Mathematical modelling of drug delivery from pH-responsive nanocontainers.

Targeted drug delivery systems represent a promising strategy to treat localised disease with minimum impact on the surrounding tissue. In particular, polymeric nanocontainers have attracted major interest because of their structural and morphological advantages and the variety of polymers that can be used, allowing the synthesis of materials capable of responding to the biochemical alterations of the environment. While experimental methodologies can provide much insight, the generation of experimental data across a wide parameter space is usually prohibitively time consuming and/or expensive. To better understand the influence of varying design parameters on the release profile and drug kinetics involved, appropriately-designed mathematical models are of great benefit. Here, we developed a continuum-scale mathematical model to describe drug transport within, and release from, a hollow nanocontainer consisting of a core and a pH-responsive polymeric shell. Our two-layer mathematical model accounts for drug dissolution and diffusion and includes a mechanism to account for trapping of drug molecules within the shell. We conduct a sensitivity analysis to assess the effect of varying the model parameters on the overall behaviour of the system. To demonstrate the usefulness of our model, we focus on the particular case of cancer treatment and calibrate the model against release profile data for two anti-cancer therapeutical agents. We show that the model is capable of capturing the experimentally observed pH-dependent release.

Modelling the Impact of Atherosclerosis on Drug Release and Distribution from Coronary Stents.

Although drug-eluting stents (DES) are now widely used for the treatment of coronary heart disease, there remains considerable scope for the development of enhanced designs which address some of the limitations of existing devices. The drug release profile is a key element governing the overall performance of DES. The use of in vitro, in vivo, ex vivo, in silico and mathematical models has enhanced understanding of the factors which govern drug uptake and distribution from DES. Such work has identified the physical phenomena determining the transport of drug from the stent and through tissue, and has highlighted the importance of stent coatings and drug physical properties to this process. However, there is limited information regarding the precise role that the atherosclerotic lesion has in determining the uptake and distribution of drug. In this review, we start by discussing the various models that have been used in this research area, highlighting the different types of information they can provide. We then go on to describe more recent methods that incorporate the impact of atherosclerotic lesions.

Presbyopia: the first stage of nuclear cataract?

Presbyopia, the inability to accommodate, affects almost everyone at middle age. Recently, it has been shown that there is a massive increase in the stiffness(1) of the lens with age and, since the shape of the lens must change during accommodation, this could provide an explanation for presbyopia. In this review, we propose that presbyopia may be the earliest observable symptom of age-related nuclear (ARN) cataract. ARN cataract is a major cause of world blindness. The genesis of ARN cataract can be traced to the onset of a barrier within the lens at middle age. This barrier restricts the ability of small molecules, such as antioxidants, to penetrate into the centre of the lens leaving the proteins in this region susceptible to oxidation and post-translational modification. Major protein oxidation and colouration are the hallmarks of ARN cataract. We postulate that the onset of the barrier, and the hardening of the nucleus, are intimately linked. Specifically, we propose that progressive age-dependent hardening of the lens nucleus may be responsible for both presbyopia and ARN cataract.

Exploración del deterioro cognitivo leve por neuroimagen / Imaging of mild cognitive impairment

La mejora en los procedimientos de las técnicas neurorradiológicas in vivo para la investigación de la estructura y el funcionamiento del cerebro de los individuos mayores ha permitido profundizar en el conocimiento de los fundamentos biológicos del envejecimiento normal y de las alteraciones psiquiátricas y neurológicas características de la edad avanzada. Mientras que los estudios posmortem se centran en las últimas etapas de una enfermedad, las técnicas de imagen funcionales y estructurales nos han permitido caracterizar los cambios que tienen lugar en el cerebro durante las primeras fases de la enfermedad de Alzheimer (EA). El desarrollo de técnicas terapéuticas más eficaces, que pueden enlentecer y, potencialmente, invertir el avance de la enfermedad, ha hecho que las técnicas basadas en la resonancia magnética sean una herramienta fundamental para detectar el estado preclínico de la EA. Por tanto, el uso de procedimientos no invasivos para identificar el deterioro cognitivo leve (DCL), considerado un estadio transitorio entre el envejecimiento normal y la EA, es un objetivo de una importancia fundamental para la salud pública mundial. En este artículo haremos una revisión de las nuevas estrategias de neuroimagen que pueden emplearse para diagnosticar el DCL (AU)

The refinement of in vivo imaging approaches to investigating the structure and function of the aging brain has provided the opportunity to strengthen our knowledge of the biological substrate of normal aging and late-life neurological and psychiatric disorders. While postmortem studies are biased toward the end stages of disease, functional and structural imaging have permitted us to characterize the brain changes accompanying early Alzheimer’s disease (AD). As more effective therapeutic approaches to slowing (and potentially reversing) disease progression are developed, the role of imaging in determining pre-AD or high-risk conditions becomes increasingly important. The goal of applying non-invasive means to identify the transition state of mild cognitive impairment (MCI) is of considerable public health importance. Further, emerging imaging strategies may be used to monitor the efficacy of therapeutic regimens (AU)

Reasons given by California physical therapists for not belonging to the american physical therapy association.

BACKGROUND AND PURPOSE: In 1997, only 22% of licensed physical therapists living in California were members of the American Physical Therapy Association (APTA). This 1998 study was designed to identify the reason(s) why most licensed physical therapists in California choose not to belong to their profession's national association and to examine the demographics of nonmembers. SUBJECTS: The subjects were a random sample of 400 California licensed physical therapists who were not members of APTA. METHODS: The survey instrument included a demographic questionnaire and statements for response using a 5-point Likert-type scale. Frequency distributions were calculated for responses and demographic data. Nonparametric analyses were used to determine statistical significance. Chi-square analysis was used to compare responses to statements by gender and by full-time versus part-time work status. Spearman rank correlation coefficients were used to determine any relationships between demographic data (eg, gender and work status). The Mann-Whitney U test was used to determine any differences in responses to specific representation questions by those respondents who worked in those environments. All statistical tests were 2-tailed tests conducted at the P(.05 level, unless otherwise indicated. Means, standard deviations, and ranges were used where appropriate. RESULTS: There was a 67% response rate. Eighty-nine percent of the respondents had been members of APTA. Eighty-eight percent of the respondents believed that APTA national dues were too high, and 90% thought California Chapter dues were too high. DISCUSSION AND CONCLUSION: Cost was the primary reason given for APTA nonmembership in California.

Complex real-world functioning and neuropsychological test performance in older adults.

In stepwise regression analyses with Independent Living Scales (ILS) summary and subscale scores as the dependent variables, 8 of 10 psychometric measures from our battery for older adults emerged as important predictors for 69 patients referred for clinical assessment. The Dementia Rating Scale (DRS) score entered first for 6/8 analyses. However, measures of confrontation naming, oral reading, verbal fluency, paragraph recall, visual perception, complex attention, and depression also added explanatory power. Multiple Rs ranged from .66 to .88 except for the Social Adjustment subscale, which correlated only with the depression scale.