Pharmacological studies on the antinociceptive, anxiolytic and antidepressant activity of Tinospora crispa

Pharmacological studies were performed in mice on the methanol extract of Tinospora crispa (TC), and of its hexane (HF) and chloroform (CF) fractions. Significant antinociceptive activity was observed for TC, HF, and CF in the acetic acid-induced writhing and formalin-induced paw licking tests. Anxiolytic and antidepressant activity were assessed using the open field, hole board, and elevated plus maze (EPM) tests. TC, HF, and CF demonstrated a significant decrease in spontaneous locomotor activity. They also showed an increase in the number of head-dippings in the hole board test, suggesting decreased fearfulness. TC, and most of its fractions, showed a significant increase of the time spent in the opened arm of the EPM, indicating reduced anxiety. A computational study (PASS prediction, molecular docking and ADME/T analyses) was performed to identify the phytochemicals responsible for activity. Syringin and secoisolariciresinol, displayed a strong predictive binding affinity towards the cyclooxygenase COX-1 and COX-2 enzymes and the KcsA potassium channel while rumphioside B showed the highest predicted binding affinity towards the human serotonin receptor. This provided some support to explain the observed in-vivo antinociceptive, anxiolytic and antidepressant effects and the traditional use of T. crispa as a remedy for pain

Impact of peer review in the radiation treatment planning process: Experience of a tertiary care university hospital in Pakistan

Purpose: To evaluate and report the frequency of changes in radiation therapy treatment plans after peer review in a simulation review meeting once a week.Materials and Methods: Between July 1 and August 31, 2016, the radiation plans of 116 patients were discussed in departmental simulation review meetings. All plans were finalized by the primary radiation oncologist before presenting them in the meeting. A team of radiation oncologists reviewed each plan, and their suggestions were documented as no change, major change, minor change, or missing contour. Changes were further classified as changes in clinical target volume, treatment field, or dose. All recommendations were stratified on the basis of treatment intent, site, and technique. Data were analyzed by Statistical Package for the Social Sciences and are presented descriptively.Results: Out of 116 plans, 26 (22.4%) were recommended for changes. Minor changes were suggested in 15 treatment plans (12.9%) and a major change in 10 (8.6%), and only one plan was suggested for missing contour. The frequency of change recommendations was greater in radical radiation plans than in palliative plans (92.3% v 7.7%). The head and neck was the most common treatment site recommended for any changes (42.3%). Most of the changes were recommended in the technique planned with three-dimensional conformal radiation therapy (50%). Clinical target volume (73.1%) was identified as the most frequent parameter suggested for any change, followed by treatment field (19.2%) and dose (0.08%).Conclusion: Peer review is an important tool that can be used to overcome deficiencies in radiation treatment plans, with a goal of improved and individualized patient care. Our study reports changes in up to a quarter of radiotherapy plans

Phytochemical screening and antibacterial activity of different fractions of Operculina turpethum root and leaf

ABSTRACT In Bangladesh, the herb Operculina turpethum is used for otitis media, suppurative sores, burns, conjunctivitis and skin diseases (eczema, abscesses, acne, scabies and warts) although the compounds responsible for the medicinal properties have not been identified. The present study has been undertaken for antibacterial activity of the ethanol, ether and chloroform extract of O. turpethum root and leaf. Antibacterial activity has been investigated against Shigella boydii, Shigella flese, Shigella dysenteriae, Escherichia coli, Proteus vulgaris, Salmonella typhi, Hafnia alvei, Staphylococcus epidermidis, Streptococcus pyogenes, Staphylococcus aureus, Enterococcus faecalis by disc diffusion and broth macro-dilution assay. The zone of inhibition has been observed with almost all bacteria with some exceptions. Minimum inhibitory concentrations (MIC) of the extracts were found to be significant

Mapping local patterns of childhood overweight and wasting in low- and middle-income countries between 2000 and 2017

A double burden of malnutrition occurs when individuals, household members or communities experience both undernutrition and overweight. Here, we show geospatial estimates of overweight and wasting prevalence among children under 5 years of age in 105 low- and middle-income countries (LMICs) from 2000 to 2017 and aggregate these to policy-relevant administrative units. Wasting decreased overall across LMICs between 2000 and 2017, from 8.4% (62.3 (55.1–70.8) million) to 6.4% (58.3 (47.6–70.7) million), but is predicted to remain above the World Health Organization’s Global Nutrition Target of <5% in over half of LMICs by 2025. Prevalence of overweight increased from 5.2% (30 (22.8–38.5) million) in 2000 to 6.0% (55.5 (44.8–67.9) million) children aged under 5 years in 2017. Areas most affected by double burden of malnutrition were located in Indonesia, Thailand, southeastern China, Botswana, Cameroon and central Nigeria. Our estimates provide a new perspective to researchers, policy makers and public health agencies in their efforts to address this global childhood syndemic

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

Genetic polymorphisms of GSTM1, GSTP1 and GSTT1 genes and lung cancer susceptibility in the Bangladeshi population

