The Navigation Guide - evidence-based medicine meets environmental health: systematic review of nonhuman evidence for PFOA effects on fetal growth.
Ontology highlight
ABSTRACT: Background
In contrast to current methods of expert-based narrative review, the Navigation Guide is a systematic and transparent method for synthesizing environmental health research from multiple evidence streams. The Navigation Guide was developed to effectively and efficiently translate the available scientific evidence into timely prevention-oriented action.Objectives
We applied the Navigation Guide systematic review method to answer the question "Does fetal developmental exposure to perfluorooctanoic acid (PFOA) or its salts affect fetal growth in animals ?" and to rate the strength of the experimental animal evidence.Methods
We conducted a comprehensive search of the literature, applied prespecified criteria to the search results to identify relevant studies, extracted data from studies, obtained additional information from study authors, conducted meta-analyses, and rated the overall quality and strength of the evidence.Results
Twenty-one studies met the inclusion criteria. From the meta-analysis of eight mouse gavage data sets, we estimated that exposure of pregnant mice to increasing concentrations of PFOA was associated with a change in mean pup birth weight of -0.023 g (95% CI: -0.029, -0.016) per 1-unit increase in dose (milligrams per kilogram body weight per day). The evidence, consisting of 15 mammalian and 6 nonmammalian studies, was rated as "moderate" and "low" quality, respectively.Conclusion
Based on this first application of the Navigation Guide methodology, we found sufficient evidence that fetal developmental exposure to PFOA reduces fetal growth in animals.
SUBMITTER: Koustas E
PROVIDER: S-EPMC4181920 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:BackgroundThe Navigation Guide methodology was developed to meet the need for a robust method of systematic and transparent research synthesis in environmental health science. We conducted a case study systematic review to support proof of concept of the method.ObjectiveWe applied the Navigation Guide systematic review methodology to determine whether developmental exposure to perfluorooctanoic acid (PFOA) affects fetal growth in humans.MethodsWe applied the first 3 steps of the Navigation Guide methodology to human epidemiological data: 1) specify the study question, 2) select the evidence, and 3) rate the quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using prespecified criteria. We evaluated each study for risk of bias and conducted meta-analyses on a subset of studies. We rated quality and strength of the entire body of human evidence.ResultsWe identified 18 human studies that met our inclusion criteria, and 9 of these were combined through meta-analysis. Through meta-analysis, we estimated that a 1-ng/mL increase in serum or plasma PFOA was associated with a -18.9 g (95% CI: -29.8, -7.9) difference in birth weight. We concluded that the risk of bias across studies was low, and we assigned a "moderate" quality rating to the overall body of human evidence.ConclusionOn the basis of this first application of the Navigation Guide systematic review methodology, we concluded that there is "sufficient" human evidence that developmental exposure to PFOA reduces fetal growth.
| S-EPMC4181929 | biostudies-literature
Project description:BackgroundThe Navigation Guide is a novel systematic review method to synthesize scientific evidence and reach strength of evidence conclusions for environmental health decision making.ObjectiveOur aim was to integrate scientific findings from human and nonhuman studies to determine the overall strength of evidence for the question "Does developmental exposure to perfluorooctanoic acid (PFOA) affect fetal growth in humans?"MethodsWe developed and applied prespecified criteria to systematically and transparently a) rate the quality of the scientific evidence as "high," "moderate," or "low"; b) rate the strength of the human and nonhuman evidence separately as "sufficient," "limited," "moderate," or "evidence of lack of toxicity"; and c) integrate the strength of the human and nonhuman evidence ratings into a strength of the evidence conclusion.ResultsWe identified 18 epidemiology studies and 21 animal toxicology studies relevant to our study question. We rated both the human and nonhuman mammalian evidence as "moderate" quality and "sufficient" strength. Integration of these evidence ratings produced a final strength of evidence rating in which review authors concluded that PFOA is "known to be toxic" to human reproduction and development based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species.ConclusionWe concluded that developmental exposure to PFOA adversely affects human health based on sufficient evidence of decreased fetal growth in both human and nonhuman mammalian species. The results of this case study demonstrate the application of a systematic and transparent methodology, via the Navigation Guide, for reaching strength of evidence conclusions in environmental health.
| S-EPMC4181930 | biostudies-literature
Project description:This is a very exciting time for medicine. We are witnessing the creation of a new approach to the prevention and treatment of cardiovascular disease. It is an omnigenic approach-powered by systems biology-to assembling patient-specific information about how genes and lifestyle interact. When combined with other new technologies such as artificial intelligence and machine learning informatics, the result will be the development of a precision form of personalized lifestyle medicine applied to cardiovascular disease. This advancement will be a gateway for change throughout the entire segment of the health care system that is focused on the many complex chronic conditions affecting our world population.
