Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation

Primary treatment for glaucoma relies on chronic instillation (daily) of intraocular pressure (IOP) lowering eye drops. Present study tends to develop and assess a novel sustained release bimatoprost loaded nanovesicular (BMT-NV) - thermosensitive in-situ gelling implant (BMT-NV- GEL-IM), for subconjunctival delivery. BMT-NVs developed using novel composition and method of preparation, (IPA/700/DEL/2014) and industrially viable methodology were characterized and evaluated comprehensively for ocular suitability. Their incorporation into an in-situ gelling formula was safe (in vitro and in vivo) and stable upon sterilization. Autoclavability was an important consideration, as a preservative-free, single-use BMT-NV- GEL-IM will avoid side- effects associated with repetitive application of drops containing preservatives like benzalkonium chloride (BAK). An extended in vitro release of BMT (80.23%) was observed for 10 days while the IOP lowering effect extended over 2 months with single subconjunctival injection of BMT-NV-GEL-IM in rats. No clinical signs of irritation, inflammation, or infection were observed in any injected eye, throughout the study, as also confirmed by histology. Furthermore, single administration of BMT-NV-GEL as topical drop lowered the IOP over 5 days. Presence of significant diffuse fluorescence in confocal microscopy of internal eye tissues post-in vivo application, as subconjunctival implant, even after 2 month and eye drops upto1 week provide direct evidence of successful sustained delivery. We thus provide an improved modality for antiglaucoma medication in patients who are challenged to adhere to a regimen of daily eye drops

In search of a theory of supercooled liquids

Despite the absence of consensus on a theory of the transition from supercooled liquids to glasses, the experimental observations suggest that a detail-independent theory should exist.Comment: Commentary. 3 pages 2 figure

Safety data on in situ gelling bimatoprost loaded nanovesicular formulations

In vitro cytotoxicity and in vivo acute and 7 days repeat-dose ocular toxicity studies, were conducted in rabbits, in accordance with the Organisation for Economic Co-operation and Development (OECD) guidelines, for bimatoprost loaded nanovesicular aqueous dispersion (BMT-NV) and its in-situ gelling sub-conjunctival implant (BMT-NV-IM). For details on the preparation and evaluation of BMT-NV and its BMT-NV-IM for the control of glaucoma, please refer to ‘Bimatoprost loaded nanovesicular long-acting sub-conjunctival in-situ gelling implant: In vitro and in vivo evaluation’ (Yadav et al., 2019). The in vivo ocular toxicity was performed only after confirming dermal safety, as required by OECD. Histological evaluation of various ocular tissues, following sub-conjunctival implantation with BMT-NV-IM, was done for ocular tolerance studies

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Agrobacterium–mediated transformation of chickpea using shoot meristem

78-84Agrobacterium-mediated gene transfer to pre-organized meristematic tissue combined with axillary regeneration was standardized for transformation and regeneration of chickpea, which otherwise was difficult to achieve from other explants. Different Agrobacterium strains harbouring binary vectors pCGP1258, containing the GUS as a reporter and bar [gene for resistance to phosphinothricin (PPT)—the active ingredient of the herbicide Basta] as the selectable marker, were used for the transformation experiments. After co-cultivation, the shoot apex explants were transferred onto a PPT-free regeneration medium and their tops (2 mm) were thoroughly wetted with PPT solution (2 mg/mL). The multiple axillary shoots developing from the shoot apices were excised and placed onto a medium containing 10 mg/L PPT. The surviving shoots were subcultured every 2nd wk onto fresh medium containing 20 mg/L PPT. After each subculture, the number of surviving shoots decreased until it stabilized. Some of the chimeric shoots surviving the PPT selection eventually developed new healthier axillary shoots, which could be rooted or grafted on in vitro grown seedling. This whole process took 6-9 months. Average transformation frequency was found between 1.29-3.33%. Transmission of the transgenes into progeny was also studied following the inheritance of uid A gene in T₁ and T₂ progenies. The overall segregation ratio among progenies of plants derived from T₀ plants appeared to be close to 3:1 Mendelian ratio, indicating integration of the transgene at single locus

Effect of Spacing and Potassium Levels on Growth and Yield of Foxtail Millet (Setaria italica L.)

