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OBJECTIVES: to provide evidence on how diet can influence health, greenhouse gas (GHG) emissions, and land use. DESIGN: cohort study. SETTING AND PARTICIPANTS: data collected in the EPIC Italy cohort (N. 47,749). MAIN OUTCOME MEASURES: hazard ratios (HR) for overall mortality and for cancer incidence in association with a sustainable diet (EAT-Lancet). RESULTS: sustainable diets are characterized by lower associated GHG emissions and lower land use (LU). Adherence to the guidelines proposed by the EAT-Lancet Commission was considered. This diet was associated with lower HRs for mortality and cancer incidence in EPIC Italy, estimated with Cox models accounting for potential confounders and stratified by sex. The hazard ratios for overall mortality showed a dose-response relationship with quartiles of diets associated with high GHG emissions, land use, and high distance from the EAT-Lancet diet calculated using a novel index, the EAT-Lancet distance index (EatDI). The HR for overall cancer incidence was also higher in the population with non-sustainable diets. CONCLUSIONS: the association among dietary GHG emissions, LU, and EatDI and overall mortality and overall cancer incidence suggests that promoting diets with low associated environmental impact can be an effective mitigation strategy with important co-benefits.
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Gases de Efeito Estufa , Neoplasias , Humanos , Estudos de Coortes , Itália/epidemiologia , Dieta , Neoplasias/epidemiologia , Neoplasias/etiologiaRESUMO
Discrepancies between total life expectancy and healthy life expectancy are in part due to unhealthy lifestyles, in which diet plays an important role. Despite this knowledge, observational studies and randomized trials have yet to show consistent improvements in health and well-being, also known as health-related quality of life (HRQoL), given the variety of elements that conform a healthy diet aside from its content. As such, we aimed to describe the evidence and common topics concerning the effects of modifiable eating behaviors and HRQoL in patients with non-communicable diseases (NCD). This scoping review of six electronic databases included 174 reports (69 % were experimental studies, 10 % longitudinal studies, and 21 % cross-sectional studies). Using VOSviewer, a bibliometric tool with text mining functionalities, we identified relevant aspects of dietary assessments and interventions. Commonly observed topics in experimental studies were those related to diet quality (micro- and macronutrients, food items, and dietary patterns). In contrast, less was found regarding eating schedules, eating locations, culturally accepted food items, and the role of food insecurity in HRQoL. Disregarding these aspects of diets may be limiting the full potential of nutrition as a key element of health and well-being in order to ensure lengthy and fulfilling lives.
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Comportamento Alimentar , Qualidade de Vida , Estudos Transversais , Dieta , Ingestão de Alimentos , Humanos , Estilo de VidaRESUMO
Recent incidents at nuclear facilities in Ukraine related to the attacks from Russian forces highlight the fragility of nuclear power plants and other nuclear facilities in war and the very real potential for another environmental nuclear disaster and associated health risks in Europe. Nuclear catastrophes from war can occur from radioactive materials released from war threatened nuclear power plants and other nuclear facilities in war zones, in addition to the direct threat from the deployment of nuclear weaponry and can result in immediate and long-term health impacts. Despite historical nuclear catastrophic events, including the Chernobyl nuclear power plant accident and atomic bombings of Hiroshima and Nagasaki, and that for more than a century epidemiologists have studied the consequences of radiation exposures, there are still major unanswered questions regarding radiation risks and human health. Epidemiologists will need to continue to quantify the health effects from exposure to environmental radiation, including background radiation, and are able to contribute to conversations about reliance on nuclear energy and alternative energy futures. As a society we are compelled to rethink our ties to nuclear energy, especially with the potential of increasing reliance on nuclear power amid oil and gas crisis and considering climate change, nuclear warfare, including nuclear weapon testing, and the fragility of humanity and health to even low doses of radiation from these and other natural and unnatural sources.
