Deciphering the Multifactorial Nature of Acinetobacter baumannii Pathogenicity

Background: Acinetobacter baumannii is an emerging bacterial pathogen that causes a broad array of infections, particularly in hospitalized patients. Many studies have focused on the epidemiology and antibiotic resistance of A. baumannii, but little is currently known with respect to its virulence potential. Methodology/Principal Findings: The aim of this work was to analyze a number of virulence-related traits of four A. baumannii strains of different origin and clinical impact for which complete genome sequences were available, in order to tentatively identify novel determinants of A. baumannii pathogenicity. Clinical strains showed comparable virulence in the Galleria mellonella model of infection, irrespective of their status as outbreak or sporadic strains, whereas a non-human isolate was avirulent. A combined approach of genomic and phenotypic analyses led to the identification of several virulence factors, including exoproducts with hemolytic, phospholipase, protease and iron-chelating activities, as well as a number of multifactorial phenotypes, such as biofilm formation, surface motility and stress resistance, which were differentially expressed and could play a role in A. baumannii pathogenicity. Conclusion/Significance: This work provides evidence of the multifactorial nature of A. baumannii virulence. While A. baumannii clinical isolates could represent a selected population of strains adapted to infect the human host, subpopulations of highly genotypically and phenotypically diverse A. baumannii strains may exist outside the hospita

Incidentally Detected Focal Fundal Gallbladder Wall Thickening at Contrast-Enhanced Computed Tomography: Prevalence and Computed Tomography Features of Malignancy.

ObjectiveThe aim of this study was to determine the prevalence and computed tomography (CT) features of malignancy in incidental focal fundal gallbladder wall thickening.MethodsPatients with incidental focal fundal gallbladder wall thickening on CT were included if they had an ultrasound or magnetic resonance imaging diagnostic of the etiology (n = 19), stability on CT for 1 year (n = 84), or pathological correlation (n = 13). Morphologies were classified as type 1 (nodular/pinched intramural low attenuation), type 2 (intramural low attenuation), type 3 (homogeneous enhancement), type 4 (nodular/pinched homogeneous enhancement), type 5 (intramural cystic spaces), or type 6 (hyperenhancing/heterogeneous enhancement).ResultsOne hundred sixteen patients had the following morphologies: type 1 (n = 57), type 2 (n = 10), type 3 (n = 6), type 4 (n = 19), type 5 (n = 14), and type 6 (n = 10). Four cases (3.4%; 95% confidence interval, 0.9%-8.6%) of malignancy were identified (type 6 in 3 and type 3 in 1).ConclusionsIncidental focal fundal gallbladder wall thickening is usually benign. Computed tomography features help distinguish benign from malignant etiologies

Clinical Importance of Incidentally Detected Hyperenhancing Liver Observations on Portal Venous Phase Computed Tomography in Patients Without Known Malignancy or Liver Disease.

ObjectiveThe aim of the study was to determine the prevalence of clinically important masses among incidental hyperenhancing liver observations on portal venous phase computed tomography (CT) in patients without known malignancy or liver disease.MethodsRetrospective search of portal venous phase CTs was performed to identify hyperenhancing liver observations in patients without cancer or liver disease. Observations were assigned a morphology of homogeneous, hemangioma, or heterogeneous. The reference standard was pathology (n = 2), liver protocol CT/magnetic resonance imaging (n = 40), follow-up portal venous phase CT for 2 years or more (n = 81), or clinical follow-up for 5 years or more (n = 107).ResultsThere were no clinically important masses among 83 observations with homogeneous morphology or 110 with hemangioma morphology. There were 2 clinically important masses (1 hepatocellular carcinoma and 1 hepatic adenoma) among 37 (5.4%) heterogeneous morphology observations.ConclusionsIncidental hyperenhancing liver observations on portal venous phase CT with homogeneous or typical hemangioma morphology in patients without known cancer or liver disease are highly likely benign

Žingsniai į sėkmę

Gali būti, kad turite gerą darbą, esate perspektyvus darbuotojas, jums sekasi, nieko netrūksta ir užtikrintai kopiate karjeros laiptais. Gali būti ir atvirkščiai – kasdien stebitės kolegų sėkme (nors jie, atrodo, turi tokį pat išsilavinimą kaip ir jūs, dirba tą patį darbą) ar pavydžiai komentuojate televizijos laidų herojų laimėjimus profesiniame ir asmeniniame gyvenime. Kiekvienas sėkmės siekia (ir pasiekia) skirtingai, tačiau yra tam tikrų dėsningumų. Siūlome susipažinti su pagrindiniais iš jų. Ir visai nesvarbu, kuriai darbuotojų kategorijai priklausote, nes vieni galbūt ko nors išmoks, kiti – tiesiog prisimins.[...]Vytauto Didžiojo universiteta

Cisplatin enhances the antitumor effect of tumor necrosis factor-related apoptosis-inducing ligand gene therapy via recruitment of the mitochondria-dependent death signaling pathway

Despite adequately expressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) receptors DR4/DR5, malignant cells are frequently refractory to the cytotoxic effect of this apoptosis-inducing ligand. The susceptibility of cancer cells to TRAIL can be potentiated by cisplatin (CDDP). This study was designed to evaluate the ability of cisplatin to enhance the cytotoxic effect of TRAIL gene therapy using the recombinant adenovirus-mediated tumor-selective expression of membrane-bound green fluorescence protein (GFP)-TRAIL fusion protein (AdVgTRAIL) on thoracic cancer cells and to elucidate the putative mechanisms responsible for this synergistic combination effect. While causing little death of cultured thoracic cancer cells by itself, AdVgTRAIL in combination with CDDP, on the other hand, mediated profound supra-additive cytotoxicity and apoptosis via a strong bystander effect. CDDP/AdVgTRAIL-induced cytotoxicity was completely abrogated either by the pancaspase inhibitor zVAD-fmk or by the selective caspase 9 inhibitor or by transient knockdown of caspase 9 by siRNA, indicating that this process was caspase-mediated and mitochondria-dependent. This was confirmed by the observation that Bcl2 overexpression protected the cells from combination-induced cytotoxicity. Robust activation of caspase 8 activity in combination-treated cells was blocked by overexpression of Bcl2, indicating that caspase 8 activation was secondary to the mitochondria-mediated amplification feedback loop. Combining CDDP with AdVgTRAIL greatly enhances its tumoricidal efficacy in cultured thoracic cancer cells in vitro. The two agents interact to mediate profound activation of caspase cascade via recruitment of the mitochondria and positive feedback loop. The CDDP/AdVgTRAIL combination also exhibits a strong antitumor effect in in vivo animal model of human cancer xenografts