scholarly journals Meta-analysis of venom toxicity of 167 most lethal ophidian species provides a basis for estimating human lethal doses

2020 ◽  
Author(s):  
Brian Hanley

Abstract Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. The largest possible meta-analysis possible at this time, it encompasses all known records of animal lethality studies over the past 100 years. These results are not artifacts of resistant test-animal-species, and show orders of magnitude beyond the 1.6 logs (40 fold change) range of lethal dose documented in literature between amphibians, lizards and mice. Methods: 1198 lethal dose study results for 167 of the most lethal venomous ophidian species in the world are analyzed. Results: LDLo does not differentiate from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that for route of inoculation, IC<IV<IP<IM<SC has good support (R2 = 0.90). However, 5% of ICs were the highest dose, and 7% of SC inoculations were the lowest dose. Within the mouse test species, for one route of inoculation, the widest LD range is 3 logs (1000 fold change, N = 14). Within mouse, for multiple routes of inoculation, the widest LD range is 3.6 logs (4,150 fold change), N = 20, SC/IM. The strongest correlate for range of lethal dose results is the number of studies (R2 = 0.56); followed by the number of test-animal-species (R2 = 0.55); then by the number of routes of inoculation (R2 = 0.43). Conclusions: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate: mean, median, minimum, range, and standard deviations. Standard deviation multiples will provide desired coverage. For estimating LD50 range and minimum lethal dose for species with little data, I recommend curating a meta-dataset of related snakes, and computational research to strengthen this.

2020 ◽  
Author(s):  
Brian Hanley

Abstract Background: This is the first meta-analysis to characterize intra-ophidian-species variation in whole venom. The largest meta-analysis possible at this time, it encompasses all known publicly available records of animal lethality studies over the past 100 years. These results are not artifacts of resistant test-animal-species, and show orders of magnitude beyond the 1.6 logs (40 fold change) range of lethal dose documented in literature between amphibians, lizards and mice. Methods: 1005 lethal dose study results for 160 of the most lethal venomous ophidian species in the world are analyzed. Results: LDLo does not differentiate from LD50 across studies, indicating the true range of toxicity is probably larger. The belief that for route of inoculation, IC<IV<IP<IM<SC has good support (R2 = 0.86). However, 8% of SC inoculations were the lowest (most toxic) dose. Within the mouse test species, for one route of inoculation, the mean LD range is 0.94 logs (8.89 fold change), and widest LD range is 2.15 logs (141 fold change, N = 26). Within 1 test species, for multiple routes of inoculation, mean LD range is 2.0 logs (98.97 fold change), and the widest LD range is 3.6 logs (4,150 fold change). For all test species and all routes of inoculation, the mean LD range is 2.97 logs (936.59 fold change) and widest LD range is 4.76 logs (57,471 fold change). The strongest correlate for range of lethal dose results is the number of studies (R2 = 0.56). The average variance appears to follow a power law from single test species and route, to single test species and multiple routes, to all test species and all routes, as a factor of 10 multiple for each. Conclusions: Scientists working with humans should use combined LDLo and LD50 meta-datasets for all data and calculate: mean, median, minimum, range, and standard deviations. Standard deviation multiples, or at minimum, standard error, will provide desired coverage. For estimating LD50 range and minimum lethal dose for species with little data, I recommend curating a meta-dataset of related snakes, and computational research to strengthen this.


Genes ◽  
2021 ◽  
Vol 12 (5) ◽  
pp. 674
Author(s):  
Han-Lin Chiang ◽  
Yih-Ru Wu ◽  
Yi-Chun Chen ◽  
Hon-Chung Fung ◽  
Chiung-Mei Chen

