Emulgel for improved topical delivery of Tretinoin: Formulation design and characterization.

OBJECTIVES: The chief objective of the present research was to reduce local side effects by reducing the dose, controlling the release, and improving the stability by developing and optimizing tretinoin (TRT)-loaded topical emulgel formulation. METHODS: TRT emulgel (TE) was prepared and optimized at varying ratios of excipients and using 32 optimal response surface design (ORSD). The TRT emulgel was optimized based on TRT content and in vitro release profile of TRT from formulated emulgel batches. The optimized TRT was characterized for physical properties, pH, viscosity, spreadability, extrudability, photomicroscopy, in vitro anti-acne, in vivo skin irritation, in vivo anti-inflammatory activity, and stability study. RESULTS: The FTIR and DSC analysis revealed the compatibility between TRT and formulation excipients of emulgel. The batch F5 of emulgel formulation displayed maximum drug content (98.69±1.26%), and controlled TRT release (78.27±0.69%). Thus, batch F5 was selected as an optimized batch for further characterization. The photomicroscopic analysis of optimized TE exhibited the presence of spherical globules. The pH and viscosity of optimized TE were found to be 6.20±0.12 and 3240cP respectively. Besides, the optimized TE showed good spreadability and extrudability. The in vitro anti-acne activity against Propionibacterium acne (P. acne) of optimized TE (diameter of zone of inhibition 34.54±0.26mm) was found to be the comparatively same as that of marketed Sotret® gel (diameter of zone of inhibition 36.13±0.43mm). Moreover, no sign of irritation was observed in rats treated with optimized TE indicating the safety of TE. Furthermore, the optimized TE displayed significant (p<0.01) in vivo anti-inflammatory activity when compared to marketed gel. Besides, optimized TE was found to be stable when stored in cool conditions for three months. CONCLUSION: Thus, the emulgel could be a promising approach for the topical delivery of TRT with improved performance and reduced side effects.

Atomic arrangements in an amorphous CoFeB ribbon extracted via an analysis of radial distribution functions.

We discuss the atomic structure of amorphous ferromagnetic FeCoB alloys, which are used widely in spintronics applications. Specifically, we obtain the pair-distribution functions for various atomic pairs based on high-energy x-ray diffraction data taken from an amorphous Co20Fe61B19specimen. We start our reverse Monte Carlo cycles to determine the disordered structure with a two-phase model in which a small amount of cobalt is mixed with Fe23B6as a second phase. The structure of the alloy is found to be heterogeneous, where the boron atoms drive disorder through the random occupation of the atomic network. Our analysis also indicates the presence of small cobalt clusters that are embedded in the iron matrix and percolating the latter throughout the structure. This morphology can explain the enhanced spin polarization observed in amorphous magnetic materials.

Genetic gain for rice yield in rainfed environments in India.

The complexity of genotype × environment interactions under drought reduces heritability, which determines the effectiveness of selection for drought tolerance and development of drought tolerant varieties. Genetic progress measured through changes in yield performance over time is important in determining the efficiency of breeding programmes in which test cultivars are replaced each year on the assumption that the new cultivars will surpass the older cultivars. The goal of our study was to determine the annual rate of genetic gain for rice grain yield in a drought-prone rainfed system in a series of multi-environment trials conducted from 2005 to 2014 under the Drought Breeding Network of Indian sites in collaboration with the International Rice Research Institute (IRRI). Our results show a positive trend in grain yield with an annual genetic yield increase of about 0.68 % under irrigated control, 0.87 % under moderate reproductive stage drought stress and 1.9 % under severe reproductive stage drought stress due to breeding efforts. The study also demonstrates the effectiveness of direct selection for grain yield under both irrigated control as well as managed drought stress screening to improve yield in typical rainfed systems. IRRI's drought breeding programme has exhibited a significant positive trend in genetic gain for grain yield over the years under both drought stress as well as favorable irrigated control conditions. Several drought tolerant varieties released from the programme have outperformed the currently grown varieties under varied conditions in the rainfed environments on farmers' fields.

Depth of soil compaction predominantly affects rice yield reduction by reproductive-stage drought at varietal screening sites in Bangladesh, India, and Nepal.

AIMS: Drought is the major constraint to rainfed rice productivity in South Asia, but few reports provide detailed characterization of the soil properties related to drought stress severity in the region. The aim of the study was to provide a compilation of drought breeding network sites and their respective levels of drought stress, and to relate soil parameters with yield reduction by drought. METHODS: This study characterized levels of drought stress and soil nutrient and physical properties at 18 geographically distributed research station sites involved in rice varietal screening in Bangladesh, India, and Nepal, as well as at farmers' fields located near the research stations. RESULTS: Based on soil resistance to penetration profiles, a hardpan was surprisingly absent at about half of the sites characterized. Significant relationships of depth of compaction and yield reduction by drought indicated the effects of soil puddling on susceptibility to cracking, rather than water retention by hardpans, on plant water availability in this region. The main difference between research stations and nearby farmers' fields was in terms of soil compaction. CONCLUSIONS: These results present an initiative for understanding the range of severities of reproductive-stage drought stress in drought-prone rainfed lowland rice-growing areas in South Asia.

