their jobs, but do not receive the bonus. The results indicate that there is a discrepancy between the language policy of Belgium (the language laws) on the one hand and the policy of company X and the language beliefs and practices of the clerks on the other. We conclude our article with a discussion about the language bonus and make an assessment about expenditure on it in Belgium, which we estimate at €51 million per year. We argue that the bonus has to be viewed as a language management strategy and thus has to be evaluated regularly to become fully effective.
http://ift.tt/2tHxIBC
SAPFLUXNET : towards a global database of sap flow measurements
Plant transpiration is the main evaporative flux from terrestrial ecosystems; it controls land surface energy balance, determines catchment hydrological responses and influences regional and global climate. Transpiration regulation by plants is a key (and still not completely understood) process that underlies vegetation drought responses and land evaporative fluxes under global change scenarios. Thermometric methods of sap flow measurement have now been widely used to quantify whole-plant and stand transpiration in forests, shrublands and orchards around the world. A large body of research has applied sap flow methods to analyse seasonal and diurnal patterns of transpiration and to quantify their responses to hydroclimatic variability, but syntheses of sap flow data at regional to global scales are extremely rare. Here we present the SAPFLUXNET initiative, aimed at building the first global database of plant-level sap flow measurements. A preliminary metadata survey launched in December 2015 showed an encouraging response by the sap flow community, with sap flow data sets from field studies representing > 160 species and > 120 globally distributed sites. The main goal of SAPFLUXNET is to analyse the ecological factors driving plant-and stand-level transpiration. SAPFLUXNET will open promising research avenues at an unprecedented global scope, namely: (i) exploring the spatio-temporal variability of plant transpiration and its relationship with plant and stand attributes, (ii) summarizing physiological regulation of transpiration by means of few water-use traits, usable for land surface models, (iii) improving our understanding of the coordination between gas exchange and plant-level traits (e.g., hydraulics) and (iv) analysing the ecological factors controlling stand transpiration and evapotranspiration partitioning. Finally, SAPFLUXNET can provide a benchmark to test models of physiological controls of transpiration, contributing to improve the accuracy of individual water stress responses, a key element to obtain robust predictions of vegetation responses to climate change.
http://ift.tt/2ugZaDw
Clustering reveals cavitation-related acoustic emission signals from dehydrating branches
The formation of air emboli in the xylem during drought is one of the key processes leading to plant mortality due to loss in hydraulic conductivity, and strongly fuels the interest in quantifying vulnerability to cavitation. The acoustic emission (AE) technique can be used to measure hydraulic conductivity losses and construct vulnerability curves. For years, it has been believed that all the AE signals are produced by the formation of gas emboli in the xylem sap under tension. More recent experiments, however, demonstrate that gas emboli formation cannot explain all the signals detected during drought, suggesting that different sources of AE exist. This complicates the use of the AE technique to measure emboli formation in plants. We therefore analysed AE waveforms measured on branches of grapevine (Vitis viniferaL. 'Chardonnay') during bench dehydration with broadband sensors, and applied an automated clustering algorithm in order to find natural clusters of AE signals. We used AE features and AE activity patterns during consecutive dehydration phases to identify the different AE sources. Based on the frequency spectrum of the signals, we distinguished three different types of AE signals, of which the frequency cluster with high 100-200 kHz frequency content was strongly correlated with cavitation. Our results indicate that cavitation-related AE signals can be filtered from other AE sources, which presents a promising avenue into quantifying xylem embolism in plants in laboratory and field conditions.
http://ift.tt/2tHuFth
Emerging role of interleukin-31 and interleukin-31 receptor in pruritus in atopic dermatitis
Abstract
Atopic dermatitis (AD) is a chronic or chronically relapsing, eczematous, severely pruritic skin disorder associated with skin barrier dysfunction. The lesional skin of AD exhibits T helper 2 (TH2)-deviated immune reactions. Interleukin-31 (IL-31), preferentially produced from TH2 cells, is a potent pruritogenic cytokine, and its systemic and local administration induces scratching behavior in rodents, dogs and monkeys. Recent clinical trials have revealed that administration of an anti-IL-31 receptor antibody significantly alleviates pruritus in patients with AD. In this review, we summarize recent topics related to IL-31 and its receptor with special references to atopic itch.
