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1.
Environ Res ; 195: 110764, 2021 Jan 23.
Artigo em Inglês | MEDLINE | ID: mdl-33497679

RESUMO

Humans are exposed to a myriad of chemical substances in both occupational and environmental settings. Persistent organic pollutants (POPs) have drawn attention for their adverse effects including cancer and endocrine disruption. Herein, the objectives were 1) to describe serum and adipose tissue retinol levels, along with serum retinol binding protein 4 (RBP4) concentrations, and 2) to assess the associations of adipose tissue POP levels with these retinoid parameters, as well as their potential interaction with the previously-observed POP-related disruption of redox microenvironment. Retinol was measured in both serum and adipose tissue along with RBP4 levels in serum samples of 236 participants of the GraMo adult cohort. Associations were explored by multivariable linear regression analyses and Weighted Quantile Sum regression. Polychlorinated biphenyls (PCBs) 180, 153 and 138 were related to decreased adipose tissue retinol levels and increased serum RBP4/retinol ratio. Dicofol concentrations > limit of detection were associated with decreased retinol levels in serum and adipose tissue. Additionally, increased adipose tissue retinol levels were linked to an attenuation in previously-reported associations of adipose tissue PCB-153 with in situ superoxide dismutase activity. Our results revealed a suggestive link between retinoids, PCBs and redox microenvironment, potentially relevant for both mechanistic and public health purposes.

2.
Reprod Toxicol ; 100: 143-154, 2021 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-33444715

RESUMO

Humans are simultaneously exposed to complex mixtures of chemicals with limited knowledge on potential health effects, therefore improved tools for assessing these mixtures are needed. As part of the Human Biomonitoring for Europe (HBM4EU) Project, we aimed to examine the combined biological activity of chemical mixtures extracted from human placentas using one in vivo and four in vitro bioassays, also known as biomarkers of combined effect. Relevant endocrine activities (proliferative and/or reporter gene assays) and four endpoints were tested: the estrogen receptor (ER), androgen receptor (AR), and aryl hydrocarbon receptor (AhR) activities, as well as thyroid hormone (TH) signaling. Correlations among bioassays and their functional shapes were evaluated. Results showed that all placental extracts agonized or antagonized at least three of the abovementioned endpoints. Most placentas induced ER-mediated transactivation and ER-dependent cell proliferation, together with a strong inhibition of TH signaling and the AR transactivity; while the induction of the AhR was found in only one placental extract. The effects in the two estrogenic bioassays were positively and significantly correlated and the AR-antagonism activity showed a positive borderline-significant correlation with both estrogenic bioassay activities. However, the in vivo anti-thyroid activities of placental extracts were not correlated with any of the tested in vitro assays. Findings highlight the importance of comprehensively mapping the biological effects of "real-world" chemical mixtures present in human samples, through a battery of in vitro and in vivo bioassays. This approach should be a complementary tool for epidemiological studies to further elucidate the combined biological fingerprint triggered by chemical mixtures.