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Acidente Nuclear de Chernobyl , Desastres , Armas Nucleares , Europa (Continente) , Humanos , Reatores NuclearesRESUMO
Consumption of ultra-processed foods (UPF) has increased worldwide during the last decades because they are hyperpalatable, cheap, and ready-to-consume products. However, uncertainty exists about their impact on health. We conducted a systematic review and meta-analysis evaluating the association of UPF consumption with all-cause mortality risk. Five bibliographic databases were searched for relevant studies. Random effects models were used to calculate pooled relative risks (RRs) and 95% confidence intervals (CIs). Of 6,951 unique citations, 40 unique prospective cohort studies comprising 5,750,133 individuals were included; publication dates ranged from 1984 to 2021. Compared with low consumption, highest consumption of UPF (RR = 1.29, 95% CI: 1.17, 1.42), sugar-sweetened beverages (RR = 1.11, 95% CI, 1.04, 1.18), artificially sweetened beverages (RR = 1.14, 95% CI, 1.05, 1.22), and processed meat/red meat (RR = 1.15, 95% CI, 1.10, 1.21) were significantly associated with increased risk of mortality. However, breakfast cereals were associated with a lower mortality risk (RR = 0.85, 95% CI, 0.79, 0.92). This meta-analysis suggests that high consumption of UPF, sugar-sweetened beverages, artificially sweetened beverages, processed meat, and processed red meat might increase all-cause mortality, while breakfast cereals might decrease it. Future studies are needed to address lack of standardized methods in UPF categorization.
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Fast Foods , Edulcorantes , Ingestão de Alimentos , Fast Foods/efeitos adversos , Humanos , Carne , Estudos Prospectivos , Edulcorantes/efeitos adversosRESUMO
OBJECTIVE: Arteriovenous malformations of the lower extremities (AVMLE) can present as simple or complex combined or syndromic forms (eg, Parkes Weber Syndrome). We aimed to characterize the differences in clinical presentation and natural history of these potentially life- and limb-threatening congenital vascular malformations. METHODS: We conducted a retrospective analysis of a consecutive series of patients with AVMLE who presented to a tertiary referral center in Switzerland between 2008 and 2018. Clinical baseline characteristics, D-dimer level, and course were summarized and differences between simple, non-syndromic and combined or syndromic AVMLE determined. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models. RESULTS: Overall, 506 patients were prospectively enrolled in the Bernese Congenital Vascular Malformation Registry, 31 (6%) with AVMLE. There were 16 women and 15 men, with a mean age of 18 years at first diagnosis (range, 1 month to 72 years). Simple AVMLE was present in 22 (71%) and combined or syndromic AVMLE with limb overgrowth in 9 patients (29%), respectively. Common symptoms and signs were pain (n = 25; 81%), swelling (n = 21; 68%), and soft tissue hypertrophy (n = 13; 42%). Among combined or syndromic patients, three patients died from wound infection with sepsis or disseminated intravascular coagulation with bleeding complications (intracranial hemorrhage and bleeding from extensive leg ulcers). Combined or syndromic patients presented more often with bleeding (67% vs 5%; P < .001), malformation-related infection (44% vs 5%; P = .017) and leg length difference (56% vs 14%; P = .049). D-dimer levels were elevated (mean, 17,256 µg/L; range, 1557-80,000 µg/L) and angiographic appearance showed complex, mixed type of AVMs, including interstitial type IV, in all patients with combined or syndromic AVMLE. CONCLUSIONS: Patients with congenital simple AVMLE most often present with benign clinical features and rarely with complications related to hemodynamic changes. Patients with combined or syndromic AVMLE often face serious outcomes dominated by complications other than direct high-flow-related heart failure.
