Genetic interactions effects for cancer disease identification using computational models: a review.

Genome-wide association studies (GWAS) provide clear insight into understanding genetic variations and environmental influences responsible for various human diseases. Cancer identification through genetic interactions (epistasis) is one of the significant ongoing researches in GWAS. The growth of the cancer cell emerges from multi-locus as well as complex genetic interaction. It is impractical for the physician to detect cancer via manual examination of SNPs interaction. Due to its importance, several computational approaches have been modeled to infer epistasis effects. This article includes a comprehensive and multifaceted review of all relevant genetic studies published between 2001 and 2020. In this contemporary review, various computational methods are as follows: multifactor dimensionality reduction-based approaches, statistical strategies, machine learning, and optimization-based techniques are carefully reviewed and presented with their evaluation results. Moreover, these computational approaches' strengths and limitations are described. The issues behind the computational methods for identifying the cancer disease through genetic interactions and the various evaluation parameters used by researchers have been analyzed. This review is highly beneficial for researchers and medical professionals to learn techniques adapted to discover the epistasis and aids to design novel automatic epistasis detection systems with strong robustness and maximum efficiency to address the different research problems in finding practical solutions effectively.

Segmentation of Breast Lesions in Ultrasound Images through Multiresolution Analysis Using Undecimated Discrete Wavelet Transform.

Earliest detection and diagnosis of breast cancer reduces mortality rate of patients by increasing the treatment options. A novel method for the segmentation of breast ultrasound images is proposed in this work. The proposed method utilizes undecimated discrete wavelet transform to perform multiresolution analysis of the input ultrasound image. As the resolution level increases, although the effect of noise reduces, the details of the image also dilute. The appropriate resolution level, which contains essential details of the tumor, is automatically selected through mean structural similarity. The feature vector for each pixel is constructed by sampling intra-resolution and inter-resolution data of the image. The dimensionality of feature vectors is reduced by using principal components analysis. The reduced set of feature vectors is segmented into two disjoint clusters using spatial regularized fuzzy c-means algorithm. The proposed algorithm is evaluated by using four validation metrics on a breast ultrasound database of 150 images including 90 benign and 60 malignant cases. The algorithm produced significantly better segmentation results (Dice coef = 0.8595, boundary displacement error = 9.796, dvi = 1.744, and global consistency error = 0.1835) than the other three state of the art methods.

Community-based control of Aedes aegypti by adoption of eco-health methods in Chennai City, India.

BACKGROUND: Dengue is highly endemic in Chennai city, South India, in spite of continuous vector control efforts. This intervention study was aimed at establishing the efficacy as well as the favouring and limiting factors relating to a community-based environmental intervention package to control the dengue vector Aedes aegypti. METHODS: A cluster randomized controlled trial was designed to measure the outcome of a new vector control package and process analysis; different data collection tools were used to determine the performance. Ten randomly selected intervention clusters (neighbourhoods with 100 houses each) were paired with ten control clusters on the basis of ecological/entomological indices and sociological parameters collected during baseline studies. In the intervention clusters, Aedes control was carried out using a community-based environmental management approach like provision of water container covers through community actors, clean-up campaigns, and dissemination of dengue information through schoolchildren. The main outcome measure was reduction in pupal indices (pupae per person index), used as a proxy measure of adult vectors, in the intervention clusters compared to the control clusters. RESULTS: At baseline, almost half the respondents did not know that dengue is serious but preventable, or that it is transmitted by mosquitoes. The stakeholder analysis showed that dengue vector control is carried out by vertically structured programmes of national, state, and local administrative bodies through fogging and larval control with temephos, without any involvement of community-based organizations, and that vector control efforts were conducted in an isolated and irregular way. The most productive container types for Aedes pupae were cement tanks, drums, and discarded containers. All ten intervention clusters with a total of 1000 houses and 4639 inhabitants received the intervention while the ten control clusters with a total of 1000 houses and 4439 inhabitants received only the routine government services and some of the information education and communication project materials. The follow-up studies showed that there was a substantial increase in dengue understanding in the intervention group with only minor knowledge changes in the control group. Community involvement and the partnership among stakeholders (particularly women's self-help groups) worked well. After 10 months of intervention, the pupae per person index was significantly reduced to 0·004 pupae per person from 1·075 (P = 0·020) in the intervention clusters compared to control clusters. There were also significant reductions in the Stegomyia indices: the house index was reduced to 4·2%, the container index to 1·05%, and the Breteau index to 4·3 from the baseline values of 19·6, 8·91, and 30·8 in the intervention arm. CONCLUSION: A community-based approach together with other stakeholders that promoted interventions to prevent dengue vector breeding led to a substantial reduction in dengue vector density.

