355 research outputs found

    Management of allergic rhinitis symptoms in the pharmacy Pocket guide 2022

    Full text link
    Allergic rhinitis (AR) management requires a coordinated effort from healthcare providers and patients. Pharmacists are key members of these integrated care pathways resolving medication-related problems, optimizing regimens, improving adherence and recommending therapies while establishing liaisons between patients and physicians.Allergic Rhinitis and its Impact on Asthma (ARIA) first published a reference document on the pharmacist's role in allergic rhinitis management in 2004. Several guidelines were developed over the past 20 years improving the care of allergic rhinitis patients through an evidence-based, integrated care approach.This ARIA/EAACI/FIP Position Paper is based on the latest ARIA in the Pharmacy guidelines and provides: (a) a structured approach to pharmacists identifying people with AR and/or allergic conjunctivitis as well as those at risk of poor disease control; (b) an evidence-based clinical decision support tool for optimising the management of allergic rhinitis in the community pharmacy; and (c) a framework of referral to the physician.This document is not intended to be a mandatory standard of care but is provided as a basis for pharmacists and their staff to develop relevant local standards of care for their patients, within their local practice environment. Pharmacy care varies between countries, and the guide should be adapted to the local situation.© 2022 The Authors. Clinical and Translational Allergy published by John Wiley & Sons Ltd on behalf of European Academy of Allergy and Clinical Immunology

    The 1501 Ma Kuonamka Large Igneous Province of northern Siberia: U-Pb geochronology, geochemistry, and links with coeval magmatism on other crustal blocks

    Get PDF
    © 2015.A new large igneous province (LIP), the 1501 ± 3 Ma Kuonamka LIP, extends across 700 km of northern Siberia and is linked with coeval dikes and sills in the formerly attached Sao Francisco craton (SFC)-Congo craton to yield a short-duration event 2000 km across. The age of the Kuonamka LIP can be summarized as 1501 ± 3 Ma (95% confidence), based on 7 U-Pb ID-TIMS ages (6 new herein) from dolerite dikes and sills across the Anabar shield and within western Riphean cover rocks for a distance of 270 km. An additional sill yielded a SIMS (CAMECA) age of 1483 ± 17 Ma and sill in the Olenek uplift several hundred kilometers farther east, a previous SIMS (SHRIMP) age of ca. 1473 Ma was obtained on a sill; both SIMS ages are within the age uncertainty of the ID-TIMS ages. Geochemical data indicate a tholeiitic basalt composition with low MgO (4-7 wt%) within-plate character based on trace element classification diagrams and source between E-MORB and OIB with only minor contamination from crust or metasomatized lithospheric mantle. Two subgroups are distinguished: Group 1 has gently sloping LREE ((La/Sm)PM = 1.9) and HREE ((Gd/Yb)PM = 1.8) patterns, slightly negative Sr and moderate TiO2 (2.2 wt%), and Group 2 has steeper LREE ((La/Sm)PM = 2.3) and HREE ((Gd/Yb)PM = 2.3), strong negative Sr anomaly, is higher in TiO2 (2.7 wt%), and is transitional from tholeiitic to weakly alkaline in composition. The slight differences in REE slopes are consistent with Group 2 on average melting at deeper levels. Proposed reconstructions of the Kuonamka LIP with 1500 Ma magmatism of the SFC-Congo craton are supported by a geochemical comparison. Specifically, the chemistry of the Chapada Diamantina and Curaga dikes of the SFC can be linked to that of Groups 1 and 2, respectively, of the Kuonamka LIP and are consistent with a common mantle source between EMORB and OIB and subsequent differentiation history. However, the coeval Humpata sills and dikes of the Angola block of the Congo craton represent a different magma batch

    Identification and Characterization of Full-Length cDNAs in Channel Catfish (Ictalurus punctatus) and Blue Catfish (Ictalurus furcatus)

