Recurrent Scedosporium apiospermum mycetoma successfully treated by surgical excision and terbinafine treatment: a case report and review of the literature

Background: Scedosporium apiospermum is an emerging opportunistic filamentous fungus, which is notorious for its high levels of antifungal ‑resistance. It is able to cause localized cutaneous or subcutaneous infections in both immu‑ nocompromised and immunocompetent persons, pulmonary infections in patients with predisposing pulmonary diseases and invasive mycoses in immunocompromised patients. Subcutaneous infections caused by this fungus frequently show chronic mycetomatous manifestation. Case report: We report the case of a 70 ‑year ‑old immunocompromised man, who developed a fungal mycetoma‑ tous infection on his right leg. There was no history of trauma; the aetiological agent was identified by microscopic examination and ITS sequencing. This is the second reported case of S. apiospermum subcutaneous infections in Hungary, which was successfully treated by surgical excision and terbinafine treatment. After 7 months, the patient remained asymptomatic. Considering the antifungal susceptibility and increasing incidence of the fungus, Sce - dosporium related subcutaneous infections reported in the past quarter of century in European countries were also reviewed. Conclusions: Corticosteroid treatment represents a serious risk factor of S. apiospermum infections, especially if the patient get in touch with manure ‑enriched or polluted soil or water. Such infections have emerged several times in European countries in the past decades. The presented data suggest that besides the commonly applied voricona‑ zole, terbinafine may be an alternative for the therapy of mycetomatous Scedosporium infections

Nomograms including the UBC® Rapid test to detect primary bladder cancer based on a multicentre dataset

Objectives: To evaluate the clinical utility of the urinary bladder cancer antigen test UBC Rapid for the diagnosis of bladder cancer (BC) and to develop and validate nomograms to identify patients at high risk of primary BC. Patients and Methods: Data from 1787 patients from 13 participating centres, who were tested between 2012 and 2020, including 763 patients with BC, were analysed. Urine samples were analysed with the UBC Rapid test. The nomograms were developed using data from 320 patients and externally validated using data from 274 patients. The diagnostic accuracy of the UBC Rapid test was evaluated using receiver-operating characteristic curve analysis. Brier scores and calibration curves were chosen for the validation. Biopsy-proven BC was predicted using multivariate logistic regression. Results: The sensitivity, specificity, and area under the curve for the UBC Rapid test were 46.4%, 75.5% and 0.61 (95% confidence interval [CI] 0.58–0.64) for low-grade (LG) BC, and 70.5%, 75.5% and 0.73 (95% CI 0.70–0.76) for high-grade (HG) BC, respectively. Age, UBC Rapid test results, smoking status and haematuria were identified as independent predictors of primary BC. After external validation, nomograms based on these predictors resulted in areas under the curve of 0.79 (95% CI 0.72–0.87) and 0.95 (95% CI: 0.92–0.98) for predicting LG-BC and HG-BC, respectively, showing excellent calibration associated with a higher net benefit than the UBC Rapid test alone for low and medium risk levels in decision curve analysis. The R Shiny app allows the results to be explored interactively and can be accessed at www.blucab-index.net. Conclusion: The UBC Rapid test alone has limited clinical utility for predicting the presence of BC. However, its combined use with BC risk factors including age, smoking status and haematuria provides a fast, highly accurate and non-invasive tool for screening patients for primary LG-BC and especially primary HG-BC

Set optimization - a rather short introduction

Recent developments in set optimization are surveyed and extended including various set relations as well as fundamental constructions of a convex analysis for set- and vector-valued functions, and duality for set optimization problems. Extensive sections with bibliographical comments summarize the state of the art. Applications to vector optimization and financial risk measures are discussed along with algorithmic approaches to set optimization problems

