Characterization of heterogeneity and spatial distribution of phases in complex solid dispersions by thermal analysis by structural characterization and X-ray micro computed tomography

Purpose: This study investigated the effect of drug-excipient miscibility on the heterogeneity and spatial distribution of phase separation in pharmaceutical solid dispersions at a micron-scale using two novel and complementary characterization techniques, thermal analysis by structural characterization (TASC) and X-ray micro-computed tomography (XCT) in conjunction with conventional characterization methods. Method: Complex dispersions containing felodipine, TPGS, PEG and PEO were prepared using hot melt extrusion-injection moulding. The phase separation behavior of the samples was characterized using TASC and XCT in conjunction with conventional thermal, microscopic and spectroscopic techniques. The in vitro drug release study was performed to demonstrate the impact of phase separation on dissolution of the dispersions. Results: The conventional characterization results indicated the phase separating nature of the carrier materials in the patches and the presence of crystalline drug in the patches with the highest drug loading (30% w/w). TASC and XCT where used to provide insight into the spatial configuration of the separate phases. TASC enabled assessment of the increased heterogeneity of the dispersions with increasing the drug loading. XCT allowed the visualization of the accumulation of phase separated (crystalline) drug clusters at the interface of air pockets in the patches with highest drug loading which led to poor dissolution performance. Semi-quantitative assessment of the phase separated drug clusters in the patches were attempted using XCT. Conclusion: TASC and XμCT can provide unique information regarding the phase separation behavior of solid dispersions which can be closely associated with important product quality indicators such as heterogeneity and microstructure

Effect of a vitamin/mineral supplement on children and adults with autism

<p>Abstract</p> <p>Background</p> <p>Vitamin/mineral supplements are among the most commonly used treatments for autism, but the research on their use for treating autism has been limited.</p> <p>Method</p> <p>This study is a randomized, double-blind, placebo-controlled three month vitamin/mineral treatment study. The study involved 141 children and adults with autism, and pre and post symptoms of autism were assessed. None of the participants had taken a vitamin/mineral supplement in the two months prior to the start of the study. For a subset of the participants (53 children ages 5-16) pre and post measurements of nutritional and metabolic status were also conducted.</p> <p>Results</p> <p>The vitamin/mineral supplement was generally well-tolerated, and individually titrated to optimum benefit. Levels of many vitamins, minerals, and biomarkers improved/increased showing good compliance and absorption. Statistically significant improvements in metabolic status were many including: total sulfate (+17%, p = 0.001), S-adenosylmethionine (SAM; +6%, p = 0.003), reduced glutathione (+17%, p = 0.0008), ratio of oxidized glutathione to reduced glutathione (GSSG:GSH; -27%, p = 0.002), nitrotyrosine (-29%, p = 0.004), ATP (+25%, p = 0.000001), NADH (+28%, p = 0.0002), and NADPH (+30%, p = 0.001). Most of these metabolic biomarkers improved to normal or near-normal levels.</p> <p>The supplement group had significantly greater improvements than the placebo group on the Parental Global Impressions-Revised (PGI-R, Average Change, p = 0.008), and on the subscores for Hyperactivity (p = 0.003), Tantrumming (p = 0.009), Overall (p = 0.02), and Receptive Language (p = 0.03). For the other three assessment tools the difference between treatment group and placebo group was not statistically significant.</p> <p>Regression analysis revealed that the degree of improvement on the Average Change of the PGI-R was strongly associated with several biomarkers (adj. R²= 0.61, p < 0.0005) with the initial levels of biotin and vitamin K being the most significant (p < 0.05); both biotin and vitamin K are made by beneficial intestinal flora.</p> <p>Conclusions</p> <p>Oral vitamin/mineral supplementation is beneficial in improving the nutritional and metabolic status of children with autism, including improvements in methylation, glutathione, oxidative stress, sulfation, ATP, NADH, and NADPH. The supplement group had significantly greater improvements than did the placebo group on the PGI-R Average Change. This suggests that a vitamin/mineral supplement is a reasonable adjunct therapy to consider for most children and adults with autism.</p> <p>Trial Registration</p> <p><b>Clinical Trial Registration Number: </b><a href="http://www.clinicaltrials.gov/ct2/show/NCT01225198">NCT01225198</a></p

