Fabrication Of Taste Masked Tablets Via Fused Deposition Modeling 3D Printing Paired With Hot-Melt Extrusion Techniques

The objective of this work was to develop taste-masked donut-shaped tablet formulations utilizing fused deposition modeling three-dimensional (3D) printing paired with hot-melt extrusion (HME) techniques. Caffeine citrate (CC) was used as the model drug for its bitter taste, and a three-point bend test was performed to assess the printability of filaments. The stiffness constant was calculated to represent the printability by fitting the breaking distances and stress data into Hooke\u27s law. Formulation F6 and F7 filaments exhibited the desired hardness with a “k” value of 48.30 ± 3.52 g/mm3 and 45.47 ± 3.51 g/mm3, respectively, and were successfully printed. The donut-shaped tablets were 3D printed with 10%, 50%, and 100% infill densities. In vitro dissolution studies were performed in simulated salivary fluid (pH 6.8, artificial saliva) to evaluate the taste masking efficiency of the printed donuts. In the first minute, the concentrations of CC observed in the dissolution media from all the printed donuts were less than the bitter threshold of CC (0.25 mg/mL). Formulation F7, which contained Eudragit® E PO copolymer, demonstrated better taste masking efficiency than formulation F6. Furthermore, both formulations F6 and F7 demonstrated immediate drug release profiles in gastric medium (10% infill, \u3e80% release within 1 h). Taste-masked CC formulations were successfully developed with donut shapes, which will enhance appeal in pediatric populations, and increase compliance and patient acceptance of the dosage form

Smoothing Spline ANOVA Models and their Applications in Complex and Massive Datasets

Complex and massive datasets can be easily accessed using the newly developed data acquisition technology. In spite of the fact that the smoothing spline ANOVA models have proven to be useful in a variety of fields, these datasets impose the challenges on the applications of the models. In this chapter, we present a selected review of the smoothing spline ANOVA models and highlight some challenges and opportunities in massive datasets. We review two approaches to significantly reduce the computational costs of fitting the model. One real case study is used to illustrate the performance of the reviewed methods

Side population rather than CD133+ cells distinguishes enriched tumorigenicity in hTERT-immortalized primary prostate cancer cells

<p>Abstract</p> <p>Background</p> <p>Subpopulations of cancer cells with the capacity of generating solid tumors have been characterized. In various cancer types, including prostate cancer cells, a side population (SP) and CD133-expressing cells have been proposed as containing a population cancer cells with stem-like ability. Therefore the aim of this work was to determine, in prostate cancer cell lines, the frequency and tumorigenic potential of SP and CD133+ cells.</p> <p>Results</p> <p><it>In vitro </it>2D colony-forming assay and sphere-forming assay, Flow cytometry analysis and magnetic cell sorting were utilized to sort CD133+, CD133- and Side population (SP) cells. Our findings indicate that CD44 and integrin α-6 are uniformly expressed in the hTERT cell lines; however, CD133 is expressed only in a small population (< 0.1%). FACS-sorted CD133+ and CD133- cells exhibited similar tumorigenicity <it>in vitro </it>and <it>in vivo</it>. Additionally, for the hTERT cells, SP rather than CD133 expression showed an 8-fold enhanced tumorigenic potential. The data suggest that SP cells, rather than those with CD133 marker, contain the rare population of CSC capable of producing prostate tumors.</p> <p>Conclusion</p> <p>Collectively, our data suggest that although CD133 is expressed only in a small population of hTERT-immortalized prostate cancer cells, it is not likely to be associated with stem cells, as CD133- and CD133+ cells exhibited similar tumorigenicity. However, SP isolated cells, appear to be enriched with tumorigenic stem-like cells capable of generating palpable tumors.</p

Complex branching patterns in a newly recognized species of Compsocradus Berry et Stein (Iridopteridales) from the Middle Devonian of north Xinjiang, China

Specimens, including the largest known axes, of an iridopteridalean plant of late Middle Devonian age are described from northern Xinjiang, China. The plant consists of three orders branching and dichotomous appendages. The first-order axis probably represents the stem. Lateral organs (lower-order branches and appendages) are attached along the primary axis in up to 10 ranks. The insertion pattern can be broken down into cycles in which one lateral is inserted in each rank, and each cycle is divided into two loose whorls; in one loose whorl, laterals occur in about half of the ranks, some adjacent, and in the other loose whorl, laterals occur in the other ranks. These ranks are believed to map the position of xylem ribs of the vascular system, which has not been preserved. The appendages are isodichotomously divided up to five times. Pairs of recurved sporangia terminate the fertile appendages. A collection of small axes (second and third order) of this plant from the same locality, lacking the distinctive branching patterns displayed in our first order axes, was recently given the name Ramophyton givetianum by D. M. Wang. Our enlarged concept of the plant includes several morphological similarities to Compsocradus laevigatus Berry et Stein from Venezuela, particularly relating to the branching pattern. The Xinjiang plant is therefore reassigned to Compsocradus givetianus (Wang DM) Fu, Wang Y, Berry et Xu comb. nov. It further increases knowledge of branching patterns amongst Iridopteridales, important for evaluating relationships to other plant groups