Preparation and characterization of curcumin-piperine dual drug loaded nanoparticles.

OBJECTIVE: To prepare curcumin-piperine (Cu-Pi) nanoparticles by various methods and to study the effect of various manufacturing parameters on Cu-Pi nanoparticles and to identify a suitable method for the preparation of Cu-Pi nanoparticles to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer. METHODS: Cu-Pi nanoparticles were prepared by thin film hydration method, solid dispersion method, emulsion polymerization method and Fessi method. Optimization was carried out to study the effect of various manufacturing parameter on the Cu-Pi nanoparticles. RESULTS: Out of four methods, Fessi method produced a minimum average particle size of 85.43 nm with a polydispersity index of 0.183 and zeta potential of 29.7 mV. Change of organic solvent (acetone or ethanol) did not have any significant effect on Cu-Pi nanoparticles. However, increase in sonication time, stirring speed, viscosity, use of 1:10:10 ratio of drug/polymer/surfactant, and use of anionic surfactant or combination of anionic surfactant with cationic polymer or combination of non-ionic surfactant with cationic polymer had a significant effect on Cu-Pi nanoparticles. CONCLUSIONS: Cu-Pi nanoparticles coated with PEG containing copolymer produced by Fessi method had a minimum average particle size, excellent polydispersity index and optimal zeta potential which fall within the acceptable limits of the study. This dual nanoparticulate drug delivery system appears to be promising to overcome oral bioavailability and cancer cell targeting limitations in the treatment of cancer.

Multi criteria decision making to select the suitable method for the preparation of nanoparticles using an analytical hierarchy process.

Selecting the right method for the preparation of nanoparticles is a crucial decision. A wrong decision can result in the product having to be formulated and developed again. One tool that can be useful in determining the most appropriate method is the Analytical Hierarchy Process (AHP). AHP has been employed in almost all areas related to decision-making problems. In this paper, the results of a case study illustrate that the AHP concept can assist designers in the effective evaluation of various methods available for the preparation of nanoparticles. This paper presents the methodology of selecting the most suitable method for preparing nanoparticles using the analytical hierarchy process.

Nanotherapeutics to overcome conventional cancer chemotherapy limitations.

Cancer is one of the major causes of death worldwide and chemotherapy is a major therapeutic approach for the treatment which may be used alone or combined with other forms of therapy. However, conventional chemotherapy suffers lack of aqueous solubility, lack of selectivity and multidrug resistance. Nanotherapeutics is rapidly progressing aimed to solve several limitations of conventional drug delivery systems. Nonspecific target of cancer chemotherapy leads to damage rapidly proliferating normal cells and can be significantly reduced through folate and transferrin mediated nanotherapeutics which are aimed to target cancerous cells. Multidrug resistance is challenge in cancer chemotherapy which can be significantly reversed by solid lipid nanoparticles, polymeric nanoparticles, mesoporous silica nanoparticles, nanoparticulated chemosensitizer, nanoparticluated poloxamer and magnetic nanoparticles. Hydrophobic nature of chemotherapeutics leads to poor aqueous solubility and low bioavailability which can be overcome by nanocrystals, albumin based nanoparticles, liposomal formulation, polymeric micelles, cyclodextrin and chitosan based nanoparticles. This review focuses the role of nanotherapeutics to overcome lack of selectivity, multidrug resistance and lack of aqueous solubility of conventional cancer chemotherapy.

Preparation and evaluation of sustained release loxoprofen loaded microspheres.

The aim of present study was to formulate and evaluate the loxoprofen loaded Sustained release microspheres by emulsion solvent evaporation technique. Ethylcellulose, a biocompatible polymer is used as the retardant material. The effects of process conditions such as drug loading, polymer type and solvent type on the characteristics of microspheres were investigated. The prepared microspheres were characterized for their particle size and drug loading and drug release. The in-vitro release studies were carried out in phosphate buffer at pH 7.4. The prepared microspheres were white, free flowing and spherical in shape. The drug-loaded microspheres showed 71.2% of entrapment and the in-vitro release studies showed that Loxoprofen microspheres of 1:3 ratios showed better sustained effect over a period of 8 hours.

Studies on community knowledge and behavior following a dengue epidemic in Chennai city, Tamil Nadu, India.

