Effects of the endocrine disruptor vinclozolin in male reproduction: a systematic review and meta-analysis†

Author(s):  
Mariana Feijó ◽  
Roberta V L Martins ◽  
Sílvia Socorro ◽  
Luísa Pereira ◽  
Sara Correia

Abstract Endocrine-disrupting chemicals have become an issue of scientific and public discussion. Vinclozolin (VNZ) is a fungicide that competitively antagonizes the binding of natural androgens to their receptor, disturbing the function of tissues that are sensitive to these hormones, as is the case of the male reproductive organs. A systematic review with meta-analyses of rodent studies was conducted to answer the following question: Does exposure to VNZ affect sperm parameters and testicular/epididymal weight? The methodology was prespecified according to the Cochrane Handbook for Systematic Reviews and PRISMA recommendations. Sixteen articles met the inclusion criteria, comprising a total of 1189 animals. The risk of publication bias was assessed using the Trim and Fill adjustment, funnel plot, and Egger regression test. Heterogeneity and inconsistency across the findings were tested using the Q-statistic and I2 of Higgins, respectively. Sensitivity was also analyzed. Statistical analysis was performed on Comprehensive Meta-Analysis software (Version 2.0), using random models and weighted mean differences along with a 95% confidence interval. Sperm motility, counts, daily sperm production (evidence of publication bias), and epididymis weight were decreased in VNZ-treated animals. Exposure length and dose, as well as the time point of exposure, influenced the obtained results. Despite the moderate/high heterogeneity observed, the sensitivity analysis overall demonstrated the robustness of the findings. The quality scores of the included studies were superior to 4 in a total of 9, then classified as good. The obtained data corroborate the capability of VNZ exposure to disrupt spermatogenic output and compromise male fertility.

2020 ◽  
Author(s):  
Nasrin Amiri Dashatan ◽  
Marzieh Ashrafmansouri ◽  
Mehdi Koushki ◽  
Nayebali Ahmadi

Abstract Background Leishmaniasis is one of the most important health problems worldwide. The evidence has suggested that resveratrol and its derivatives have anti-leishmanial effects; however, the results are inconsistent and inconclusive. The aim of this study was to assess the effect of resveratrol and its derivatives on the Leishmania viability through a systematic review and meta-analysis of available relevant studies. Methods The electronic databases PubMed, ScienceDirect, Embase, Web of Science and Scopus were queried between October 2000 and April 2020 using a comprehensive search strategy. The eligible articles selected and data extraction conducted by two reviewers. Mean differences of IC50 (concentration leading to reduction of 50% of Leishmania) for each outcome was calculated using random-effects models. Sensitivity analyses and prespecified subgroup were conducted to evaluate potential heterogeneity and the stability of the pooled results. Publication bias was evaluated using the Egger’s and Begg’s tests. We also followed the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) guidelines for this review. Results Ten studies were included in the meta-analysis. We observed that RSV and its derivatives had significant reducing effects on Leishmania viability in promastigote [24.02 µg/ml; (95% CI 17.1, 30.8); P < 0.05; I2 = 99.8%; P heterogeneity = 0.00] and amastigote [18.3 µg/ml; (95% CI 13.5, 23.2); P < 0.05; I2 = 99.6%; P heterogeneity = 0.00] stages of Leishmania. A significant publication bias was observed in the meta-analysis. Sensitivity analyses showed a similar effect size while reducing the heterogeneity. Subgroup analysis indicated that the pooled effects of leishmanicidal of resveratrol and its derivatives were affected by type of stilbenes and Leishmania species. Conclusions Our findings clearly suggest that the strategies for the treatment of leishmaniasis should be focused on natural products such as RSV and its derivatives. Further study is needed to identify the mechanisms mediating this protective effects of RSV and its derivatives in leishmaniasis.


