Integrating epidemiology and toxicology in neurotoxicity risk assessment

2007 ◽  
Vol 26 (4) ◽  
pp. 283-293 ◽  
Author(s):  
William K Boyes ◽  
Virginia C Moser ◽  
Andrew M Geller ◽  
Vernon A Benignus ◽  
Philip J Bushnell ◽  
...  

Neurotoxicity risk assessments depend on the best available scientific information, including data from animal toxicity studies, human experimental studies and human epidemiology studies. There are several factors to consider when evaluating the comparability of data from studies. Regarding the epidemiology literature, issues include choice of study design, use of appropriate controls, methods of exposure assessment, subjective or objective evaluation of neurological status, and assessment and statistical control of potential confounding factors, including co-exposure to other agents. Animal experiments must be evaluated regarding factors such as dose level and duration, procedures used to assess neurological or behavioural status, and appropriateness of inference from the animal model to human neurotoxicity. Major factors that may explain apparent differences between animal and human studies include: animal neurological status may be evaluated with different procedures than those used in humans; animal studies may involve shorter exposure durations and higher dose levels; and most animal studies evaluate a single substance whereas humans typically are exposed to multiple agents. The comparability of measured outcomes in animals and humans may be improved by considering functional domains rather than individual test measures. The application of predictive models, weight of evidence considerations and meta-analysis can help evaluate the consistency of outcomes across studies. An appropriate blend of scientific information from toxicology and epidemiology studies is necessary to evaluate potential human risks of exposure to neurotoxic substances. Human & Experimental Toxicology (2007) 26, 283-293

2014 ◽  
Vol 17 (2) ◽  
pp. 84-90 ◽  
Author(s):  
Seok Won Chung ◽  
Sae Hoon Kim ◽  
Joo Han Oh

In conducting animal studies using rotator cuff, researchers should select the appropriate types of animals and experimental models. This should also be followed by complete understanding of the selected experimental animals as well as the methods for evaluating the results. Thus, researchers could minimize errors and failure in conducting animal experimental studies. Further, this will provide a basis of establishing new idea and theory about rotator cuff diseases.


2022 ◽  
Vol 12 ◽  
Author(s):  
Lite Ge ◽  
Jing Zhao ◽  
Huiyin Deng ◽  
Chunli Chen ◽  
Zhiping Hu ◽  
...  

BackgroundMultiple preclinical studies have demonstrated that bone‐marrow derived mesenchymal stromal (stem) cells [MSC(M)] positively influence the severity of sepsis symptoms and mortality in rodent models. However, this remains an inconclusive finding.ObjectiveTo review the effect of naïve MSC(M) in rodent models of sepsis.MethodsThe PubMed, EMBASE, and Web of Science databases were searched up to August 31, 2021. Inclusion criteria according to PICOS criteria were as follows: (1) population: rodents; (2) intervention: unmodified MSC(M); (3) comparison: not specified; (4) primary outcome: the effects of MSC(M) cell therapy on the mortality of rodent models of sepsis and endotoxemia; (5) study: experimental studies. Multiple prespecified subgroup and meta-regression analysis were conducted. Following quality assessment, random effects models were used for this meta-analysis.The inverse variance method of the fixed effects model was used to calculate the pooled odds ratios (ORs) and their 95% confidence intervals (CIs).Resultstwenty-four animal studies met the inclusion criteria. Our results revealed an overall OR difference between animals treated with naïve MSC(M) and controls for mortality rate was 0.34(95% confidence interval: 0.27-0.44; P < 0.0001). Significant heterogeneity among studies was observed.ConclusionsThe findings of this meta-analysis suggest that naïve MSC(M) therapy decreased mortality in rodent models of sepsis. Additionally, we identified several key knowledge gaps, including the lack of large animal studies and uncertainty regarding the optimal dose of MSC(M) transplantation in sepsis. Before MSC(M) treatment can advance to clinical trials, these knowledge gaps must be addressed.


