Evaluation of prescriptions from tertiary care hospitals across India for deviations from treatment guidelines & their potential consequences.

BACKGROUND OBJECTIVES: Irrational prescribing practices have major consequences on patient safety and also increase the economic burden. Real-life examples of impact of irrational prescription have potential to improve prescribing practices. In this context, the present study aimed to capture and evaluate the prevalence of deviations from treatment guidelines in the prescriptions, potential consequence/s of the deviations and corrective actions recommended by clinicians. METHODS: It was a cross-sectional observational study conducted in the outpatient departments of tertiary care hospitals in India wherein the 13 Indian Council of Medical Research Rational Use of Medicines Centres are located. Prescriptions not compliant with the standard treatment guidelines and incomplete prescriptions with respect to formulation, dose, duration and frequency were labelled as 'prescriptions having deviations'. A deviation that could result in a drug interaction, lack of response, increased cost, preventable adverse drug reaction (ADR) and/or antimicrobial resistance was labelled as an 'unacceptable deviation'. RESULTS: Against all the prescriptions assessed, about one tenth of them (475/4838; 9.8%) had unacceptable deviations. However, in 2667/4838 (55.1%) prescriptions, the clinicians had adhered to the treatment guidelines. Two thousand one hundred and seventy-one prescriptions had deviations, of which 475 (21.9%) had unacceptable deviations with pantoprazole (n=54), rabeprazole+domperidone (n=35) and oral enzyme preparations (n=24) as the most frequently prescribed drugs and upper respiratory tract infection (URTI) and hypertension as most common diseases with unacceptable deviations. The potential consequences of deviations were increase in cost (n=301), ADRs (n=254), drug interactions (n=81), lack of therapeutic response (n=77) and antimicrobial resistance (n=72). Major corrective actions proposed for consideration were issuance of an administrative order (n=196) and conducting online training programme (n=108). INTERPRETATION CONCLUSIONS: The overall prevalence of deviations found was 45 per cent of which unacceptable deviations was estimated to be 9.8 per cent. To minimize the deviations, clinicians recommended online training on rational prescribing and administrative directives as potential interventions.

Screening for potential novel probiotic Levilactobacillus brevis RAMULAB52 with antihyperglycemic property from fermented Carica papaya L.

Probiotics are live microorganisms with various health benefits when consumed in appropriate amounts. Fermented foods are a rich source of these beneficial organisms. This study aimed to investigate the probiotic potential of lactic acid bacteria (LAB) isolated from fermented papaya (Carica papaya L.) through in vitro methods. The LAB strains were thoroughly characterized, considering their morphological, physiological, fermentative, biochemical, and molecular properties. The LAB strain's adherence and resistance to gastrointestinal conditions, as well as its antibacterial and antioxidant capabilities, were examined. Moreover, the strains were tested for susceptibility against specific antibiotics, and safety evaluations encompassed the hemolytic assay and DNase activity. The supernatant of the LAB isolate underwent organic acid profiling (LCMS). The primary objective of this study was to assess the inhibitory activity of α-amylase and α-glucosidase enzymes, both in vitro and in silico. Gram-positive strains that were catalase-negative and carbohydrate fermenting were selected for further analysis. The LAB isolate exhibited resistance to acid bile (0.3% and 1%), phenol (0.1% and 0.4%), and simulated gastrointestinal juice (pH 3-8). It demonstrated potent antibacterial and antioxidant abilities and resistance to kanamycin, vancomycin, and methicillin. The LAB strain showed autoaggregation (83%) and adhesion to chicken crop epithelial cells, buccal epithelial cells, and HT-29 cells. Safety assessments indicated no evidence of hemolysis or DNA degradation, confirming the safety of the LAB isolates. The isolate's identity was confirmed using the 16S rRNA sequence. The LAB strain Levilactobacillus brevis RAMULAB52, derived from fermented papaya, exhibited promising probiotic properties. Moreover, the isolate demonstrated significant inhibition of α-amylase (86.97%) and α-glucosidase (75.87%) enzymes. In silico studies uncovered that hydroxycitric acid, one of the organic acids derived from the isolate, interacted with crucial amino acid residues of the target enzymes. Specifically, hydroxycitric acid formed hydrogen bonds with key amino acid residues, such as GLU233 and ASP197 in α-amylase, and ASN241, ARG312, GLU304, SER308, HIS279, PRO309, and PHE311 in α-glucosidase. In conclusion, Levilactobacillus brevis RAMULAB52, isolated from fermented papaya, possesses promising probiotic properties and exhibits potential as an effective remedy for diabetes. Its resistance to gastrointestinal conditions, antibacterial and antioxidant abilities, adhesion to different cell types, and significant inhibition of target enzymes make it a valuable candidate for further research and potential application in the field of probiotics and diabetes management.