3.
Sci Total Environ ; 769: 144563, 2021 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-33485193

RESUMO

OBJECTIVE: To examine the association between urinary metabolites of organophosphate (OP) pesticides and serum concentrations of thyroid and reproductive hormones in male adolescents and to assess the potential effect of interactions between OP pesticides and paraoxonase 1 (PON1) polymorphisms on hormone levels. METHODS: Study subjects (N = 117) were male 16- to 17-year-olds from the Environment and Childhood (INMA)-Granada cohort in Spain. Concentrations of 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of chlorpyrifos/chlorpyrifos-methyl, 2-isopropyl-6-methyl-4-pyrimidinol (IMPy), a metabolite of diazinon, and diethylthiophosphate (DETP) and diethyldithiophosphate (DEDTP), non-specific metabolites of OP pesticides, were measured in a spot urine sample from each subject and adjusted for creatinine. Levels of reproductive hormones (total testosterone [TT], estradiol [E2], dehydroepiandrosterone sulfate [DHEAS], sex hormone binding globulin [SHBG], luteinizing hormone [LH], follicle stimulating hormone [FSH], anti-Müllerian hormone [AMH], insulin growth factor 1 [IGF-1], and prolactin), thyroid hormones (free thyroxine [FT4], total triiodothyronine [TT3], and thyroid stimulating hormone [TSH]), and PON1 Q192R and L55M polymorphisms were determined in blood drawn during the same clinical visit. RESULTS: Multiple linear regression models showed that detectable levels of TCPy were associated with an increase in DHEAS and decreases in E2, FSH, and AMH; detectable IMPy with increases in E2, DHEAS, FSH, AMH, and prolactin and decreases in SHBG and LH; and detectable DETP with marginally-significant increases in TT and TT3 and decreases in FSH, AMH, and prolactin. The effect of IMPy and DETP on DHEAS and TT levels, respectively, was higher in subjects that carried the PON1 55MM genotype, while the effect of TCPy, IMPy, and DETP on thyroid hormone levels was higher in PON1 192QR/RR or 55MM genotype carriers. CONCLUSIONS: In male adolescents, non-occupational exposure to OP pesticides was associated with several changes in reproductive and thyroid hormone levels, and the magnitude of some associations was greater in adolescents genetically more susceptible to OP pesticide exposure who carry the PON1 55MM genotype.

4.
Environ Int ; 146: 106257, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33395925

RESUMO

Effect biomarkers can be used to elucidate relationships between exposure to environmental chemicals and their mixtures with associated health outcomes, but they are often underused, as underlying biological mechanisms are not understood. We aim to provide an overview of available effect biomarkers for monitoring chemical exposures in the general and occupational populations, and highlight their potential in monitoring humans exposed to chemical mixtures. We also discuss the role of the adverse outcome pathway (AOP) framework and physiologically based kinetic and dynamic (PBK/D) modelling to strengthen the understanding of the biological mechanism of effect biomarkers, and in particular for use in regulatory risk assessments. An interdisciplinary network of experts from the European chapter of the International Society for Exposure Science (ISES Europe) and the Organization for Economic Co-operation and Development (OECD) Occupational Biomonitoring activity of Working Parties of Hazard and Exposure Assessment group worked together to map the conventional framework of biomarkers and provided recommendations for their systematic use. We summarized the key aspects of this work here, and discussed these in three parts. Part I, we inventory available effect biomarkers and promising new biomarkers for the general population based on the H2020 Human Biomonitoring for Europe (HBM4EU) initiative. Part II, we provide an overview AOP and PBK/D modelling use that improved the selection and interpretation of effect biomarkers. Part III, we describe the collected expertise from the OECD Occupational Biomonitoring subtask effect biomarkers in prioritizing relevant mode of actions (MoAs) and suitable effect biomarkers. Furthermore, we propose a tiered risk assessment approach for occupational biomonitoring. Several effect biomarkers, especially for use in occupational settings, are validated. They offer a direct assessment of the overall health risks associated with exposure to chemicals, chemical mixtures and their transformation products. Promising novel effect biomarkers are emerging for biomonitoring of the general population. Efforts are being dedicated to prioritizing molecular and biochemical effect biomarkers that can provide a causal link in exposure-health outcome associations. This mechanistic approach has great potential in improving human health risk assessment. New techniques such as in silico methods (e.g. QSAR, PBK/D modelling) as well as 'omics data will aid this process. Our multidisciplinary review represents a starting point for enhancing the identification of effect biomarkers and their mechanistic pathways following the AOP framework. This may help in prioritizing the effect biomarker implementation as well as defining threshold limits for chemical mixtures in a more structured way. Several ex vivo biomarkers have been proposed to evaluate combined effects including genotoxicity and xeno-estrogenicity. There is a regulatory need to derive effect-based trigger values using the increasing mechanistic knowledge coming from the AOP framework to address adverse health effects due to exposure to chemical mixtures. Such a mechanistic strategy would reduce the fragmentation observed in different regulations. It could also stimulate a harmonized use of effect biomarkers in a more comparable way, in particular for risk assessments to chemical mixtures.

