Ultrasensitive quantification of cardiac troponin I by a Single Molecule Counting method: analytical validation and biological features.

AIM: To evaluate analytical and biological characteristics of the Singulex Clarity® cTnI assay, based upon Single Molecule Counting technology. METHODS: Assay's analytical sensitivity, precision, linearity, hook effect, cross-reactivity or interference by endogenous and exogenous substances, stability, 99th reference percentile [p99th] in EDTA plasma were evaluated in single or multi-site studies. RESULTS: Detection limit was 0.12 ng/L. Sensitivity was 0.14 ng/L at 20% CV (functional sensitivity) and 0.53 ng/L at 10% CV. Imprecision was 3.16%-10.0% in a multi-lot, single-site study, and 5.5%-12.0% in a single-lot, multi-site study; assay was linear from 0.08 to 25,000 ng/L. No hook effect was observed; any cross-reactivity/interference exceeded the 10%. Healthy subjects were recruited using clinical history, normal NT-proBNP and eGFR (n = 560) or plasma creatinine (n = 535) as inclusion criteria. cTnI was detectable in 96.8% of healthy subjects. The p99th were 8.01 (eGFR used) and 8.15 ng/L (plasma creatinine); both were measured with ≤5.7% CV. Median cTnI were significantly higher in older and male than in young and female subjects. CONCLUSIONS: The Singulex Clarity cTnI assay show analytical features and % detection in healthy subjects that improve the corresponding values of most of the existing high-sensitivity cTnI assays.

Systematic Transcreation of Self-Help Smoking Cessation Materials for Hispanic/Latino Smokers: Improving Cultural Relevance and Acceptability.

Smoking-related illnesses are the leading causes of death among Hispanics/Latinos. Yet, there are few smoking cessation interventions targeted for this population. The goal of this study was to "transcreate" an existing, previously validated, English language self-help smoking cessation intervention, titled Forever Free®: Stop Smoking for Good, for Spanish-speaking smokers. Rather than simply translating the materials, our transcreation process involved culturally adapting the intervention to enhance acceptability and receptivity of the information. We utilized a multiphase qualitative approach (focus groups and learner verification interviews) to develop a linguistically and culturally relevant intervention for the diverse sub-ethnic groups of Hispanic/Latino smokers. Focus group findings indicated a need to underscore several additional cultural characteristics and themes such as the need to address familism and unique stressors faced by immigrants and to provide information regarding nicotine replacement therapy. Learner verification findings indicated a need to further emphasize financial and social benefits of quitting smoking and to discuss how family and friends can support the quit attempt. These steps led to the development of a Spanish-language smoking cessation intervention titled, Libre del cigarillo, por mi familia y por mí: Guía para dejar de fumar, that is currently being tested in a national randomized controlled trial.

Computationally efficient methodology for atomic-level characterization of dendrimer-drug complexes: a comparison of amine- and acetyl-terminated PAMAM.

PAMAM dendrimers have been widely studied as a novel means for controlled drug delivery; however, computational study of dendrimer-drug complexation is made difficult by the conformational flexibility of dendrimers and the nonspecific nature of the dendrimer-drug interactions. Conventional protocols for studying drug binding have been designed primarily for protein substrates, and, therefore, there is a need to establish new protocols to deal with the unique aspects of dendrimers. In this work, we generate cavities in generation-5 polyamidoamine (PAMAM) dendrimers at selected distances from the center of mass of the dendrimer for the insertion of the model drug: dexamethasone 21-phosphate or Dp21. The complexes are then allowed to equilibrate with distance between centers of mass of the drug and dendrimers confined to selected ranges; the free energy of complexation is estimated by the MM-GBSA (MM, molecular mechanics; GB, generalized Born; SA, surface area) method. For both amine- and modified acetyl-terminated PAMAM at both low and neutral pH, the most favorable free energy of complexation is associated with Dp21 at distance of 15-20 Å from the center of mass of the dendrimer and that smaller or larger distances yield considerably weaker affinity. In agreement with experimental results, we find acetyl-terminated PAMAM at neutral pH to form the least stable complex with Dp21. The greatest affinity is seen in the case of acetyl-terminated PAMAM at low pH, which appears to be due a complex balance of different contributions, which cannot be attributed to electrostatics, van der Waals interactions, hydrogen bonds, or charge-charge interactions alone.