Different patterns of NF-κB and Notch1 signaling contribute to tumor-induced lymphangiogenesis of esophageal squamous cell carcinoma

<p>Abstract</p> <p>Background</p> <p>Lymph node involvement and tumor-induced lymphangiogenesis appear as the earliest features of esophageal squamous cell carcinoma (ESCC), although the molecular regulatory mechanisms involved have remained unclear. Our aim was to investigate the contribution of NF-κB and Notch1 signaling to lymph node involvement and tumor-induced lymphangiogenesis in ESCC.</p> <p>Material and methods</p> <p>NF-κB and Notch1 expression in 60 tissue samples of ESCC were assessed by immunohistochemical staining. The correlations of NF-κB and Notch1 with lymph node involvement, lymphatic vessel density (LVD), podoplanin, and vascular endothelial growth factor-C (VEGF-C) were further evaluated to determine the association of NF-κB and Notch1 expression with tumor-induced lymphangiogenesis.</p> <p>Results</p> <p>Chi-square tests revealed that NF-κB and Notch1 expression in ESCC tissues were significant associated with lymph node metastasis, LVD, podoplanin, and VEGF-C expression. Strong expression of NF-κB, but weak expression of Notch1, was observed in tumor tissues with lymph nodes involvement (<it>P </it>< 0.05 for both). The mean histoscores of LVD, podoplanin, and VEGF-C staining were higher in high-NF-κB-expressing tissue than in low-expressing tissue (<it>P </it>< 0.05 for each). In contrast, the mean histoscores of LVD and VEGF-C staining were lower in high-Notch1-expressing tissue than in low-expressing tissue (<it>P </it>< 0.05 for both). A multiple factors analysis of LVD and VEGF-C further demonstrated that LVD and VEGF-C status were significantly correlated with NF-κB and Notch1 expression in tumors. NF-κB and Notch1 expression were also significantly inversely correlated (<it>P </it>< 0.05).</p> <p>Conclusion</p> <p>These results suggest that different patterns of NF-κB and Notch1 signaling contribute to lymph nodes metastasis and tumor-induced lymphangiogenesis of ESCC, and reveal that up-regulation of NF-κB is associated with down-regulation of Notch1 in tumor tissue.</p

Evaluation of left ventricular function in patients with coronary slow flow: A systematic review and meta-analysis

Background: Coronary slow flow (CSF) is an angiographic finding defined as delayed distal vessel perfusion without severe stenosis of the epicardial coronary arteries. However, definite alterations in left ventricular (LV) function in patients with CSF remains inconsistent. This study aimed to clarify the changes in LV function in patients with CSF and explore the factors that may influence LV function. Methods: PubMed, Embase, and Cochrane Library databases were systematically searched. Standardized mean differences and 95% confidence intervals (CI) for the LV function parameters were calculated. Subgroup analysis, meta-regression analysis, and correlation analysis were performed to explore the factors influencing LV function. Results: Twenty-two studies (1101 patients with CSF) were included after searching three databases. In patients with CSF, LV ejection function in patients with CSF was marginally lower (61.8%; 95% CI: 61.0%, 62.7%), global longitudinal strain was decreased (–18.2%; 95% CI: –16.7%, –19.7%). Furthermore, left atrial diameter, left atrial volume index, and E/e′ were significantly increased, while E/A and e’ were significantly decreased. The mean thrombolysis in myocardial infarction frame count (TFC) was linearly associated with LV function; the larger the mean TFC, the greater the impairment of LV function. Conclusions: Left ventricular systolic and diastolic functions were impaired in patients with CSF, and this impairment was aggravated with increasing mean TFC

Primary cardiac osteosarcoma in a 42-year-old woman

We describe here a 42-year-old woman who was admitted to hospital with a pedunculated mass in her left atrium. She was diagnosed with a primary cardiac osteosarcoma with special immunohistochemical characteristics. Echocardiography and computed tomography can be used to differentiate cardiac osteosarcomas from routine intracardiac tumors. The patient was treated by surgical removal of the mass. Two years later, she has shown no evidence of disease recurrence. We discuss primary osteosarcomas in the cardiac cavity and their management