FORMULATION AND DEVELOPMENT OF MICROSPHERES FOR THE TREATMENT OF FAMILIAL ADENOMATOUS POLYPOSIS

Objective: Familial adenomatous polyposis (FAP) also known as familial polyposis coli, is a hereditary disease characterized by progressive appearance of numerous polyps mainly in the large intestine. Polyps are initially benign but can easily become cancerous and as such it is a life threatening condition. Celecoxib, a cyclooxygenase-2 (COX-2) inhibitor is thought to induce cell death, and thus prevent or delay the growth of polyps. So in the present study celecoxib loaded microspheres were prepared using control release Hydroxy propyl methyl cellulose (HPMC K4M) and pH dependent polymer eudragit L 100-55 in different ratios (1:1 to 1:4) respectively. The main objective of the study is to identify the polymer concentration required to prevent the drug release in stomach region and promotes in intestinal region.Methods: Emulsification solvent evaporation method was selected for the preparation and all the optimized formulations were evaluated for drug-polymer interactions, percentage yield, micrometric properties, entrapment efficiency, particle size analysis, differential scanning calorimetry and in vitro dissolution study.Results: Drug and polymer interactions were evaluated by using FTIR and DSC. The FTIR spectrum and DSC thermograms stated that drug and polymer are compatible to each other. The micrometric properties of drug loaded microspheres were carried out and they were found to be as the angle of repose (18.26 °-40.69 °), bulk density (0.2846-0.3875), tapped density (0.4111-0.5428), Carr's index (9.66-14.77), Hausner's ratio (1.112-1.2642) which were within the limits. In vitro dissolution, drug release was found to be from 4.5 to 6.5 h for the prepared four formulations (F1–F4). From the kinetic data modeling the order of drug release was found to be zero order and korsmeyer-peppas with n value above 0.5 for all the formulations indicating non-fickian diffusion.Conclusion: All the result demonstrated that celecoxib microspheres can be effectively used in the treatment of familial adenomatous polyposi

A Review

Ovarian cancer is the most common cause of death among gynecological malignancies. We discuss different types of clinical and nonclinical features that are used to study and analyze the differences between benign and malignant ovarian tumors. Computer-aided diagnostic (CAD) systems of high accuracy are being developed as an initial test for ovarian tumor classification instead of biopsy, which is the current gold standard diagnostic test. We also discuss different aspects of developing a reliable CAD system for the automated classification of ovarian cancer into benign and malignant types. A brief description of the commonly used classifiers in ultrasound-based CAD systems is also given

Linear and nonlinear analysis of normal and CAD-affected heart rate signals

Coronary Artery Disease (CAD) is one of the dangerous cardiac disease, often may lead to sudden cardiac death. It is difficult to diagnose CAD by manual inspection of electrocardiogram (ECG) signals. To automate this detection task, in this study, we extracted the Heart Rate (HR) from the ECG signals and used them as base signal for further analysis. We then analyzed the HR signals of both normal and CAD subjects using (i) time domain, (ii) frequency domain and (iii) nonlinear techniques. The following are the nonlinear methods that were used in this work: Poincare plots, Recurrence Quantification Analysis (RQA) parameters, Shannon entropy, Approximate Entropy (ApEn), Sample Entropy (SampEn), Higher Order Spectra (HOS) methods, Detrended Fluctuation Analysis (DFA), Empirical Mode Decomposition (EMD), Cumulants, and Correlation Dimension. As a result of the analysis, we present unique recurrence, Poincare and HOS plots for normal and CAD subjects. We have also observed significant variations in the range of these features with respect to normal and CAD classes, and have presented the same in this paper. We found that the RQA parameters were higher for CAD subjects indicating more rhythm. Since the activity of CAD subjects is less, similar signal patterns repeat more frequently compared to the normal subjects. The entropy based parameters, ApEn and SampEn, are lower for CAD subjects indicating lower entropy (less activity due to impairment) for CAD. Almost all HOS parameters showed higher values for the CAD group, indicating the presence of higher frequency content in the CAD signals. Thus, our study provides a deep insight into how such nonlinear features could be exploited to effectively and reliably detect the presence of CAD

Effect of complex wavelet transform filter on thyroid tumor classification in three-dimensional ultrasound

