Matrix effect in bio-analysis of illicit drugs with LC-MS/MS: Influence of ionization type, sample preparation, and biofluid

AbstractThe purpose of the present work was to evaluate the synergistic effect of ionization type, sample preparation technique, and bio-fluid on the presence of matrix effect in quantitative liquid chromatography (LC)-MS/MS analysis of illicit drugs by post-column infusion experiments with morphine (10-μg/mL solution). Three bio-fluids (urine, oral fluid, and plasma) were pretreated with four sample preparation procedures [direct injection, dilution, protein precipitation, solid-phase extraction (SPE)] and analyzed by both LC-electrospray ionization (ESI)-MS/MS and LC-atmospheric pressure chemical ionization (APCI)-MS/MS. Our results indicated that both ionization types showed matrix effect, but ESI was more susceptible than APCI. Sample preparation could reduce (clean up) or magnify (pre-concentrate) matrix effect. Residual matrix components were specific to each bio-fluid and interfered at different time points in the chromatogram. We evaluated matrix effect in an early stage of method development and combined optimal ionization type and sample preparation technique for each bio-fluid. Simple dilution of urine was sufficient to allow for the analysis of the analytes of interest by LC-APCI-MS/MS. Acetonitrile protein precipitation provided both sample clean up and concentration for oral fluid analysis, while SPE was necessary for extensive clean up of plasma prior to LC-APCI-MS/MS

A semantic web approach for built heritage representation

In a built heritage process, meant as a structured system of activities aimed at the investigation, preservation, and management of architectural heritage, any task accomplished by the several actors involved in it is deeply influenced by the way the knowledge is represented and shared. In the current heritage practice, knowledge representation and management have shown several limitations due to the difficulty of dealing with large amount of extremely heterogeneous data. On this basis, this research aims at extending semantic web approaches and technologies to architectural heritage knowledge management in order to provide an integrated and multidisciplinary representation of the artifact and of the knowledge necessary to support any decision or any intervention and management activity. To this purpose, an ontology-based system, representing the knowledge related to the artifact and its contexts, has been developed through the formalization of domain-specific entities and relationships between them

Cholinergic neural activity directs retinal layer-specific angiogenesis and blood retinal barrier formation.

Blood vessels in the central nervous system (CNS) develop unique features, but the contribution of CNS neurons to regulating those features is not fully understood. We report that inhibiting spontaneous cholinergic activity or reducing starburst amacrine cell numbers prevents invasion of endothelial cells into the deep layers of the retina and causes blood-retinal-barrier (BRB) dysfunction in mice. Vascular endothelial growth factor (VEGF), which drives angiogenesis, and Norrin, a Wnt ligand that induces BRB properties, are decreased after activity blockade. Exogenous VEGF restores vessel growth but not BRB function, whereas stabilizing beta-catenin in endothelial cells rescues BRB dysfunction but not vessel formation. We further identify that inhibiting cholinergic activity reduces angiogenesis during oxygen-induced retinopathy. Our findings demonstrate that neural activity lies upstream of VEGF and Norrin, coordinating angiogenesis and BRB formation. Neural activity originating from specific neural circuits may be a general mechanism for driving regional angiogenesis and barrier formation across CNS development

Auditory Processing Performance of the Middle-Aged and Elderly: Auditory or Cognitive Decline?