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Malformações Arteriovenosas Intracranianas , Adolescente , Feminino , Seguimentos , Humanos , Malformações Arteriovenosas Intracranianas/complicações , Hemorragias Intracranianas , Masculino , Estudos Retrospectivos , Resultado do TratamentoRESUMO
BACKGROUND: PIK3CA (activating mutations of the p110α subunit of phosphatidylinositol 3-kinases)-related overgrowth spectrums (PROS) include a variety of clinical presentations that are associated with hypertrophy of different parts of the body. We performed a systematic literature review to assess the current treatment options and their efficacy and safety for PROS. METHODS: A literature search was performed in Embase, MEDLINE (Ovid), Web of Science Core Collection, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov, and Google Scholar to retrieve studies on the treatment of hypertrophy in PROS. Randomized controlled trials, cohort studies, and case series with ≥10 patients were included in the present review. The titles, abstracts, and full text were assessed by two reviewers independently. The risk of bias was assessed using the Newcastle-Ottawa scale. RESULTS: We included 16 studies of the treatment of hypertrophy in PROS patients, 13 (81.3%) from clinical retrospective studies and 3 (13.7%) from prospective cohort studies. The risk of bias grade was low for 2, medium for 12, and high for 2 studies. Of the 16 studies, 13 reported on surgical treatment and 3 reported pharmacologic treatment using phosphatidylinositol-3-kinase (PI3K)/mammalian target of rapamycin (mTOR) pathway inhibitors in PROS patients. In 3 studies, PROS was defined by a mutation in the PIK3CA gene, and 13 studies relied on a clinical definition of PROS. Surgical therapy was beneficial for a specific subgroup of PROS (macrodactyly). However, little has been reported concerning surgery and the potential benefits for other PROS entities. The reported side effects after surgical therapy were mostly prolonged wound healing or scarring. PI3K/mTOR pathway inhibition was beneficial in patients with PROS by reducing hypertrophy and systemic symptoms. The adverse effects reported included infection, changes in blood count, liver enzymes, and metabolic measures. CONCLUSIONS: Surgery is a locally limited treatment option for specific types of PROS. A promising treatment option for PROS is pharmacologic PIK3CA inhibition. However, the level of evidence on the treatment of overgrowth in PROS patients is limited.
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Classe I de Fosfatidilinositol 3-Quinases/antagonistas & inibidores , Hipertrofia/terapia , Inibidores de MTOR/uso terapêutico , Inibidores de Fosfoinositídeo-3 Quinase/uso terapêutico , Procedimentos Cirúrgicos Operatórios , Classe I de Fosfatidilinositol 3-Quinases/genética , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Predisposição Genética para Doença , Humanos , Hipertrofia/diagnóstico , Hipertrofia/enzimologia , Hipertrofia/genética , Inibidores de MTOR/efeitos adversos , Terapia de Alvo Molecular , Mutação , Fenótipo , Inibidores de Fosfoinositídeo-3 Quinase/efeitos adversos , Transdução de Sinais , Procedimentos Cirúrgicos Operatórios/efeitos adversos , Síndrome , Resultado do TratamentoRESUMO
This narrative review discusses the current understanding, knowledge gaps and challenges in expanding our knowledge of the association between menopause and the reproductive aging process and cardiometabolic disease (CMD) in women, with a focus on type 2 diabetes and cardiovascular disease. The physiological changes that occur at different stages of the reproductive life span, as well as type of menopause and timing, are factors widely associated with CMD risk; however, the underlying mechanisms remain either unclear or insufficiently studied. Decreased ovarian estrogen production and relative androgen excess around menopause onset are the most studied factors linking menopause and cardiometabolic health; nevertheless, the evidence is not persuasive and other hypotheses might explain the changes in CMD risk during menopausal transition. In this context, hormone therapy has been widely adopted in the treatment and prevention of CMD, although uncertainty regarding its cardiometabolic effects has raised the need to optimize therapeutic modalities. Mechanisms such as the "iron overload theory" and new "omics" platforms could provide new insights into potential pathways underlying the association between menopause and cardiometabolic health, such as the DNA damage response. Although it has been widely reported that environmental and lifestyle factors affect both menopause and cardiometabolic health, there is little evidence on the role of these exposures in menopause-associated CMD risk.