5.
Emerg Microbes Infect ; : 1-52, 2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33306459

RESUMO

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

6.
Environ Health ; 19(1): 107, 2020 Oct 13.
Artigo em Inglês | MEDLINE | ID: mdl-33050930

RESUMO

BACKGROUND: Exposure to perfluorinated-alkyl-acids (PFAAs) is ubiquitous. PFAAs are hormone-disrupting compounds that are strongly suspected to affect mother-child-health such as fetal growth. Thyroid disruption is a plausible mechanism of action. We aim to summarize the epidemiological evidence for the relation between prenatal and postnatal exposure to PFAAs and disruption of thyroid homeostasis in mothers and/or infants. METHOD: Fifteen original publications on PFAAs concentrations and thyroid hormones (TH) in pregnant women and/or infants were found upon a literature search in the PubMed database. Information on exposure to seven PFAAs congeners [Perfluorooctane sulfonate (PFOS), Perfluorooctanoate (PFOA), Perfluorohexane sulfonate (PFHxS), Perfluorononanoic acid (PFNA), Perfluorodecanoic acid (PFDA), Perfluoroundecanoic acid (PFUnA), and Perfluorododecanoic acid (PFDoA)] and thyroid stimulating hormone (TSH), free and total thyroxine (FT4 and TT4), free and total triiodothyronine (FT3 and TT3), T3RU (Free triiodothyronine resin uptake) and FT4-index (FT4I) levels were recorded. We evaluated sampling of maternal TH by trimester, and infant TH by sex stratification. Reported associations between mother or infant PFAAs and TH were not uniformly assessed in the selected studies. RESULTS: Ten out of the fifteen studies examined maternal PFAAs concentration and TSH level. Seven studies showed significant associations between TSH and exposure to six PFAAs congeners, most of them were positive. Maternal T4 and T3 were investigated in nine studies and five studies found inverse associations between exposure to six PFAAs congeners and TH (TT3, TT4, FT3, FT4 and FT4I) levels. Eight of the fifteen studies investigated PFAAs concentrations and infant TSH. Infant TSH level was significantly affected in four studies, positively in three studies. Nine studies investigated infant T4 and T3 and seven studies found significant associations with PFAAs exposure. However, both inverse and positive significant associations with infant TH were found eliciting no clear direction. CONCLUSION: Results indicate a mainly positive relationship between maternal PFAAs concentrations and TSH levels, and suggestion of an inverse association with T4 and/or T3 levels. Associations of infant TH with PFAAs concentration were less consistent.

7.
medRxiv ; 2020 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-33052352

RESUMO

COVID-19 is a respiratory illness caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and declared by the World Health Organization a global public health emergency. Among the severe outbreaks across South America, Uruguay has become known for curtailing SARS-CoV-2 exceptionally well. To understand the SARS-CoV-2 introductions, local transmissions, and associations with genomic and clinical parameters in Uruguay, we sequenced the viral genomes of 44 outpatients and inpatients in a private healthcare system in its capital, Montevideo, from March to May 2020. We performed a phylogeographic analysis using sequences from our cohort and other studies that indicate a minimum of 23 independent introductions into Uruguay, resulting in five major transmission clusters. Our data suggest that most introductions resulting in chains of transmission originate from other South American countries, with the earliest seeding of the virus in late February 2020, weeks before the borders were closed to all non-citizens and a partial lockdown implemented. Genetic analyses suggest a dominance of S and G clades (G, GH, GR) that make up >90% of the viral strains in our study. In our cohort, lethal outcome of SARS-CoV-2 infection significantly correlated with arterial hypertension, kidney failure, and ICU admission (FDR < 0.01), but not with any mutation in a structural or non-structural protein, such as the spike D614G mutation. Our study contributes genetic, phylodynamic, and clinical correlation data about the exceptionally well-curbed SARS-CoV-2 outbreak in Uruguay, which furthers the understanding of disease patterns and regional aspects of the pandemic in Latin America.