2020 ◽  
Vol 4 (1) ◽  
pp. e100108
Author(s):  
Fiona J Ramage ◽  
Alexander S Clewlow ◽  
Lynda M Williams ◽  
Malcolm R Macleod ◽  
Rosamund F Langston

Introduction and objectiveThe Western diet that comprises high levels of long-chain saturated fats and sugar is associated not only with metabolic disorders such as obesity and type 2 diabetes but also has been recently linked to brain changes and cognitive dysfunction. However, in animal studies, reported effects are variable, and the mechanisms underlying these effects are unclear. In the proposed review, we aim to summarise the diverse evidence of the effects of so-called ‘high-fat’ and ketogenic diets on behavioural measures of cognition in postweaning mice and rats, relative to animals on standard diets and to determine potential underlying mechanisms of high-fat diet-induced effects.Search strategyA comprehensive search strategy was designed to retrieve studies reporting use of a high-fat or ketogenic diet in postweaning mice and rats that included cognitive assessments. Three databases (Medline, SCOPUS and Web of Science) were searched and 4487 unique references were retrieved.Screening and annotationStudies were screened for inclusion by two independent reviewers, with 330 studies retained for analysis. Characteristics of disease model choice, experimental design, intervention use and outcome assessment are to be extracted using the Systematic Review Facility (http://syrf.org.uk/) tool. Studies will be assessed for study quality and risk of bias and confidence of mechanistic involvement.Data management and reportingFor cognitive outcomes, effect sizes will be calculated using normalised mean difference and summarised using a random effects model. The contribution of potential sources of heterogeneity to the observed effects of diet on cognition will be assessed using multivariable meta-regression, with partitioning of heterogeneity as a sensitivity analysis. A preliminary version of this protocol was published on 9 April 2019 on the Collaborative Approach to Meta-Analysis and Review of Animal Data from Experimental Studies website (http://www.dcn.ed.ac.uk/camarades/research.html%23protocols).Ethics and disseminationNo ethical approval is required as there are no subjects in the proposed study.


2021 ◽  
Author(s):  
Huriye Atilgan ◽  
Max Doody ◽  
David K Oliver ◽  
Thomas M McGrath ◽  
Andrew M Shelton ◽  
...  

The claustrum is the most densely interconnected region in the human brain. Despite the accumulating data from clinical and experimental studies, the functional role(s) of the claustrum remain unknown. Here, we systematically review claustrum lesion studies and discuss their functional implications. Claustral lesions are associated with an array of signs and symptoms, including changes in cognitive, perceptual and motor abilities; electrical activity; mental state; and sleep. The wide range of symptoms observed following claustral lesions suggests that the claustrum may either have a number of distinct functions, or a global function that impacts many neural processes. We further discuss the implications of these lesions in the context of recent evidence linking the claustrum to sensory perception, sleep, and salience as well as highlighting an underexplored link between the claustrum and pain. We hypothesize that the claustrum is connected to multiple brain networks, both ancient and advanced, which underly fundamental functions as well as higher cognitive processes. Extensive evidence derived from human lesion studies and animal experiments provides unequivocal evidence for a key function of the claustrum as a multifunctional node in numerous networks.


2014 ◽  
Vol 62 (4) ◽  
pp. 371-376 ◽  
Author(s):  
Leonardo Bueno TORCATO ◽  
Paulo Renato Junqueira ZUIM ◽  
Daniela Atili BRANDINI ◽  
Rosse Mary FALCÓN-ANTENUCCI

OBJECTIVE: The aim of this study was to gather information and discuss the predictability of implant-supported prostheses in patients with bruxism by performing a literature review. METHODS: In order to select the studies included in this review, a detailed search was performed in PubMed and Medline databases, using the following key words: bruxism, dental implants, implant supported prosthesis, and dental restoration failure. Items that were included are: case reports, randomized controlled trials, in vitro studies, literature and systematic reviews, with or without meta-analysis, of the last 20 years that addressed the theme. Articles without abstracts, animal studies, articles in languages other than English and articles from journals unrelated to the dental field were excluded. RESULTS: after analysis according to inclusion and exclusion criteria, 28 articles were selected from a total of 54. It is known from the array of scientific articles which have assessed, either through retrospective, prospective or experimental studies, that the biomechanical and biological impact of bruxism on implant-supported prostheses is small, and that the literature has contributed little to exemplify the prosthetic limits of safety for the specialist from a clinical point of view. CONCLUSION: Although there is still no general consensus on this matter, most of the literature review articles do provide clinical guidelines that contribute to implant supported prostheses longevity and stability in patients with bruxism.


