Development and evaluation of floating microspheres of curcumin in alloxan-induced diabetic rats

Purpose: To prepare and evaluate floating microspheres of curcumin for prolonged gastric residence and to study their effect on alloxan-induced diabetic rats.Methods: Floating microsphere were prepared by emulsion-solvent diffusion method, using hydroxylpropyl methylcellulose, chitosan and Eudragit S 100 polymer in varying proportions. Ethanol/dichloromethane blend was used as solvent in a ratio of 1:1. The floating microspheres were evaluated for flow properties, particle size, incorporation efficiency, as well as in-vitro floatability and drug release. The anti-diabetic activity of the floating microspheres of batch FM4 was performed on alloxaninduced diabetic rats.Result: The floating microspheres had particle size, buoyancy, drug entrapment efficiency and yield in the ranges of 255.32 - 365.65 μm, 75.58 - 89.59, 72.6 - 83.5, and 60.46 - 80.02 %, respectively. Maximum drug release after 24 h was 82.62 % for formulation FM4 and 73.879, 58.613 and 46.106 % for formulations FM1, FM2, and FM3 respectively. In-vivo data obtained over a 120-h period indicate that curcumin floating microspheres from batch FM4 showed the better glycemic control than control and a commercial brand of the drug.Conclusion: The developed floating curcumin delivery system seems economical and effective in diabetes management in rats, and enhances the bioavailability of the drug.Keywords: Gastro-retentive, Sustained release, Bioavailability, Curcumin, Floating microspheres, Diabete

The global burden of adolescent and young adult cancer in 2019 : a systematic analysis for the Global Burden of Disease Study 2019

Background In estimating the global burden of cancer, adolescents and young adults with cancer are often overlooked, despite being a distinct subgroup with unique epidemiology, clinical care needs, and societal impact. Comprehensive estimates of the global cancer burden in adolescents and young adults (aged 15-39 years) are lacking. To address this gap, we analysed results from the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2019, with a focus on the outcome of disability-adjusted life-years (DALYs), to inform global cancer control measures in adolescents and young adults. Methods Using the GBD 2019 methodology, international mortality data were collected from vital registration systems, verbal autopsies, and population-based cancer registry inputs modelled with mortality-to-incidence ratios (MIRs). Incidence was computed with mortality estimates and corresponding MIRs. Prevalence estimates were calculated using modelled survival and multiplied by disability weights to obtain years lived with disability (YLDs). Years of life lost (YLLs) were calculated as age-specific cancer deaths multiplied by the standard life expectancy at the age of death. The main outcome was DALYs (the sum of YLLs and YLDs). Estimates were presented globally and by Socio-demographic Index (SDI) quintiles (countries ranked and divided into five equal SDI groups), and all estimates were presented with corresponding 95% uncertainty intervals (UIs). For this analysis, we used the age range of 15-39 years to define adolescents and young adults. Findings There were 1.19 million (95% UI 1.11-1.28) incident cancer cases and 396 000 (370 000-425 000) deaths due to cancer among people aged 15-39 years worldwide in 2019. The highest age-standardised incidence rates occurred in high SDI (59.6 [54.5-65.7] per 100 000 person-years) and high-middle SDI countries (53.2 [48.8-57.9] per 100 000 person-years), while the highest age-standardised mortality rates were in low-middle SDI (14.2 [12.9-15.6] per 100 000 person-years) and middle SDI (13.6 [12.6-14.8] per 100 000 person-years) countries. In 2019, adolescent and young adult cancers contributed 23.5 million (21.9-25.2) DALYs to the global burden of disease, of which 2.7% (1.9-3.6) came from YLDs and 97.3% (96.4-98.1) from YLLs. Cancer was the fourth leading cause of death and tenth leading cause of DALYs in adolescents and young adults globally. Interpretation Adolescent and young adult cancers contributed substantially to the overall adolescent and young adult disease burden globally in 2019. These results provide new insights into the distribution and magnitude of the adolescent and young adult cancer burden around the world. With notable differences observed across SDI settings, these estimates can inform global and country-level cancer control efforts. Copyright (C) 2021 The Author(s). Published by Elsevier Ltd.Peer reviewe