In 2001, a major dengue outbreak was recorded in Chennai city, with 737 cases (90%) out of a total of 861 cases recorded from Tamil Nadu state. A KAP survey was carried out to assess the community knowledge, attitude and practice on dengue fever (DF), following the major dengue outbreak in 2001. A pre- tested, structured questionnaire was used for data collection. The multistage cluster sampling method was employed and 640 households (HHs) were surveyed. Among the total HHs surveyed, 34.5% of HHs were aware of dengue and only 3.3% of HHs knew that virus is the causative agent for DF. Majority of the HHs (86.5%) practiced water storage and only 3% of them stored water more than 5 days. No control measures were followed to avoid mosquito breeding in the water holding containers by majority of HHs (65%). Sixty percent of HHs did not know the biting behaviour of dengue vector mosquitoes. The survey results indicate that the community knowledge was very poor on dengue, its transmission, vector breeding sources, biting behavior and preventive measures. The lack of basic knowledge of the community on dengue epidemiology and vector bionomics would be also a major cause of increasing trend of dengue in this highly populated urban environment. There is an inevitable need to organize health education programmes about dengue disease to increase community knowledge and also to sensitize the community to participate in integrated vector control programme to resolve the dengue problem.

Design, in vitro and in vivo evaluation of glipizide Eudragit microparticles.

Glipizide microparticles made with Eudragit (RS 100 and RL 100), prepared by emulsion solvent evaporation technique were evaluated for various in-vitro properties viz. encapsulation efficiency, particle size and surface morphology, drug release pattern and in-vivo hypoglycaemic activity. The optimized formulation parameters were used to prepare smooth and spherical microparticles (2-32 microm) with higher entrapment efficiency (67-89%). Drug release patterns of glipizide microparticles of Eudragit RS 100 and Eudragit RL 100 with drug-to-polymer ratio of 1 : 4 (i.e. EGM14 and ELGM14) have shown gradual and extended release for 24 h with cumulative release of glipizide to the extent of 72.3% and 83.9%, respectively. However, EGM14 showed a significant in-vivo hypoglycaemic effect up to 12 h in rabbits while ELGM14 showed for 9 h. Hence, glipizide microparticles of Eudragit RS 100 (glipizide: polymer 1 : 4) is better suited for oral sustained release formulation.

Intramolecular charge transfer effects on flutamide drug.

Spectral characteristics of flutamide drug have been studied in various solvents and beta-cyclodextrin (beta-CD). The inclusion complex of flutamide with beta-CD is analysed by UV-visible, fluorimetry, FT-IR, 1H NMR, SEM, DSC and AM1 methods. In all solvents, flutamide exhibits a dual fluorescence. The longer wavelength emission (A band approximately 380 nm) is due to intramolecular charge transfer state (ICT) and the shorter wavelength emission (B band approximately 285 nm) originates from a locally excited state. In beta-CD, the increase in the fluorescence intensity of 'A' band indicates ICT emission enhanced in the beta-CD medium. beta-CD studies shows isopropyl group is present in the interior part of the beta-CD cavity whereas amino and CF(3) groups are present in the outside of the beta-CD cavity. A mechanism is proposed to explain the 1:1 inclusion process.

Antimicrobial resistance of bacterial agents of the upper respiratory tract in South Indian population.

The study was aimed at determining bacterial agents of the upper respiratory tract and the susceptibility patterns of isolates to antibiotics. The throat swab samples from 250 patients suspected of upper respiratory tract infection (URTI) were obtained from the General Medicine outpatient department of a Rural Health Centre of Rajah Muthiah Medical College and Hospital (RMMC and H), Annamalai University, Chidambaram, Tamilnadu, India and inoculated in the culture medium. The bacterial infection was confirmed only in 228 patients. The organisms isolated on medium were identified by their cultural, morphological and biochemical characteristics. Staphylocccus aureus was identified as the most prevalent bacterial isolate (45.61%) followed by ß hemolytic streptococci (22.51%). Thirty four strains (14.91%) were identified as Klebsiella penumoniae, 19 (8.33%) as Pseudomonas aeruginosa and the rest belonged to a hemolytic streptococci, Escherichia coli and Haemophitus influenzae. All Staphylococcus spp, were resistant to penicillin., ampicillin and co-trimoxazole. All the isolates were resistant to at least one antibiotic. The overall resistance rates were generally low for gentaruicin, cefixine and ceftazidime respectively.

Control of urinary risk factors of stone formation by Salvadora persica in experimental hyperoxaluria.