2021 ◽  
Vol 2021 ◽  
pp. 1-35
Author(s):  
Hanieh Malmir ◽  
Hanieh-Sadat Ejtahed ◽  
Ahmad-Reza Soroush ◽  
Amir Mohammad Mortazavian ◽  
Noushin Fahimfar ◽  
...  

Despite the proposed role of the gut microbiota-bone axis, findings on the association between probiotic consumption and bone health are conflicting. This systematic review aimed to assess the effect of probiotic consumption on bone health parameters. A systematic literature search of relevant reports published in PubMed/Medline, Web of Science, SCOPUS, EMBASE, and Google scholar before December 2020 was conducted. All clinical trials or experimental studies, which examined the relationship between probiotic consumption and bone health parameters, were included. No limitation was applied during the search. After screening articles based on inclusion criteria, 44 studies remained. In clinical trials, probiotic consumption affects bone health parameters such as serum calcium levels (3.82; 95% CI: 1.05, 6.59 mmol/l), urinary calcium levels (4.85; 95% CI: 1.16, 8.53 mmol/l), and parathyroid hormone (PTH) levels (−5.53; 95% CI: −9.83, −0.86 ng/l). In most studies, Lactobacillus species such as L. helveticus, L. reuteri, and L. casei were consumed and women aged 50 years or older were assessed. Spinal and total hip bone mineral density (BMD) was not affected significantly by probiotic consumption. In 37 animal experiments, probiotic or symbiotic feeding mostly had effects on bone health parameters. Some strains of Bifidobacterium and Lactobacillus including L. reuteri, L. casei, L. paracasei, L. bulgaricus, and L. acidophilus have indicated beneficial effects on bone health parameters. In conclusion, this systematic review and meta-analysis indicate that probiotic supplementation might improve bone health. Further studies are needed to decide on the best probiotic species and appropriate dosages.


2019 ◽  
Vol 2019 ◽  
pp. 1-36 ◽  
Author(s):  
Xiao-lin Fan ◽  
Mei-ling Yu ◽  
Shu-Ping Fu ◽  
Yi Zhuang ◽  
Sheng-feng Lu

Background. Simple obesity has become a global risk to health of human beings. Acupuncture, as one of traditional Chinese medicine therapies, has been widely used in obesity treatment in recent years. However, the individual heterogeneity which makes acupuncture’s efficiency unstable leads to some controversy. So more evidence-based results are necessary to judge the effectiveness of acupuncture in treatment of simple obesity. Compared with clinical trials, animal experiments are controllable, and the underlying mechanism is more likely to be explored. Last but not the least, more and more experimental studies on acupuncture for animal obesity have been published. Therefore, we conducted the systematic review and meta-analysis to evaluate the effectiveness of acupuncture in treating simple obesity in animal experiments. Methods. Randomized Controlled Trials (RCTs) on acupuncture for simple obesity animal models were searched from six databases: PubMed, MEDLINE, CNKI, VIP, WanFang Date, and CMB from inception to February 2017 and updated on April 12, 2019. RevMan 5.3 software was used for meta-analysis. Treatment effects were summarized as relative risk (RR) and Standard mean difference (SMD) with 95% of confidence interval (CI). Results. A total of 108 trials involving 5731 rats were included. Meta-analysis showed that acupuncture had better effect on reducing weight (SMD -2.60, 95%CI: -2.93 to -2.26, p<0.00001) and Lee’s index (SMD -2.62, 95%CI:-3.18 to -2.06, p<0.00001) compared with control group. However, the methodological quality of included studies was generally poor. Details of blinding were not reported in most studies. In spite of high heterogeneity being observed on the merged data, sensitivity analysis using the leave-one-out approach, subgroup analysis based on different acupuncture techniques, and rat strains and meta-regression all failed to find the sources of heterogeneity. The asymmetric funnel plot suggested publication bias. Besides, adverse events were not reported in any reports. Conclusions. Our review provided positive evidence of acupuncture for simple obesity. Unfortunately, none of the firm conclusions can be drawn due to methodological flaws, high heterogeneity, and publication bias. More high-quality trials are needed in future to get objective conclusions.


