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

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

Medications That Cause Dry Mouth As an Adverse Effect in Older People : A Systematic Review and Metaanalysis

OBJECTIVES: To assess and quantify the risk of drug-induced dry mouth as a side effect in older people. DESIGN: Systematic review and meta analysis. SETTING: A search of the literature was undertaken using Medline, Embase, Cochrane, Web of Science, and PubMed from 1990 to 2016. PARTICIPANTS: Older people (aged ≥60) who participated in intervention or observational studies investigating drug use as an exposure and xerostomia or salivary gland hypofunction as adverse drug outcomes. MEASUREMENTS: Two pairs of authors screened titles and abstracts of studies for relevance. Two authors independently extracted data, including study characteristics, definitions of exposure and outcome, and methodological quality. For the metaanalyses, random-effects models were used for pooling the data and I2 statistics for exploring heterogeneity. RESULTS: Of 1,544 potentially relevant studies, 52 were deemed eligible for inclusion in the final review and 26 in meta analyses. The majority of studies were of moderate methodological quality. In the intervention studies, urological medications (odds ratio (OR) = 5.91, 95% confidence interval (CI) = 4.04–8.63; I2 = 62%), antidepressants (OR = 4.74, 95% CI = 2.69–8.32, I2 = 21%), and psycholeptics (OR = 2.59, 95% CI = 1.79–3.95, I2 = 0%) were significantly associated with dry mouth. In the observational studies, numbers of medications and several medication classes were significantly associated with xerostomia and salivary gland hypofunction

Gleason score and laterality concordance between prostate biopsy and prostatectomy specimens

Objectives: Prostate biopsy involvement and Gleason score guide treatment decisions in prostate cancer. We evaluated concordance in Gleason score and laterality between biopsy and radical retropubic prostatectomy (RRP) specimens and factors that influenced this relationship. Material and Methods: We reviewed 538 prostate cancer diagnoses at a Veterans Affairs medical center (2000-2005) to identify men with prostate biopsy and RRP specimens. During this time there was a move from limited (6 core) to extended (12 core) biopsy schemes. Discordance in Gleason score was defined as any change in Gleason score. Results: 152 men underwent RRP with biopsy showing Gleason < 7 in 56%, 7 in 36%, and > 7 in 8%. Biopsy involvement was unilateral in 59% and bilateral in 41%. Compared to the biopsy, RRP Gleason score was concordant in 76 (50%), higher in 51 (34%), and lower in 25 (16%). Bilateral involvement was concordant in 97%, while unilateral involvement was concordant in only 20%. Both Gleason score and laterality were concordant in only 26%. Gleason concordance was higher in those with 8 or more cores compared to < 8 cores taken (54% vs. 34%, p = 0.046), but concordance was not affected by age, PSA, prostate volume, or length of time from biopsy to RRP. During later years, concordance did not improve despite taking more cores. Conclusions: Prostate biopsy underestimated prostatectomy Gleason score in 34% of men and bilateral involvement in 80% of those with unilateral disease on biopsy. Taking at least eight cores improves the accuracy of the prostate biopsy