8.
Br J Nutr ; : 1-23, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33054875

RESUMO

Intermittent food restriction (IFR) is used mainly for weight loss, however, its effects on adipose tissue are not known when alternating with obesogenic diet. To demonstrate its effects on morphological dynamics of fat deposits, female Wistar were distributed into the groups: standard control (ST-C), with commercial diet; DIO control (DIO-C), with a diet that induces obesity (DIO) during the first and last 15 days, replaced by a standard diet for 30 intermediate days; standard restricted (ST-R), with standard diet during the first and last 15 days, with six cycles of IFR at 50% of ST-C; and DIO restricted (DIO-R), in DIO during the first and last 15 days, with six cycles of IFR at 50% of DIO-C. At 105 days of life, white adipose tissue (WAT) and brown adipose tissue (BAT) deposits were collected, weighed and histology performed. IFR groups showed higher food intake (DIO-R: 670.8±31.86kcal/g vs DIO-C: 606.5±26.23kcal/g, p<0.0001), energy efficiency (DIO-R: 3.80±0.15 g/kcal vs DIO-C: 3.26±0.17 g/kcal, p<0.0001), WAT (DIO-R: 5.65±0.30g/100g, ST-R: 3.64±0.23g/100g vs. DIO-C: 4.56±0.30g/100g, ST-C: 2.87±0.31g/100g, p<0.0001) and BAT (DIO-R: 0.13±0.004g/100g vs DIO-C: 0.13±0.005g/100g, p<0.0001) than its respective controls. Furthermore, IFR groups presented hypertrophy of WAT and BAT, as well as fibrosis in BAT. Thus, IFR can establish prospective resistance to weight loss by favoring changes in adipose tissue morphology, increased energy intake, and efficiency. Finally, the DIO diet before and after IFR aggravates the damages caused by the restriction.

9.
Adv Ther ; 37(12): 4996-5009, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33067698

RESUMO

INTRODUCTION: The phase 3 ALCYONE study demonstrated significantly longer progression-free and overall survival (PFS/OS) and higher overall response rates (ORR) with daratumumab plus bortezomib, melphalan, and prednisone (D-VMP) versus VMP alone in transplant-ineligible patients with newly diagnosed multiple myeloma (NDMM). In Latin America, bortezomib- or thalidomide-based regimens remain standard of care (SoC) for this population. No head-to-head trials have compared D-VMP with SoC regimens used in Latin America. METHODS: Propensity score matching (PSM) was used to control for baseline differences between patient populations and compare outcomes for D-VMP versus SoC regimens used in Latin America. Data for the D-VMP cohort were from the D-VMP arm of the ALCYONE trial (n = 350). Data for the SoC cohort were from the retrospective, observational Hemato-Oncology Latin America (HOLA) study, which included patients with NDMM who did not receive a transplant (n = 729). Propensity scores were estimated using logistic regression. Exact, optimal, and nearest-neighbor PSM were applied to pick the best-performing method. Doubly robust estimation was the base case, since some baseline imbalances persisted. RESULTS: All 350 patients from the D-VMP arm of ALCYONE were included in OS/PFS analyses and 338 in ORR analysis; 478 and 324 patients, respectively, from HOLA were included in these analyses. Naïve comparison revealed important differences in baseline characteristics (age, chronic kidney disease, hypercalcemia, and International Staging System [ISS] stage). After nearest-neighbor matching, baseline characteristics, except ISS stage, were well balanced; comparisons favored D-VMP over SoC for OS (hazard ratio = 0.41; 95% confidence interval [CI] 0.25-0.66; P = 0.002) and PFS (hazard ratio = 0.48; 95% CI 0.35-0.67; P < 0.001). After exact matching, imbalances remained in age and ISS stage; comparisons favored D-VMP over SoC for ORR (odds ratio = 5.44; 95% CI 2.65-11.82; P < 0.001). CONCLUSION: In transplant-ineligible patients with NDMM, D-VMP showed superior effectiveness versus bortezomib- and thalidomide-based regimens, supporting adoption of daratumumab-containing regimens in Latin America.