Parkinson’s disease (PD) is a neurodegenerative disease with the pathological hallmark of Lewy bodies and Lewy neurites composed of α-synuclein. The SNP rs591323 is one of the risk loci located near the FGF20 gene that has been implicated in PD. The variation of FGF20 in the 3′ untranslated region was shown to increase α-synuclein expression. We examined the association of rs591323 with the risk of PD in a Taiwanese population and conducted a meta-analysis, including our study and two other studies from China, to further confirm the role of this SNP in Taiwanese/Chinese populations. A total of 586 patients with PD and 586 health controls (HCs) were included in our study. We found that the minor allele (A) and the AA + GA genotype under the dominant model are significantly less frequent in PD than in controls. The meta-analysis consisted of 1950 patients with PD and 2073 healthy controls from three studies. There was significant association between rs591323 and the risk of PD in the additive (Z = −3.96; p < 0.0001) and the dominant models (Z = −4.01; p < 0.0001). Our study results and the meta-analysis support the possible protective role of the rs591323 A allele in PD in Taiwanese/Chinese populations.


2021 ◽  
pp. 088506662199275
Author(s):  
Rupesh Raina ◽  
Nirav Agrawal ◽  
Kirsten Kusumi ◽  
Avisha Pandey ◽  
Abhishek Tibrewal ◽  
...  

Objective: Continuous kidney replacement therapy (CKRT) is the primary therapeutic modality utilized in hemodynamically unstable patients with severe acute kidney injury. As the circuit is extracorporeal, it poses an increased risk of blood clotting and circuit loss; frequent circuit losses affect the provider’s ability to provide optimal treatment. The objective of this meta-analysis is to evaluate the safety and efficacy of the extracorporeal anticoagulants in the pediatric CKRT population. Data Sources: We conducted a literature search on PubMed/Medline and Embase for relevant citations. Study Selection: Studies were included if they involved patients under the age of 18 years undergoing CKRT, with the use of anticoagulation (heparin, citrate, or prostacyclin) as a part of therapy. Only English articles were included in the study. Data Extraction: Initial search yielded 58 articles and a total of 24 articles were included and reviewed. A meta-analysis was performed focusing on the safety and effectiveness of regional citrate anticoagulation (RCA) vs unfractionated heparin (UFH) anticoagulants in children. Data Synthesis: RCA had statistically significantly longer circuit life of 50.65 hours vs. UFH of 42.10 hours. Two major adverse effects metabolic alkalosis and electrolyte imbalance seen more commonly in RCA compared to UFH. There was not a significant difference in the risk of systemic bleeding when comparing RCA vs. UFH. Conclusion: RCA is the preferred anticoagulant over UFH due to its significantly longer circuit life, although vigilant circuit monitoring is required due to the increased risk of electrolyte disturbances. Prostacyclin was not included in the meta-analysis due to the lack of data in pediatric patients. Additional studies are needed to strengthen the study results further.


2021 ◽  
Vol 10 (6) ◽  
pp. 1244
Author(s):  
Stinne Tranekær ◽  
Dennis Lund Hansen ◽  
Henrik Frederiksen

Background: Warm autoimmune haemolytic anaemia (wAIHA) is a haemolytic disorder, most commonly seen among adults and is classified as either primary or secondary to an underlying disease. We describe the age and sex distribution and the proportion of secondary wAIHA. Method: We retrieved 2635 published articles, screened abstracts and titles, and identified 27 articles eligible for full-text review. From these studies, we extracted data regarding number of patients, sex distribution, age at diagnosis, number of patients with secondary wAIHA, and whether the patients were diagnosed through local or referral centres. All data were weighted according to the number of included patients in each study. Results: 27 studies including a total of 4311 patients with wAIHA, of which 66% were females, were included. The median age at diagnosis was 68.7 years, however, wAIHA affected all ages. The mean proportion of secondary wAIHA was 49%, most frequently secondary to systemic lupus erythematosus. The proportions of secondary wAIHA reported from primary vs. referral centres were 35% vs. 59%, respectively. Conclusion: This review consolidates previously reported gender distribution. The higher proportion of secondary wAIHA in referral centres suggests that the most severely affected patients are disproportionally more frequent in such facilities.