Global burden of 288 causes of death and life expectancy decomposition in 204 countries and territories and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BACKGROUND Regular, detailed reporting on population health by underlying cause of death is fundamental for public health decision making. Cause-specific estimates of mortality and the subsequent effects on life expectancy worldwide are valuable metrics to gauge progress in reducing mortality rates. These estimates are particularly important following large-scale mortality spikes, such as the COVID-19 pandemic. When systematically analysed, mortality rates and life expectancy allow comparisons of the consequences of causes of death globally and over time, providing a nuanced understanding of the effect of these causes on global populations. METHODS The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 cause-of-death analysis estimated mortality and years of life lost (YLLs) from 288 causes of death by age-sex-location-year in 204 countries and territories and 811 subnational locations for each year from 1990 until 2021. The analysis used 56 604 data sources, including data from vital registration and verbal autopsy as well as surveys, censuses, surveillance systems, and cancer registries, among others. As with previous GBD rounds, cause-specific death rates for most causes were estimated using the Cause of Death Ensemble model-a modelling tool developed for GBD to assess the out-of-sample predictive validity of different statistical models and covariate permutations and combine those results to produce cause-specific mortality estimates-with alternative strategies adapted to model causes with insufficient data, substantial changes in reporting over the study period, or unusual epidemiology. YLLs were computed as the product of the number of deaths for each cause-age-sex-location-year and the standard life expectancy at each age. As part of the modelling process, uncertainty intervals (UIs) were generated using the 2·5th and 97·5th percentiles from a 1000-draw distribution for each metric. We decomposed life expectancy by cause of death, location, and year to show cause-specific effects on life expectancy from 1990 to 2021. We also used the coefficient of variation and the fraction of population affected by 90% of deaths to highlight concentrations of mortality. Findings are reported in counts and age-standardised rates. Methodological improvements for cause-of-death estimates in GBD 2021 include the expansion of under-5-years age group to include four new age groups, enhanced methods to account for stochastic variation of sparse data, and the inclusion of COVID-19 and other pandemic-related mortality-which includes excess mortality associated with the pandemic, excluding COVID-19, lower respiratory infections, measles, malaria, and pertussis. For this analysis, 199 new country-years of vital registration cause-of-death data, 5 country-years of surveillance data, 21 country-years of verbal autopsy data, and 94 country-years of other data types were added to those used in previous GBD rounds. FINDINGS The leading causes of age-standardised deaths globally were the same in 2019 as they were in 1990; in descending order, these were, ischaemic heart disease, stroke, chronic obstructive pulmonary disease, and lower respiratory infections. In 2021, however, COVID-19 replaced stroke as the second-leading age-standardised cause of death, with 94·0 deaths (95% UI 89·2-100·0) per 100 000 population. The COVID-19 pandemic shifted the rankings of the leading five causes, lowering stroke to the third-leading and chronic obstructive pulmonary disease to the fourth-leading position. In 2021, the highest age-standardised death rates from COVID-19 occurred in sub-Saharan Africa (271·0 deaths [250·1-290·7] per 100 000 population) and Latin America and the Caribbean (195·4 deaths [182·1-211·4] per 100 000 population). The lowest age-standardised death rates from COVID-19 were in the high-income super-region (48·1 deaths [47·4-48·8] per 100 000 population) and southeast Asia, east Asia, and Oceania (23·2 deaths [16·3-37·2] per 100 000 population). Globally, life expectancy steadily improved between 1990 and 2019 for 18 of the 22 investigated causes. Decomposition of global and regional life expectancy showed the positive effect that reductions in deaths from enteric infections, lower respiratory infections, stroke, and neonatal deaths, among others have contributed to improved survival over the study period. However, a net reduction of 1·6 years occurred in global life expectancy between 2019 and 2021, primarily due to increased death rates from COVID-19 and other pandemic-related mortality. Life expectancy was highly variable between super-regions over the study period, with southeast Asia, east Asia, and Oceania gaining 8·3 years (6·7-9·9) overall, while having the smallest reduction in life expectancy due to COVID-19 (0·4 years). The largest reduction in life expectancy due to COVID-19 occurred in Latin America and the Caribbean (3·6 years). Additionally, 53 of the 288 causes of death were highly concentrated in locations with less than 50% of the global population as of 2021, and these causes of death became progressively more concentrated since 1990, when only 44 causes showed this pattern. The concentration phenomenon is discussed heuristically with respect to enteric and lower respiratory infections, malaria, HIV/AIDS, neonatal disorders, tuberculosis, and measles. INTERPRETATION Long-standing gains in life expectancy and reductions in many of the leading causes of death have been disrupted by the COVID-19 pandemic, the adverse effects of which were spread unevenly among populations. Despite the pandemic, there has been continued progress in combatting several notable causes of death, leading to improved global life expectancy over the study period. Each of the seven GBD super-regions showed an overall improvement from 1990 and 2021, obscuring the negative effect in the years of the pandemic. Additionally, our findings regarding regional variation in causes of death driving increases in life expectancy hold clear policy utility. Analyses of shifting mortality trends reveal that several causes, once widespread globally, are now increasingly concentrated geographically. These changes in mortality concentration, alongside further investigation of changing risks, interventions, and relevant policy, present an important opportunity to deepen our understanding of mortality-reduction strategies. Examining patterns in mortality concentration might reveal areas where successful public health interventions have been implemented. Translating these successes to locations where certain causes of death remain entrenched can inform policies that work to improve life expectancy for people everywhere. FUNDING Bill & Melinda Gates Foundation