Objective: To verify possible associations between polymorphisms of glutathione S-transferase Mu (GSTM1), glutathione S-transferase θ (GSTT1) and glutathione S-transferase Pi (GSTP1) genes and susceptibility to lung cancer. Methods: A total of 106 lung cancer patients and 116 controls were enrolled in a case-control study. The GSTM1 and GSTT1 were analyzed using PCR while GSTP1 was analyzed using PCR-restriction fragment length polymorphism. Risk of lung cancer was estimated as odds ratio at 95% confidence interval using unconditional logistic regression models adjusting for age, sex, and tobacco use. Results: GSTM1 null and GSTT1 null genotypes did not show a significant risk for developing lung cancer. A significantly elevated lung cancer risk was associated with GSTP1 heterozygous, mutant and combined heterozygous+mutant variants of rs1695. When classified by tobacco consumption status, no association with risk of lung cancer was found in case of tobacco smokers and nonsmokers carrying null and present genotypes of GSTM1 and GSTT1. There is a three-fold (approximately) increase in the risk of lung cancer in case of both heterozygous (AG) and heterozygous+mutant homozygous (AG+GG) genotypes whereas there is an eight-fold increase in risk of lung cancer in cases of GG with respect to AA genotype in smokers. Conclusions: Carrying the GSTM1 and GSTT1 null genotype is not a risk factor for lung cancer and GSTP1Ile105Val is associated with elevated risk of lung cancer

Phytochemical investigations and antioxidant potential of roots of Leea macrophylla (Roxb.)

Abstract Background Oleanolic acid (NZ-15), 7 α, 28-olean diol (NZ-38) and Stigmasterol (NZ-14) were isolated from the ethanolic extracts of the roots of Leea macrophylla (Family: Leeaceae) by using chromatographic analysis. This is the first report of isolation of these compounds from this plant. Their structures were constructed by spectroscopic analysis and by comparing the data with the published one. Subsequently the ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property. Methods The ethanolic extract was fractionated with two organic solvents and all the fractions were studied to evaluate their in vitro antioxidant property by DPPH free radical scavenging assay, superoxide anion radical scavenging assay, nitric oxide radical scavenging assay, and reducing power assay. Results In the DPPH free radical scavenging assay and superoxide radical scavenging assay, the ethyl acetate soluble fraction of ethanolic extract revealed the highest free radical scavenging activity with IC50 value of 2.65 and 155.62 μg/ml, respectively as compared to standard ascorbic acid (IC50 value of 5.8 and 99.66 μg/ml). Ethyl acetate fraction also possessed highest reducing power activity with an EC50 value of 15.27 μg/ml compared to ascorbic acid (EC50 0.91 μg/ml). On the other hand, the carbon tetrachloride fraction exhibited most significant NO scavenging activity with IC50 value of 277.8 μg/ml that was even higher than that of standard ascorbic acid (IC50 value 356.04 μg/ml). In addition, the total phenolic contents of these extract and fractions were evaluated using Folin-Ciocalteu reagent and varied from 7.93 to 50.21 mg/g dry weight expressed as gallic acid equivalents (GAE). Conclusions This study showed that different extracts of roots of L. macrophylla possess potential DPPH, superoxide, and NO free radical scavenging activities. The antioxidant activities of the plant extracts might be due to the presence of oleanolic acid, oleanolic acid derivative 7 α, 28-olean diol and stigmasterol

Antipyretic and hepatoprotective potential of Tinospora crispa and investigation of possible lead compounds through in silico approaches

This research describes an investigation of the antipyretic and hepatoprotective properties of both a crude organic extract and various subfractions of the ethnomedicinal plant Tinospora crispa, using appropriate animal models. In an attempt to identify potential lead hepatoprotective compounds, in silico experiments were utilized. Antipyretic activity was assessed via the Brewer's yeast-induced pyrexia method, while hepatoprotective effects were evaluated in a carbon tetrachloride (CCl4)-induced animal model. A computer-aided prediction of activity spectra for substances (PASS) model was applied to a selection of documented phytoconstituents, with the aim of identifying those compounds with most promising hepatoprotective effects. Results were analyzed using Molinspiration software. Our results showed that both the methanol extract (METC) and various subfractions (pet ether, PEFTC; n-hexane, NHFTC; and chloroform, CFTC) significantly (p &lt; .05) reduced pyrexia in a dose-dependent manner. In CCl4-induced hepatotoxicity studies, METC ameliorated elevated hepatic markers including serum alanine amino transferase (ALT), aspartate amino transferase (AST), alkaline phosphatase (ALP), and total bilirubin. Malondialdehyde (MDA) levels were significantly reduced, while superoxide dismutase (SOD) levels were significantly increased. Among a selection of metabolites of T. crispa, genkwanin was found to be the most potent hepatoprotective constituent using PASS predictive models. These results demonstrate that both the methanolic extract of T. crispa and those fractions containing genkwanin may offer promise in reducing pyrexia and as a source of potential hepatoprotective agents