From QTL to variety-harnessing the benefits of QTLs for drought, flood and salt tolerance in mega rice varieties of India through a multi-institutional network.

Rice is a staple cereal of India cultivated in about 43.5Mha area but with relatively low average productivity. Abiotic factors like drought, flood and salinity affect rice production adversely in more than 50% of this area. Breeding rice varieties with inbuilt tolerance to these stresses offers an economically viable and sustainable option to improve rice productivity. Availability of high quality reference genome sequence of rice, knowledge of exact position of genes/QTLs governing tolerance to abiotic stresses and availability of DNA markers linked to these traits has opened up opportunities for breeders to transfer the favorable alleles into widely grown rice varieties through marker-assisted backcross breeding (MABB). A large multi-institutional project, "From QTL to variety: marker-assisted breeding of abiotic stress tolerant rice varieties with major QTLs for drought, submergence and salt tolerance" was initiated in 2010 with funding support from Department of Biotechnology, Government of India, in collaboration with International Rice Research Institute, Philippines. The main focus of this project is to improve rice productivity in the fragile ecosystems of eastern, northeastern and southern part of the country, which bear the brunt of one or the other abiotic stresses frequently. Seven consistent QTLs for grain yield under drought, namely, qDTY1.1, qDTY2.1, qDTY2.2, qDTY3.1, qDTY3.2, qDTY9.1 and qDTY12.1 are being transferred into submergence tolerant versions of three high yielding mega rice varieties, Swarna-Sub1, Samba Mahsuri-Sub1 and IR 64-Sub1. To address the problem of complete submergence due to flash floods in the major river basins, the Sub1 gene is being transferred into ten highly popular locally adapted rice varieties namely, ADT 39, ADT 46, Bahadur, HUR 105, MTU 1075, Pooja, Pratikshya, Rajendra Mahsuri, Ranjit, and Sarjoo 52. Further, to address the problem of soil salinity, Saltol, a major QTL for salt tolerance is being transferred into seven popular locally adapted rice varieties, namely, ADT 45, CR 1009, Gayatri, MTU 1010, PR 114, Pusa 44 and Sarjoo 52. Genotypic background selection is being done after BC2F2 stage using an in-house designed 50K SNP chip on a set of twenty lines for each combination, identified with phenotypic similarity in the field to the recipient parent. Near-isogenic lines with more than 90% similarity to the recipient parent are now in advanced generation field trials. These climate smart varieties are expected to improve rice productivity in the adverse ecologies and contribute to the farmer's livelihood.

Predicting coronary heart disease in remote settings: a prospective, cross-sectional observational study.

BACKGROUND: Coronary heart disease (CHD) places a major burden on the Australian health care system. Determining the likelihood of CHD in a patient presenting with chest pain can be particularly difficult in a remote setting where access to transportation and specialised investigations including myocardial stress studies and coronary angiography can be difficult and delayed. The objective is to develop a predictive model for determining the risk of CHD, including the value of high sensitivity C-reactive protein (hsCRP), in patients presenting with chest pain with a particular emphasis on resources and information likely to be available in a remote primary health care setting. METHODS: A prospective, cross-sectional observational study of patients with no prior diagnosis of CHD presenting to a specialist chest pain assessment clinic at Cairns Hospital from November 2012 to May 2013. RESULTS: Out of the 163 participants included in the study analyses, a total of 38 were classified as CHD likely (23.3% (95% CI 17.1-30.6)). Logistic regression modelling identified two factors that were independently associated with likely CHD, namely the presence of typical chest pain (OR 83.7 (95% CI 21.7-322.1)) and an abnormal baseline ECG (OR 12.8 (95% CI 1.9-86.0)). CONCLUSION: In this study, it was demonstrated that the presence of typical chest pain and an abnormal resting ECG, remain the cornerstone of predicting a subsequent diagnosis of CHD. This information is easily accessible in remote primary health care and should be utilised to expedite assessment in patients presenting with symptoms suggestive of CHD.

Drought yield index to select high yielding rice lines under different drought stress severities.

BACKGROUND: Drought is the most severe abiotic stress reducing rice yield in rainfed drought prone ecosystems. Variation in intensity and severity of drought from season to season and place to place requires cultivation of rice varieties with different level of drought tolerance in different areas. Multi environment evaluation of breeding lines helps breeder to identify appropriate genotypes for areas prone to similar level of drought stress. From a set of 129 advanced rice (Oryza sativa L.) breeding lines evaluated under rainfed drought-prone situations at three locations in eastern India from 2005 to 2007, a subset of 39 genotypes that were tested for two or more years was selected to develop a drought yield index (DYI) and mean yield index (MYI) based on yield under irrigated, moderate and severe reproductive-stage drought stress to help breeders select appropriate genotypes for different environments. RESULTS: ARB 8 and IR55419-04 recorded the highest drought yield index (DYI) and are identified as the best drought-tolerant lines. The proposed DYI provides a more effective assessment as it is calculated after accounting for a significant genotype x stress-level interaction across environments. For rainfed areas with variable frequency of drought occurrence, Mean yield index (MYI) along with deviation in performance of genotypes from currently cultivated popular varieties in all situations helps to select genotypes with a superior performance across irrigated, moderate and severe reproductive-stage drought situations. IR74371-70-1-1 and DGI 75 are the two genotypes identified to have shown a superior performance over IR64 and MTU1010 under all situations. CONCLUSION: For highly drought-prone areas, a combination of DYI with deviation in performance of genotypes under irrigated situations can enable breeders to select genotypes with no reduction in yield under favorable environments compared with currently cultivated varieties. For rainfed areas with variable frequency of drought stress, use of MYI together with deviation in performance of genotypes under different situations as compared to presently cultivated varieties will help breeders to select genotypes with superior performance under all situations.