Microplastic contamination in Indian rural and urban lacustrine ecosystems.

This study investigates the microplastics (MPs) pollution of the lacustrine ecosystems of Tamil Nadu, South India. It examines the seasonal distribution, characteristics and morphology of MPs and assesses the risk posed by MPs pollution. MPs abundance in the 39 rural and urban lakes studied varies from 16 ± 2.69 to 118.17 ± 22.17 items/L (water) and 19.50 ± 4.75 to 156.23 ± 36.41 items/kg (sediment). The water and sediment of urban lakes show average MPs abundances of 88.06 items/L and 115.24 items/kg respectively, while the rural lakes exhibit average MPs abundances of 42.98 items/L and 53.29 items/kg. The results demonstrate that study areas with more residential and urban centers with higher population density and larger discharge of sewage have greater MP abundance. Urban zones have greater MP diversity integrated index (MPDII = 0.73) than rural zones (MPDII = 0.59). Fibres are the dominant group and polyethylene and polypropylene are the most commonly found polymers, possibly gaining entry through land-based plastic litter and urban activities in this region. The weathering index values, 50 % of MPs exhibit high degree of oxidation (WI >0.31) with an age of >10 years. SEM-EDAX results reveal that the weathered MPs from urban lakes have a wider variety of metal elements (Al, Cr, Mn, Co, Ni, Cu, Zn, As, Sr, Hg, Pb and Cd) than those from rural lakes (Na, Cl, Si, Mg, Al, Cu). Though PLI shows low risk (<10) in terms of abundance, PHI reflects pollution status III (10-100) and IV (100-1000) in rural areas and IV and V (>1000) in urban areas based on the toxicity score of the polymer. Ecological risk assessment shows minor risks (<150) at present. The assessment indicates the risk posed by the MPs to the lakes studied and emphasizes the necessity for best MP management practices in future.

Seasonal and spatial variations in the distribution pattern, sources and impacts of microplastics along different coastal zones of Tamil Nadu, India.

We investigated spatiotemporal variations of microplastics (MPs) in Coromandel Coast, Palk Bay, Gulf of Mannar, and West Coast of Tamil Nadu, India. MPs abundance varies from 37 ± 1.52 to 189 ± 9.02 items/kg in sediment and 23 ± 15.25 to 155.25 ± 4.16 items/L in water. Highest abundance in monsoon by riverine inflow transports plastic waste to the ocean. MPs sizes 0.5-1 mm are dominant in summer with 16 polymers, while 3-4 mm dominates the monsoon with 23 polymers. Carbonyl Index shows high MP oxidation (>0.31), unrelated to spatiotemporal changes. SEM-EDAX shows weathered MPs carrying hazardous metals. High MP diversity (MPDII = 0.77) of Coromandel Coast points to many sources of pollution and the need for immediate control measures. Pollution load values indicate low degree of MP pollution (<10), polymer hazard index shows level III (10-100) and IV (100-1000), and ecological risk assessment shows minor risks (<150) at present.

A method for DNA extraction and molecular identification of Aphids.