2021 ◽  
Vol 19 (1) ◽  
Author(s):  
Runqing Li ◽  
Junjie Liu ◽  
Yushan Li ◽  
Quanxian Wang

Abstract Background Published studies have shown contradictory results regarding the relationship between somatometric parameters and varicoceles. We performed a systematic review and meta-analysis to investigate the possible effects of age, height, weight, and body mass index (BMI) on the presence and severity of varicoceles. Methods Databases including EMBASE, MEDLINE, PubMed, Cochrane Library, China National Knowledge Infrastructure (CNKI), Web of Science, and Google Scholar were systematically searched to identify relevant articles published up to March 2020. Two researchers independently identified eligible articles and extracted data. Cochran’s Q statistic and I2 statistics were used to assess heterogeneity. Meta-analysis was performed using StataSE 12.0 software (StataCorp LP, USA). Random-effects models were used to obtain the weighted mean differences (WMDs) and 95% confidence intervals (CIs). Publication bias was assessed using Begg’s funnel plot and Egger’s regression test. Results The search strategy produced 272 articles, of which 18 articles were eligible according to the inclusion/exclusion criteria. A total of 56,325 patients with varicocele and 1,334,694 patients without varicocele were included in the meta-analysis to evaluate the effect of somatometric parameters on the presence and severity of varicocele. The overall results demonstrated that the presence of varicoceles was significantly associated with height (WMD = 1.41, 95% CI = 1.07 to 1.74, P < 0.001) and inversely correlated with BMI (WMD = − 1.35, 95% CI = -1.67 to − 1.03, P < 0.001) but not with age (WMD = -0.93, 95% CI = -2.19 to 0.33, P = 0.149) or weight (WMD = 0.24, 95% CI = -2.24 to 2.72, P = 0.850). The severity of varicocele was inversely correlated with increased BMI but not with age. Conclusion The presence of varicoceles was significantly associated with height and inversely correlated with BMI.


2021 ◽  
Vol 5 (1) ◽  
pp. e100135
Author(s):  
Xue Ying Zhang ◽  
Jan Vollert ◽  
Emily S Sena ◽  
Andrew SC Rice ◽  
Nadia Soliman

ObjectiveThigmotaxis is an innate predator avoidance behaviour of rodents and is enhanced when animals are under stress. It is characterised by the preference of a rodent to seek shelter, rather than expose itself to the aversive open area. The behaviour has been proposed to be a measurable construct that can address the impact of pain on rodent behaviour. This systematic review will assess whether thigmotaxis can be influenced by experimental persistent pain and attenuated by pharmacological interventions in rodents.Search strategyWe will conduct search on three electronic databases to identify studies in which thigmotaxis was used as an outcome measure contextualised to a rodent model associated with persistent pain. All studies published until the date of the search will be considered.Screening and annotationTwo independent reviewers will screen studies based on the order of (1) titles and abstracts, and (2) full texts.Data management and reportingFor meta-analysis, we will extract thigmotactic behavioural data and calculate effect sizes. Effect sizes will be combined using a random-effects model. We will assess heterogeneity and identify sources of heterogeneity. A risk-of-bias assessment will be conducted to evaluate study quality. Publication bias will be assessed using funnel plots, Egger’s regression and trim-and-fill analysis. We will also extract stimulus-evoked limb withdrawal data to assess its correlation with thigmotaxis in the same animals. The evidence obtained will provide a comprehensive understanding of the strengths and limitations of using thigmotactic outcome measure in animal pain research so that future experimental designs can be optimised. We will follow the Preferred Reporting Items for Systematic Reviews and Meta-Analyses reporting guidelines and disseminate the review findings through publication and conference presentation.


2021 ◽  
Author(s):  
Yan Yu ◽  
Jiasu Liu

Objectives: This meta-analysis aimed to identify the therapeutic effect of 0.01% atropine with on ocular axial elongation for myopia children. Methods: We searched PubMed, Cochrane Library, and CBM databases from inception to July 2021. Meta-analysis was conducted using STATA version 14.0 and Review Manager version 5.3 softwares. We calculated the weighted mean differences(WMD) to analyze the change of ocular axial length (AL) between orthokeratology combined with 0.01% atropine (OKA) and orthokeratology (OA) alone. The Cochran's Q-statistic and I2 test were used to evaluate potential heterogeneity between studies. To evaluate the influence of single studies on the overall estimate, a sensitivity analysis was performed. We also performed sub group and meta-regression analyses to investigate potential sources of heterogeneity. We conducted Begger's funnel plots and Egger's linear regression tests to investigate publication bias. Results: Nine studies that met all inclusion criteria were included in this meta-analysis. A total of 191 children in OKA group and 196 children in OK group were assessed. The pooled summary WMD of AL change was -0.90(95%CI=-1.25~-0.55) with statistical significance(t=-5.03, p<0.01), which indicated there was obvious difference between OKA and OK in myopic children. Subgroup analysis also showed that OKA treatment resulted in significantly less axial elongation compared to OK treatment alone according to SER. We found no evidence for publication bias. Conclusions:  Our meta-analysis indicates 0.01% atropine atropine is effective in slowing axial elongation in myopia children with orthokeratology.