Ultrasonography has great potential in differentiating malignant thyroid nodules from the benign ones. However, visual interpretation is limited by interobserver variability, and further, the speckle distribution poses a challenge during the classification process. This article thus presents an automated system for tumor classification in three-dimensional contrast-enhanced ultrasonography data sets. The system first processes the contrast-enhanced ultrasonography images using complex wavelet transform-based filter to mitigate the effect of speckle noise. The higher order spectra features are then extracted and used as input for training and testing a fuzzy classifier. In the off-line training system, higher order spectra features are extracted from a set of images known as the training images. These higher order spectra features along with the clinically assigned ground truth are used to train the classifier and obtain an estimate of the classifier or training parameters. The ground truth tells the class label of the image (i.e. whether the image belongs to a benign or malignant nodule). During the online testing phase, the estimated classifier parameters are applied on the higher order spectra features that are extracted from the testing images to predict their class labels. The predicted class labels are compared with their corresponding original ground truth to evaluate the performance of the classifier. Without utilizing the complex wavelet transform filter, the fuzzy classifier demonstrated an accuracy of 91.6%, while utilizing the complex wavelet transform filter, the accuracy significantly boosted to 99.1%

De Sitter vacua from N=2 gauged supergravity

Typical de Sitter (dS) vacua of gauged supergravity correspond to saddle points of the potential and often the unstable mode runs into a singularity. We explore the possibility to obtain dS points where the unstable mode goes on both sides into a supersymmetric smooth vacuum. Within N=2 gauged supergravity coupled to the universal hypermultiplet, we have found a potential which has two supersymmetric minima (one of them can be flat) and these are connected by a de Sitter saddle point. In order to obtain this potential by an Abelian gauging, it was important to include the recently proposed quantum corrections to the universal hypermultiplet sector. Our results apply to four as well as five dimensional gauged supergravity theories.Comment: 25 pages, 1 figure, add refs and corrected typo

Lack of significant association of an insertion/deletion polymorphism in the angiotensin converting enzyme (ACE) gene with tropical calcific pancreatitis

BACKGROUND: The genetic basis of tropical calcific pancreatitis (TCP) is different and is explained by mutations in the pancreatic secretory trypsin inhibitor (SPINK1) gene. However, mutated SPINK1 does not account for the disease in all the patients, neither does it explain the phenotypic heterogeneity between TCP and fibro-calculous pancreatic diabetes (FCPD). Recent studies suggest a crucial role for pancreatic renin-angiotensin system during chronic hypoxia in acute pancreatitis and for angiotensin converting enzyme (ACE) inhibitors in reducing pancreatic fibrosis in experimental models. We investigated the association of ACE gene insertion/deletion (I/D) polymorphism in TCP patients using a case-control approach. Since SPINK1 mutations are proposed a modifier role, we also investigated its interaction with the ACE gene variant. METHODS: We analyzed the I/D polymorphism in the ACE gene (g.11417_11704del287) in 171 subjects comprising 91 TCP and 80 FCPD patients and compared the allelic and genotypic frequency in them with 99 healthy ethnically matched control subjects. RESULTS: We found 46% and 21% of TCP patients, 56% and 19.6% of FCPD patients and 54.5% and 19.2% of the healthy controls carrying the I/D and D/D genotypes respectively (P>0.05). No significant difference in the clinical picture was observed between patients with and without the del allele at the ACE in/del polymorphism in both categories. No association was observed with the presence or absence of N34S SPINK1 mutation in these patients. CONCLUSION: We conclude that the ACE insertion/deletion variant does not show any significant association with the pathogenesis, fibrosis and progression of tropical calcific pancreatitis and the fibro-calculous pancreatic diabetes

Genome Evolution and the Emergence of Fruiting Body Development in Myxococcus xanthus

BACKGROUND: Lateral gene transfer (LGT) is thought to promote speciation in bacteria, though well-defined examples have not been put forward. METHODOLOGY/PRINCIPLE FINDINGS: We examined the evolutionary history of the genes essential for a trait that defines a phylogenetic order, namely fruiting body development of the Myxococcales. Seventy-eight genes that are essential for Myxococcus xanthus development were examined for LGT. About 73% of the genes exhibit a phylogeny similar to that of the 16S rDNA gene and a codon bias consistent with other M. xanthus genes suggesting vertical transmission. About 22% have an altered codon bias and/or phylogeny suggestive of LGT. The remaining 5% are unique. Genes encoding signal production and sensory transduction were more likely to be transmitted vertically with clear examples of duplication and divergence into multigene families. Genes encoding metabolic enzymes were frequently acquired by LGT. Myxobacteria exhibit aerobic respiration unlike most of the delta Proteobacteria. M. xanthus contains a unique electron transport pathway shaped by LGT of genes for succinate dehydrogenase and three cytochrome oxidase complexes. CONCLUSIONS/SIGNIFICANCE: Fruiting body development depends on genes acquired by LGT, particularly those involved in polysaccharide production. We suggest that aerobic growth fostered innovation necessary for development by allowing myxobacteria access to a different gene pool from anaerobic members of the delta Proteobacteria. Habitat destruction and loss of species diversity could restrict the evolution of new bacterial groups by limiting the size of the prospective gene pool

