ANTI-ANEMIC ACTIVITY OF SPROUTS OF VIGNA RADIATA L. IN MALE ALBINO RATS

Objective: To evaluate the anti-anemic activity of sprouts of Vigna radiata L. against phenyl hydrazine induced anemic rats.Methods: Rats were divided into 4 groups of 6 each. Group 1 was given normal saline and served as control and all other groups were given 40 mg/kg b. w of phenyl hydrazine for 2 d to induce anemia. Group 3 was treated with Bioferon (230 mg/kg) and served as the standard. Group 4 was treated with sprouted Vigna radiata L. (600 mg/kg bw). All the treatments were given orally. On completion of the experimental period, all the test substance/vehicle-treated rats were sacrificed and the plasma separated was used for estimating various biochemical as well as hematological parameters as per standard procedures. Results: The experimental rats treated with sprouted Vigna radiata L. at the dose level 600 mg/kg bw for 13 d revealed significant changes in biochemical and hematological parameters compared to phenyl hydrazine induced anemic rats.Conclusion: The present study concluded that the sprouted Vigna radiata L. inhibits anemia induced by phenyl hydrazine in male albino rats. Â

Anatomical studies on the leaf and stem of Tinospora formanii Udayan & Pradeep (Menispermaceae), an endemic species to Southern Western Ghats, Kerala, India

The anatomical studies on leaf and stem of T. formanii Udayan & Pradeep an endemic species to southern Western Ghats, Kerala, India was carried out focusing on its macroscopic, microscopic, maceration along with organoleptic evaluation. Distinguishing characters of the stem revealed the presence of calcium oxalate crystals, simple and compound starch grains and pitted lignified fibers. Leaf anatomy showed the anomocytic and paracytic stomata, pitted lignified fibers, spiral vessels, non-glandular small trichomes, C or half-moon shaped vascular bundle, surrounded with sclerenchymatous tissues and rosette and prism shaped calcium oxalate crystals. Whereas, maceration studies revealed the presence of spiral and scalar form vessel, fibers, calcium oxalate crystals, simple starch grains. These anatomical studies are vital in the present-day trade scenario not only helpful in the proper identification of the genuine materials in use but also to distinguish different species of Tinospora, where the stem and leaf are often admixed with other species of Tinospora in the crude drug markets

3-(4-Methoxy­phen­yl)-6-(phenyl­sulfon­yl)perhydro-1,3-thiazolo[3′,4′:1,2]pyrrolo[4,5-c]pyrrole

In the title compound, C21H24N2O3S2, the three five-membered rings adopt envelope conformations. The dihedral angle between the two aromatic rings is 68.4 (1)°. C—H⋯O inter­actions link the mol­ecules into a chain and the chains are cross-linked via C—H⋯π inter­actions involving the meth­oxy­phenyl ring

1′-Phenyl-6′-thia­cyclo­heptane-1-spiro-2′-perhydro­pyrrolizine-3′-spiro-3′′-indoline-2,2′′-dione

The thia­zolidine ring and the pyrrolidine ring in the title compound, C25H26N2O2S, both adopt an envelope conformation. The seven-membered ring has a twist-chair conformation. The crystal packing is stabilized by inter­molecular N—H⋯O hydrogen bonds

Evaluation of antihypercholesterolemic effect using Memecylon edule Roxb. ethanolic extract in cholesterol-induced Swiss albino mice

Purpose/Aim: In the present study, we investigate the antihypercholesterolemic effect of the ethanolic extract of Memecylon edule in in vivo. Methods: Cholesterol (1%) -induced experimental groups were treated with 100 mg/kg and 200 mg/kg M. edule ethanolic extract. The study period of antihypercholesterolemia, the mice body weight, lipid profile, serum enzymes (such as superoxide dismutase, catalase, and glutathione peroxidase), liver marker enzyme, and histopathological study of liver tissues were examined. Results: The M. edule-treated groups have exhibited significant changes in total cholesterol, very-low-density lipoprotein, and low-density lipoprotein, and eventually increased the high-density-lipoprotein activity in serum. Also, it reduced the malondialdehyde level and increased the antioxidant-enzyme activities. The activity is mainly the presence of flavonoids, tannins, saponins, and glycosides in the ethanolic extract of M. edule. Conclusion; The M. edule extract contains a different class of secondary metabolites, which reduces the hypercholesterolemic condition in the experimental animal model. The results explored the M. edule extract as a potent drug for hypercholesterolemic condition