This article is protected by copyright. All rights reserved.
http://ift.tt/2sDHccn
Meat allergy associated with α-Gal – Closing diagnostic gaps by anti-α-Gal IgE immune profiling
Abstract
Background
Glycoproteins and glycolipids of some mammalian species contain the disaccharide galactosyl-α-(1,3)-galactose (α-Gal). It is known that α-Gal is immunogenic in humans and causes glycan-specific IgG and also IgE responses with clinical relevance. α-Gal is part of the IgE-reactive monoclonal therapeutic antibody cetuximab and is associated with delayed anaphylaxis to red meat. In this study, different alpha-Gal-containing analytes are examined in singleplex and multiplex assays to resolve individual sensitization patterns with IgE against α-Gal.
Methods
Three serum groups, α-Gal-associated meat allergy (MA) patients, idiopathic anaphylaxis (IA) patients with suspected meat allergy and non-meat-allergic healthy control individuals (HC), were analyzed via singleplex allergy diagnostics and a newly established immunoblot diagnostic system. The new dot blot detection system resolved individual IgE sensitization profiles for α-Gal-containing analytes cetuximab, bovine thyroglobulin and HSA-conjugated α-Gal.
Results
Singleplex allergy diagnostics using the α-Gal-analytes cetuximab and bovine thyroglobulin confirms the history of meat allergy patients in 91% and 88% of the cases, respectively. A novel dot-blot-based assay system for the detection of IgE against α-Gal reveals individual IgE sensitization profiles for α-Gal-containing analytes. An α-Gal-associated IgE cross-reactivity profile (IgE against cetuximab, bovine thyroglobulin and HSA-α-Gal) was identified, which is associated with meat allergy.
Conclusions
Detection of individual sensitization patterns with different α-Gal-containing analytes provides the basis for an individual allergy diagnosis for α-Gal sensitized patients. Higher amounts of α-Gal in pork and beef innards compared to muscle meat as indicated by a higher staining intensity are a plausible explanation for the difference in allergic symptom severity.
This article is protected by copyright. All rights reserved.
http://ift.tt/2t8oHAj
Repetitive Sinus-Related Symptoms May Accelerate the Progression of Chronic Maxillary Atelectasis
Chronic maxillary atelectasis (CMA) is characterized by a progressive decrease in maxillary sinus volume. The factors that promote the stage progression of CMA remain poorly understood. Here, we describe the time course of anatomical changes in a 40-year-old woman with stage II CMA that progressed to stage III disease. She did not show stage progression until she started to develop repetitive sinus-related symptoms. The stage progression was characterized by ocular symptoms. The repetitive inflammatory episodes may have increased the negative pressure in the affected sinus and weakened the bone walls, thereby promoting stage progression. Thus, a history of repetitive sinus-related symptoms may be a risk factor for stage progression in CMA.
http://ift.tt/2tALwh2
New tumour entities in the 4th edition of the World Health Organization Classification of Head and Neck tumours: odontogenic and maxillofacial bone tumours
Abstract
The latest (4th) edition of the World Health Organization Classification of Head and Neck tumours has recently been published with a number of significant changes across all tumour sites. In particular, there has been a major attempt to simplify classifications and to use defining criteria which can be used globally in all situations, avoiding wherever possible the use of complex molecular techniques which may not be affordable or widely available. This review summarises the changes in Chapter 8: Odontogenic and maxillofacial bone lesions. The most significant change is the re-introduction of the classification of the odontogenic cysts, restoring this books status as the only text which classifies and defines the full range of lesions of the odontogenic tissues. The consensus group considered carefully the terminology of lesions and were concerned to ensure that the names used properly reflected the best evidence regarding the true nature of specific entities. For this reason, this new edition restores the odontogenic keratocyst and calcifying odontogenic cyst to the classification of odontogenic cysts and rejects the previous terminology (keratocystic odontogenic tumour and calcifying cystic odontogenic tumour) which were intended to suggest that they are true neoplasms. New entities which have been introduced include the sclerosing odontogenic carcinoma and primordial odontogenic tumour. In addition, some previously poorly defined lesions have been removed, including the ameloblastic fibrodentinoma, ameloblastic fibro-odontoma, which are probably developing odontomas, and the odontoameloblastoma, which is not regarded as an entity. Finally, the terminology "cemento" has been restored to cemento-ossifying fibroma and cemento-osseous dysplasias, to properly reflect that they are of odontogenic origin and are found in the tooth-bearing areas of the jaws.