Pediatric DXA: clinical applications

Normal bone mineral accrual requires adequate dietary intake of calcium, vitamin D and other nutrients; hepatic and renal activation of vitamin D; normal hormone levels (thyroid, parathyroid, reproductive and growth hormones); and neuromuscular functioning with sufficient stress upon the skeleton to induce bone deposition. The presence of genetic or acquired diseases and the therapies that are used to treat them can also impact bone health. Since the introduction of clinical DXA in pediatrics in the early 1990s, there has been considerable investigation into the causes of low bone mineral density (BMD) in children. Pediatricians have also become aware of the role adequate bone mass accrual in childhood has in preventing osteoporotic fractures in late adulthood. Additionally, the availability of medications to improve BMD has increased with the development of bisphosphonates. These factors have led to the increased utilization of DXA in pediatrics. This review summarizes much of the previous research regarding BMD in children and is meant to assist radiologists and clinicians with DXA utilization and interpretation

Bayesian network student modeling of novice C programmers

Intelligent Tutoring Systems must make use of student models to represent the knowledge of their users. Although there are currently several different implementations of Bayesian network student models in existence, they all model the students current state of knowledge only. They do not address the need to come up with a way to integrate the representation of misconceptions that may exist in a students mind into their network. Because the presence of misconceptions can affect the thought processes of students, the ability to model them in a Bayesian network student model should improve that models ability to make approximations about the user. The aim of this research is to design a Bayesian network student model for Novice C Programmers. Keywords: Intelligent Tutoring System, Bayesian network, Student Model, Misconceptio

Genomic organization and chromosome localization of the murine homeobox gene Pmx.

Homeobox genes are expressed in very specific temporal and spatial patterns and function as transcriptional regulators of developmental processes. The murine homeobox gene, Pmx (paired mesoderm homeobox), is expressed in a mesodermally restricted pattern in embryos and most abundantly in cardiac, skeletal, and smooth muscle tissues in adults. Previously, this murine gene was named K-2 and mHox, while the human homolog was named Phox1. In this report, the localization of Pmx has been determined by interspecific backcross analysis. The Pmx gene is located on Chromosome 1, approximately 3.3 cM distal to the Gsh-4 homeobox locus. The sequence of the Pmx transcript has been extended toward the 5\u27 end and corresponds in size to one of the transcripts previously detected by Northern blot analysis. Sequence analysis indicates that Pmx is the first characterized mammalian gene to encode a paired type homeodomain, but not a paired domain. The Pmx gene includes at least five exons spanning a minimum of 60 kb of genomic DNA, making this the largest known murine homeobox gene

A study on the impacts of expectations, motives, and preparedness on the academic performance of DLSU freshman accountancy students

Accountancy is one of the most challenging programs in the business field. Correspondingly, accountancy students have been struggling with their academics primarily due to the gaps in existing curricula in accounting education. A few studies address this gap by examining the impact of expectations, motives, and preparedness on academic performance; however, none of the studies were conducted in the Philippine setting and in the context of the Bachelor of Science in Accountancy program at De La Salle University- Manila (DLSU). Hence, this paper assessed the impacts of expectations, motives, and preparedness on the academic performance of freshmen accountancy students from DLSU. Through a self-administered online survey, a total of 213 valid responses were gathered and analyzed using multiple linear regression. The results revealed that preparedness has a positive influence on academic performance measured by term GPA, suggesting that students who are more college-prepared perform better academically. Furthermore, motives had a negative influence on term GPA, denoting that having high motives for attending university and taking up a degree in accountancy can lead to lower academic performance. To improve students’ academic outcomes, it is recommended for school administrators, faculty members, and accountancy students to foster a more productive and positive learning environment