Aphid species (Insecta, Hemiptera) are economically important invasive pest throughout the world, though their identification is intricate due to tiny size and inconspicuous nature of morphology. Mitochondrial cytochrome c oxidase I (mtCOI) region has been proven to be a standard barcode to identify the diverse array of insect groups. Isolation of good quality DNA is a fundamental first step in insect DNA barcoding which is obtained by standardizing the DNA isolation method. In this study, we demonstrate a modified CTAB method for the isolation of DNA to maximize the quality and yield from small aphids. This method will help the researchers to efficiently isolate DNA from small aphid and the method can be utilized for other small insects as well. We evaluated the quality of the isolated DNA and the mtCOI gene region were subjected to PCR amplification. Further, the gene segment was sequenced and gene annotation was done by NCBI BLAST program through which the insect was found to be Aphis gossypii. This study provides a set of molecular tools that can be used for identification of insect at species level through DNA barcoding and biodiversity analysis.•Detailed method to maximize quality and quantity of genomic DNA isolated from aphids.•Molecular identification of aphids using mtCOI gene amplification and sequence validation.•First report on Aphis gossypii infecting Solanum trilobatum provides insights of pest identification and management.

Production and characterization of enriched vermicompost from banana leaf biomass waste activated by biochar integration.

Vermicomposting uses less energy and requires fewer infrastructures, and it is capable of restoring soil nutrition and carbon. Banana cultivation produces lots of trash in a single crop season, with 30 tonnes of waste generated per acre. The biodegradable fraction of banana leaf waste is thrown out in large quantities from temples, markets place wedding halls, hotels, and residential areas. Vermicomposting can be used for recovering lignin, cellulose, pectin, and hemicellulose from banana leaves. Earthworm digests organic materials with the enzymes produced in gut microflora. Biochar adds bulk to vermicomposting, increases its value as fertilizer. The goal of this study was to amend biochar (0, 2, 4 and 6%) with banana leaf waste (BLW) + cow dung (CD) in three different combinations (1:1, 2:1 and 3:1) using Eisenia fetida to produce enriched vermicompost. In the vermicompost with biochar groups, there were higher levels of physicochemical parameters, as well as macro- and micronutrient contents. The growth and reproduction of earthworms were higher in groups with biochar. A maximum of 1.82, 1.18 and 1.67% of total nitrogen, total phosphorus and total potassium was found in the final vermicompost recovered from BLW + CD (1:1) amended with 4% biochar; while the other treatments showed lower levels of nutrients. A lower C/N ratio of 18.14 was observed in BLW + CD (1:1) + 4% biochar followed by BLW + CD (1:1) + 2% biochar amendment (19.92). The FTIR and humification index studies show that degradation of organic matter has occurred in the final vermicompost and the substrates with 4% biochar in 1:1 combination showed better degradation and this combination can be used for nutrient rich vermicompost production.

Microplastic pollution and its implicated risks in the estuarine environment of Tamil Nadu, India.

Estuaries are transition zones between freshwater and seawater. There are only few studies on microplastic (MPs) pollution in estuaries. In this study, investigating the spatiotemporal variations of MPs in water, sediment and biota samples of 19 estuaries in Tamil Nadu, India, we assessed the chemical and human exposure risks of MPs. MPs extracted by digestion and density separation and characterized them using microscope, Fourier transform infrared spectroscopy and scanning electron microscopy with energy dispersive analysis of X-rays. MP abundancesin summer and monsoon range from 31.7 ± 3.8 to 154.7 ± 4.2 items/L in water and 51.7 ± 3.6 to 171.4 ± 9.1 items/kg in sediment. Highest MPs abundance is found in water and sediment of the urbanized Adayar estuary. MP levels are higher in monsoon than in summer (P < 0.05) due to the discharge of wastewater via storm water outlets. More small-size MPs are found in summer (<0.5-1 mm) while monsoon has a greater diversity of MP polymers (MPDII: 0.81). MP abundance in fish varies from 0.01 ± 0.003 to 0.15 ± 0.03 items/g, and in shellfish from 0.75 ± 0.12 to 9.7 ± 0.28 items/g. In fish, more MPs are found in intestine than in gill or muscle. Shell fishes contain more MPs than fishes. In all the matrices, fibers of different sizes, and polymers of polyethylene and polypropylene are commonly found. An average local person is likely to ingest 781 items of MPs via fish and 2809 items via shellfish annually. Polymer hazard index shows hazard levels of IV to V indicating the serious MP pollution trend, which poses a risk to the biota. In conclusion, MPs observed in this study show that estuaries are a major pathway for land-derived plastics to reach the ocean. The results will help implement remedial/clean-up measures for the estuary for better ecosystem conservation.

