Interaction of intestinal nucleoside transporter hCNT2 with amino acid ester prodrugs of floxuridine and 2-bromo-5,6-dichloro-1-beta-D-ribofuranosylbenzimidazole

Amino acid ester prodrugs of antiviral and anticancer nucleoside drugs were developed to improve oral bioavailability or to reduce systemic toxicity. We studied the interaction of human concentrative nucleoside transporter (hCNT2) cloned from intestine with various amino acid ester prodrugs of floxuridine (FUdR) and 5,6-dichloro-2-bromo-1-beta-D-ribofuranosylbenzimidazole (BDCRB). Na(+)-dependent uptakes of [(3)H]-inosine and [(3)H]-adenosine were measured in U251 cells transiently expressing intestinal hCNT2. FUdR significantly inhibited the uptake of both [(3)H]-inosine and [(3)H]-adenosine (60-70% of control), while its amino acid ester prodrugs including Val, Phe, Pro, Asp, and Lys esters exhibited markedly decreased inhibition potency (10-30% of control). On the other hand, BDCRB and its amino acid prodrugs markedly inhibited the uptake of both [(3)H]-inosine and [(3)H]-adenosine. Val, Phe, and Pro ester prodrugs of BDCRB showed similar inhibition capacities as parent compound BDCRB (80-90% for adenosine and 60-80% for inosine). The amino acid site of attachment (3'- and 5'-monoesters) and stereochemistry (L- and D-amino acid esters), did not significantly affect the uptake of [(3)H]-inosine and [(3)H]-adenosine. These results demonstrate that the hCNT2 favorably interacts with BDCRB and its amino acid prodrugs, compared to those of FUdR, and that neutral amino acid esters of BDCRB have a high affinity toward this transporter. Therefore, the intestinal hCNT2 may be a target transporter as a factor for modulating oral pharmacokinetics of BDCRB prodrugs.     

Towards building a photo-realistic virtual human face for craniomaxillofacial diagnosis and treatment planning

The aim of this investigation was to assess the feasibility of building a virtual human face digitally by superimposing a photo-realistic three-dimensional (3D) soft-tissue surface on bone in the correct relationship and evaluating the registration errors associated with this method. The 3D soft-tissue surface of the face was captured using a fast stereophotogrammetry method and the underlying bone was recorded using a 3D computed tomography (CT) scanner. Using the Procrustes registration method, the outer surface of the 3D CT scan and the photo-realistic soft-tissue surfaces were merged into a single Virtual Reality Modelling Language (VRML) file and displayed using a standard VRML viewer. Quantitative measurements of registration errors were calculated in the reconstructed human head models using the signed closest point distance from the photo-realistic skin surface to the transformed CT skin surface. The registration errors between most parts of the aligned surfaces were within +/-1.5mm. The errors were relatively large around the eyebrows, eyelids and cheeks. Simultaneous recording of the face and skull may reduce this error.     

Validation and reproducibility of a high-resolution three-dimensional facial imaging system

OBJECTIVE: To assess the accuracy and reproducibility of a high-resolution three-dimensional imaging system (Di3D). DESIGN: The three-dimensional imaging system was validated in vitro using 12 adult facial plaster casts, which had landmarks marked, and the positions of the landmarks on the three-dimensional images captured by Di3D were compared with those obtained by a coordinate measuring machine (CMM). METHODS: Operator error was measured by repeatedly locating landmarks on the three-dimensional image. Reproducibility error of the images was calculated by capturing three-dimensional images of the facial casts on two separate occasions; the Euclidean distance between the two matched sets of coordinates was then calculated. The Di3D system error was assessed by calculating the three-dimensional global positions of landmarks on the three-dimensional images and comparing them with those obtained by CMM (gold standard). RESULTS: The operator error in placement of landmarks on the three-dimensional model was 0.07mm, range 0.02-0.11mm. The reproducibility of the Di3D capture was 0.13mm, range 0.11-0.14mm. The mean distance between the CMM and Di3D landmarks, which constitutes the Di3D system error, was an average of 0.21mm, range 0.14-0.32mm. CONCLUSIONS: The Di3D system error was within 0.2mm, which is clinically acceptable, and offers considerable improvement in stereophotogrammetry for facial capture and analysis.     

Dermatopathia pigmentosa reticularis

Abstract:  Dermatopathia pigmentosa reticularis is a rare inherited pigmentary disorder of the skin characterized by generalized reticulate hyperpigmentation, nonscarring alopecia and onychodystrophy. The reticulate pigmentation occurs at birth or during early childhood. We hereby report a 12-year-old Indian patient with this disorder.     

U turn to venous air embolism

There is a definitive risk of venous air embolism when the fluid infusion is complete and the drip set is still open in a glass bottle. We have devised a novel way of preventing the chances of air embolism when the fluid in the glass bottle finishes. It really gives a “U” turn to the chances of venous air embolism.     

