Analytical Validation of Cxbladder Detect, Triage, and Monitor: Assays for Detection and Management of Urothelial Carcinoma.

: Cxbladder assays are reverse transcription-quantitative polymerase chain reaction (RT-qPCR) tests incorporating five genetic biomarkers (, , , , and ) to provide risk stratification for urothelial carcinoma (UC) in patients with hematuria or undergoing surveillance for recurrent disease. This study evaluated the analytical validity of the Cxbladder Detect, Triage, and Monitor assays. Pre-specified acceptance criteria, including the assays' fundamental aspects (sample and reagent stability, RNA extraction quality, RT-qPCR linearity, and analytical sensitivity and specificity), accuracy and precision, and reproducibility between laboratories.

Guidance on Mitigating the Risk of Transmitting Respiratory Infections During Nebulization by the COPD Foundation Nebulizer Consortium.

Background: Nebulizers are used commonly for inhaled drug delivery. Because they deliver medication through aerosol generation, clarification is needed on what constitutes safe aerosol delivery in infectious respiratory disease settings. The COVID-19 pandemic highlighted the importance of understanding the safety and potential risks of aerosol-generating procedures.

The Role of Suboptimal Concentrations of Nebulized Tobramycin in Driving Antimicrobial Resistance in Isolates in Cystic Fibrosis.

Background: Antimicrobial resistance in may be driven by exposure to suboptimal concentrations of tobramycin antibiotic delivered by less efficient nebulizers.

Methods: isolates (no. = 114; 32 first + 82 chronic) were challenged in vitro employing extrapolated peak and trough concentrations of tobramycin inhalation solution (TIS), corresponding to 3 nebulizers: Pari LC Plus, Sidestream12NEB400, and MistyNeb2035G.

A multigene urine test for the detection and stratification of bladder cancer in patients presenting with hematuria.

Purpose: We investigated whether the RNA assay uRNA® and its derivative Cxbladder® have greater sensitivity for the detection of bladder cancer than cytology, NMP22™ BladderChek™ and NMP22™ ELISA, and whether they are useful in risk stratification.

Materials And Methods: A total of 485 patients presenting with gross hematuria but without a history of urothelial cancer were recruited prospectively from 11 urology clinics in Australasia. Voided urine samples were obtained before cystoscopy.

Development of a multiplex RNA urine test for the detection and stratification of transitional cell carcinoma of the bladder.

Purpose: New markers that enable the percentage of transitional cell carcinomas (TCC) of the bladder that are diagnosed before invasion of the bladder muscle layers to be increased would reduce the morbidity and mortality associated with this disease. The purpose of this study was to develop a simple, accurate urine test based on mRNA markers and simple gene signatures that (a) could detect TCC before muscle invasion while maintaining high specificity in patients with hematuria or urinary tract infections and (b) identify patients most likely to have grade 3 or stage > or =T1 disease.

Experimental Design: RNA markers with high overexpression in stage Ta tumors and/or T1 to T4 tumors but low expression in blood or inflammatory cells were characterized by quantitative reverse transcription-PCR using 2 mL of voided urine from 75 TCC patients and 77 control patients with other urological diseases.

Differential effects of RU486 reveal distinct mechanisms for glucocorticoid repression of prostaglandin E release.

In A549 pulmonary cells, the dexamethasone- and budesonide-dependent repression of interleukin-1beta-induced prostaglandin E2 release was mimicked by the steroid antagonist, RU486. Conversely, whereas dexamethasone and budesonide were highly effective inhibitors of interleukin-1beta-induced cyclooxygenase (COX)/prostaglandin E synthase (PGES) activity and COX-2 expression, RU486 (<1 microm) was a poor inhibitor, but was able to efficiently antagonize the effects of dexamethasone and budesonide. In addition, both dexamethasone and RU486 repressed [3H]arachidonate release, which is consistent with an effect at the level of phospholipase A2 activity.

Inhibitors of protein kinase C (PKC) prevent activated transcription: role of events downstream of NF-kappaB DNA binding.

In pulmonary A549 cells, the protein kinase C (PKC) inhibitor, Ro 31-8220, and the phosphotidylcholine-specific phospholipase C inhibitor, D609, prevent NF-kappaB-dependent transcription, yet NF-kappaB DNA binding is unaffected (Bergmann, M., Hart, L., Lindsay, M.

ICAM-1 expression is highly NF-kappaB-dependent in A549 cells. No role for ERK and p38 MAPK.

The transcription factor nuclear factor kappaB (NF-kappaB) is an activator of multiple cytokines, chemokines and adhesion molecules, which are important in inflammatory diseases such as asthma, and is consequently considered as an attractive therapeutic target. In the present study, a constitutively active dominant version of IkappaBalpha, IkappaBalphaDN, was introduced into A549 pulmonary cells by adenovirus-mediated delivery. The dominant IkappaB, but not a null viral vector, prevented the induction of NF-kappaB-dependent transcription by both tumor necrosis factor alpha (TNFalpha) and interleukin-1beta (IL-1beta).

Adenovirus-mediated delivery and expression of a cAMP-dependent protein kinase inhibitor gene to BEAS-2B epithelial cells abolishes the anti-inflammatory effects of rolipram, salbutamol, and prostaglandin E2: a comparison with H-89.

cAMP-elevating drugs are thought to mediate their biological effects by activating the cAMP/cAMP-dependent protein kinase (PKA) cascade. However, this hypothesis is difficult to confirm due to a lack of selective inhibitors. Here, we have probed the role of PKA in mediating inhibitory effects of several cAMP-elevating drugs in BEAS-2B epithelial cells using an adenovirus vector encoding a PKA inhibitor protein (PKIalpha) and have compared it to H-89, a commonly used small molecule PKA inhibitor.

IL-1beta-dependent activation of NF-kappaB mediates PGE2 release via the expression of cyclooxygenase-2 and microsomal prostaglandin E synthase.

Prostaglandin (PG) E2 release is induced in pulmonary A549 cells by the NF-kappaB-activating stimuli interleukin-1beta (IL-1beta) and phorbol 12-myristate 13-acetate (PMA). Adenoviral over-expression of IkappaBalphaDeltaN, a dominant NF-kappaB inhibitor, prevents NF-kappaB-dependent transcription and was used to qualify the role of NF-kappaB in the release of PGE2. IkappaBalphaDeltaN repressed IL-1beta-induced, but not PMA-induced, cycloxygenase-2 (COX-2) and microsomal prostaglandin E synthase (mPGES) expression.