10.
Environ Int ; 146: 106191, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-33068852

RESUMO

Humans are exposed to a large number of chemicals from sources such as the environment, food, and consumer products. There is growing concern that human exposure to chemical mixtures, especially during critical periods of development, increases the risk of adverse health effects in newborns or later in life. Historically, the one-chemical-at-a-time approach has been applied both for exposure assessment and hazard characterisation, leading to insufficient knowledge about human health effects caused by exposure to mixtures of chemicals that have the same target. To circumvent this challenge researchers can apply in vitro assays to analyse both exposure to and human health effects of chemical mixtures in biological samples. The advantages of using in vitro assays are: (i) that an integrated effect is measured, taking combined mixture effects into account and (ii) that in vitro assays can reduce complexity in identification of Chemicals of Emerging Concern (CECs) in human tissues. We have reviewed the state-of-the-art on the use of receptor-based in vitro assays to assess human exposure to chemical mixtures and related health impacts. A total of 43 studies were identified, in which endpoints for the arylhydrocarbon receptor (AhR), the estrogen receptor (ER), and the androgen receptor (AR) were used. The majority of studies reported biological activities that could be associated with breast cancer incidence, male reproductive health effects, developmental toxicities, human demographic characteristics or lifestyle factors such as dietary patterns. A few studies used the bioactivities to check the coverage of the chemical analyses of the human samples, whereas in vitro assays have so far not regularly been used for identifying CECs in human samples, but rather in environmental matrices or food packaging materials. A huge field of novel applications using receptor-based in vitro assays for mixture toxicity assessment on human samples and effect-directed analysis (EDA) using high resolution mass spectrometry (HRMS) for identification of toxic compounds waits for exploration. In the future this could lead to a paradigm shift in the way we unravel adverse human health effects caused by chemical mixtures.

11.
Environ Int ; 144: 105811, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32866736

RESUMO

Human biomonitoring (HBM) studies have demonstrated widespread and daily exposure to bisphenol A (BPA). Moreover, BPA structural analogues (e.g. BPS, BPF, BPAF), used as BPA replacements, are being increasingly detected in human biological matrices. BPA and some of its analogues are classified as endocrine disruptors suspected of contributing to adverse health outcomes such as altered reproduction and neurodevelopment, obesity, and metabolic disorders among other developmental and chronic impairments. One of the aims of the H2020 European Human Biomonitoring Initiative (HBM4EU) is the implementation of effect biomarkers at large scales in future HBM studies in a systematic and standardized way, in order to complement exposure data with mechanistically-based biomarkers of early adverse effects. This review aimed to identify and prioritize existing biomarkers of effect for BPA, as well as to provide relevant mechanistic and adverse outcome pathway (AOP) information in order to cover knowledge gaps and better interpret effect biomarker data. A comprehensive literature search was performed in PubMed to identify all the epidemiologic studies published in the last 10 years addressing the potential relationship between bisphenols exposure and alterations in biological parameters. A total of 5716 references were screened, out of which, 119 full-text articles were analyzed and tabulated in detail. This work provides first an overview of all epigenetics, gene transcription, oxidative stress, reproductive, glucocorticoid and thyroid hormones, metabolic and allergy/immune biomarkers previously studied. Then, promising effect biomarkers related to altered neurodevelopmental and reproductive outcomes including brain-derived neurotrophic factor (BDNF), kisspeptin (KiSS), and gene expression of nuclear receptors are prioritized, providing mechanistic insights based on in vitro, animal studies and AOP information. Finally, the potential of omics technologies for biomarker discovery and its implications for risk assessment are discussed. To the best of our knowledge, this is the first effort to comprehensively identify bisphenol-related biomarkers of effect for HBM purposes.