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Doenças Cardiovasculares , Diabetes Mellitus Tipo 2 , Menopausa/fisiologia , Envelhecimento , Doenças Cardiovasculares/etiologia , Diabetes Mellitus Tipo 2/etiologia , Feminino , Humanos , Reprodução , Saúde da MulherRESUMO
BACKGROUND: Unhealthy diets, the rise of non-communicable diseases, and the declining health of the planet are highly intertwined, where food production and consumption are major drivers of increases in greenhouse gas emissions, substantial land use, and adverse health such as cancer and mortality. To assess the potential co-benefits from shifting to more sustainable diets, we aimed to investigate the associations of dietary greenhouse gas emissions and land use with all-cause and cause-specific mortality and cancer incidence rates. METHODS: Using data from 443 991 participants in the European Prospective Investigation into Cancer and Nutrition (EPIC) study, a multicentre prospective cohort, we estimated associations between dietary contributions to greenhouse gas emissions and land use and all-cause and cause-specific mortality and incident cancers using Cox proportional hazards regression models. The main exposures were modelled as quartiles. Co-benefits, encompassing the potential effects of alternative diets on all-cause mortality and cancer and potential reductions in greenhouse gas emissions and land use, were estimated with counterfactual attributable fraction intervention models, simulating potential effects of dietary shifts based on the EAT-Lancet reference diet. FINDINGS: In the pooled analysis, there was an association between levels of dietary greenhouse gas emissions and all-cause mortality (adjusted hazard ratio [HR] 1·13 [95% CI 1·10-1·16]) and between land use and all-cause mortality (1·18 [1·15-1·21]) when comparing the fourth quartile to the first quartile. Similar associations were observed for cause-specific mortality. Associations were also observed between all-cause cancer incidence rates and greenhouse gas emissions, when comparing the fourth quartile to the first quartile (adjusted HR 1·11 [95% CI 1·09-1·14]) and between all-cause cancer incidence rates and land use (1·13 [1·10-1·15]); however, estimates differed by cancer type. Through counterfactual attributable fraction modelling of shifts in levels of adherence to the EAT-Lancet diet, we estimated that up to 19-63% of deaths and up to 10-39% of cancers could be prevented, in a 20-year risk period, by different levels of adherence to the EAT-Lancet reference diet. Additionally, switching from lower adherence to the EAT-Lancet reference diet to higher adherence could potentially reduce food-associated greenhouse gas emissions up to 50% and land use up to 62%. INTERPRETATION: Our results indicate that shifts towards universally sustainable diets could lead to co-benefits, such as minimising diet-related greenhouse gas emissions and land use, reducing the environmental footprint, aiding in climate change mitigation, and improving population health. FUNDING: European Commission (DG-SANCO), the International Agency for Research on Cancer (IARC), MRC Early Career Fellowship (MR/M501669/1).
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Dieta , Gases de Efeito Estufa , Estudos de Coortes , Dieta/estatística & dados numéricos , Saúde Ambiental , Humanos , Estudos ProspectivosRESUMO
Mechanisms underlying adverse birth and later in life health effects from exposure to air pollution during the prenatal period have not been not fully elucidated, especially in the context of mixtures. We assessed the effects of prenatal exposure to mixtures of air pollutants of particulate matter (PM), PM2.5, PM10, nitrogen oxides, NO2, NOx, ultrafine particles (UFP), and oxidative potential (OP) of PM2.5 on infant birthweight in four European birth cohorts and the mechanistic underpinnings through cross-omics of metabolites and inflammatory proteins. The association between mixtures of air pollutants and birthweight z-scores (standardized for gestational age) was assessed for three different mixture models, using Bayesian machine kernel regression (BKMR). We determined the direct effect for PM2.5, PM10, NO2, and mediation by cross-omic signatures (identified using sparse partial least-squares regression) using causal mediation BKMR models. There was a negative association with birthweight z-scores and exposure to mixtures of air pollutants, where up to -0.21 or approximately a 96 g decrease in birthweight, comparing the 75th percentile to the median level of exposure to the air pollutant mixture could occur. Shifts in birthweight z-scores from prenatal exposure to PM2.5, PM10, and NO2 were mediated by molecular mechanisms, represented by cross-omics scores. Interleukin-17 and epidermal growth factor were identified as important inflammatory responses underlyingair pollution-associated shifts in birthweight. Our results signify that by identifying mechanisms through which mixtures of air pollutants operate, the causality of air pollution-associated shifts in birthweight is better supported, substantiating the need for reducing exposure in vulnerable populations.