A field experiment was conducted to determine the influence of spacing and potassium levels on foxtail millet (Setaria italica L.) during the (Zaid) 2022 with 9 treatments with Factor I (viz. spacing at 25ⅹ10 cm, 30ⅹ10 cm and 35ⅹ10 cm) respectively and Factor II (viz. potassium at 10, 20 and 30 kg/ha). The soil experimental plot was sandy loam texture. The experiment laid out in factorial Randomized Block Design at Crop Research Farm, Department of Agronomy, Faculty of Agriculture, SHUATS, Prayagraj (U.P). Giving of Spacing 30×10cm + 30 kg/ha Potassium recorded highest plant height in treatment 6 (104.40 cm), plant dry weight in treatment 9 (12.58g), treatment 6 is highest grain yield (2.11 t/ha) and stover yield (3.95 t/ha)

Development of stevioside Pluronic-F-68 copolymer based PLA-nanoparticles as an antidiabetic nanomedicine

Stevioside (FDA approved nontoxic natural non-caloric sweetener) has been reported to have very good antidiabetic potential but its use as therapeutic drug is restricted in human due to its deprived intestinal absorption and poor bioavailability. We have nano-bioconjugated this molecule on biodegradable Pluronic-F-68 copolymer based PLA nanoparticles by nanoprecipitation method (spherical, size range 110–130 nm) to overcome deprived intestinal absorption and to enhance the bioavailability. The drug loading calculated by the standard calibrated HPLC was 16.32 ± 4% (w/w). The in vitro release study showed the initial burst followed by the sustained release. The half release and complete release were observed on 25 ± 4 h and 200 ± 10 h respectively. This newly formulated nanostevioside showed very high potential to be used as antidiabetic nanomedicine for safe and effective use in vivo

Assessment of Gene Action and Identification of Heterotic Hybrids for Enhancing Yield in Field Pea

Eight field pea parental lines and their twenty-eight F1s resulting from diallel design (excluding reciprocal) were analyzed for their combining ability and heterosis for yield and associated traits. ANOVA revealed significant variation among parents and among hybrids for days to 50% flowering, plant height, total number of pods, effective pods, seeds per pod, 100-seed weight, biological yield and seed yield; pod length also revealed significant differences among hybrids, suggesting the occurrence of considerable variability for studied traits. Crosses P-1541-16 × P-92-97-11 and P-1541-16 × P-1297-97 displayed significant heterosis over better-parent and control varieties for seed yield and associated traits. Combining ability analysis showedthat SCAvariance was considerably higher than corresponding GCAvariance for all traits. Genotype Aman and P-1297-97 were identified as good general combiners for seed yield, while cross P-1541-16 × P-1297-97, Aman × EC-564817, P-1541-16 × P-92-97-11 and P-1297-97 × P-92-97-11 were identified as specific cross-combiners for most of the studied traits. Consequently, these crosses might be exploited in future breeding programs to find desired segregants. PCA explained 81.68% and 83.34% variability in parents and crosses, respectively, for yield component. Furthermore, trait association between GCA effects and SCA effects demonstrates that biological yield, total number of pods, and effective pods exhibit additive gene action, but 100-seed weight exhibits non-additive gene action

Not Available

Not AvailablePolyoxin D zinc salt 5%SC is a new, medium risk fungicide.The compatibility of the fungicide @ 600 and 1200 ppm was investigated withTrichoderma viride, Bacillus subtilis, Pseudomonas fluorescence, Ampelomyces quisqualis, Beauveria bassiana, Metarhizium anisopliae and Paecilomyces lilacinus under in vitro conditions. It was observed that Polyoxin –D zinc salt @ 600 and 1200 ppm were compatible with Trichoderma viride, Bacillus subtilis and Pseudomonas fluorescens, Ampelomyces quisqualis, Metarhizium anisopliae and Paecilomyces lilacinus but in case of Beauveria bassiana the fungicide was incompatible. Thus Polyoxin D zinc salt 5% SC @ 600 ppm may be recommended against powdery mildew of grapes and may be used in tandem with the bio control agents used in grapes.Not Availabl