Urolithiasis, the process of formation of stones in the kidneys and urinary tract, is the major clinical manifestation of hyperoxaluria. Ethylene glycol feeding resulted in hyperoxaluria with increased renal excretion of oxalate, sodium, calcium and phosphate and a decrease in the excretion of magnesium. Supplementation with an aqueous and alcoholic extract of the leaves of Salvadora persica significantly reduced elevated urinary oxalate levels, indicating a regenerative action on endogenous oxalate synthesis. The deposition of stone-forming constituents in the kidneys of calculogenic rats was also significantly lowered by curative and preventive treatments with the aqueous and alcoholic extracts of Salvadora persica. The high serum creatinine level observed in ethylene glycol-treated rats was also reduced following treatment with the extracts. Histopathological findings showed signs of improvement after treatment with the extracts. These observations led to the conclusion that the aqueous and alcoholic extracts of the leaves of Salvadora persica are endowed with antiurolithiatic properties.

Studies on community knowledge and behavior following a dengue epidemic in Chennai city, Tamil Nadu, India

In 2001, a major dengue outbreak was recorded in Chennai city, with 737 cases (90%) out of a total of 861 cases recorded from Tamil Nadu state. A KAP survey was carried out to assess the community knowledge, attitude and practice on dengue fever (DF), following the major dengue outbreak in 2001. A pre- tested, structured questionnaire was used for data collection. The multistage cluster sampling method was employed and 640 households (HHs) were surveyed. Among the total HHs surveyed, 34.5% of HHs were aware of dengue and only 3.3% of HHs knew that virus is the causative agent for DF. Majority of the HHs (86.5%) practiced water storage and only 3% of them stored water more than 5 days. No control measures were followed to avoid mosquito breeding in the water holding containers by majority of HHs (65%). Sixty percent of HHs did not know the biting behaviour of dengue vector mosquitoes. The survey results indicate that the community knowledge was very poor on dengue, its transmission, vector breeding sources, biting behavior and preventive measures. The lack of basic knowledge of the community on dengue epidemiology and vector bionomics would be also a major cause of increasing trend of dengue in this highly populated urban environment. There is an inevitable need to organize health education programmes about dengue disease to increase community knowledge and also to sensitize the community to participate in integrated vector control programme to resolve the dengue problem.

Spectral characteristics of tramadol in different solvents and beta-cyclodextrin.

Effect of solvents and beta-cyclodextrin on the absorption and fluorescence spectra of tramadol drug has been investigated and compared with anisole. The solid inclusion complex of tramadol with beta-CD is investigated by FT-IR, (1)H NMR, scanning electron microscope (SEM), DSC and semiempirical methods. The thermodynamic parameter (DeltaG) of inclusion process is determined. A solvent study shows (i) the spectral behaviour of both tramadol and anisole molecules is similar to each other and (ii) the cyclohexanol group in tramadol is not effectively conjugated with anisole group. However, in beta-CD, due to space restriction of the CD cavity, a weak interaction is present between the above groups in tramadol. beta-Cyclodextrin studies show that tramadol forms 1:2 inclusion complex with beta-CD. A mechanism is proposed for the inclusion process.

Poly(D,L-lactic-co-glycolic acid) nanoencapsulation reduces Erlotinib-induced subacute toxicity in rat.

Erlotinib-HCl is a quinazoline derivative used as a drug in the therapy of non-small-cell lung cancer. The present study was conducted to compare the subacute toxicity induced by Erlotinib-HCl delivered to rats as nanoparticles and as free drug. Wistar rats were orally administered with a daily dosage of 200 mg kg(-1) Erlotinib-HCl either as free drug or as Poly(D,L-lactic-co-glycolic acid) (PLGA) encapsulated nanoparticles. After four weeks of treatment, the animals were analyzed for toxicological changes. Although nanoparticulate form of the drug did not induce any toxicity, free drug significantly reduced the levels of white blood cells (WBC), red blood cells (RBC) and haemoglobin, while increasing the levels of neutrophils and corpuscular haemoglobin. Moreover, aspartate aminotransferase (AST) and alanine aminotransferase (ALT) levels were significantly increased in the animals administered with free drug. Histopathological studies confirmed significant damage to the internal organs of animals treated with free drug. Whereas, the internal organs of animals treated with the drug encapsulated in PLGA nanoparticles were more or less similar to the healthy organs. Our results show that Erlotinib-HCl delivered in the form of nanoparticles has less toxic effect than the free drug in experimental rats.

Hepatoprotective and antioxidant effects of Commiphora berryi (Arn) Engl bark extract against CCl(4)-induced oxidative damage in rats.