Toksični učinci patulina na timus mužjaka štakora u razvoju

Patulin is a mycotoxin produced by several Penicillium, Aspergillus, and Byssachlamys species growing on food products. In this study, we investigated the effects of patulin on the thymus of growing male rats aged fi ve to six weeks. The rats were receiving it orally at a dose of 0.1 mg kg-1 bw a day for either 60 or 90 days. At the end of the experiment, the thymus was examined for histopathology by light microscopy and for epidermal growth factor (EGF) and its receptor (EGFR) by immunolocalisation. For morphometry we used the Bs200prop program to analyse images obtained with the Olympus BX51 light microscope. Cell ultrastructure was studied by electron microscopy. In rats treated with patulin, the thymus showed haemorrhage, plasma cell hyperplasia, a dilation and fi brosis in the cortex, enlarged interstitial tissue between the thymic lobules, enlarged fat tissue, thinning of the cortex, and blurring of the cortico-medullary demarcation. Electron microscopy showed signs of cell destruction, abnormalities of the nucleus and organelles, and loss of mitochondrial cristae. However, no differences were observed in thymus EGF and EGFR immunoreactivity between treated and control rats.Patulin je mikotoksin koji proizvode plijesni sojeva Penicillium, Aspergillus i Byssachlamys na različitim prehrambenim proizvodima kao podlozi. Učinke patulina istražili smo na timusu mužjaka štakora u razvoju (dobi 5 do 6 tjedana). Mikotoksin je životinjama davan per os u dnevnoj dozi 0,1 mg kg-1 tj. t. 60 odnosno 90 dana. Na kraju pokusa štakori su žrtvovani, timus je podvrgnut histološkim analizama s pomoću svjetlosne mikroskopije, a imunocitokemijskim je metodama istražena stanična lokalizacija epidermalnog faktora rasta (EGF) i njegova receptora (EGFR). Morfometrijska analiza provedena je s pomoću računalnog programa Bs200prop povezanog u sustav sa svjetlosnim mikroskopom Olympus BX51. Elektronskomikroskopski je istražena ultrastruktura stanica timusa. Utvrđeno je da patulin izaziva krvaranja u timusu, hiperplaziju plazma-stanica, dilataciju i fi brozu u kortikalnoj regiji timusa, širenje intersticijskog tkiva između režnjeva timusa, povećanje masnih stanica, smanjenje debljine kore timusa te nestanak kortiko-medularne demarkacije. Elektronskomikroskopski u tkivu timusa štakora tretiranih patulinom uočeni su znakovi raspadanja stanica, abnormalnosti jezgre i organela te gubitak mitohondrijskih krista. Unatoč navedenomu, na presjecima tkiva kontrolnih štakora i štakora tretiranih patulinom nismo utvrdili razlike u imunoreaktivnosti EGF i EGFR, što bi trebalo dodatno istražiti osjetljivijim molekularnim metodama

A Comprehensive Sequence and Disease Correlation Analyses for the C-Terminal Region of CagA Protein of Helicobacter pylori

Chronic Helicobacter pylori infection is known to be associated with the development of peptic ulcer, gastric cancer and gastric lymphoma. Currently, the bacterial factors of H. pylori are reported to be important in the development of gastroduodenal diseases. CagA protein, encoded by the cagA, is the best studied virulence factor of H. pylori. The pathogenic CagA protein contains a highly polymorphic Glu-Pro-Ile-Tyr-Ala (EPIYA) repeat region in the C-terminal. This repeat region is reported to be involved in the pathogenesis of gastroduodenal diseases. The segments containing EPIYA motifs have been designated as segments A, B, C, and D; however the classification and disease relation are still unclear. This study used 560 unique CagA sequences containing 1,796 EPIYA motifs collected from public resources, including 274 Western and 286 East Asian strains with clinical data obtained from 433 entries. Fifteen types of EPIYA or EPIYA-like sequences are defined. In addition to four previously reported major segment types, several minor segment types (e.g., segment B′, B′′) and more than 30 sequence types (e.g., ABC, ABD) were defined using our classification method. We confirm that the sequences from Western and East Asian strains contain segment C and D, respectively. We also confirm that strains with two EPIYA segment C have a greater chance of developing gastric cancer than those with one segment C. Our results shed light on the relationships between the types of CagAs, the country of origin of each sequence type, and the frequency of gastric disease