Assessment of spatial-temporal changes in water bodies and its influencing factors using remote sensing and GIS - a model study in the southeast coast of India.

Concerns have been raised about the threat of ecological imbalance due to the loss of water bodies in densely populated areas. The present study explored the changes in water bodies in terms of area, number, and size in northern districts of Tamil Nadu, India, between 1978 and 2018 using satellite data, geographic information system, spatial analysis, ground truth verification, and field validation. The analysis indicated that the water bodies' area has reduced by 3027 ha and 4363 ha in the Kancheepuram and Tiruvallur Districts, respectively. Almost 179 water bodies have entirely disappeared, and 628 water bodies have been partly converted for other purposes. Of the disappeared water bodies, small, medium, and large water bodies account for 53, 93, and 33, respectively. The main reason for the changes in water bodies was the conversion to agriculture and buildings. Overall, the water bodies' area and number have been reduced by 9% and 12%, respectively, while the population has grown by 37%. The water bodies lost due to anthropogenic activities demand the scientific inventory of water bodies and integrated water resources management at a state or national level with strict monitoring regulations to protect them.

Multi-criteria coastal environmental vulnerability assessment using analytic hierarchy process based uncertainty analysis integrated into GIS.

Changes in environmental conditions influence vulnerability due to interacting stresses and pressures across the nations and regions. Coastal resources are under severe stress due to climate change, growing trade and commerce, and the human population depends on them. The coastal vulnerability to changing climatic variables has created a major concern at regional, national and global scales. The present model study assessed the coastal vulnerability of the densely populated districts in South India, which are prone to extreme climatic events at a higher frequency. The seven crucial influencing variables that have been selected for the study were sea-level rise, coastal elevation, coastal slope, extreme rainy days, historical shoreline change, tidal range, and geomorphology. The identified variables were ranked by relative importance and linked by weightage using analytical hierarchy process-based uncertainty analysis. Mapped and reclassified variables have been integrated to derive the overall vulnerability using geospatial techniques. The study shows that the coast has experienced high vulnerability to SLR impact, extreme rainfall, geomorphology, and elevation; medium vulnerability to the shoreline change and least vulnerable to coastal slope and tidal range. Of the coastal regions studied, 29% and 14.3% had high vulnerability; 70.5% and 85.7% had medium vulnerability in the two selected densely populated districts (Kancheepuram and Tiruvallur District). Applying geospatial techniques to assess the environmental vulnerability resulted in reliable and informative maps which will serve as a model to determine the critical coastal regions to plan for the conservation and adaptation measures.

A Biofloc-Based Aquaculture System Bio-augmented with Probiotic Bacteria Bacillus tequilensis AP BFT3 Improves Culture Environment, Production Performances, and Proteomic Changes in Penaeus vannamei.

Experiments were conducted to evaluate the probiotic effect of bio-augmented Bacillus tequilensis AP BFT3 on improving production, immune response, and proteomic changes of Penaeus vannamei reared in a biofloc system. Penaeus vannamei larvae (PL13) were stocked in 100-L tanks at a rate of 100 no per tank to study the effect of B. tequilensis AP BFT3 with and without biofloc (BFT-PRO and PRO). Control tanks devoid of probiotic strain were maintained in a clear water system. The growth and survival considerably increased in probiotic added biofloc reared shrimp than probiotic added clear water reared ones and control. Water quality significantly improved in probiotic added (PRO) and biofloc-probiotics (BFT-PRO) system than control. Microbiological investigations indicate increased heterotrophic bacterial load in BFT-PRO compared to the PRO and control. The quality of the isolated microbes was analyzed in terms of enzyme production, and an abundance of enzyme-producing bacterial population was observed in BFT-PRO shrimp. Immune-related genes were significantly upregulated in BFT-PRO shrimp, followed by the PRO and control. The proteomic data (2D gel electrophoresis and MALDI-TOF) of muscle tissue from the experimental animals identified 11 differentially expressed proteins. The Daxx OS and Lit v 1 tropomyosin was found upregulated in BFT-PRO shrimps. Downregulation of Na+/K+ATPase was observed in biofloc with probiotic-supplied groups. The findings revealed that the BFT system's efficacy could be improved through the addition of probiotics. The addition of B. tequilensis AP BFT3 as a probiotic in biofloc induced the expression of essential proteins, reducing contracting diseases during culture.

