Multifocal Aggressive Squamous Cell Carcinomas Induced by Prolonged Voriconazole Therapy: A Case Report

Voriconazole is a treatment for severe fungal infections. Prolonged voriconazole therapy may induce skin reactions, with 1% of severe photosensitivity accidents. Recently the imputability of voriconazole in skin carcinogenesis has been suggested. This report concerns a 55-year-old man suffering from pulmonary aspergillosis who presented a phototoxic reaction a few months after introduction of voriconazole, followed by multiple squamous cell carcinomas of sun-exposed skin areas. After voriconazole discontinuation, no new carcinoma was observed. The detection of EBV and HPV in skin lesions was negative. Exploration of gene mutations involved in skin carcinogenesis showed two variants of the MICR gene. The occurrence of multiple, recurrent, aggressive squamous cell carcinomas is rare with voriconazole, but its imputability is strongly suggested. A plausible hypothesis is that several factors including voriconazole uptake, immunosuppression, and genetic background could explain the phenotype of fast-developing skin carcinomas. Voriconazole therapy should be accompanied by stringent photoprotection and skin monitoring

Nematic liquid crystal alignment on chemical patterns

Patterned Self-Assembled Monolayers (SAMs) promoting both homeotropic and planar degenerate alignment of 6CB and 9CB in their nematic phase, were created using microcontact printing of functionalised organothiols on gold films. The effects of a range of different pattern geometries and sizes were investigated, including stripes, circles and checkerboards. EvanescentWave Ellipsometry was used to study the orientation of the liquid crystal (LC) on these patterned surfaces during the isotropic-nematic phase transition. Pretransitional growth of a homeotropic layer was observed on 1 ¹m homeotropic aligning stripes, followed by a homeotropic mono-domain state prior to the bulk phase transition. Accompanying Monte-Carlo simulations of LCs aligned on nano-patterned surfaces were also performed. These simulations also showed the presence of the homeotropic mono-domain state prior to the transition.</p

Evaluating the usability of a visual feature modeling notation

International audienceFeature modeling is a popular Software Product Line Engineering (SPLE) technique used to describe variability in a product family. A usable feature modeling tool environment should enable SPLE practitioners to produce good quality models, in particular, models that effectively communicate modeled information. FAMILIAR is a text-based environment for manipulating and composing Feature Models (FMs). In this paper we present extensions we made to FAMILIAR to enhance its usability. The extensions include a visualization of FMs, or more precisely , a feature diagram rendering mechanism that supports the use of a combination of text and graphics to describe FMs, their configurations, and the results of FM analyses. We also present the results of a preliminary evaluation of the environment's usability. The evaluation involves comparing the use of the extended environment with the previous text-based console-driven version. The preliminary experiment provides some evidence that use of the new environment results in increased cognitive effectiveness of novice users and improved quality of new FMs

Vitellogenin Underwent Subfunctionalization to Acquire Caste and Behavioral Specific Expression in the Harvester Ant Pogonomyrmex barbatus

PMCID: PMC3744404This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose. The work is made available under the Creative Commons CC0 public domain dedication

Toward an MRI-based nomogram for the prediction of transperineal prostate biopsy outcome: A physician and patient decision tool

PURPOSE: To develop and internally validate a nomogram using biparametric magnetic resonance imaging (B-MRI)-derived variables for the prediction of prostate cancer at transperineal sector-guided prostate biopsy (TPSB). SUBJECTS/PATIENTS AND METHODS: Consecutive patients referred to our institution with raised prostate-specific antigen (PSA), abnormal prostate examination, or persistent suspicion of prostate cancer after previous transrectal biopsy between July 2012 and November 2015 were reviewed from a prospective database. All patients underwent prebiopsy B-MRI with T2-weighted and diffusion-weighted imaging sequences, followed by 24 to 40 core TPSB with additional targeted cores using cognitive registration. Univariable and multivariable logistic regression analysis was used to determine predictors of prostate cancer outcomes. Multivariable coefficients were used to construct 2 MRI-based nomograms to predict any and significant (Gleason 4 or maximum cancer core length ≥6mm) prostate cancer at TPSB. Bootstrap resamples were used for internal validation. Accuracy was assessed by calculating the concordance index. RESULTS: In total, 615 men were included in the study. Prostate cancer was diagnosed in 317 (51.5%) men with significant cancer diagnosed in 237 (38.5%) men. Age, Prostate Imaging Reporting and Data System (PI-RADS) score, PSA, PSA density, and primary biopsy were predictors of prostate cancer at TPSB on univariable analysis (P<0.0001). PSA showed strong correlation with PSA density and was excluded. The remaining variables were all independent predictors of prostate cancer on multivariable analysis (P<0.0001) and used to generate the nomograms. Both nomograms showed good discrimination for prostate cancer, with a concordance index of 87% for any cancer and 92% for significant disease. Using a nomogram-derived probability threshold of<15%, 111 (18.0%) biopsies can be saved, at the expense of 3 missed significant prostate cancers. CONCLUSIONS: These internally validated MR-based nomograms were able to accurately predict TPSB outcomes for prostate cancer, especially significant disease. Our findings support the combination of prebiopsy MRI results and clinical factors as part of the biopsy decision-making process