2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Mistire Teshome Guta ◽  
Tiwabwork Tekalign ◽  
Nefsu Awoke ◽  
Robera Olana Fite ◽  
Getahun Dendir ◽  
...  

Aims. This systemic review and meta-analysis were aimed at determining the level of anxiety and depression among cystic fibrosis patients in the world. Methods. We conducted a systematic search of published studies from PubMed, EMBASE, MEDLINE, Cochrane, Scopus, Web of Science, CINAHL, and manually on Google Scholar. This meta-analysis follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The quality of studies was assessed by the modified Newcastle-Ottawa Scale (NOS). Meta-analysis was carried out using a random-effects method using the STATA™ Version 14 software. Trim and fill analysis was done to correct the presence of significant publication bias. Result. From 419,820 obtained studies, 26 studies from 2 different parts of the world including 9766. The overall global pooled prevalence of anxiety and depression after correction for publication bias by trim and fill analysis was found to be 24.91(95% CI: 20.8-28.9) for anxiety. The subgroup analyses revealed with the lowest prevalence, 23.59%, (95% CI: 8.08, 39.09)) in North America and the highest, 26.77%, (95% CI: 22.5, 31.04) seen in Europe for anxiety and with the highest prevalence, 18.67%, (95% CI: 9.82, 27.5) in North America and the lowest, 13.27%, (95% CI: -10.05, 16.5) seen in Europe for depression. Conclusion. The global prevalence of anxiety and depression among cystic fibrosis patients is common. Therefore, close monitoring of the patient, regularly screening for anxiety and depression, and appropriate prevention techniques is recommended.


2020 ◽  
pp. 000486742096374 ◽  
Author(s):  
Brenton Eyre-Watt ◽  
Eesharnan Mahendran ◽  
Shuichi Suetani ◽  
Joseph Firth ◽  
Steve Kisely ◽  
...  

Background: Lithium in drinking water may have significant mental health benefits. We investigated the evidence on the association between lithium concentrations in drinking water and their neuropsychiatric outcomes. Methods: We conducted a systematic review and meta-analysis and searched Pubmed, Embase, Web of Science, PsycINFO and CINAHL up to 19 January 2020, for peer-reviewed research examining the association between lithium concentrations in drinking water and neuropsychiatric outcomes. We used a pairwise analysis and a random effects model to meta-analyse suicide rates and psychiatric hospital admissions. We assessed for publication bias using Egger’s test and Duval and Tweedie’s Trim and Fill analysis. Results: Twenty-seven studies including 113 million subjects were included in this systematic review. Meta-analysis of 14 studies including 94 million people found higher lithium concentrations were associated with reduced suicide rates ( r = −0.191, 95% confidence interval = [−0.287, −0.090], p < 0.001) and meta-analysis of two studies including 5 million people found higher lithium concentrations were associated with fewer hospital admissions ( r = −0.413, 95% confidence interval = [−0.689, −0.031], p = 0.035). We found significant heterogeneity between studies ( Q = 67.4, p < 0.001, I2 = 80.7%) and the presence of publication bias (Egger’s test; t value = 2.90, p = 0.013). Other included studies did not provide sufficient data to analyse other neuropsychiatric outcomes quantitatively. Conclusion: Higher lithium concentrations in drinking water may be associated with reduced suicide rates and inpatient psychiatric admissions. The relationship with other neuropsychiatric outcomes and complications remains unclear. Further research is required before any public health recommendations can be made. Trial registration number: The study was registered with PROSPERO, number CRD42018090145.