2016 ◽  
Vol 79 (12) ◽  
pp. 2196-2210 ◽  
Author(s):  
IAN YOUNG ◽  
BARBARA J. WILHELM ◽  
SARAH CAHILL ◽  
REI NAKAGAWA ◽  
PATRICIA DESMARCHELIER ◽  
...  

ABSTRACT Pork is one of the major food sources of human salmonellosis worldwide, and beef products have been implicated in numerous foodborne outbreaks. Thus, effective interventions to reduce Salmonella contamination during beef and pork processing are of interest to both regulators and the meat industry. We conducted a rapid systematic review and meta-analysis of literature investigating the efficacy of slaughter and processing interventions to control Salmonella in beef and pork. Review steps included a comprehensive search strategy, relevance screening of abstracts, relevance confirmation of articles, data extraction, risk-of-bias assessment, meta-analysis (where appropriate), and a weight-of-evidence assessment. A total of 191 relevant experimental studies were identified. The results of two controlled trials indicated that hot water and steam treatments were effective for reducing the prevalence of Salmonella on beef carcasses (relative risk [RR] = 0.11; 95% confidence interval [CI]: 0.02, 0.58), whereas in four trials, prechill organic acid washes were effective for reducing Salmonella on pork carcasses (RR = 0.32; 95% CI: 0.13, 0.78), with high confidence in the estimates of effect. In four quasi-experimental studies, postexsanguination chemical washes were effective for reducing the prevalence of Salmonella on cattle hides, with low confidence in the specific estimate of effect; however, moderate confidence was found for the effect estimates of scalding (RR =0.20; 95% CI: 0.14, 0.29) and singeing (RR = 0.34; 95% CI: 0.22, 0.52) of pork carcasses. The overall evidence supports enhanced reductions of Salmonella through a multihurdle approach. Various slaughter and processing interventions can contribute to reduction of Salmonella on beef and pork carcasses, depending on the context of application, and an appropriate combination should be selected, validated, and verified by establishment operators under their local conditions.


2020 ◽  
Author(s):  
Rosanna Pinto ◽  
Lucia Ardoino ◽  
Paola Giardullo ◽  
Paola Villani ◽  
Carmela Marino

Abstract Background. An Italian project aims to review the scientific literature on the possible carcinogenicity of radiofrequency (100 kHz – 300 GHz) electromagnetic field (RF-EMF) exposure. The ENEA team has to carry out a systematic review of the in vivo studies on this topic. Objectives: Development of a protocol for a systematic review (meta-analysis included) to investigate the potential carcinogenic risk following RF-EMF in vivo exposure to doses above or within legal limits. The aim of this review is - to provide a descriptive and, if possible, a quantitative summaries of the results of the examined RF-EMF in vivo studies, together with an assessment of the consistency of observations and of the causes of heterogeneity. - to assess the weight of evidence to support or refute the hypothesis of carcinogenic effects caused by RF-EMF exposure and to draw conclusions about the potential for carcinogenicity of RF-EMF exposure.Methods: We will search for relevant studies in electronic academic databases and in the reference list of selected papers and reviews on the topic, including the descriptive reviews on RF-EMF carcinogenic effect carried out by international panels of experts since 2011. PECO’s statements were defined: experimental studies on rodents of both sexes, all ages and species, all genetic background (Population) exposed to RF-EMF alone, or in combination with other physical or chemical agents (Exposure); only studies reporting outcome data in exposed and sham control groups (Comparison);all types of cancer with all tumor-related outcome measures (Outcome) will be included.Only peer-reviewed articles written in English will be considered without limit in publication date.Eligibility criteria were defined for screening of papers, moreover the risk of bias assessment will be performed using a specific risk of bias tool for animal studies. Only studies with "definitely low and/or probably low risk of bias" will be included in the analysis. A meta-analysis will be performed, if feasible, for all outcome measures: for subgroup analysis a minimum of 3 studies per subgroup will be required. If meta-analysis will not be possible, data will be reported through the descriptive summary.Systematic review registration: PROSPERO CRD42020191105.


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