Spatial and vertical distribution of microplastics and their ecological risk in an Indian freshwater lake ecosystem.

This study investigated the spatial and vertical distribution of microplastics (MPs) in the water and sediment samples collected from different locations in Kodaikanal Lake, a very popular tourist location. The lake provides water to placesdownstream. MPs are found in the surface water, surface sediment and core sediment, with their respective values of abundance being 24.42 ± 3.22 items/ l, 28.31 ± 5.29 items/ kg, and 25.91 ± 7.11 items/ kg. Spatially, abundance, colour, type and size of MPs vary in the samples of surface water and sediment. The highest levels of MPs are found in the lakes' outlet region. MPs detected are primarily fibres and fragments 3-5 mm in size with PE and PP being the predominant polymers. Seven sampling points were selected to investigate the vertical distribution of MPs. In the core sediment, the abundance and size of MPs decrease with depth. This probably indicates the presence of more MPs in the recent sediment. The core sediment is dominated by sand silt clay fractions, which facilitates potential downward infiltration of fine MPs. SEM images of MPs reveal that the degree of weathering increases with depth, and EDAX shows that smooth MP surface displays a lesser adhesion ability than the rough surface. Plastic wastes generated by tourism are the important source of MPs in the lake. The lake has high PHI values (>1000) due to MPs with high hazard score polymers (PS and PEU), whereas the PLI values (1.33) indicate low level of MP pollution representing a minor ecological risk. The MP level in Kodaikanal Lake is influenced by the lake's hydrology and the sources of pollution. Although the impacts of MP pollution on the health and functioning of the environment is uncertain, observing, understanding and halting of further MP contamination in the Kodaikanal Lakes is important.

Efficacy and safety of capecitabine and oxaliplatin (CAPOX) treatment in colorectal cancer: An observational study from a tertiary cancer center in South India.

Background: ">5-fluorouracil (5-FU) was the standard treatment care for colorectal cancer (CRC), however, its efficacy was limited due to safety concerns. Capecitabine and oxaliplatin (CAPOX) treatment was found equivalent to 5-FU in efficacy and preferred now due to easy management and convenience in administration. Hence, the present study aims to determine the efficacy and safety associated with CAPOX treatment in a real world non clinical setting. Methods: ">145 treatment-naive and newly diagnosed CRC patients were recruited in the study. Each patient received oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000 mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. Results: In the adjuvant setting, the observed disease-free survival rate was 62% (n=34) in the colon and 67% (n=15) in the rectum cancer patients at 2 years. The observed overall survival rate in the colon and rectal cancer was 80% (n=44) and 83% (n=18) respectively at 2 years. In the palliative setting the observed progression-free survival rate was 28% (n=13) in the colon and 33% (n=7) in rectal cancer patients at 2 years. The observed OSR at 2 years was 64% (n=30) in the colon and 67% (n=14) in the rectal cancer patients. Thrombocytopenia (17, 11.7%) and diarrhea (8, 5.5%) were the most commonly observed grade 3/4 hematological and gastrointestinal toxicities. Hand-foot syndrome and peripheral neuropathy were the major contributors for dose reduction (14, 9.6%), treatment delay (8, 5.4%), and drug discontinuation (9, 6.1%) in the study cohort. Conclusion: CAPOX treatment was found to be effective but associated with several dose-limiting toxicities.

Cellular and molecular immune response and production performance of Indian white shrimp Penaeus indicus (H. Milne-Edwards, 1837), reared in a biofloc-based system with different protein levels of feed.