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Poluentes Atmosféricos , Poluição do Ar , Efeitos Tardios da Exposição Pré-Natal , Poluentes Atmosféricos/análise , Poluentes Atmosféricos/toxicidade , Poluição do Ar/efeitos adversos , Poluição do Ar/análise , Teorema de Bayes , Peso ao Nascer , Exposição Ambiental/análise , Monitoramento Ambiental , Feminino , Humanos , Lactente , Material Particulado/efeitos adversos , Material Particulado/análise , GravidezRESUMO
An increasing number of findings from epidemiological studies support associations between exposure to air pollution and the onset of several diseases, including pulmonary, cardiovascular and neurodegenerative diseases, and malignancies. However, intermediate, and potentially mediating, biological mechanisms associated with exposure to air pollutants are largely unknown. Previous studies on the human exposome have shown that the expression of certain circulating microRNAs (miRNAs), regulators of gene expression, are altered upon exposure to traffic-related air pollutants. In the present study, we investigated the relationship between particulate matter (PM) smaller than 2.5 µm (PM2.5), PM2.5 absorbance (as a proxy of black carbon and soot), and ultrafine-particles (UFP, smaller than 0.1 µm), measured in healthy volunteers by 24 h personal monitoring (PEM) sessions and global expression levels of peripheral blood miRNAs. The PEM sessions were conducted in four European countries, namely Switzerland (Basel), United Kingdom (Norwich), Italy (Turin), and The Netherlands (Utrecht). miRNAs expression levels were analysed using microarray technology on blood samples from 143 participants. Seven miRNAs, hsa-miR-24-3p, hsa-miR-4454, hsa-miR-4763-3p, hsa-miR-425-5p, hsa-let-7d-5p, hsa-miR-502-5p, and hsa-miR-505-3p were significantly (FDR corrected) expressed in association with PM2.5 personal exposure, while no significant association was found between miRNA expression and the other pollutants. The results obtained from this investigation suggest that personal exposure to PM2.5 is associated with miRNA expression levels, showing the potential for these circulating miRNAs as novel biomarkers for air pollution health risk assessment.
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MicroRNAs , Material Particulado , Europa (Continente) , Perfilação da Expressão Gênica , Humanos , Itália , Países Baixos , Suíça , Reino UnidoRESUMO
BACKGROUND: Socio-economic inequalities in mortality are well established, yet the contribution of intermediate risk factors that may underlie these relationships remains unclear. We evaluated the role of multiple modifiable intermediate risk factors underlying socio-economic-associated mortality and quantified the potential impact of reducing early all-cause mortality by hypothetically altering socio-economic risk factors. METHODS: Data were from seven cohort studies participating in the LIFEPATH Consortium (total n = 179 090). Using both socio-economic position (SEP) (based on occupation) and education, we estimated the natural direct effect on all-cause mortality and the natural indirect effect via the joint mediating role of smoking, alcohol intake, dietary patterns, physical activity, body mass index, hypertension, diabetes and coronary artery disease. Hazard ratios (HRs) were estimated, using counterfactual natural effect models under different hypothetical actions of either lower or higher SEP or education. RESULTS: Lower SEP and education were associated with an increase in all-cause mortality within an average follow-up time of 17.5 years. Mortality was reduced via modelled hypothetical actions of increasing SEP or education. Through higher education, the HR was 0.85 [95% confidence interval (CI) 0.84, 0.86] for women and 0.71 (95% CI 0.70, 0.74) for men, compared with lower education. In addition, 34% and 38% of the effect was jointly mediated for women and men, respectively. The benefits from altering SEP were slightly more modest. CONCLUSIONS: These observational findings support policies to reduce mortality both through improving socio-economic circumstances and increasing education, and by altering intermediaries, such as lifestyle behaviours and morbidities.
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Disparidades nos Níveis de Saúde , Mortalidade , Adulto , Causas de Morte , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mortalidade/tendências , Fatores SocioeconômicosRESUMO
A correction to this paper has been published and can be accessed via link at the top of the paper.
RESUMO
The prenatal period represents a critical window of susceptibility to inorganic arsenic (iAs) exposure from contaminated drinking water. Ingested iAs undergoes hepatic methylation generating mono and di-methyl arsenicals (MMAs and DMAs, respectively), a process that facilitates urinary arsenic (As) elimination. Differences in pregnant women's metabolism of As as indicated by greater proportions of MMAs and smaller proportions of DMAs in urine are a risk factor for adverse birth outcomes. One carbon metabolism (OCM), the nutritionally-regulated pathway essential for supplying methyl groups, plays a role in As metabolism and is understudied during the prenatal period. In this cross-sectional study from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort in Gómez Palacio, Mexico, we assessed the relationships among OCM indicators (e.g. maternal serum B12, folate, and homocysteine (Hcys)), and levels of iAs and its metabolites in maternal urine and in neonatal cord serum. The prevalence of folate sufficiency (folate levels > 9 nmol/L) in the cohort was high 99%, and hyperhomocysteinemia (Hcys levels > 10.4 µmol/L) was low (8%). However, 74% of the women displayed a deficiency in B12 (serum levels < 148 pmol/L). Association analyses identified that infants born to mothers in the lowest tertile of serum folate had significantly higher mean levels of %MMA in cord serum relative to folate replete women. In addition, elevated maternal Hcys was associated with total As in maternal urine and cord serum as well as cord serum %MMAs. The results from this study indicate that maternal OCM status may influence the distribution of As metabolites in cord serum.