Physics Potential of the ICAL detector at the India-based Neutrino Observatory (INO)

The upcoming 50 kt magnetized iron calorimeter (ICAL) detector at the India-based Neutrino Observatory (INO) is designed to study the atmospheric neutrinos and antineutrinos separately over a wide range of energies and path lengths. The primary focus of this experiment is to explore the Earth matter effects by observing the energy and zenith angle dependence of the atmospheric neutrinos in the multi-GeV range. This study will be crucial to address some of the outstanding issues in neutrino oscillation physics, including the fundamental issue of neutrino mass hierarchy. In this document, we present the physics potential of the detector as obtained from realistic detector simulations. We describe the simulation framework, the neutrino interactions in the detector, and the expected response of the detector to particles traversing it. The ICAL detector can determine the energy and direction of the muons to a high precision, and in addition, its sensitivity to multi-GeV hadrons increases its physics reach substantially. Its charge identification capability, and hence its ability to distinguish neutrinos from antineutrinos, makes it an efficient detector for determining the neutrino mass hierarchy. In this report, we outline the analyses carried out for the determination of neutrino mass hierarchy and precision measurements of atmospheric neutrino mixing parameters at ICAL, and give the expected physics reach of the detector with 10 years of runtime. We also explore the potential of ICAL for probing new physics scenarios like CPT violation and the presence of magnetic monopoles.Comment: 139 pages, Physics White Paper of the ICAL (INO) Collaboration, Contents identical with the version published in Pramana - J. Physic

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

31st Annual Meeting and Associated Programs of the Society for Immunotherapy of Cancer (SITC 2016) : part two

Background The immunological escape of tumors represents one of the main ob- stacles to the treatment of malignancies. The blockade of PD-1 or CTLA-4 receptors represented a milestone in the history of immunotherapy. However, immune checkpoint inhibitors seem to be effective in specific cohorts of patients. It has been proposed that their efficacy relies on the presence of an immunological response. Thus, we hypothesized that disruption of the PD-L1/PD-1 axis would synergize with our oncolytic vaccine platform PeptiCRAd. Methods We used murine B16OVA in vivo tumor models and flow cytometry analysis to investigate the immunological background. Results First, we found that high-burden B16OVA tumors were refractory to combination immunotherapy. However, with a more aggressive schedule, tumors with a lower burden were more susceptible to the combination of PeptiCRAd and PD-L1 blockade. The therapy signifi- cantly increased the median survival of mice (Fig. 7). Interestingly, the reduced growth of contralaterally injected B16F10 cells sug- gested the presence of a long lasting immunological memory also against non-targeted antigens. Concerning the functional state of tumor infiltrating lymphocytes (TILs), we found that all the immune therapies would enhance the percentage of activated (PD-1pos TIM- 3neg) T lymphocytes and reduce the amount of exhausted (PD-1pos TIM-3pos) cells compared to placebo. As expected, we found that PeptiCRAd monotherapy could increase the number of antigen spe- cific CD8+ T cells compared to other treatments. However, only the combination with PD-L1 blockade could significantly increase the ra- tio between activated and exhausted pentamer positive cells (p= 0.0058), suggesting that by disrupting the PD-1/PD-L1 axis we could decrease the amount of dysfunctional antigen specific T cells. We ob- served that the anatomical location deeply influenced the state of CD4+ and CD8+ T lymphocytes. In fact, TIM-3 expression was in- creased by 2 fold on TILs compared to splenic and lymphoid T cells. In the CD8+ compartment, the expression of PD-1 on the surface seemed to be restricted to the tumor micro-environment, while CD4 + T cells had a high expression of PD-1 also in lymphoid organs. Interestingly, we found that the levels of PD-1 were significantly higher on CD8+ T cells than on CD4+ T cells into the tumor micro- environment (p < 0.0001). Conclusions In conclusion, we demonstrated that the efficacy of immune check- point inhibitors might be strongly enhanced by their combination with cancer vaccines. PeptiCRAd was able to increase the number of antigen-specific T cells and PD-L1 blockade prevented their exhaus- tion, resulting in long-lasting immunological memory and increased median survival