Acute toxicity and bioaccumulation of tributyltin in tissues of Urolophus jamaicensis (yellow stingray).

Tributyltin oxide (TBTO) is the main constituent of tin-based antifouling marine paint used on the hulls of ships to prevent the growth of fouling organisms. TBTO was shown to be hazardous to nontarget organisms. The stingray, Urolophus jamaicensis, may represent the ideal study organism for the adverse effects of TBTO to elasmobranches. This study investigated the toxicity and accumulation of tin in the gill tissue of the stingray U. jamaicensis after acute exposure to TBTO. This work demonstrates the alterations in the morphological architecture of the gill using electron and light microscopy, the induction of stress proteins, and peroxidative damage in response to tributyltin (TBT) exposure. A captured population of U. jamaicencis was housed in isolated, static tank systems. After a minimum 30-d acclimation period, the animals were exposed to one of 5 experimental doses of TBTO (4 microg/L, 2 microg/L, 1 microg/L, 0.5 microg/L, or 0.05 microg/L). A sixth group served as a control population. At 3h following treatment, animals were sacrificed and gill tissue was extracted, processed, and stored for analysis. Results indicate that U. jamaicensis is hypersensitive to TBT exposure. The elasmobranch gill showed a distorted, swollen epithelium with exfoliation following acute exposure to as little as 0.05 microg/L TBTO for 3 h. Graphite furnace atomic absorption spectroscopy (GFAAS) results indicate that tissues of treated animals contained a significantly increased tin concentration as compared to controls. Western blot analysis demonstrated the induction of the stress proteins Hsp 70 and HO1. 4-Hydroxynonenol (4HNE) adduct formation determined by Western blot analysis provides further evidence that observed membrane degradation is a result of lipid peroxidation.

Breastfeeding and childhood cancer.

Total duration of breastfeeding and of exclusive breastfeeding was studied and compared in 99 childhood cancer cases and 90 controls. The difference between the average duration of breastfeeding in cases and controls was significant (p < 0.05), but when average duration of exclusive breastfeeding was compared in cases and controls the difference was highly significant (p < 0.001). In lymphoma cases and controls the difference between the average duration of breastfeeding was moderately significant (p < 0.01). However, when average duration of exclusive breastfeeding was compared in lymphoma cases and controls the difference was highly significant (p < 0.001). When other cancer groups and controls were compared with respect to their total duration of breastfeeding and duration of exclusive breastfeeding the differences when insignificant (p > 0.05). Cases and controls were not different with respect to their age, sex, birth year, birth order, age and educational status of mothers, smoking of fathers and socioeconomic status. However, a positive family history of cancer was obtained in 4 (4%) of cases whereas in controls it was obtained in only 1 (1.1%).

PIP: Between April 1991 and June 1992 in India, physicians compared data on 99 childhood cancer cases with data on 90 sex, age, and hospital matched controls to examine the relationship between duration of total breast feeding and exclusive breast feeding and childhood cancer. Most of the children were patients at G.S.V.M. Medical College in Kanpur or at K.G. Medical College in Lucknow. Cases and controls were essentially the same in respect to birth order, age and educational status of mothers, smoking of fathers, and socioeconomic status. 65.7% of cases had leukemia. The duration of total breast feeding was significantly longer for controls than cases (10 months vs. 8 months; p .05). The difference between mean duration of exclusive breast feeding between mean duration of exclusive breast feeding between cases and controls was significant (4.6 months vs. 3.2 months; p .001). Controls were more likely to have undergone a longer duration of total breast feeding and exclusive breast feeding than were lymphoma cases (10 months vs. 6.15 months; p .01 and 4.6 months vs. 3 months; p .001, respectively). 58% of lymphoma cases had non-Hodgkins lymphoma. When the researchers compared other cancer groups and controls, no significant difference between the 2 groups existed in respect to total breast feeding and exclusive breast feeding. These results suggest that breast feeding has a protective effect against childhood cancer. Further, they indicate that exclusive breast feeding provides more beneficial immunological effects than breast feeding supplemented by artificial feeding. The high rate of breast feeding in India may explain the low incidence of childhood cancer in India (e.g., around 6/100,000 vs. 18/100,000 in Israel).