Oxidative damage is involved in the pathogenesis of various hepatic injuries. In the present study the capacity of Commiphora berryi (Arn) Engl bark as an antioxidant to protect against CCl(4)-induced oxidative stress and hepatotoxicity in Albino Wistar rats was investigated. Intraperitoneal injection of CCl(4), administered twice a week, produced a marked elevation in the serum levels of aspartate transaminase, alanine transaminase, alkaline phosphatase and bilirubin. Histopathological analysis of the liver of CCl(4)-induced rats revealed marked liver cell necrosis with inflammatory collections that were conformed to increase in the levels of SOD, GPx and CAT. Daily oral administration of methanolic extract of C. berryi (Arn) Engl bark at 100 and 200mg/kg doses for 15 days produced a dose-dependent reduction in the serum levels of liver enzymes. Treatment with C. berryi normalized various biochemical parameters of oxidative stress and was compared with standard Silymarin. Therefore, the results of this study show that C. berryi (Arn) Engl bark can be proposed to protect the liver against CCl(4)-induced oxidative damage in rats, and the hepatoprotective effect might be correlated with its antioxidant and free radical scavenger effects.

Natural vertical transmission of dengue viruses by Aedes aegypti in Chennai, Tamil Nadu, India.

BACKGROUND & OBJECTIVE: Dengue viruses are spread and maintained in an Aedes aegypti-human- Ae. aegypti cycle in urban areas of the tropics. Dengue viruses are also maintained in nature by vertical transmission by Ae. aegypti. A study was undertaken in Chennai, a known endemic city in south India, to comprehend the natural vertical transmission dynamics in Ae. aegypti and to assess its epidemiological importance. METHODS: Ae. aegypti males collected in resting and landing collections were tested for dengue virus infection by antigen-capture enzyme-linked immunosorbent assay (ELISA) and further examined by insect bioassay, Toxorhynchites splendens inoculation-indirect immunofluorescence technique (Toxo-IFA) using serotype-specific monoclonal antibodies (Mabs), if found positive by ELISA. RESULTS: Of the 509 pools of Ae. aegypti males (n=5408) screened, 15 pools, collected in April, June- July, November-December in 2003 and March, May in 2004, were found positive for dengue virus infection and the minimum infection rate (MIR) among adult males was high in June 2003 (28.0/ 1000). Three positive pools could be serotyped as dengue-2 (2 pools) and dengue-3 (1 pool). INTERPRETATION & CONCLUSION: Dengue virus isolations from wild caught males of Ae. aegypti indicate the occurrence of transovarial transmission. Vertical transmission was mainly observed in summer months when dengue infections in humans were low suggesting that dengue viruses adopt a novel strategy of surviving adverse climatic conditions.

Evaluation of antiaggressive activity of Eclipta alba in experimental animals.

The occurrence of aggression for prolonged periods of time could have a hazardous impact on the health and social wellbeing of the individual. Aggression can ensue due to exposure to an intimidating situation. Aggression is prominently seen when a disturbance occurs in the fine balance of neurotransmitters such as 5-hydroxytryptamine, gamma- aminobutyric acid, dopamine and their receptor subtypes. The present study investigated the ability of 100 and 200mg/kg of aqueous extract of Eclipta alba to circumvent aggression. Foot shock induced aggression and water competition test were utilized as models for screening of antiaggressive activity. Eclipta alba significantly minimized dominance (p<0.05) which is correlated to the level of aggression particularly with 200mg/kg in the water competition test. A tangible behavioral submission was observed with 100 and 200mg/kg and of Eclipta alba in the foot shock induced test.

Standardization of a Siddha formulation Amukkara curanam by HPTLC.

Amukkara curanam, a Siddha formulation, currently used in all types of gastric disorders, rheumatic pain, insomnia and sexual insufficiency, was investigated for the estimation of the marker compounds, withaferine A and piperine contents in a prepared standard formulation and a commercial formulation by using HPTLC method of analysis. The two formulations were subjected to methanol, ethyl acetate and chloroform extractions by using Soxhhlet apparatus The chromatogram was developed using chloroform: methanol (8.5:1.5 v/v) and toluene: ethyl acetate (7:3 v/v) as mobile phases for the estimation of withferine A and piperine respectively. The detection and quantification were performed at a wavelength of 220 nm for withaferine A and 254 nm for piperine. The linear regression analysis of calibration plots of withferine A and piperine exhibited linear relationship in the range of 5-15 microg and 50-150 ng respectively, while the % recovery was found to be 94.52% w/w of withaferine A and 98.73% w/w of piperine, thus proving the accuracy and precision of the analysis. Methanol and ethyl acetate were found to be the suitable solvents for the extraction of withaferin A and piperine respectively. The withaferine A content in standard formulation was found to be much higher in all the three extracts than that of the commercial sample. However, the piperine content in all the three extracts of standard formulation was slightly lower than the respective extracts of commercial formulation. The proposed HPTLC method was found to be rapid, simple and accurate for quantitative estimation of withferine A and piperine in different formulation extracts.