http://ift.tt/2tAPzK5
Frankfurter Slapstick : Benjamin, Kracauer, and Adorno on American screen comedy
Scrutinizing the writings by Walter Benjamin, Siegfried Kracauer, and Theodor W. Adorno and connecting them to specific comedy scenes and tropes, this essay explores the fascination for American slapstick comedies and comedians by the philosophers of the Frankfurt School. Although often critical of mass entertainment, Benjamin, Kracauer, and Adorno admired the way slapstick film elevated motion and speed to an art form that answered to the rhythms and dangers of an industrialized society. For these writers, slapstick's crude and anarchic humor and anthropomorphizing of everyday objects offered a means of resistance against the forces of modernization through ludic encounters.
http://ift.tt/2tgXYQt
Superconducting and magnetic properties of Sn-doped EuBa2Cu3O7-δ compound
Influence of Sn-substitution on structural, superconducting and magnetic properties of EuBa2Cu3O7-delta (Eu-123) compound was studied by X-ray diffraction and SQUID magnetic measurements. Transition process from normal to superconducting state and temperature dependences of zero field cooling and field cooling characteristics of magnetic moment and magnetization curves were measured and analysed. Samples of the nominal composition of EuBa2Cu3-xSnxO7-delta with x ranging from 0.0 to 1.5 were prepared by the solid state reaction technique. The increasing Sn-content decreases the volume of the main superconducting phase (Eu-123) and for higher Sn-contents, semiconducting tetragonal Eu3Ba3Cu6O14 (Eu-336) and Ba-Sn-O phases are the dominant ones.
http://ift.tt/2tAVj6F
Study on longitudinal temperature distribution of fire-induced ceiling flow in tunnels with different sectional coefficients
This paper proposes two prediction models for the maximum smoke temperature rise and the temperature distribution in tunnel fires, in which sectional coefficient zeta was introduced to describe geometrical characteristic of the tunnel section. At first, the theoretical analysis was conducted. The dimensionless maximum smoke temperature rise was deduced by applying the dimensional analysis method while the smoke temperature exponential decay law was proposed based on the one-dimensional theory. Then, CFD simulations were conducted in nine tunnels with different cross sectional shapes by Fire Dynamics Simulator, version 5.5. With the 'numerical experiments', two prediction models for the maximum smoke temperature and the smoke temperature distribution were obtained. Meanwhile, complementary experiments were conducted in a 1/10 scale tunnel in order to provide a verification. The experiment results show a good agreement with the numerical simulations. Moreover, the proposed prediction models were compared with the prediction models proposed by Kurioka model and Li model. (C) 2016 Elsevier Ltd. All rights reserved.
http://ift.tt/2shQ9IH
Analytic approach to the study of the electric magnetic asymmetry of the dimension-2 condensate
Recent work by Chernodub and Ilgenfritz has uncovered nontrivial temperature dependence in the electric magnetic asymmetry in the dimension-2 condensate. This asymmetry measures the difference between the spatial and the temporal components of the < A(mu)(2)> condensate. Lattice computations have shown very interesting phenomena. The asymmetry shows a jump at the deconfinement phase transition, beyond which it approaches its perturbative value. At temperatures lower than the critical temperature, it shows an exponential behavior with a mass in the exponent smaller than the lowest glueball mass. In this talk we present the research done on this asymmetry, using a generalization of analytical methods developed to study < A(mu)(2)>. The purpose is to shed more insight on the findings of Chernodub and Ilgenfritz.