    Get PDF
    Background: Genome annotation projects, gene functional studies, and phylogenetic analyses for a given organism all greatly benefit from access to a validated full-length cDNA resource. While increasingly common in model species, fulllength cDNA resources in aquaculture species are scarce. Methodology and Principal Findings: Through in silico analysis of catfish (Ictalurus spp.) ESTs, a total of 10,037 channel catfish and 7,382 blue catfish cDNA clones were identified as potentially encoding full-length cDNAs. Of this set, a total of 1,169 channel catfish and 933 blue catfish full-length cDNA clones were selected for re-sequencing to provide additional coverage and ensure sequence accuracy. A total of 1,745 unique gene transcripts were identified from the full-length cDNA set, including 1,064 gene transcripts from channel catfish and 681gene transcripts from blue catfish, with 416 transcripts shared between the two closely related species. Full-length sequence characteristics (ortholog conservation, UTR length, Kozak sequence, and conserved motifs) of the channel and blue catfish were examined in detail. Comparison of gene ontology composition between full-length cDNAs and all catfish ESTs revealed that the full-length cDNA set is representative of the gene diversity encoded in the catfish transcriptome. Conclusions: This study describes the first catfish full-length cDNA set constructed from several cDNA libraries. The catfish full-length cDNA sequences, and data gleaned from sequence characteristics analysis, will be a valuable resource fo

    Presence of two alternative kdr-like mutations, L1014F and L1014S, and a novel mutation, V1010L, in the voltage gated Na+ channel of Anopheles culicifacies from Orissa, India

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Knockdown resistance in insects resulting from mutation(s) in the voltage gated Na<sup>+ </sup>channel (VGSC) is one of the mechanisms of resistance against DDT and pyrethroids. Recently a point mutation leading to Leu-to-Phe substitution in the VGSC at residue 1014, a most common <it>kdr </it>mutation in insects, was reported in <it>Anopheles culicifacies</it>-a major malaria vector in the Indian subcontinent. This study reports the presence of two additional amino acid substitutions in the VGSC of an <it>An. culicifacies </it>population from Malkangiri district of Orissa, India.</p> <p>Methods</p> <p><it>Anopheles culicifacies sensu lato (s.l.) </it>samples, collected from a population of Malkangiri district of Orissa (India), were sequenced for part of the second transmembrane segment of VGSC and analyzed for the presence of non-synonymous mutations. A new primer introduced restriction analysis-PCR (PIRA-PCR) was developed for the detection of the new mutation L1014S. The <it>An. culicifacies </it>population was genotyped for the presence of L1014F substitution by an amplification refractory mutation system (ARMS) and for L1014S substitutions by using a new PIRA-PCR developed in this study. The results were validated through DNA sequencing.</p> <p>Results</p> <p>DNA sequencing of <it>An. culicifacies </it>individuals collected from district Malkangiri revealed the presence of three amino acid substitutions in the IIS6 transmembrane segments of VGSC, each one resulting from a single point mutation. Two alternative point mutations, 3042A>T transversion or 3041T>C transition, were found at residue L1014 leading to Leu (TTA)-to-Phe (TTT) or -Ser (TCA) changes, respectively. A third and novel substitution, Val (GTG)-to-Leu (TTG or CTG), was identified at residue V1010 resulting from either of the two transversions–3028G>T or 3028G>C. The L1014S substitution co-existed with V1010L in all the samples analyzed irrespective of the type of point mutation associated with the latter. The PIRA-PCR strategy developed for the identification of the new mutation L1014S was found specific as evident from DNA sequencing results of respective samples. Since L1014S was found tightly linked to V1010L, no separate assay was developed for the latter mutation. Screening of population using PIRA-PCR assays for 1014S and ARMS for 1014F alleles revealed the presence of all the three amino acid substitutions in low frequency.</p> <p>Conclusions</p> <p>This is the first report of the presence of L1014S (homologous to the <it>kdr-e </it>in <it>An. gambiae</it>) and a novel mutation V1010L (resulting from G-to-T or -C transversions) in the VGSC of <it>An. culicifacies </it>in addition to the previously described mutation L1014F. The V1010L substitution was tightly linked to L1014S substitution. A new PIRA-PCR strategy was developed for the detection of L1014S mutation and the linked V1010L mutation.</p

    LTC: a novel algorithm to improve the efficiency of contig assembly for physical mapping in complex genomes