The present study focuses on the immunity and growth of Penaeus indicus fed with varying protein levels (25%, 30%, and 35%) in a biofloc based rearing system. A 120 days growth trial was carried out using juvenile Penaeus indicus (0.71 ± 0.01) with dietary protein level, 25% (LP), 30% (MP), and 35% (HP), and a control diet-fed with 35% acted as control group resulting in 4 treatments each with four replicates and were randomly assigned 16 tank units (7500 L each). A combination of different carbon sources (molasses, wheat flour, and rice bran in 2:1:1 ratio), yeast and a probiotic (Bacillus sp.) consortium were used for the development of biofloc. At the end of the trial, the growth parameters of shrimps viz., initial weight, feed conversion ratio (FCR), and daily growth coefficient (DGC) were computed. The results indicated that shrimp fed with medium (30%) protein (MP) diet recorded significantly (P < 0.05) improved growth performance compared to high protein fed group (35%) and low protein (25%) fed group (LP) in a biofloc system and control group (35%). The immunological parameters such as hemagglutination activity (HA) assay, serum protein, lysozyme, phenol oxidase (PO), and inhibition of superoxide dismutase (SOD) activity were observed in serum, plasma, and hemocyte lysate supernatant (HLS). The HA activity, PO activity in plasma was found to be higher in high protein fed animals, whereas medium protein resulted in enhanced PO activity in serum. Similarly, lysozyme and SOD were inhibited well in high protein fed animals compared to the low protein fed group. The vital immune genes's mRNA profiling showed a potential rise in the expressional pattern in MP and HP treatments compared to LP and control. BGBP (beta-1,3-glucan binding protein) and hemocyanin mRNA transcript levels were highly upregulated in the HP (5 fold) and moderately expressed in MP (2 fold) and LP (1-2 fold). The transcripts of peroxinectin, antimicrobial peptides like crustin showed significant upregulation in HP followed by in MP and LP and control. Likewise, other immune genes, such as SOD, prophenoloxidase (proPO), showed a similar trend in a marginal way, indicating immunomodulation in the biofloc groups. This study suggested that biofloc with high protein (35%) supplementation can substantially enhance the immune response of shrimps, although medium protein level (30%) is optimum for improving the survival, growth, and in turn economic return in Indian white shrimp.

COVID-19 lockdown improved the health of coastal environment and enhanced the population of reef-fish.

Reduction in the impact of human-induced factors is capable of enhancing the environmental health. In view of COVID-19 pandemic, lockdowns were imposed in India. Travel, fishing, tourism and religious activities were halted, while domestic and industrial activities were restricted. Comparison of the pre- and post-lockdown data shows that water parameters such as turbidity, nutrient concentration and microbial levels have come down from pre- to post-lockdown period, and parameters such as dissolved oxygen levels, phytoplankton and fish densities have improved. The concentration of macroplastics has also dropped from the range of 138 ± 4.12 and 616 ± 12.48 items/100 m2 to 63 ± 3.92 and 347 ± 8.06 items/100 m2. Fish density in the reef areas has increased from 406 no. 250 m-2 to 510 no. 250 m-2. The study allows an insight into the benefits of effective enforcement of various eco-protection regulations and proper management of the marine ecosystems to revive their health for biodiversity conservation and sustainable utilization.

Screening of Weight-Loss Herbal Products for Synthetic Anti-Obesity Adulterants: A Target-Oriented Analysis by Liquid Chromatography-Tandem Mass Spectrometry.

BACKGROUND: The medical and social impact of being overweight, as well as the difficulty in making long-term changes in diet, physical activity, and pitfalls associated with allopathic management, lure obese individuals to over-the-counter weight-loss herbal products (WHPs). However, the safety of herbals is questionable, as reports from all over the world suggest adulteration with synthetic weight loss agents. Objective: The present study was carried out to develop a rapid and sensitive method to screen potential weight loss adulterants in WHPs. Methodology: We procured 33 licensed brands of WHPs that are available in Puducherry (India) and through web stores. Drug-free spiked herbal matrices were used for internal proficiency testing. Spiked herbal matrices and samples were extracted and centrifuged. The supernatant was collected and subjected to liquid chromatography-tandem mass spectrometry analyses. Isocratic elution was carried out by the mobile phase of methanol: 0.1% v/v formic acid (70%:30% v/v) through a C18 column. Analytes were monitored in electrospray ionization positive and negative modes, and an multiple reaction monitoring (MRM) scan was used. Results: Run time was 12 min. Intra- and inter-day precision was < 15% and recoveries were in the range of 99% to 115%. Limit of quantification (LOQ) of the analytes were in the range of 0.1 to 0.3 ng/ml. Conclusion: We developed a sensitive and rapid validated method for the detection of potential adulterants in WHPs. None of the WHPs analyzed were found to contain adulterants. The proposed method will be useful for routine monitoring. WHPs analyzed in this study were not adulterated indicating that WHPs from licensed sources are reliable.