http://ift.tt/2tBm3ns
Application of the package SIESTA to linear models of a molecular chromium-based ring
We investigate for the first time the electronic and magnetic properties of the linear models of Cr(8)F(8)(Piv)(16) molecular ring using the SIESTA package In the first step the proper values of the SIESTA parameters and the optimal basis set needed for the convergence of the total energy are established Next the estimates of the magnetic coupling J confirming the previous density functional theory calculations are presented.
http://ift.tt/2syb4f3
Formation and annealing of micropores in hematite
In iron oxide powders positrons are trapped in the surface layers and the value of the S-parameter is an indicator of the total specific surface, including external surface and internal surfaces of micropores. The evolution of micropores is followed when alpha-FeOOH is thermally decomposed into alpha-Fe2O3. It is shown that the micropore formation is not linked to the decomposition process, but that they also form in hematite synthesized from a ferrihydrite precursor in aqueous solution.
http://ift.tt/2tgYbCW
Commercial land deals and the interactions between investors and local people: Evidence from western Ethiopia
The current study explores transnational land deals from a regional perspective and investigates investor local people interactions and the factors that underpin them. Empirical analysis utilizes survey data from the Benishangul-Gumuz region, a topographically low-lying region of Ethiopia. Descriptive statistics and ordinal regression model (ORM) was used to analyze data. We explored the factors that determine investor-local people interactions (ILPI) with possible dyadic outcomes which range from confrontation to collaboration. Notwithstanding the conventional centre-periphery discourses on availability of 'unutilized' cultivable lands, findings show that land is already under the pressure of competing demands in the region for transnational and local, private and government, small-scale and agro-industrial purposes. We have observed that the investor-local people interaction is a complex construct influenced by multiple socioeconomic, managerial, and governance-related factors. While community consultation, land use class, local employment, and investors' role in developing an own water source have a significant effect upon ILPI, the influence of other factors such as compensation for expropriated property and farm distance from a community village is observable but insignificant. Though consideration of those factors which underpin investor-local people collaborative interaction is important, synchronizing existing land uses and prioritizing competing demands for land is equally important. Building regional capacity with an inclusive local development outlook is essential. (C) 2017 Published by Elsevier Ltd.
http://ift.tt/2si5g5d
Synthesis of 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans via diastereoselective reductive cyclization of γ-chloroimines and γ-chloroketones
A new diastereoselective synthetic approach towards 1,2,3-trisubstituted pyrrolidines and 2,3-disubstituted tetrahydrofurans is described. The synthesis of the pyrrolidines involves reductive cyclization of gamma-chloroketimines, which were generated in situ from the reaction of 3-substituted 5-chloro-2-pentanones and a primary amine. Various reduction conditions were explored to induce a diastereoselective reductive cyclization. 2,3-Disubstituted tetrahydrofurans were obtained by the direct reduction of 3-substituted 5-chloro-2-pentanones with sodium borohydride.
http://ift.tt/2tAak8Y
Use of functionalized β-lactams as building blocks in heterocyclic chemistry
beta-Lactams represent flexible building blocks suitable for the preparation of a large variety of nitrogen-containing target compounds. In the present study, the formerly neglected synthetic potential of 4-haloalkyl-beta-lactams has been elaborated in detail with a focus on the preparation of different mono- and bicyclic heterocycles. A first approach involved ring transformations of these halogenated building blocks toward stereodefined aziridines, azetidines, pyrrolidines, and piperidines via intermediate aziridinium or azetidinium ions. In a second part, novel and stereoselective entries into 1,4- and 3,4-fused bicyclic beta-lactams were developed through either a radical or an ionic cyclization protocol. Furthermore, the ring enlargement of halogenated beta-lactams into functionalized mono- and bicyclic pyrrolidin-2-ones was established as the aza-analog of the cyclobutylmethylcarbenium ion to cyclopentylcarbenium ion rearrangement. Finally, chiral versions toward azetidin-2-ones and ring transformation products were elaborated, involving the synthesis of 3(S)-alkoxy-4(S)-[1(S)-chloroethyl]azetidin-2-ones and the preparation of bicyclic beta-lactams annelated to piperazines, morpholines, and diazepanes.
http://ift.tt/2shP3gi
Εγγραφή σε:
Αναρτήσεις (Atom)