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>Physical maps are the substrate of genome sequencing and map-based cloning and their construction relies on the accurate assembly of BAC clones into large contigs that are then anchored to genetic maps with molecular markers. High Information Content Fingerprinting has become the method of choice for large and repetitive genomes such as those of maize, barley, and wheat. However, the high level of repeated DNA present in these genomes requires the application of very stringent criteria to ensure a reliable assembly with the FingerPrinted Contig (FPC) software, which often results in short contig lengths (of 3-5 clones before merging) as well as an unreliable assembly in some difficult regions. Difficulties can originate from a non-linear topological structure of clone overlaps, low power of clone ordering algorithms, and the absence of tools to identify sources of gaps in Minimal Tiling Paths (MTPs).</p> <p>Results</p> <p>To address these problems, we propose a novel approach that: (i) reduces the rate of false connections and Q-clones by using a new cutoff calculation method; (ii) obtains reliable clusters robust to the exclusion of single clone or clone overlap; (iii) explores the topological contig structure by considering contigs as networks of clones connected by significant overlaps; (iv) performs iterative clone clustering combined with ordering and order verification using re-sampling methods; and (v) uses global optimization methods for clone ordering and Band Map construction. The elements of this new analytical framework called Linear Topological Contig (LTC) were applied on datasets used previously for the construction of the physical map of wheat chromosome 3B with FPC. The performance of LTC vs. FPC was compared also on the simulated BAC libraries based on the known genome sequences for chromosome 1 of rice and chromosome 1 of maize.</p> <p>Conclusions</p> <p>The results show that compared to other methods, LTC enables the construction of highly reliable and longer contigs (5-12 clones before merging), the detection of "weak" connections in contigs and their "repair", and the elongation of contigs obtained by other assembly methods.</p

    Competitive Reporter Monitored Amplification (CMA) - Quantification of Molecular Targets by Real Time Monitoring of Competitive Reporter Hybridization

    Get PDF
    Background: State of the art molecular diagnostic tests are based on the sensitive detection and quantification of nucleic acids. However, currently established diagnostic tests are characterized by elaborate and expensive technical solutions hindering the development of simple, affordable and compact point-of-care molecular tests. Methodology and Principal Findings: The described competitive reporter monitored amplification allows the simultaneous amplification and quantification of multiple nucleic acid targets by polymerase chain reaction. Target quantification is accomplished by real-time detection of amplified nucleic acids utilizing a capture probe array and specific reporter probes. The reporter probes are fluorescently labeled oligonucleotides that are complementary to the respective capture probes on the array and to the respective sites of the target nucleic acids in solution. Capture probes and amplified target compete for reporter probes. Increasing amplicon concentration leads to decreased fluorescence signal at the respective capture probe position on the array which is measured after each cycle of amplification. In order to observe reporter probe hybridization in real-time without any additional washing steps, we have developed a mechanical fluorescence background displacement technique. Conclusions and Significance: The system presented in this paper enables simultaneous detection and quantification of multiple targets. Moreover, the presented fluorescence background displacement technique provides a generic solution fo

    SynBlast: Assisting the analysis of conserved synteny information

    Get PDF
    <p>Abstract</p> <p>Motivation</p> <p>In the last years more than 20 vertebrate genomes have been sequenced, and the rate at which genomic DNA information becomes available is rapidly accelerating. Gene duplication and gene loss events inherently limit the accuracy of orthology detection based on sequence similarity alone. Fully automated methods for orthology annotation do exist but often fail to identify individual members in cases of large gene families, or to distinguish missing data from traceable gene losses. This situation can be improved in many cases by including conserved synteny information.</p> <p>Results</p> <p>Here we present the <monospace>SynBlast</monospace> pipeline that is designed to construct and evaluate local synteny information. <monospace>SynBlast</monospace> uses the genomic region around a focal reference gene to retrieve candidates for homologous regions from a collection of target genomes and ranks them in accord with the available evidence for homology. The pipeline is intended as a tool to aid high quality manual annotation in particular in those cases where automatic procedures fail. We demonstrate how <monospace>SynBlast</monospace> is applied to retrieving orthologous and paralogous clusters using the vertebrate <it>Hox </it>and <it>ParaHox </it>clusters as examples.</p> <p>Software</p> <p>The <monospace>SynBlast</monospace> package written in <monospace>Perl</monospace> is available under the GNU General Public License at <url>http://www.bioinf.uni-leipzig.de/Software/SynBlast/</url>.</p