Influence of DPYD*9A, DPYD*6 and GSTP1 ile105val Genetic Polymorphisms on Capecitabine and Oxaliplatin (CAPOX) Associated Toxicities in Colorectal Cancer (CRC) Patients.

AIM: CAPOX treatment in CRC patients was reported to cause several dose-limiting toxicities, and are found responsible for treatment interruption or even discontinuation. Therefore there is a critical need for identifying the predictive biomarkers for such toxicities to prevent them. The aim of our present study is to find the influence of DPYD*9A, DPYD*6 and GSTP1 ile105val gene polymorphisms on CAPOX treatment-associated toxicities in south Indian patients with CRC. PATIENTS AND METHODS: We have recruited 145 newly diagnosed and treatment naive CRC patients in the study. Each Patient received a standard treatment schedule of oxaliplatin 130 mg/m2 infusion over 2 hours on day 1 and oral capecitabine 1000mg/m2 in divided doses twice daily for the next 14 days of a 21-day cycle. 5 ml of the venous blood was collected from each patient and genomic DNA extraction and genotyping. The genotyping analysis of the selected genetic polymorphisms was carried out by real-time PCR using TaqMan SNP genotyping assays obtained from applied biosystems. RESULTS: The major dose-limiting toxicities observed with CAPOX treatment were thrombocytopenia, HFS and PN. DPYD*9A carries were found to be at higher risk for HFS, diarrhoea and thrombocytopenia when compared to patients with wild allele. No significant association was found between DPYD*6, GSTP1 ile105val polymorphisms and CAPOX related toxicities except for thrombocytopenia. CONCLUSION: A significant association was observed between DPYD*9A polymorphism and CAPOX induced dose-limiting toxicities strengthening its role as a predictive biomarker.

Comparison and ranking of superelasticity of different austenite active nickel-titanium orthodontic archwires using mechanical tensile testing and correlating with its electrical resistivity.

INTRODUCTION: The application of light and continuous forces for optimum physiological response and the least damage to the tooth supporting structures should be the primary aim of an orthodontist. Nickel-titanium (NiTi) alloys with their desirable properties are one of the natural choices of the clinicians. AIM: This study was aimed to compare and rank them based on its tensile strength and electrical resistivity. MATERIALS AND METHODS: The sample consisted of eight groups of 0.017 inch × 0.025 inch rectangular archwires from eight different manufacturers, and five samples from each group for tensile testing and nine samples for electrical resistivity tests were used. Data for stress at 10% strain and the initial slope were statistically analyzed with an analysis of variance and Scheffe tests with P < 0.05. The stress/strain plots of each product were ranked for superelastic behavior. The rankings of the wires tested were based primarily on the unloading curve's slope which is indicative of the magnitude of the deactivation force and secondarily on the length of the horizontal segment which is indicative of continuous forces during deactivation. For calculating the electric resistivity, the change in resistance after inducing strain in the wires was taken into account for the calculation of degree of martensite transformation and for ranking. RESULTS: In tensile testing Ortho Organizers wires ranked first and GAC Lowland NiTi wires ranked last. For resistivity tests Ormco A wires were found superior and Morelli remained last. CONCLUSION: these rankings should be correlated clinically and need further studies.

A rapid and efficient protocol for in vitro multiplication of genetically uniform Stevia rebaudiana (Bertoni).