Large expert-curated database for benchmarking document similarity detection in biomedical literature search

Document recommendation systems for locating relevant literature have mostly relied on methods developed a decade ago. This is largely due to the lack of a large offline gold-standard benchmark of relevant documents that cover a variety of research fields such that newly developed literature search techniques can be compared, improved and translated into practice. To overcome this bottleneck, we have established the RElevant LIterature SearcH consortium consisting of more than 1500 scientists from 84 countries, who have collectively annotated the relevance of over 180 000 PubMed-listed articles with regard to their respective seed (input) article/s. The majority of annotations were contributed by highly experienced, original authors of the seed articles. The collected data cover 76% of all unique PubMed Medical Subject Headings descriptors. No systematic biases were observed across different experience levels, research fields or time spent on annotations. More importantly, annotations of the same document pairs contributed by different scientists were highly concordant. We further show that the three representative baseline methods used to generate recommended articles for evaluation (Okapi Best Matching 25, Term Frequency-Inverse Document Frequency and PubMed Related Articles) had similar overall performances. Additionally, we found that these methods each tend to produce distinct collections of recommended articles, suggesting that a hybrid method may be required to completely capture all relevant articles. The established database server located at https://relishdb.ict.griffith.edu.au is freely available for the downloading of annotation data and the blind testing of new methods. We expect that this benchmark will be useful for stimulating the development of new powerful techniques for title and title/abstract-based search engines for relevant articles in biomedical research.Peer reviewe

The 2021 WHO catalogue of Mycobacterium tuberculosis complex mutations associated with drug resistance: a genotypic analysis.

Background: Molecular diagnostics are considered the most promising route to achievement of rapid, universal drug susceptibility testing for Mycobacterium tuberculosis complex (MTBC). We aimed to generate a WHO-endorsed catalogue of mutations to serve as a global standard for interpreting molecular information for drug resistance prediction. Methods: In this systematic analysis, we used a candidate gene approach to identify mutations associated with resistance or consistent with susceptibility for 13 WHO-endorsed antituberculosis drugs. We collected existing worldwide MTBC whole-genome sequencing data and phenotypic data from academic groups and consortia, reference laboratories, public health organisations, and published literature. We categorised phenotypes as follows: methods and critical concentrations currently endorsed by WHO (category 1); critical concentrations previously endorsed by WHO for those methods (category 2); methods or critical concentrations not currently endorsed by WHO (category 3). For each mutation, we used a contingency table of binary phenotypes and presence or absence of the mutation to compute positive predictive value, and we used Fisher's exact tests to generate odds ratios and Benjamini-Hochberg corrected p values. Mutations were graded as associated with resistance if present in at least five isolates, if the odds ratio was more than 1 with a statistically significant corrected p value, and if the lower bound of the 95% CI on the positive predictive value for phenotypic resistance was greater than 25%. A series of expert rules were applied for final confidence grading of each mutation. Findings: We analysed 41 137 MTBC isolates with phenotypic and whole-genome sequencing data from 45 countries. 38 215 MTBC isolates passed quality control steps and were included in the final analysis. 15 667 associations were computed for 13 211 unique mutations linked to one or more drugs. 1149 (7·3%) of 15 667 mutations were classified as associated with phenotypic resistance and 107 (0·7%) were deemed consistent with susceptibility. For rifampicin, isoniazid, ethambutol, fluoroquinolones, and streptomycin, the mutations' pooled sensitivity was more than 80%. Specificity was over 95% for all drugs except ethionamide (91·4%), moxifloxacin (91·6%) and ethambutol (93·3%). Only two resistance mutations were identified for bedaquiline, delamanid, clofazimine, and linezolid as prevalence of phenotypic resistance was low for these drugs. Interpretation: We present the first WHO-endorsed catalogue of molecular targets for MTBC drug susceptibility testing, which is intended to provide a global standard for resistance interpretation. The existence of this catalogue should encourage the implementation of molecular diagnostics by national tuberculosis programmes. Funding: Unitaid, Wellcome Trust, UK Medical Research Council, and Bill and Melinda Gates Foundation