    Absence of knockdown resistance suggests metabolic resistance in the main malaria vectors of the Mekong region

    Get PDF
    <p>Abstract</p> <p>Background</p> <p>As insecticide resistance may jeopardize the successful malaria control programmes in the Mekong region, a large investigation was previously conducted in the Mekong countries to assess the susceptibility of the main malaria vectors against DDT and pyrethroid insecticides. It showed that the main vector, <it>Anopheles epiroticus</it>, was highly pyrethroid-resistant in the Mekong delta, whereas <it>Anopheles minimus sensu lato </it>was pyrethroid-resistant in northern Vietnam. <it>Anopheles dirus sensu stricto </it>showed possible resistance to type II pyrethroids in central Vietnam. <it>Anopheles subpictus </it>was DDT- and pyrethroid-resistant in the Mekong Delta. The present study intends to explore the resistance mechanisms involved.</p> <p>Methods</p> <p>By use of molecular assays and biochemical assays the presence of the two major insecticide resistance mechanisms, knockdown and metabolic resistance, were assessed in the main malaria vectors of the Mekong region.</p> <p>Results</p> <p>Two FRET/MCA assays and one PCR-RFLP were developed to screen a large number of <it>Anopheles </it>populations from the Mekong region for the presence of knockdown resistance (<it>kdr</it>), but no <it>kdr </it>mutation was observed in any of the study species. Biochemical assays suggest an esterase mediated pyrethroid detoxification in <it>An. epiroticus </it>and <it>An. subpictus </it>of the Mekong delta. The DDT resistance in <it>An. subpictus </it>might be conferred to a high GST activity. The pyrethroid resistance in <it>An. minimus s.l</it>. is possibly associated with increased detoxification by esterases and P450 monooxygenases.</p> <p>Conclusion</p> <p>As different metabolic enzyme systems might be responsible for the pyrethroid and DDT resistance in the main vectors, each species may have a different response to alternative insecticides, which might complicate the malaria vector control in the Mekong region.</p

    Polygenic Hyperlipidemias and Coronary Artery Disease Risk

    Get PDF
    Background:Hyperlipidemia is a highly heritable risk factor for coronary artery disease (CAD). While monogenic familial hypercholesterolemia associates with severely increased CAD risk, it remains less clear to what extent a high polygenic load of a large number of LDL (low-density lipoprotein) cholesterol (LDL-C) or triglyceride (TG)-increasing variants associates with increased CAD risk.Methods:We derived polygenic risk scores (PRSs) with approximate to 6M variants separately for LDL-C and TG with weights from a UK Biobank-based genome-wide association study with approximate to 324K samples. We evaluated the impact of polygenic hypercholesterolemia and hypertriglyceridemia to lipid levels in 27 039 individuals from the National FINRISK Study (FINRISK) cohort and to CAD risk in 135 638 individuals (13 753 CAD cases) from the FinnGen project (FinnGen).Results:In FINRISK, median LDL-C was 3.39 (95% CI, 3.38-3.40) mmol/L, and it ranged from 2.87 (95% CI, 2.82-2.94) to 3.78 (95% CI, 3.71-3.83) mmol/L between the lowest and highest 5% of the LDL-C PRS distribution. Median TG was 1.19 (95% CI, 1.18-1.20) mmol/L, ranging from 0.97 (95% CI, 0.94-1.00) to 1.55 (95% CI, 1.48-1.61) mmol/L with the TG PRS. In FinnGen, comparing the highest 5% of the PRS to the lowest 95%, CAD odds ratio was 1.36 (95% CI, 1.24-1.49) for the LDL-C PRS and 1.31 (95% CI, 1.19-1.43) for the TG PRS. These estimates were only slightly attenuated when adjusting for a CAD PRS (odds ratio, 1.26 [95% CI, 1.16-1.38] for LDL-C and 1.24 [95% CI, 1.13-1.36] for TG PRS).Conclusions:The CAD risk associated with a high polygenic load for lipid-increasing variants was proportional to their impact on lipid levels and partially overlapping with a CAD PRS. In contrast with a PRS for CAD, the lipid PRSs point to known and directly modifiable risk factors providing additional guidance for clinical translation.</div
    corecore