Trends in Neurosurgical Teleconsultation Services Across the Globe During COVID-19 Pandemic

Background: Global use of telemedicine has increased rapidly during the coronavirus disease 2019 (COVID-19) pandemic to bridge the gap in existing health care services. Intercontinental trends in neurosurgeons' perception and practices of telemedicine have been sparingly reported. Methods: We conducted an online anonymized and validated survey using a structured questionnaire to gain insight into neurosurgeons' experience with telemedicine across various continents and rated its usefulness on a 5-point Likert scale. Results: We received 286 responses across 5 continents. There was a trend to support a major paradigm shift favoring teleconsultations during the COVID-19 pandemic in respondents from North America (P = 0.06). Signed prescriptions were e-mailed along with video-based teleconsultations preferentially in Europe and North America. In comparison, audio- or text-based teleconsultations along with unsigned prescriptions were prevalent in Asia and Africa (P = 0.0005). Acceptability and perceived usefulness for telemedicine during the pandemic were similar across the globe, regardless of neurosurgeons' experience (mean satisfaction score 3.72 ± 1.09; P = 0.62). A majority of neurosurgeons from Asia and South America complained of difficulties during teleconsultations owing to lack of appropriate infrastructure, internet connectivity/prescription-related issues, and potential risk of litigation (P = 0.0005). Approximately 46% of neurosurgeons, predominantly from Europe and North America, thought that telemedicine could play a vital role in clinical practice even after the COVID-19 pandemic subsides (mean satisfaction score 3.26 ± 1.16; P = 0.007). Conclusions: Telemedicine in neurosurgery is a viable alternative to physical outpatient services during the COVID-19 pandemic and could potentially play a vital role after the pandemic

An assessment of the variation in the practice of lumbar discectomy and its role in axial back pain

Background: Lumbar discectomy is performed for symptomatic lumbar disc herniation and is one of the most widely performed spinal surgical procedures worldwide in a variety of ways. This survey aimed at providing an overview/perspective of different practice patterns and the impact of lumbar discectomy on axial back pain with or without sciatica. Methods: An online survey was performed using the application “Google Forms.” The link to the questionnaire was distributed to neurosurgeons through personal E-mail and social media platforms. Results: We received 333 responses. The largest percentage of responses across five continents was from Asia (66.97%, n = 223). The mean age of the respondents was 40.08 ± 10.5 years. A total of 66 respondents (20%) had a spine practice of 7%–90%, and 28 respondents had a spine practice of 90%–100% (8.4%). The number of respondents who practiced microscopic discectomy using a tubular retractor (n = 143 respondents, 42.9%) was nearly equal to the number of respondents who practiced open discectomy (n = 142 respondents, 42.6%). An almost equal proportion of respondents believed discectomy does not help in relieving axial back pain. Only 20.4% (n = 68) of respondents recommend bed rest for a longer duration postoperatively. Conclusions: Our survey revealed that only 22.2% of spine surgeons recommended discectomy in patients with radiological disc herniation with axial back pain alone and preferred a minimally invasive method of discectomy. Almost half of them believed discectomy to be ineffective for axial low back pain and only a few recommended prolonged bed rest postoperatively

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Not AvailableDry root rot (Rhizoctonia bataticola) is an important disease of lentils (Lens culinaris Medik.).To gain an insight into the molecular aspects of host-pathogen interactions, the RNA-seq approach was used in lentils following inoculation with R.bataticola. The RNA-Seq has generated >450 million high-quality reads (HQRs) and nearly 96.97% were properly aligned to the reference genome. Very high similarity in FPKM (fragments per kilobase of exon per million mapped fragments) values (R > 0.9) among biological replicates showed the consistency of the RNA-Seq results. The study revealed various DEGs (differentially expressed genes) that were associated with changes in phenolic compounds, transcription factors (TFs), antioxidants, receptor kinases, hormone signals which corresponded to the cell wall modification enzymes, defense-related metabolites, and jasmonic acid (JA)/ethylene (ET) pathways. Gene ontology (GO) categorization also showed similar kinds of significantly enriched similar GO terms. Interestingly, of the total unigenes (42,606), 12,648 got assembled and showed significant hit with Rhizoctonia species. String analysis also revealed the role of various disease responsive proteins viz., LRR family proteins, LRR-RLKs, protein kinases, etc. in the host-pathogen interaction. Insilico validation analysis was performed using Genevestigator® and DEGs belonging to six major defense-response groups viz., defense-related enzymes, disease responsive genes, hormones, kinases, PR (pathogenesis related) proteins, and TFs were validated. For the first time some key miRNA targets viz. miR156, miR159, miR167, miR169, and miR482 were identified from the studied transcriptome, which may have some vital role in Rhizoctonia-based responses in lentils. The study has revealed the molecular mechanisms of the lentil/R.bataticola interactions and also provided a theoretical approach for the development of lentil genotypes resistant to R.bataticolaNot Availabl