Stevia rebaudiana (Bertoni), commonly called candy leaf or sweet leaf, endemic to South America, is an important medicinal plant. As a source of low calorie natural sweetener 'stevoside', it is used in obesity, diabetes, treatment of heartburn and tooth decay, and also serves as a food supplement. Large scale commercial propagation of S. rebaudiana demands a suitable protocol. Here, we propose an improved protocol for in vitro multiplication of S. rebaudiana from nodal explants. In this protocol, the effect of laboratory grade urea on multiple shoot induction from nodal explants was studied. The nodal explants were initially cultured on Murashige and Skoog (MS) basal media for 2 weeks which facilitated the axillary bud break. Further, culturing of these explants on MS medium fortified with 6 benzyl amninopurine (BAP) (2 mg/L) and Naphthalene acetic acid (NAA) (1 mg/L) with and .without urea (5 mg/L) for a period of 40 days revealed maximum shoot production of 44.56 from a single nodal explant in media supplemented with urea as compared to 22.44 without urea. The differences in the number of shoots produced were significant and these shoots readily rooted in MS media with NAA (4 mg/L). Primary and secondary hardening was successful in these plants. There were no visible morphological abnormalities observed in the micropropagated plantlets. Genetic analysis from random samples also revealed that these plants are genetically uniform. The advantage of the present protocol is that the complete process of multiple shoot induction, rooting and hardening could be completed within a period of 6 months as compared to the existing protocols.

Some newer marker phytoconstituents in methanolic extract of Moringa oleifera leaves and evaluation of its immunomodulatory and splenocytes proliferation potential in rats.

OBJECTIVES: The present study was undertaken to unravel the newer marker phytoconstituents in methanolic extract of Moringa oleifera leaves (MOLE) and evaluation of its immunomodulatory and splenocytes proliferation potential in rats. MATERIALS AND METHODS: Hot methanolic extract of MOLE was subjected to gas chromatography-mass spectrometry (GC-MS) analysis. Immunomodulatory potential was studied in four groups of rats following administration of MOLE at 62.5 and 125 mg/kg for 21 days, followed by immunization with Salmonella typhimurium "O" antigen and antibody titer determined using indirect enzyme-linked immunosorbent assay kit. Total lymphocytes and T- and B-lymphocytes count were determined in control and after MOLE administration (62.5 and 125 mg/kg) to rats for 42 days. Splenocytes (2 × 10(6) spleen cells/ml) from MOLE treated rats were harvested and stimulated using concanavalin A and optical density (OD) and stimulation index were determined. Splenocytes from healthy control rats were also collected and treated in vitro with different concentrations of MOLE (5, 10, 25, 50, and 100 µg/ml) and concanavalin A to determine effect of MOLE on OD and stimulation index. RESULTS: GC-MS analysis revealed presence of 9,12,15-octadecatrienoic acid ethyl ester, 6-octadecenoic acid, cis-vaccenic acid and 2-octyl-cyclopropaneoctanal in MOLE. MOLE at 125 mg/kg increased the antibody titer by 50%. Although there was slight decline in lymphocytes count (total, B- and T-lymphocytes) in MOLE treated rats, percentage of T-lymphocytes was increased nonsignificantly. Ex vivo and in vitro studies revealed marked increase in OD and stimulation index indicating MOLE-induced splenocytes proliferation. CONCLUSION: GC-MS study revealed four new compounds in MOLE apart from promising its immunomodulatory potential based on humoral immune response, percentage increase in T-lymphocytes count, and induction of splenocytes proliferation.

To Evaluate the Effect of Edrophonium on Blood Glucose Levels in Euglycemic Albino Rats Through OGTT.

OBJECTIVE: To evaluate the effect of Edrophonium on blood glucose levels in euglycemic albino rats through OGTT. MATERIALS AND METHODS: Twelve Swiss albino rats weighing around 150-200 gms of either sex were randomly selected from the central animal facility, JSSMC, Mysore and divided into two groups. The control group received distilled water (25ml/kg body wt.) per orally, test groups received Edrophonium (6.3mg/kg/day) intravenously for five days. On the fifth day, following overnight fasting, half an hour after drug administration in all the groups of rats Oral Glucose Tolerance Test was performed, by administering oral glucose in dose of 0.6gm/kg body weight. The capillary blood glucose levels were measured at 0, 60 and 150 min, by rat tail snipping method using (ACCUCHEK) glucometer. RESULTS: The Capillary Blood Glucose levels of Edrophonium group was less when compared to control group at all-time intervals. CONCLUSION: Edrophonium showed the hypoglycemic activity when given for five days intravenously in euglycemic albino rats through Oral Glucose Tolerance Test.