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Arsênio/urina , Biomarcadores/sangue , Biomarcadores/urina , Exposição Ambiental/análise , Ácido Fólico/sangue , Homocisteína/sangue , Adulto , Estudos de Coortes , Estudos Transversais , Água Potável/efeitos adversos , Exposição Ambiental/efeitos adversos , Feminino , Sangue Fetal/química , Humanos , Recém-Nascido , Masculino , Metilação , México , Gravidez , Gestantes , Análise de Regressão , Vitamina B 12/sangue , Adulto JovemRESUMO
Prenatal inorganic arsenic (iAs) exposure is associated with health effects evident at birth and later in life. An understanding of the relationship between prenatal iAs exposure and alterations in the neonatal metabolome could reveal critical molecular modifications, potentially underpinning disease etiologies. In this study, nuclear magnetic resonance (NMR) spectroscopy-based metabolomic analysis was used to identify metabolites in neonate cord serum associated with prenatal iAs exposure in participants from the Biomarkers of Exposure to ARsenic (BEAR) pregnancy cohort, in Gómez Palacio, Mexico. Through multivariable linear regression, ten cord serum metabolites were identified as significantly associated with total urinary iAs and/or iAs metabolites, measured as %iAs, %monomethylated arsenicals (MMAs), and %dimethylated arsenicals (DMAs). A total of 17 metabolites were identified as significantly associated with total iAs and/or iAs metabolites in cord serum. These metabolites are indicative of changes in important biochemical pathways such as vitamin metabolism, the citric acid (TCA) cycle, and amino acid metabolism. These data highlight that maternal biotransformation of iAs and neonatal levels of iAs and its metabolites are associated with differences in neonate cord metabolomic profiles. The results demonstrate the potential utility of metabolites as biomarkers/indicators of in utero environmental exposure.
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Arsênio , Metabolômica , Arsenicais , Exposição Ambiental , Feminino , Humanos , Recém-Nascido , México , GravidezRESUMO
BACKGROUND: Prenatal exposure to inorganic arsenic (iAs) is associated with dysregulated fetal gene and protein expression. Potential biological mechanisms that underlie these changes include, but are not limited to, changes to the epigenome. OBJECTIVE: The aim of the present study was to identify whether the expression of key genes, proteins, or both and their associated biological pathways are perturbed by compiling datasets from studies on prenatal arsenic exposure. METHODS: We compiled datasets from 12 studies that analyzed the relationship between prenatal iAs exposure and changes to the fetal epigenome (5-methyl cytosine), transcriptome (mRNA expression), and/or proteome (protein expression). FINDINGS: Across the 12 studies, a set of 845 unique genes was identified and found to enrich for their role in biological pathways, including the peroxisome proliferator-activated receptor, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, and the glucocorticoid receptor. Tumor necrosis factor was identified as a putative cellular regulator underlying most (n = 277) of the identified iAs-associated gene or protein expression changes. CONCLUSIONS: The identification of the common set of genes across numerous human cohorts suggests a conserved biological response to prenatal arsenic exposure. The genes/proteins and their associated pathways may be useful in future mechanistic investigations of iAs associated diseases.