2021 ◽  
Author(s):  
Jinghan J Chen ◽  
Mathura Thiyagarajah ◽  
Jianmeng Song ◽  
Clara Chen ◽  
Nathan Herrmann ◽  
...  

Abstract Background: Increasing evidence implicates oxidative stress (OS) in Alzheimer Disease (AD) and Mild Cognitive Impairment (MCI). Depletion of the brain antioxidant glutathione (GSH) may be important in OS-mediated neurodegeneration, though studies of post-mortem brain GSH changes in AD have been inconclusive. Recent in vivo measurements of brain and blood GSH may shed light on GSH changes earlier in the disease.Aim: To quantitatively review in vivo GSH in AD and MCI compared to healthy controls (HC) using meta-analyses. Method: Studies with in vivo brain or blood GSH levels in MCI or AD with a HC group were identified using Medline, PsychInfo, and Embase (1947-June 2020). Standardized mean differences (SMD) and 95% confidence intervals (CI) were calculated for outcomes using random effects models. Outcome measures included brain GSH (Meshcher-Garwood Point Resolved Spectroscopy (MEGA-PRESS) versus non-MEGA-PRESS), and blood GSH (intracellular versus extracellular) in AD and MCI. The Q statistic and Egger’s test were used to assess heterogeneity and risk of publication bias, respectively. Results: For brain GSH, 4 AD (AD=135, HC=223) and 4 MCI (MCI=213, HC=211) studies were included. For blood GSH, 26 AD (AD=1203, HC=1135) and 7 MCI (MCI=434, HC=408) studies were included. Brain GSH overall did not differ in AD or MCI compared to HC; however, the subgroup of studies using MEGA-PRESS reported lower brain GSH in AD (SMD [95%CI] -1.45 [-1.83, -1.06], p<0.001) and MCI (-1.15 [-1.71, -0.59], z=4.0, p<0.001). AD had lower intracellular and extracellular blood GSH overall (-1.10 [-1.58, -0.62], z=4.46, p<0.001). In a subgroup analysis, intracellular GSH was lower in MCI (-0.66 [-1.11, -0.21], p=0.025). Heterogeneity was observed throughout (I2 >85%) and not fully accounted by subgroup analysis. Egger’s test indicated risk of publication bias.Conclusion: Blood intracellular GSH decrease is seen in MCI, while both intra- and extracellular decreases were seen in AD. Brain GSH is decreased in AD and MCI in subgroup analysis. Potential bias and heterogeneity suggest the need for measurement standardization and additional studies to explore sources of heterogeneity.


2015 ◽  
Author(s):  
Farhan Mohammad ◽  
Joses Ho ◽  
Jia Hern Woo ◽  
Chun Lei Lim ◽  
Dennis Jun Jie Poon ◽  
...  

AbstractRodent defense behavior assays have been widely used as preclinical models of anxiety to study possibly therapeutic anxiety-reducing interventions. However, some proposed anxiety-modulating factors—genes, drugs and stressors—have had discordant effects across different studies. To reconcile the effect sizes of purported anxiety factors, we conducted systematic review and meta-analyses of the literature on ten anxiety-linked interventions, as examined in the elevated plus maze, open field and light-dark box assays. Diazepam, 5-HT1A receptor gene knockout and overexpression, SERT gene knockout and overexpression, pain, restraint, social isolation, corticotropin-releasing hormone and Crhr1 were selected for review. Eight interventions had statistically significant effects on rodent anxiety, while Htr1a overexpression and Crh knockout did not. Evidence for publication bias was found in the diazepam, Htt knockout, and social isolation literatures. The Htr1a and Crhr1 results indicate a disconnect between preclinical science and clinical research. Furthermore, the meta-analytic data confirmed that genetic SERT anxiety effects were paradoxical in the context of the clinical use of SERT inhibitors to reduce anxiety.HighlightsMeta-analysis shows eight rodent anxiety factors have at least moderate effects.Publication bias affects four of the anxiety interventions.Preclinical rodent anxiety results appear disconnected from clinical efforts.Serotonin transporter gene lesion effects are paradoxical with reuptake inhibitors clinical use.