BACKGROUND: Despite the well-established relationship between aging and auditory processing decline, identifying the extent to which age effect is the main factor on auditory processing performance remains a great challenge due to the co-occurrence of age-related hearing loss and age-related cognitive decline as potential confounding factors. PURPOSE: To investigate the effects of age-related hearing loss and working memory on the clinical evaluation of auditory processing of middle-aged and elderly. RESEARCH DESIGN: Cross-sectional study. STUDY SAMPLE: A total of 77 adults between 50 and 70 yr of age were invited to participate in the study. DATA COLLECTION AND ANALYSIS: The participants were recruited from a larger study that focused on the assessment and management of sensory and cognitive skills in elderly participants. Only participants with normal hearing or mild-to-moderate age-related hearing loss, with no evidence of cognitive, psychological, or neurological conditions were included. Speech-in-noise, dichotic digit, and frequency pattern tests were conducted as well as a working memory test. The hearing loss effect was investigated using an audibility index, calculated from the audiometric threshold. The performance on the digit span test was used to investigate working memory effects. Both hearing loss and working memory effects were investigated via correlation and regression analyses, partialling out age effects. The significance level was set at p < 0.05. RESULTS: The results demonstrated that, while hearing loss was associated to the speech-in-noise performance, working memory was associated to the frequency pattern and dichotic digit performances. Regression analyses confirmed the relative contribution of hearing loss to the variance in speech-in-noise and working memory test to the variance in frequency pattern and dichotic digit test performance. CONCLUSIONS: The performance decline of the elderly in auditory processing tests may be partially attributable to the working memory performance and, consequently, to the cognitive decline exhibited by this population. Mild-to-moderate hearing loss seems to affect performance on specific auditory processing tasks, such as speech in noise, reinforcing the idea that auditory processing disorder in the elderly might also be associated to auditory peripheral deficits

Evaluating the Integration of Chromosomal Microarray Analysis with Karyotyping for Improved Detection of Chromosomal Abnormalities in Recurrent Pregnancy Loss: A Meta-Narrative Review

Investigating genetic abnormalities in recurrent pregnancy loss (RPL) is critical due to the large number of unexplained cases, which account for around 50%. While routine karyotyping of products of conception (POC) is widely employed, its efficacy is limited by a high failure rate in cytogenetics laboratories. Thus, Chromosomal Microarray Analysis (CMA) offers a potential option, with a success rate of more than 90% when karyotyping fails. Unlike karyotyping, CMA allows a full genome investigation without the requirement for live cultures, allowing the discovery of a variety of genetic abnormalities linked to pregnancy loss, including copy number variations, deletions, duplications, and aneuploidy. These abnormalities are prevalent, representing 47.4% of first-trimester losses and 10.9% of second and third-trimester losses. Therefore, this study seeks to increase diagnostic accuracy and identify genetic variables contributing to RPL by evaluating the efficacy of combining CMA and karyotyping. This meta-narrative review serves to evaluate this combined approach as an improved method for developing individualized treatment programs and providing support to afflicted individuals and couples.https://openworks.mdanderson.org/rmps24/1008/thumbnail.jp

A constitutive model for cytoskeletal contractility of smooth muscle cells

The constitutive model presented in this article aims to describe the main bio-chemo-mechanical features involved in the contractile response of smooth muscle cells, in which the biochemical response is modelled by extending the four-state Hai–Murphy model to isotonic contraction of the cells and the mechanical response is mainly modelled based on the phosphorylation-dependent hyperbolic relation between isotonic shortening strain rate and tension. The one-dimensional version of the model is used to simulate shortening-induced deactivation with good agreement with selected experimental measurements. The results suggest that the Hai–Murphy biochemical model neglects the strain rate effect on the kinetics of cross-bridge interactions with actin filaments in the isotonic contractions. The two-dimensional version and three-dimensional versions of the model are developed using the homogenization method under finite strain continuum mechanics framework. The two-dimensional constitutive model is used to simulate swine carotid media strips under electrical field stimulation, experimentally investigated by Singer and Murphy, and contraction of a hollow airway and a hollow arteriole buried in a soft matrix subjected to multiple calcium ion stimulations. It is found that the transverse deformation may have significant influence on the response of the swine carotid medium. In both cases, the orientation of the maximal value of attached myosin is aligned with the orientation of maximum principal stress

Strategic Planning for Local Tourism Destinations: An Analysis of Tourism

This paper reports on a study of the planning practices of local tourism destinations. The tourism plans of 30 local tourism destinations in Queensland, Australia were analyzed to determine the extent to which sustainability principles, namely strategic planning and stakeholder participation, were integrated into the planning process. Utilizing a tourism planning process evaluation instrument developed by Simpson (2001), it was found that local tourism destinations are not integrating sustainability principles in their planning processes