| S-EPMC6438082 | biostudies-literature
Project description:Although considerable evidence suggests that in utero arsenic exposure affects children's health, these data are mainly from areas of the world where groundwater arsenic levels far exceed the World Health Organization limit of 10 μg/L. We, and others, have found that more common levels of in utero arsenic exposure may also impact children's health. However, the underlying molecular mechanisms are poorly understood. To address this issue, we analyzed the expression of key developmental genes in fetal placenta in a birth cohort of women using unregulated water supplies in a US region with elevated groundwater arsenic. We identified several genes whose expression associated with maternal arsenic exposure in a fetal sex-specific manner. In particular, expression of the HEDGEHOG pathway component, GLI3, in female placentae was both negatively associated with arsenic exposure and positively associated with infant birth weight. This suggests that modulation of GLI3 in the fetal placenta, and perhaps in other fetal tissues, contributes to arsenic's detrimental effects on fetal growth. We showed previously that arsenic-exposed NIH3T3 cells have reduced GLI3 repressor protein. Together, these studies identify GLI3 as a key signaling node that is affected by arsenic, mediating a subset of its effects on developmental signaling and fetal health.
| S-EPMC4535308 | biostudies-literature
Project description:Primary aldosteronism is the most common single cause of hypertension and is potentially curable when only one adrenal gland is the culprit. The importance of primary aldosteronism to public health derives from its high prevalence but huge under-diagnosis (estimated to be <1% of all affected individuals), despite the consequences of poor blood pressure control by conventional therapy and enhanced cardiovascular risk. This state of affairs is attributable to the fact that the tools used for diagnosis or treatment are still those that originated in the 1970-1990s. Conversely, molecular discoveries have transformed our understanding of adrenal physiology and pathology. Many molecules and processes associated with constant adrenocortical renewal and interzonal metamorphosis also feature in aldosterone-producing adenomas and aldosterone-producing micronodules. The adrenal gland has one of the most significant rates of non-silent somatic mutations, with frequent selection of those driving autonomous aldosterone production, and distinct clinical presentations and outcomes for most genotypes. The disappearance of aldosterone synthesis and cells from most of the adult human zona glomerulosa is the likely driver of the mutational success that causes aldosterone-producing adenomas, but insights into the pathways that lead to constitutive aldosterone production and cell survival may open up opportunities for novel therapies.
| S-EPMC7615304 | biostudies-literature
Project description:This study, a tribute to Aristotle's 2400 years, used a juxtaposition of valid Aristotelian arguments to the paradoxes formulated by Zeno the Eleatic, in order to investigate the electrophysiological correlates of attentional and /or memory processing effects in the course of deductive reasoning. Participants undertook reasoning tasks based on visually presented arguments which were either (a) valid (Aristotelian) statements or (b) paradoxes. We compared brain activation patterns while participants maintained the premises / conclusions of either the valid statements or the paradoxes in working memory (WM). Event-related brain potentials (ERPs), specifically the P300 component of ERPs, were recorded during the WM phase, during which participants were required to draw a logical conclusion regarding the correctness of the valid syllogisms or the paradoxes. During the processing of paradoxes, results demonstrated a more positive event-related potential deflection (P300) across frontal regions, whereas processing of valid statements was associated with noticeable P300 amplitudes across parieto-occipital regions. These findings suggest that paradoxes mobilize frontal attention mechanisms, while valid deduction promotes parieto-occipital activity associated with attention and/or subsequent memory processing.
| S-EPMC5199053 | biostudies-literature
Project description:Thoracic ultrasound (TUS) has become an essential procedure in respiratory medicine. Due to its intrinsic safety and versatility, it has been applied in patients affected by several respiratory diseases both in intensive care and outpatient settings. TUS can complement and often exceed stethoscope and radiological findings, especially in managing pleural diseases. We hereby aimed to describe the establishment, development, and optimization in a large, tertiary care hospital of a pleural clinic, which is dedicated to the evaluation and monitoring of patients with pleural diseases, including, among others, pleural effusion and/or thickening, pneumothorax and subpleural consolidation. The clinic was initially meant to follow outpatients undergoing medical thoracoscopy. In this scenario, TUS allowed rapid and regular assessment of these patients, promptly diagnosing recurrence of pleural effusion and other complications that could be appropriately managed. Over time, our clinic has rapidly expanded its initial indications thus becoming the place to handle more complex respiratory patients in collaboration with, among others, thoracic surgeons and oncologists. In this article, we critically describe the strengths and pitfalls of our "pleural clinic" and propose an organizational model that results from a synergy between respiratory physicians and other professionals. This model can inspire other healthcare professionals to develop a similar organization based on their local setting.