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Arsênio/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Receptores de Glucocorticoides/genética , Transdução de Sinais/efeitos dos fármacos , 5-Metilcitosina , Linfócitos B , Epigenômica , Feminino , Humanos , Receptores Ativados por Proliferador de Peroxissomo , Gravidez , Efeitos Tardios da Exposição Pré-Natal , Receptores de Glucocorticoides/metabolismo , ToxicogenéticaRESUMO
Environmental exposure to heavy metals is a potentially modifiable risk factor for preeclampsia (PE). Toxicologically, there are known interactions between the toxic metal cadmium (Cd) and essential metals such as selenium (Se) and zinc (Zn), as these metals can protect against the toxicity of Cd. As they relate to preeclampsia, the interaction between Cd and these essential metals is unknown. The aims of the present study were to measure placental levels of Cd, Se, and Zn in a cohort of 172 pregnant women from across the southeast US and to examine associations of metals levels with the odds of PE in a nested case-control design. Logistic regressions were performed to assess odds ratios (OR) for PE with exposure to Cd controlling for confounders, as well as interactive models with Se or Zn. The mean placental Cd level was 3.6 ng/g, ranging from 0.52 to 14.5 ng/g. There was an increased odds ratio for PE in relationship to placental levels of Cd (OR = 1.5; 95% CI: 1.1-2.2). The Cd-associated OR for PE increased when analyzed in relationship to lower placental Se levels (OR = 2.0; 95% CI: 1.1-3.5) and decreased with higher placental Se levels (OR = 0.98; 95% CI: 0.5-1.9). Similarly, under conditions of lower placental Zn, the Cd-associated OR for PE was elevated (OR = 1.8; 95% CI: 0.8-3.9), whereas with higher placental Zn it was reduced (OR = 1.3; 95% CI: 0.8-2.0). Data from this pilot study suggest that essential metals may play an important role in reducing the odds of Cd-associated preeclampsia and that replication in a larger cohort is warranted.
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Cádmio/toxicidade , Exposição Materna , Placenta/metabolismo , Pré-Eclâmpsia/induzido quimicamente , Pré-Eclâmpsia/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Humanos , Projetos Piloto , Placenta/química , Gravidez , Fatores de Risco , Selênio/metabolismo , Estados Unidos , Zinco/metabolismoRESUMO
BACKGROUND: Exposure to inorganic arsenic (iAs) from drinking water is a global public health problem, yet much remains unknown about the extent of exposure in susceptible populations. OBJECTIVES: We aimed to establish the Biomarkers of Exposure to ARsenic (BEAR) prospective pregnancy cohort in Gómez Palacio, Mexico, to better understand the effects of iAs exposure on pregnant women and their children. METHODS: Two hundred pregnant women were recruited for this study. Concentrations of iAs in drinking water (DW-iAs) and maternal urinary concentrations of iAs and its monomethylated and dimethylated metabolites (MMAs and DMAs, respectively) were determined. Birth outcomes were analyzed for their relationship to DW-iAs and to the concentrations and proportions of maternal urinary arsenicals. RESULTS: DW-iAs for the study subjects ranged from < 0.5 to 236 µg As/L. More than half of the women (53%) had DW-iAs that exceeded the World Health Organization's recommended guideline of 10 µg As/L. DW-iAs was significantly associated with the sum of the urinary arsenicals (U-tAs). Maternal urinary concentrations of MMAs were negatively associated with newborn birth weight and gestational age. Maternal urinary concentrations of iAs were associated with lower mean gestational age and newborn length. CONCLUSIONS: Biomonitoring results demonstrate that pregnant women in Gómez Palacio are exposed to potentially harmful levels of DW-iAs. The data support a relationship between iAs metabolism in pregnant women and adverse birth outcomes. The results underscore the risks associated with iAs exposure in vulnerable populations.
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Arsênio/toxicidade , Tamanho Corporal , Poluentes Ambientais/toxicidade , Idade Gestacional , Exposição Materna/estatística & dados numéricos , Adulto , Arsênio/metabolismo , Arsênio/urina , Biomarcadores/metabolismo , Água Potável/química , Poluentes Ambientais/metabolismo , Feminino , Humanos , Recém-Nascido , Masculino , México , Gravidez , Estudos ProspectivosRESUMO
Synthesis of the bis-spiroacetal core of 13-desmethyl spirolideâ C has been completed based on a sila-Stetter-acetalization process. The acylsilane and enone partners in the Stetter reaction were prepared in 7 and 11 steps, respectively, from (S) and (R)-aspartic acid. The quaternary center at C19 in the enone moiety was controlled by relying on the Seebach's chiral self-reproduction method using an enantiopure (S)-lactic acid based dioxolanone. The final acid-catalyzed spiroacetalization provided the desired spiroacetal as a mixture of diastereoisomers in 13 linear steps. Whatever the conditions used, the non-natural transoid isomer was formed preferentially. However, both cisoid and transoid isomers were isolated pure and their structure assigned unambiguously through NMR spectroscopic studies.