12.
Artigo em Inglês | MEDLINE | ID: mdl-32967807

RESUMO

INTRODUCTION: Daratumumab is a CD38-targeting monoclonal antibody with established efficacy and safety in patients with relapsed or refractory multiple myeloma (RRMM). We report results of an early access protocol (EAP) of daratumumab monotherapy for RRMM in a cohort of Brazilian patients. METHODS: Patients with RRMM and ≥3 prior lines of therapy, including a proteasome inhibitor (PI) and an immunomodulatory drug (IMiD), or who were double refractory to both a PI and IMiD received daratumumab, 16 mg/kg, intravenously weekly for 8 weeks, biweekly for 16 weeks, and every 4 weeks thereafter until disease progression, unacceptable toxicity, loss of clinical benefit, or study conclusion or if daratumumab became available with reimbursement. RESULTS: Forty-nine patients received ≥1 dose of daratumumab. The median (range) duration of treatment was 6.4 (0.3-11.8) months, with a median (range) of 8 (1-13) treatment cycles. Grade 3/4 treatment-emergent adverse events (TEAEs) were reported in 38.8% of patients, most frequently neutropenia and pneumonia (10.2% each). Seven (14.3%) patients discontinued treatment due to TEAEs; 3 patients discontinued due to daratumumab-related TEAEs. Serious TEAEs occurred in 38.8% of patients. Infusion-related reactions were reported in 25 (51.0%) patients, were primarily grade 1/2, and the majority (23 patients) occurred during the first infusion. Twenty (40.8%) patients achieved a partial response or better; median progression-free survival was 8.25 (95% confidence interval, 5.55-17.54) months. CONCLUSION: In this EAP, daratumumab monotherapy in Brazilian patients showed a safety and efficacy profile consistent with clinical studies of daratumumab monotherapy in patients with heavily pretreated RRMM. ClinicalTrials.gov identifier: NCT02477891.

13.
J Clin Microbiol ; 58(12)2020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-32938737

RESUMO

Infection by Trypanosoma cruzi (Chagas disease [ChD]) affects around 7 million people in the Americas, most of whom are unaware of their status due to lack of clinical manifestations and poor access to diagnosis. Rapid diagnostic tests (RDTs) are widely used for screening for different infections (HIV, hepatitis B, and syphilis), and their application for ChD would facilitate access to diagnosis, especially in remote areas where health services have scarce resources. We conducted a prospective intervention study in 2018 to evaluate in the field two in vitro RDTs for ChD, authorized by the National Administration of Medicaments, Aliments, and Medical Technologies of Argentina (ANMAT), in areas of endemicity and nonendemicity in Argentina. We recruited 607 volunteers older than 18 years in Salta province and the city of Buenos Aires. The RDTs Ab Standard Diagnostics SD Bioline (SD) and Check Chagas Wiener Lab (WL) were performed in situ with whole-blood samples, and confirmatory serology was done at a reference center. The rate of infection with T. cruzi was 17.8% (108/607). The SD test showed 97.2% sensitivity (95% confidence interval [CI], 93.5 to 100) and 91.7% specificity (95% CI, 96.2 to 99.2%), and the WL test showed 93.4% sensitivity (95% CI, 88.2 to 98.6%) and 99.1% specificity (95% CI, 91.9 to 100%). The sensitivity and specificity for the two RDTs tested were higher than previously reported. These results encourage the use of the tested RDTs in Salta province and for further field studies for the implementation of these RDTs in other epidemiological scenarios. This will be very important to improve access to diagnosis of Chagas and its clinical management as a neglected disease, especially in remote areas with health access barriers.