Impact of selected pre-processing techniques on prediction of risk of early readmission for diabetic patients in India

Diabetes is associated with increased risk of hospital readmission. Predicting risk of readmission of diabetic patients can facilitate implementing appropriate plans to prevent these readmissions. But the real-world medical data is noisy, inconsistent, and incomplete. So before building the prediction model, it is essential to pre-process the data efficiently and make it appropriate for predictive modelling. The objective of this study is to assess the impact of selected pre-processing techniques on the prediction of risk of 30-day readmission among patients with diabetes in India. De-identified electronic medical records data was used from a reputed hospital in the National Capital Region in India and included diabetes patients ≥18 years old discharged from hospital in 2012 to 2015 (n = 9381). This paper focused on data pre-processing steps to improve readmission prediction outcomes. The impact of different pre-processing choices including feature selection, missing value imputation and data balancing on the classifier performance of logistic regression, Naïve Bayes, and decision tree was assessed on various performance metrics such as area under curve, precision, recall, and accuracy. This comprehensive experimental study, first time done from Indian healthcare perspective, offered empirical evidence that most proposed models with pre-processing techniques significantly outperform the baseline methods (without any pre-processing) with respect to selected evaluation criteria. Area under curve (AUC) was highly increased with the use of oversampling technique as data is skewed on class label Readmission. Recall was the biggest gainer with range increasing from 0.02–0.23 to 0.78–0.85, and there was also an increase in AUC from range 0.56–0.68 to 0.83–0.86 by using pre-processing approach. Data pre-processing has a significant effect on hospital readmission predictive accuracy for patients with diabetes, with certain schemes proving inferior to competitive approaches. In addition, it is found that the impact of pre-processing schemes varies by technique, signifying formulation of different best practices to aid better results of a specific technique.     

How accurate are rapid prototyped (RP) final orthognathic surgical wafers? A pilot study

Computer packages have been introduced to simulate the movements of the jaw in three dimensions to facilitate planning of treatment. After final 3-dimensional virtual planning, a rapid prototype wafer can be manufactured and used in theatre. Our aim was to assess the accuracy of rapid prototyping of virtual wafers derived from laser scanned dental models using CAD/CAM software. Upper and lower plaster models from 10 orthognathic patients, the articulated models, and the conventional wafers were scanned. The virtual wafers were made from CAD/CAM software, and printed on a stereolithographic printer. We also scanned the articulated models with rapid prototype wafers in place. The validity of the final rapid prototype wafer was measured by the accuracy with which upper and lower models related to one another. The absolute mean error of the rapid prototype wafer when aligned with the dental models was 0.94 (0.09) mm. The absolute distance of the 2 models articulated by conventional and rapid prototype wafers ranged from 0.04 - 1.73 mm. The rapid prototype wafers were able to orientate the upper and lower dental models with an absolute mean error of 0.94 (0.09) mm, but it ranged from 0.04-1.73 mm.     

The virtual human face: Superimposing the simultaneously captured 3D photorealistic skin surface of the face on the untextured skin image of the CBCT scan

The aim of this study was to evaluate the impact of simultaneous capture of the three-dimensional (3D) surface of the face and cone beam computed tomography (CBCT) scan of the skull on the accuracy of their registration and superimposition. 3D facial images were acquired in 14 patients using the Di3d (Dimensional Imaging, UK) imaging system and i-CAT CBCT scanner. One stereophotogrammetry image was captured at the same time as the CBCT and another 1 h later. The two stereophotographs were individually superimposed over the CBCT using VRmesh. Seven patches were isolated on the final merged surfaces. For the whole face and each individual patch: maximum and minimum range of deviation between surfaces; absolute average distance between surfaces; and standard deviation for the 90th percentile of the distance errors were calculated. The superimposition errors of the whole face for both captures revealed statistically significant differences (P = 0.00081). The absolute average distances in both separate and simultaneous captures were 0.47 and 0.27 mm, respectively. The level of superimposition accuracy in patches from separate captures was 0.3–0.9 mm, while that of simultaneous captures was 0.4 mm. Simultaneous capture of Di3d and CBCT images significantly improved the accuracy of superimposition of these image modalities.     

Examination of tumour histopathology and gene expression in a neu/S100A4 transgenic model of metastatic breast cancer

Elevated levels of the calcium-binding protein S100A4 have been causally linked to the metastatic spread of breast cancer cells in several in vitro and in vivo model systems and, more recently, correlated with patient death in a series of human breast cancer specimens. In transgenic mice expressing MMTV-neu transgenes in mammary gland, additional expression of S100A4 transgenes results in an enhanced metastatic capability. Despite this phenotypic difference arising from elevated S100A4, it is now shown that the primary breast tumours in all mice examined are histopathologically very similar and resemble those human tumours associated with elevated c-erbB-2. Using a panel of genes identified by suppression subtractive hybridization of cDNAs from individual primary tumours and a metastasis, some cDNAs were found to exhibit a differential pattern of expression associated with the expression of S100A4 protein (including osteopontin, S100A9, claudin 2 and several Expressed Sequence Tags sequences). Whilst confirming differential expression of these genes, it was demonstrated that individual primary tumours of matched transgenic status, histology and grade exhibit some degree of heterogeneity at the mRNA level by reverse Northern and Northern hybridizations. This intertumour heterogeneity of mRNA level was confirmed by cDNA array analysis and suggests that even in a transgenic model, which exhibits far less variation than the human disease, there may be multiple mechanisms of disease progression.