2021 ◽  
Vol 12 ◽  
Author(s):  
Rune Strømme ◽  
Karine Holthe Børstad ◽  
Andrea Eftang Rø ◽  
Eilin Kristine Erevik ◽  
Dominic Sagoe ◽  
...  

Objectives: The aim of the present meta-analysis was to synthesize results from the association between problem gambling (PG) and dimensions of the five factor model of personality and to identify potential moderators (gambling diagnosis: yes/no, comorbidity: yes/no and trait assessment: four or fewer items vs. five items or more) of these associations in meta-regressions.Methods: Searches were conducted in six databases; Medline, Web of Science, PsychInfo, Google Scholar, OpenGrey, and Cochrane Library (conducted on February, 22, 2021). Included studies: (1) reported a relationship between PG and at least one of the personality traits in the five-factor model, (2) contained information of zero-order correlations or sufficient data for such calculations, and (3) were original articles published in any European language. Case-studies, qualitative studies, and reviews were excluded. All articles were independently screened by two authors. Final agreement was reached through discussion or by consulting a third author. Risk of bias of the included studies was assessed by the Newcastle-Ottawa Scale. Data were synthesized using a random effects model.Results: In total 28 studies, comprising 20,587 participants, were included. The correlations between PG and the traits were as follows: Neuroticism: 0.273 (95% CI = 0.182, 0.358), conscientiousness −0.296 (95% CI = −0.400, −0.185), agreeableness −0.163 (95% CI = −0.223, −0.101), openness −0.219 (95% CI = −0.308, −0.127), and extroversion −0.083 (95% CI = −0.120, −0.046). For all meta-analyses the between study heterogeneity was significant. Presence of gambling diagnosis was the only moderator that significantly explained between-study variance showing a more negative correlation to extroversion when participants had a gambling diagnosis compared to when this was not the case.Discussion: The results indicated some publication bias. Correcting for this by a trim-and-fill procedure showed however that the findings were consistent. Clinicians and researchers should be aware of the associations between personality traits and PG. Previous studies have for example showed neuroticism to be related to treatment relapse, low scores on conscientiousness to predict treatment drop-out and agreeableness to reduce risk of treatment drop-out.Systematic Review Registration: PROSPERO (CRD42021237225).


2021 ◽  
Author(s):  
Marianna Rosso ◽  
Robin Wirz ◽  
Ariane Vera Loretan ◽  
Nicole Alessandra Sutter ◽  
Charlène Tatiana Pereira da Cunha ◽  
...  

Animal research on anxiety and anxiety disorders relies on valid animal models of anxiety. However, the validity of widely used rodent behavioural tests of anxiety has repeatedly been questioned, as they often fail to produce consistent results across independent replicate studies using different study populations or different anxiolytic compounds. In this study, we assessed the sensitivity of behavioural tests of anxiety in mice to detect anxiolytic effects of drugs prescribed to treat anxiety in humans. To this end, we conducted a pre-registered systematic review of studies reporting tests of anxiolytic compounds against a control treatment using common behavioural tests of anxiety in mice. PubMed and EMBASE were searched on August 21 st 2019 for studies published in English and 814 papers were identified for inclusion. Risk of bias was assessed based on Syrcle’s risk of bias tool and the Camarades study quality checklist on a randomly selected subsample of 180 papers. Meta-analyses on effect sizes of treatments using standardized mean differences (Hedges’ g) showed that only two of 17 test measures reliably detected effects of anxiolytic compounds other than diazepam. Further, we report considerable variation in both direction and size of effects of most anxiolytics on most outcome variables, indicating poor replicability of test results. This was corroborated by high heterogeneity in most test measures. Finally, we found an overall high risk of bias. Our findings indicate a general lack of sensitivity of common behavioural tests of anxiety in mice to anxiolytic compounds and cast serious doubt on both construct and predictive validity of most of those tests. The use of animals to model human conditions can be justified only if the expected results are informative, reproducible, and translatable. In view of scientifically valid and ethically responsible research, we call for a revision of behavioural tests of anxiety in mice and the development of more predictive tests .


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