The “Is mpMRI Enough” or IMRIE Study: A Multicentre Evaluation of Prebiopsy Multiparametric Magnetic Resonance Imaging Compared with Biopsy

Background: Multiparametric magnetic resonance imaging (mpMRI) is now recommended prebiopsy in numerous healthcare regions based on the findings of high-quality studies from expert centres. Concern remains about reproducibility of mpMRI to rule out clinically significant prostate cancer (csPCa) in real-world settings. / Objective: To assess the diagnostic performance of mpMRI for csPCa in a real-world setting. / Design, setting, and participants: A multicentre, retrospective cohort study, including men referred with raised prostate-specific antigen (PSA) or an abnormal digital rectal examination who had undergone mpMRI followed by transrectal or transperineal biopsy, was conducted. Patients could be biopsy naïve or have had previous negative biopsies. / Outcome measurements and statistical analysis: The primary definition for csPCa was International Society of Urological Pathology (ISUP) grade group (GG) ≥2 (any Gleason ≥7); the accuracy for other definitions was also evaluated. / Results and limitations: Across ten sites, 2642 men were included (January 2011–November 2018). Mean age and PSA were 65.3 yr (standard deviation [SD] 7.8 yr) and 7.5 ng/ml (SD 3.3 ng/ml), respectively. Of the patients, 35.9% had “negative MRI” (scores 1–2); 51.9% underwent transrectal biopsy and 48.1% had transperineal biopsy, with 43.4% diagnosed with csPCa overall. The sensitivity and negative predictive value (NPV) for ISUP GG ≥ 2 were 87.3% and 87.5%, respectively. The NPVs were 87.4% and 88.1% for men undergoing transrectal and transperineal biopsy, respectively. Specificity and positive predictive value of MRI were 49.8% and 49.2%, respectively. The sensitivity and NPV increased to 96.6% and 90.6%, respectively, when a PSA density threshold of 0.15 ng/ml/ml was used in MRI scores 1–2; these metrics increased to 97.5% and 91.2%, respectively, for PSA density 0.12 ng/ml/ml. ISUP GG ≥ 3 (Gleason ≥4 + 3) was found in 2.4% (15/617) of men with MRI scores 1–2. They key limitations of this study are the heterogeneity and retrospective nature of the data. / Conclusions: Multiparametric MRI when used in real-world settings is able to rule out csPCa accurately, suggesting that about one-third of men might avoid an immediate biopsy. Men should be counselled about the risk of missing some significant cancers. / Patient summary: Multiparametric magnetic resonance imaging (MRI) is a useful tool for ruling out prostate cancer, especially when combined with prostate-specific antigen density (PSAD). Previous results published from specialist centres can be reproduced at smaller institutions. However, patients and their clinicians must be aware that an early diagnosis of clinically significant prostate cancer could be missed in nearly 10% of patients by relying on MRI and PSAD alone

