68 research outputs found
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
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
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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
Hematopoietic and hepatoprotective activity of Basella alba L. fruit extract in experimental animal model
843-851Basella alba L. fruit extract (BAFE) has been used in rural eastern India by the traditional practitioners to treat anemia during pregnancy. In the present study, we have demostrated the hematopoietic and hepatoprotective activity of BAFE in animal model. Male Swiss albino rats were divided into: Gr. I, sham control; Gr. II, disease control (anemia or hepatotoxicity); Gr. III, standard drug treated; Gr. IV, BAFE treated (low dose); and Gr.V, BAFE treated (high dose). Anemia was induced in animals through blood loss at regular intervals and hematological, cytokine, antioxidant parameters and RBC morphology were done. Hepatotoxicity was induced in animals by CCl4 (1 mL/kg/p.o.) and serum biochemistry, cytokine, antioxidant parameters and histology were done. There was a significant improvement of hematology (Hb, TC of RBC, TC of WBC, hematocrit, serum iron, TIBC), cytokine (IL 1β), antioxidant (SOD, catalase, LPO, GSH) and RBC morphology in BAFE treated animals when compared to Gr. II animals. Significant improvement in biochemical (AST, ALT, γGT, ACP, ALP and total bilirubin), cytokine (IL 1β, IL 4, IL 12, IL 17, cathepsin K and TNF α), antioxidant (SOD, catalase, LPO and GSH) and liver histology were observed in BAFE treated animals when compared to Gr. II animals. The present study confirmed the hematopoietic and hepatoprotective activity of BAFE in animal model and warrants further studies
Inhibition of toxic actions of phospholipase A2 isolated & characterized from the Indian Banded Krait (Bungarus fasciatus) venom by synthetic herbal compounds
Phospholipase A2 (PLA2) is one of the major constituents of krait venom
associated with several pathophysiological actions like myotoxicity, cardiotoxicity, neurotoxicity, 12&6
As there was no specific antiserum available against :7%5&3%2+5 venom by CM-cellulose and HPLC, of 13.17
kDa and a minor band of 7.3 kDa using ESI-MS. The 13.17 kDa PLA2 sequence was NLYQFKNMIQC.
The 7.3 kDa toxin sequence was RKCLTKYSQDNES and was found to be <10 per cent w/w. Anti PLA2
rabbit antiserum produced faint precipitant band in immunogel diffusion and showed low titre value.
The commercial polyvalent snake venom antiserum, anti PLA2 rabbit antiserum and the synthetic herbal
compounds neutralized the PLA2 induced toxicities at different intensities.
Our results suggested that synthetic herbal compound (BA) along with
antiserum might provide effective protection against PLA2 induced toxicities of $:7%5&3%2+5 venom
Nanotechnology in snake venom research—an overview
707-715Nanotechnology has revolutionized the paradigm of today’s upcoming biological sciences through its applications in the field of biomedical research. One such promising aspect is by interfacing this modern technology with snake venom research. Snake venom is a valuable resource of bioactive molecules, which has shown efficient and promising contributions in biomedical research. The potentiality of merging these two unique fields lies in the approach of interfacing active bioactive molecules derived from snake venoms, which would yield better therapeutic molecules for future applications in terms of drug delivery, enhanced stability, reduced toxicity, bioavailability and targeted drug delivery. Available literature on nanoconjugation of snake venom bioactive molecules have suggest that these molecules have better therapeutic advantage in several fields of biomedical research viz., arthritis, cancer, etc. Another perspective in snake venom research could be green synthesis or herbal based synthesis of nanoparticles, which has shown enhanced effect in snake venom neutralizing capacity. Therefore, in terms of snake venom therapeutic potential and development of snake venom antidote, nanotechnology is a prodigious tool to be taken into serious consideration by the researchers. In this review, a comprehensive overview has been given on bridging nanoparticles with active biomolecules derived from snake venoms/herbs, current scientific evidences and records in this field, present trends and developments in nanotechnology in venom research along with future prospects in this arena. This may open new domains in snake venom research using nanotechnology in the near future
Snake venom as therapeutic agents: From toxin to drug development
1353-1358<span style="font-size:
16.0pt;mso-bidi-font-size:8.0pt;font-family:" arial","sans-serif";color:black"="">Snake
bite injuries and death are socio-medical problems of considerable magnitude.
In India a large number of people suffer and die every year due to snake venom
poisoning. Snake venom, though greatly feared, is a natural biological resource,
containing several components that could be of potential therapeutic value. Use
of snake venom in different pathophysiological conditions has been mentioned in
Ayurveda, homeopathy and folk medicine. It is well known that snake venom is
complex mixture of enzymes, peptides and proteins of low molecular mass with specific
chemical and biological activities. Snake venom contains several neurotoxic,
cardiotoxic, cytotoxic, nerve growth factor, lectins, disintrigrins, haemorrhagins
and many other different enzymes. These proteins not only inflict death to
animals and humans, but can also be used for the treatment or thrombosis, arthritis, cancer
and many other diseases. An overview of various snake venom
<span style="font-size:16.0pt;mso-bidi-font-size:8.0pt;line-height:115%;
font-family:" arial","sans-serif";mso-fareast-font-family:"times="" new="" roman";="" color:black;mso-ansi-language:en-us;mso-fareast-language:en-us;mso-bidi-language:="" ar-sa"="">components that have prospects in health and diseases are discussed in
this review.</span
Daboia Russellii and Naja Kaouthia Venom Neutralization by Lupeol Acetate Isolated From the Root Extract of Indian Sarsaparilla Hemidesmus Indicus R.Br.
The present study reports the isolation and purification of lupeol acetate from the methanolic root extract of Indian medicinal plant Hemidesmus
indicus (L.) R.Br. (family: Asclepiadaceae) which could neutralize venom induced action of Daboia russellii and Naja kaouthia on experimental
animals. Lupeol acetate could significantly neutralize lethality, haemorrhage, defibrinogenation, edema, PLA2 activity induced by Daboia russellii
venom. It also neutralized Naja kaouthia venom induced lethality, cardiotoxicity, neurotoxicity and respiratory changes in experimental animals.
Lupeol acetate potentiated the protection by snake venom antiserum action against Daboia russellii venom induced lethality in male albino mice.
Venom induced changes in lipid peroxidation and super oxide dismutase activity was antagonized by lupeol acetate. Snake venom neutralization
by lupeol acetate and its possible mechanism of action has been discussed
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