| S-EPMC10598727 | biostudies-literature
Project description:BACKGROUND:There are reports of developmental and reproductive health effects associated with the widely used biocide triclosan. OBJECTIVE:Apply the Navigation Guide systematic review methodology to answer the question: Does exposure to triclosan have adverse effects on human development or reproduction? METHODS:We applied the first 3 steps of the Navigation Guide methodology: 1) Specify a study question, 2) Select the evidence, and 3) Rate quality and strength of the evidence. We developed a protocol, conducted a comprehensive search of the literature, and identified relevant studies using pre-specified criteria. We assessed the number and type of all relevant studies. We evaluated each included study for risk of bias and rated the quality and strength of the evidence for the selected outcomes. We conducted a meta-analysis on a subset of suitable data. RESULTS:We found 4282 potentially relevant records, and 81 records met our inclusion criteria. Of the more than 100 endpoints identified by our search, we focused our evaluation on hormone concentration outcomes, which had the largest human and non-human mammalian data set. Three human studies and 8 studies conducted in rats reported thyroxine levels as outcomes. The rat data were amenable to meta-analysis. Because only one of the human thyroxine studies quantified exposure, we did not conduct a meta-analysis of the human data. Through meta-analysis of the data for rats, we estimated for prenatal exposure a 0.09% (95% CI: -0.20, 0.02) reduction in thyroxine concentration per mg triclosan/kg-bw in fetal and young rats compared to control. For postnatal exposure we estimated a 0.31% (95% CI: -0.38, -0.23) reduction in thyroxine per mg triclosan/kg-bw, also compared to control. Overall, we found low to moderate risk of bias across the human studies and moderate to high risk of bias across the non-human studies, and assigned a "moderate/low" quality rating to the body of evidence for human thyroid hormone alterations and a "moderate" quality rating to the body of evidence for non-human thyroid hormone alterations. CONCLUSION:Based on this application of the Navigation Guide systematic review methodology, we concluded that there was "sufficient" non-human evidence and "inadequate" human evidence of an association between triclosan exposure and thyroxine concentrations, and consequently, triclosan is "possibly toxic" to reproductive and developmental health. Thyroid hormone disruption is an upstream indicator of developmental toxicity. Additional endpoints may be identified as being of equal or greater concern as other data are developed or evaluated.
| S-EPMC4951161 | biostudies-literature
Project description:Environmental phenols are used commonly in personal care products and exposure is widespread in pregnant women. In this study, we sought to assess the association between maternal urinary phenol concentrations in pregnancy and fetal growth. The study population included 476 mothers who participated in the prospective LIFECODES birth cohort between 2006 and 2008 at Brigham and Women's Hospital in Boston, Massachusetts, USA. Dichlorophenols (DCPs), benzophenone-3, parabens, triclosan, triclocarban, and bisphenol-S were measured in urine from three time points during pregnancy and averaged. Outcome measures were all standardized to create gestational-age specific z-scores and included: 1) birth weight; 2) ultrasound parameters measured at up to two time points in pregnancy (head and abdominal circumference and femur length); and 3) ultrasound estimates of fetal weight from two time points in combination with birth weight. Models were stratified to investigate sex differences. Inverse associations were observed between average 2,4- and 2,5-DCP concentrations and birth weight z-scores in males. For example, an interquartile range difference in 2,4-DCP was associated with a 0.18 standard deviation decrease in birth weight z-score (95% confidence interval [CI]=-0.33, -0.02). These associations were observed in models that included repeated ultrasound estimates of fetal weight during gestation as well. Also in males, we noted inverse associations between average triclosan exposure over pregnancy and estimated fetal weight combined with birth weight in repeated measures models. For females, associations were generally null. However, mothers with a detectable concentration of bisphenol-S at any of the study visits had lower weight females. In conclusion, we observed inverse associations between indicators of maternal phenol exposure during pregnancy and fetal growth, with several differences observed by sex.
| S-EPMC5899051 | biostudies-literature
Project description:OBJECTIVE:To evaluate prospectively the performance of Fetal Intelligent Navigation Echocardiography (FINE) applied to spatiotemporal image correlation (STIC) volume datasets of the normal fetal heart. METHODS:In all women between 19 and 30 weeks' gestation with a normal fetal heart, an attempt was made to acquire STIC volume datasets of the apical four-chamber view if the following criteria were met: (1) fetal spine located between 5- and 7-o'clock positions; (2) minimal or absent shadowing (including a clearly visible transverse aortic arch); (3) absence of fetal breathing, hiccups, or movement; and (4) adequate image quality. Each STIC volume successfully acquired was evaluated by STICLoop™ to determine its appropriateness before applying the FINE method. Visualization rates of fetal echocardiography views using diagnostic planes and/or Virtual Intelligent Sonographer Assistance (VIS-Assistance®) were calculated. RESULTS:One or more STIC volumes (365 in total) were obtained successfully in 72.5% (150/207) of women undergoing ultrasound examination. Of the 365 volumes evaluated by STICLoop, 351 (96.2%) were considered to be appropriate. From the 351 STIC volumes, only one STIC volume per patient (n = 150) was analyzed using the FINE method, and consequently nine fetal echocardiography views were generated in 76-100% of cases using diagnostic planes only, in 98-100% of cases using VIS-Assistance only, and in 98-100% of cases when using a combination of diagnostic planes and/or VIS-Assistance. CONCLUSIONS:In women between 19 and 30 weeks' gestation with a normal fetal heart undergoing prospective sonographic examination, STIC volumes can be obtained successfully in 72.5% of cases. The FINE method can be applied to generate nine standard fetal echocardiography views in 98-100% of these cases using a combination of diagnostic planes and/or VIS-Assistance. This suggests that FINE could be implemented in fetal cardiac screening programs. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.
| S-EPMC5898803 | biostudies-literature