Protective effects of antiâ C5a peptide antibodies in experimental sepsis

We evaluated antibodies to different peptide regions of rat C5a in the sepsis model of cecal ligation and puncture (CLP) for their protective effects in rats. Rabbit polyclonal antibodies were developed to the following peptide regions of rat C5a: aminoâ terminal region (A), residues 1â 16; middle region (M), residues 17â 36; and the carboxylâ terminal region (C), residues 58â 77. With rat neutrophils, the chemotactic activity of rat C5a was significantly inhibited by antibodies with the following rank order: antiâ C > antiâ M â « antiâ A. In vivo, antibodies to the M and C (but not A) regions of C5a were protective in experimental sepsis, as determined by survival over a 10â day period, in a doseâ dependent manner. The relative protective efficacies of antiâ C5a preparations (in descending order of efficacy) were antiâ C â ¥ antiâ M â « antiâ A. In CLP rats, a delay in infusion of antibodies, which were injected at 6 or 12 h after CLP, still resulted in significant improvement in survival rates. These in vivo and in vitro data suggest that there are optimal targets on C5a for blockade during sepsis and that delayed infusion of antiâ C5a antibody until after onset of clinical evidence of sepsis still provides protective effects.Peer Reviewedhttps://deepblue.lib.umich.edu/bitstream/2027.42/154417/1/fsb2fj000653fje-sup-0001.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154417/2/fsb2fj000653fje.pdfhttps://deepblue.lib.umich.edu/bitstream/2027.42/154417/3/fsb2fj000653fje-sup-0002.pd

Applying the ALARA concept to the evaluation of vesicoureteric reflux

The voiding cystourethrogram (VCUG) is a widely used study to define lower urinary tract anatomy and to diagnose vesicoureteric reflux (VUR) in children. We examine the technical advances in the VCUG and other examinations for reflux that have reduced radiation exposure of children, and we give recommendations for the use of imaging studies in four groups of children: (1) children with urinary tract infection, (2) siblings of patients with VUR, (3) infants with antenatal hydronephrosis (ANH), and (4) children with a solitary functioning kidney. By performing examinations with little to no radiation, carefully selecting only the children who need imaging studies and judiciously timing follow-up examinations, we can reduce the radiation exposure of children being studied for reflux

FungalRV: adhesin prediction and immunoinformatics portal for human fungal pathogens

<p>Abstract</p> <p>Background</p> <p>The availability of sequence data of human pathogenic fungi generates opportunities to develop Bioinformatics tools and resources for vaccine development towards benefitting at-risk patients.</p> <p>Description</p> <p>We have developed a fungal adhesin predictor and an immunoinformatics database with predicted adhesins. Based on literature search and domain analysis, we prepared a positive dataset comprising adhesin protein sequences from human fungal pathogens <it>Candida albicans, Candida glabrata, Aspergillus fumigatus, Coccidioides immitis, Coccidioides posadasii, Histoplasma capsulatum, Blastomyces dermatitidis, Pneumocystis carinii, Pneumocystis jirovecii and Paracoccidioides brasiliensis</it>. The negative dataset consisted of proteins with high probability to function intracellularly. We have used 3945 compositional properties including frequencies of mono, doublet, triplet, and multiplets of amino acids and hydrophobic properties as input features of protein sequences to Support Vector Machine. Best classifiers were identified through an exhaustive search of 588 parameters and meeting the criteria of best Mathews Correlation Coefficient and lowest coefficient of variation among the 3 fold cross validation datasets. The "FungalRV adhesin predictor" was built on three models whose average Mathews Correlation Coefficient was in the range 0.89-0.90 and its coefficient of variation across three fold cross validation datasets in the range 1.2% - 2.74% at threshold score of 0. We obtained an overall MCC value of 0.8702 considering all 8 pathogens, namely, <it>C. albicans, C. glabrata, A. fumigatus, B. dermatitidis, C. immitis, C. posadasii, H. capsulatum </it>and <it>P. brasiliensis </it>thus showing high sensitivity and specificity at a threshold of 0.511. In case of <it>P. brasiliensis </it>the algorithm achieved a sensitivity of 66.67%. A total of 307 fungal adhesins and adhesin like proteins were predicted from the entire proteomes of eight human pathogenic fungal species. The immunoinformatics analysis data on these proteins were organized for easy user interface analysis. A Web interface was developed for analysis by users. The predicted adhesin sequences were processed through 18 immunoinformatics algorithms and these data have been organized into MySQL backend. A user friendly interface has been developed for experimental researchers for retrieving information from the database.</p> <p>Conclusion</p> <p>FungalRV webserver facilitating the discovery process for novel human pathogenic fungal adhesin vaccine has been developed.</p

Medicatie minderen bij ouderem meningen van patient, apotheker en huisarts vergeleken

OBJECTIVE: To study the opinion of elderly patients with polypharmacy regarding their medication and to study the differences in valuation of this medication between patient, Community pharmacist and general practitioner (GP). DESIGN Interviews and questionnaires. METHODS: Patients with 7 or more chronically used drugs were interviewed with the Patients Attitudes Towards Deprescribing questionnaire. Furthermore patients were asked to name their medication by heart, to rate the assumed importance of each currently used drug on a numeric rating scale (0-10) and to name three drugs they wanted to continue as well as three drugs they would prefer to stop. These last two questions were also presented to their GPs and Community pharmacists. RESULTS: 40 patients (mean age 79 years, average 11 drugs) were interviewed. The median number of drugs spontaneously recalled by name by the patient was 2. Though 85% of the patients believes all used drugs are necessary, 98% of them stated they would like to stop drugs if the GP said it was possible. Patients scored the importance of their drugs slightly higher than pharmacists or GPs (mean score: 7,5 versus 6,7 versus 6,9). Rating of importance for all groups seemed not to be based on comparison of numbers needed to treat. CONCLUSION: Patients consider their current medication useful and necessary, but almost all of them are Willing to stop some drugs. Their spontaneous knowledge of the drugs used seems low. Before performing medication reviews, GPs and pharmacists should test the patients' knowledge and provide them with Information necessary for making the right decisions

Impaired executive functions in Duchenne muscular dystrophy in a Brazilian cohort

Duchenne Muscular Dystrophy (DMD) is a severe, progressive neuromuscular disorder caused by mutations in the DMD gene which codes for dystrophin and is associated with a wide spectrum of developmental cognitive disabilities. Here, a cohort of Brazilian DMD and healthy boys (N = 62) was recruited to investigate the link between mutations on the DMD gene and spatial working memory, associative learning, set-shifting, and planning performance. The findings showed that executive functioning was significantly affected by the absence of the full-length DMD gene product Dp427. Although a larger cohort is needed to confirm initial findings, mutations on the dystrophin gene upstream exon 45 had little impact, while mutations downstream exon 45, especially affecting the expression of the DMD gene product Dp140 and Dp71, led to severe executive dysfunction. The mapping of neurocognitive-genetic associations in DMD is essential to the understanding of developmental disorders and their relationship with mental retardation and the design of effective gene therapies targeting the restoration of DMD gene products, especially the smaller ones