Involvement of the V2 Vasopressin Receptor in Adaptation to Limited Water Supply

Mammals adapted to a great variety of habitats with different accessibility to water. In addition to changes in kidney morphology, e.g. the length of the loops of Henle, several hormone systems are involved in adaptation to limited water supply, among them the renal-neurohypophysial vasopressin/vasopressin receptor system. Comparison of over 80 mammalian V2 vasopressin receptor (V2R) orthologs revealed high structural and functional conservation of this key component involved in renal water reabsorption. Although many mammalian species have unlimited access to water there is no evidence for complete loss of V2R function indicating an essential role of V2R activity for survival even of those species. In contrast, several marsupial V2R orthologs show a significant increase in basal receptor activity. An increased vasopressin-independent V2R activity can be interpreted as a shift in the set point of the renal-neurohypophysial hormone circuit to realize sufficient water reabsorption already at low hormone levels. As found in other desert mammals arid-adapted marsupials show high urine osmolalities. The gain of basal V2R function in several marsupials may contribute to the increased urine concentration abilities and, therefore, provide an advantage to maintain water and electrolyte homeostasis under limited water supply conditions

Genomic Organization and Evolution of the Vomeronasal Type 2 Receptor-Like (OlfC) Gene Clusters in Atlantic Salmon, Salmo salar

There are three major multigene superfamilies of olfactory receptors (OR, V1R, and V2R) in mammals. The ORs are expressed in the main olfactory organ, whereas the V1Rs and V2Rs are located in the vomeronasal organ. Fish only possess one olfactory organ in each nasal cavity, the olfactory rosette; therefore, it has been proposed that their V2R-like genes be classified as olfactory C family G protein-coupled receptors (OlfC). There are large variations in the sizes of OR gene repertoires. Previous studies have shown that fish have between 12 and 46 functional V2R-like genes, whereas humans have lost all functional V2Rs, and frog sp. have more than 240. Pseudogenization of V2R genes is a prevalent event across species. In the mouse and frog genomes, there are approximately double the number of pseudogenes compared with functional genes. An oligonucleotide probe was designed from a conserved sequence from four Atlantic salmon OlfC genes and used to screen the Atlantic salmon bacterial artificial chromosome (BAC) library. Hybridization-positive BACs were matched to fingerprint contigs, and representative BACs were shotgun cloned and sequenced. We identified 55 OlfC genes. Twenty-nine of the OlfC genes are classified as putatively functional genes and 26 as pseudogenes. The OlfC genes are found in two genomic clusters on chromosomes 9 and 20. Phylogenetic analysis revealed that the OlfC genes could be divided into 10 subfamilies, with nine of these subfamilies corresponding to subfamilies found in other teleosts and one being salmon specific. There is also a large expansion in the number of OlfC genes in one subfamily in Atlantic salmon. Subfamily gene expansions have been identified in other teleosts, and these differences in gene number reflect species-specific evolutionary requirements for olfaction. Total RNA was isolated from the olfactory epithelium and other tissues from a presmolt to examine the expression of the odorant genes. Several of the putative OlfC genes that we identified are expressed only in the olfactory epithelium, consistent with these genes encoding odorant receptors

Transperineal prostate biopsies for diagnosis of prostate cancer are well tolerated: a prospective study using patient-reported outcome measures

We aimed to determine short-term patient-reported outcomes in men having general anesthetic transperineal (TP) prostate biopsies. A prospective cohort study was performed in men having a diagnostic TP biopsy. This was done using a validated and adapted questionnaire immediately post-biopsy and at follow-up of between 7 and 14 days across three tertiary referral hospitals with a response rate of 51.6%. Immediately after biopsy 43/201 (21.4%) of men felt light-headed, syncopal, or suffered syncope. Fifty-three percent of men felt discomfort after biopsy (with 95% scoring <5 in a 0-10 scale). Twelve out of 196 men (6.1%) felt pain immediately after the procedure. Despite a high incidence of symptoms (e.g., up to 75% had some hematuria, 47% suffered some pain), it was not a moderate or serious problem for most, apart from hemoejaculate which 31 men suffered. Eleven men needed catheterization (5.5%). There were no inpatient admissions due to complications (hematuria, sepsis). On repeat questioning at a later time point, only 25/199 (12.6%) of men said repeat biopsy would be a significant problem despite a significant and marked reduction in erectile function after the procedure. From this study, we conclude that TP biopsy is well tolerated with similar side effect profiles and attitudes of men to repeat biopsy to men having TRUS biopsies. These data allow informed counseling of men prior to TP biopsy and a benchmark for tolerability with local anesthetic TP biopsies being developed for clinical use.Boris Hadaschik received funding from the German Research Foundation and the European Foundation for Urology. Karan Wadhwa is sponsored by a Medical Research Council Research Training Fellowship. No other funding was received for this work