Helicobacter pylori Perturbs Iron Trafficking in the Epithelium to Grow on the Cell Surface

Helicobacter pylori (Hp) injects the CagA effector protein into host epithelial cells and induces growth factor-like signaling, perturbs cell-cell junctions, and alters host cell polarity. This enables Hp to grow as microcolonies adhered to the host cell surface even in conditions that do not support growth of free-swimming bacteria. We hypothesized that CagA alters host cell physiology to allow Hp to obtain specific nutrients from or across the epithelial barrier. Using a polarized epithelium model system, we find that isogenic ΔcagA mutants are defective in cell surface microcolony formation, but exogenous addition of iron to the apical medium partially rescues this defect, suggesting that one of CagA's effects on host cells is to facilitate iron acquisition from the host. Hp adhered to the apical epithelial surface increase basolateral uptake of transferrin and induce its transcytosis in a CagA-dependent manner. Both CagA and VacA contribute to the perturbation of transferrin recycling, since VacA is involved in apical mislocalization of the transferrin receptor to sites of bacterial attachment. To determine if the transferrin recycling pathway is involved in Hp colonization of the cell surface, we silenced transferrin receptor expression during infection. This resulted in a reduced ability of Hp to colonize the polarized epithelium. To test whether CagA is important in promoting iron acquisition in vivo, we compared colonization of Hp in iron-replete vs. iron-deficient Mongolian gerbils. While wild type Hp and ΔcagA mutants colonized iron-replete gerbils at similar levels, ΔcagA mutants are markedly impaired in colonizing iron-deficient gerbils. Our study indicates that CagA and VacA act in concert to usurp the polarized process of host cell iron uptake, allowing Hp to use the cell surface as a replicative niche

Antimicrobial resistance (AMR) nanomachines: mechanisms for fluoroquinolone and glycopeptide recognition, efflux and/or deactivation

In this review, we discuss mechanisms of resistance identified in bacterial agents Staphylococcus aureus and the enterococci towards two priority classes of antibiotics—the fluoroquinolones and the glycopeptides. Members of both classes interact with a number of components in the cells of these bacteria, so the cellular targets are also considered. Fluoroquinolone resistance mechanisms include efflux pumps (MepA, NorA, NorB, NorC, MdeA, LmrS or SdrM in S. aureus and EfmA or EfrAB in the enterococci) for removal of fluoroquinolone from the intracellular environment of bacterial cells and/or protection of the gyrase and topoisomerase IV target sites in Enterococcus faecalis by Qnr-like proteins. Expression of efflux systems is regulated by GntR-like (S. aureus NorG), MarR-like (MgrA, MepR) regulators or a two-component signal transduction system (TCS) (S. aureus ArlSR). Resistance to the glycopeptide antibiotic teicoplanin occurs via efflux regulated by the TcaR regulator in S. aureus. Resistance to vancomycin occurs through modification of the D-Ala-D-Ala target in the cell wall peptidoglycan and removal of high affinity precursors, or by target protection via cell wall thickening. Of the six Van resistance types (VanA-E, VanG), the VanA resistance type is considered in this review, including its regulation by the VanSR TCS. We describe the recent application of biophysical approaches such as the hydrodynamic technique of analytical ultracentrifugation and circular dichroism spectroscopy to identify the possible molecular effector of the VanS receptor that activates expression of the Van resistance genes; both approaches demonstrated that vancomycin interacts with VanS, suggesting that vancomycin itself (or vancomycin with an accessory factor) may be an effector of vancomycin resistance. With 16 and 19 proteins or protein complexes involved in fluoroquinolone and glycopeptide resistances, respectively, and the complexities of bacterial sensing mechanisms that trigger and regulate a wide variety of possible resistance mechanisms, we propose that these antimicrobial resistance mechanisms might be considered complex ‘nanomachines’ that drive survival of bacterial cells in antibiotic environments