2021 ◽  
Vol 99 (Supplement_3) ◽  
pp. 468-469
Author(s):  
Shane Gadberry ◽  
David Lalman ◽  
Frank White ◽  
Sara Linneen ◽  
Paul A Beck

Abstract This meta-analysis investigated the impacts of monensin on performance of stocker cattle on high-forage diets. The stocker performance analysis resulted from 38 experiments with 73 mean comparisons; bloat analysis was conducted with 12 experiments with 23 mean comparisons. The metaphor package (version 2.4-0) for R (version 4.0.3; www.r-project.org) was used to determine the overall effect size of monensin compared to a negative control. Each study’s n, means, and SEM or P-value was used to calculate the mean difference and estimate of within study variance for responses of interest. Moderators of monensin response considered in the analysis were delivery method, dose, study duration, initial calf BW, diet ME and CP, and forage category. Initial BW and basal ADG averaged 236 ± 45.9 kg and 0.72 ± 0.28 kg/day, respectively. In the ADG analysis the only significant moderator of those considered was length of the study (P &lt; 0.01), as duration of the study increased the ADG response to monensin decreased by 0.0007 kg/day. For the average 112-day length of study, the average monensin response is estimated to be 0.0784 kg/day increase in average daily gain. Sufficient information was presented in only 18 citations representing 40 mean comparisons for determining the effect of monensin on BW at the end of the experiment, estimated by (P &lt; 0.01) monensin response (increased ending BW, kg) = 22.3 – 0.05 (initial calf BW, kg). Thus, for the average initial BW of 235 kg the average monensin response is estimated to be 10.6 kg increase in average ending BW. The incidence (-20%) and severity (-0.7 bloat scores) of bloat was found to be reduced in bloat prone pastures. There is ample evidence that monensin increases performance of growing calves on high forage diets along with reducing the incidence and severity of bloat.


2021 ◽  
Author(s):  
◽  
Divakaran Reddy

Tax compliance is the willingness of taxpayers to obey tax rules of a nation, whilst tax noncompliance is the unwilling behaviour of citizens to act under tax regulations. Taxpayer compliance enables the government to collect tax revenues, which is one of the most important sources of government income. Altering the non-compliant behaviour of citizens is an important barometer for increasing tax revenues that contribute to the socio-economic development of a nation. Numerous quondam studies have been conducted strikingly in the past few decades on taxpayer compliance. However, there is a dearth of sufficient research currently on tax noncompliance behaviour. Moreover, the phenomenon of tax noncompliance has limited exploration from the vantage point of meta-analysis of primary research studies conducted, focussing on interrogating, and systematically categorising their results. Resultantly, the purpose of this study was to examine the previously related primary studies to determine those factors that have been judged to have influenced the tax compliance behaviour of citizens. This study has adopted the quantitative research approach and followed the preferred reporting items for systematic review (PRISMA) method and meta-analysis to provide an accurate estimate of the relationship that exists in a population of relevant tax noncompliance behavioural studies. The population comprised of 45 international studies conducted between the period 2015 to 2020 is selected for analysis. The study results indicate that the quality of tax administration systems and public trust in institutional governance are factors that have influenced taxpayer compliance positively. Poor government accountability mechanisms entrenched tax gaps, and developing public trust in government institutions were found to be universal to promote voluntary taxpayer compliance. This study has contributed significantly to the open discussion on tax compliance among researchers, governments, and businesses.


2021 ◽  
Author(s):  
Ricardo Faustino ◽  
Miguel Faria ◽  
Monica Teixeira ◽  
Filipe Palavra ◽  
Maria Do Ceu Costa ◽  
...  

Coronaviruses have been responsible for major epidemic crises in 2003 with SARS-CoV-1, in 2012 with MERS-CoV and in 2019 with SARS-CoV-2 (COVID-19), causing serious atypical pneumonia in humans. We intend, with this systematic analysis and meta-analysis, to clarify the prevalence of the various strains of coronavirus in different animal species. For this purpose, we carried out an electronic survey using Pubmed's Veterinary Science search tool to conduct a systematic assessment of published studies reporting the prevalence of different strains of coronavirus in different animal species between 2015 and 2020. We conducted different analysis to assess sensitivity, publication bias, and heterogeneity, using random and fixed effects. The final meta-analysis included 42 studies for systematic review and 29 in the meta-analysis. For the geographic regions with a prevalence greater than or equal to 0.20 (Forest plot overall; prevalence = 0.20, p < 0.01, Q = 10476.22 and I2 = 100%), the most commonly detected viruses were: enteric coronavirus (ECoV), pigeon-dominant coronavirus, (PdCoV), Avian coronavirus M41, Avian coronavirus C46, Avian coronavirus A99, Avian coronavirus JMK, MERS-CoV, Bovine coronavirus, Ro-BatCoV GCCDC1, Alphacoronavirus, Betacoronavirus, Deltacoronavirus, Gamacoronavirus and human coronaviruses (HCoVs). The wide presence of different strains of coronavirus in different animal species on all continents demonstrates the great biodiversity and ubiquity of these viruses. The most recent epidemiological crises caused by coronavirus demonstrates our unpreparedness to anticipate and mitigate emerging risks, as well as the need to implement new epidemiological surveillance programs for viruses. Combined with the need to create advanced training courses in One Health, this is paramount in order to ensure greater effectiveness in fighting the next pandemics.


2019 ◽  
Vol 25 (4) ◽  
pp. 270-281
Author(s):  
Asadollah Asadi ◽  
◽  
Arash Abdolmaleki ◽  
◽  

Aims Nanoparticles (particles with a diameter of 10-500 nm) are currently used in the cosmetics industry as well as for pharmaceuticals, diagnostic imaging, and tissue engineering. Since these nanoparticles are used in industry and drug delivery, they can also be used by pregnant women. Thus, the current study investigated the teratogenic and cytotoxic effects of Zinc Sulfide (ZnS) nanoparticles on the embryo and their fibroblastic cell culture. Methods & Materials Zinc sulfide (ZnS) nanoparticles were synthesized. Then, nanoparticles at the concentrations of 5, 10, 15, 30, and 40 mg/mL/egg were injected into the air sac of the eggs in three replicates on the third day of incubation. Next, the treated and control eggs, on day 19 of incubation were opened, and embryos were weighted, and the relevant mortality rate was recorded. Fibroblast cells were isolated, cultured, and treated from the control embryo, and morphological changes and cell survival percentages were recorded. Findings The obtained results revealed that the embryos’ survival rate depends on the nanoparticle concentration. As a result, at the highest concentration, only 36.32% of the embryos survived, and the lethal dose 50% (LD50) was equal to 32.47 mg/egg. Morphological study of the treated embryos club foot and skeletal staining suggested the deletion of caudal vertebrate. The cytotoxicity study results of ZnS nanoparticles on fibroblastic cells indicated the survival fractions of 88.45%, 68.75%, and 49.32%, respectively, and its IC50 value was measured aas1460 μM. Conclusion The present study results suggested that ZnS nanoparticles had no significant toxic effects on the embryos and culture of chicken fibroblastic cells at low concentrations.


2017 ◽  
Vol 2017 ◽  
pp. 1-13 ◽  
Author(s):  
Hongchang Yang ◽  
Xueping Wu ◽  
Min Wang

We aimed to use the pairwise and network meta-analysis to estimate the effects of different meditation exercises on the control of systolic blood pressure (SBP) and diastolic blood pressure (DBP). Randomized controlled trials (RCTs) were retrieved from PubMed and Embase up to June 2016, which are published in English and reported on meditation exercise for hypertensive patients. Risks of bias assessment of the included studies were assessed by Cochrane Collaboration Recommendations and network meta-analysis was performed by ADDIS. Mean difference (MD) and its 95% confidence interval (CI) were used as the effect size. A number of 19 RCTs were included in this study. Results of pairwise comparisons indicated that meditation exercise could significantly decrease the SBP and DBP, compared with other interventions (MD = −7.10, 95% CI: −10.82 to −3.39; MD = −4.02, 95% CI: −6.12 to −1.92). With good consistence and convergence, network meta-analysis showed that there were no significant differences between meditation and other interventions on SBP. For DBP, Qigong was significantly lower than “no intervention” (MD = −11.73, 95% CI: −19.85 to −3.69). Qigong may be the optimal exercise way in lowering SBP and DBP of hypertensive patients, but a detailed long-term clinical research should be needed in the future.


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