14.
Int J Hyg Environ Health ; 230: 113597, 2020 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-32795877

RESUMO

Developmental exposure to bisphenol A (BPA) and other phenolic endocrine disrupting chemicals (EDCs) may affect child neurodevelopment, but data on the effects of prenatal exposure to phenols on cognitive function remain sparse. Our aim was to examine the association of placental concentrations of several phenolic EDCs, including BPA, parabens (PBs), and benzophenones (BzPs), with cognitive development in preschool children from the Environment and Childhood (INMA) Project in Spain. Concentrations of BPA, four PBs (methylparaben [MePB], ethylparaben [EtPB], propylparaben [PrPB], and butylparaben [BuPB]), and six BzPs (BzP-1, BzP-2, BzP-3, BzP-6, BzP-8, and 4-hydroxybenzophenone [4-OH-BzP]) were measured in 490 placenta samples randomly selected from five INMA cohorts collected between 2000 and 2008. Neuropsychological assessment of cognitive and motor function was performed with the McCarthy Scales of Children's Abilities (MSCA) at the age of 4-5 years. Associations were assessed in a sub-sample of 191 mother-child pairs using linear and logistic regression models adjusted for confounding factors. PB compounds were detected in more than 71% of placentas, BPA in 62%, 4-OH-BzP in 50%, and the remaining BzPs in <9% of the samples. Because of the low detection frequency of BzP compounds, only 4-OH-BzP was included in the exposure-outcome analyses. After adjustment for confounders, BPA was associated with greater odds of scoring lower (below the 20th percentile) in the verbal (third vs. first exposure tertile: odds ratio [OR] = 2.78, 95% confidence interval [CI] = 1.00; 5.81, p-trend = 0.05) and gross motor (detected vs. undetected: OR = 1.75, 95%CI = 1.06; 9.29) areas, and these associations were only significant for boys. Regarding PB compounds, PrPB was associated with lower scores in memory (detected vs. undetected: ß = -4.96, 95%CI = -9.54; -0.31), span memory (OR = 2.50, 95%CI = 0.95; 6.92 and 2.71, 95%CI = 0.97; 6.64, respectively for second and third tertiles, p-trend = 0.03), and motor function (ß = -5.15, 95%CI = -9.26; -0.01 for third vs. first exposure tertile, p-trend = 0.04). EtPB and total PBs concentrations in the second tertile were also associated with poorer visual function of posterior cortex and worse quantitative performance, respectively, but linear trends were not statistically significant. The associations of BPA and PrPB with poorer verbal, memory, and motor skills are novel observations that warrant further attention. Larger prospective studies are required to confirm whether prenatal exposure to BPA and other phenolic EDCs is associated with impaired cognitive development.

15.
J Glaucoma ; 29(9): 756-760, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32618804

RESUMO

PRéCIS:: Intraocular pressure (IOP) measurement differences with Goldmann applanation tonometry (GAT) and dynamic contour tonometry (DCT) are affected by atmospheric pressure inside a hyperbaric chamber. PURPOSE: To compare IOP measurements obtained with GAT and DCT in 22 normal individuals at different atmospheric pressures simulated in a hyperbaric chamber. METHODS: The IOP of both eyes of 22 healthy volunteers was measured using GAT and DCT at 4 different atmospheric pressure levels.Starting at 1 Queretaro atmospheric pressure (QATM), the IOP was measured with GAT and DCT. The atmospheric pressure was then increased to 1.1 QATM (equivalent to 1032 m above sea level), 1.2 QATM (equivalent to 315 m above sea level), and 1.25 QATM (equivalent to sea level), starting 5 minutes after reaching each level. The limits of agreement between various measurements with each tonometer were calculated using the Bland-Altman plots. RESULTS: The first 4 subjects were used to measure feasibility, consistency, variability, and the time needed for IOP to return to baseline after each atmospheric pressure increase.For the entire 44 eyes, the mean GAT IOP at 1 QATM was 12.23 mm Hg (range, 8 to 20 mm Hg; SD, 2.84) and mean DCT was 16.36 (range, 12.1 to 25.3; SD, 2.84), with a mean 4.14 mm Hg difference (range, -0.1 to 7.5 mm Hg; SD, 1.62; P<0.001).Using the second measurements of the first 4 subjects and those after 5 minutes of adaptation for the rest of the group at 1.1 QATM, mean GAT IOP was 11.05±2.68 mm Hg and mean DCT IOP was 15.60±3.02 mm Hg, for a mean difference between instruments of 4.56±1.81 mm Hg (P<0.001).At 1.2 QATM, mean GAT IOP was 11.14±2.53 mm Hg and mean DCT IOP was 15.39±2.91 mm Hg. The difference between instruments was 4.25±2.12 mm Hg (P<0.001).At 1.25 QATM, the mean GAT IOP was 12.39±3.11 mm Hg and mean DCT IOP was 14.91±2.73 mm Hg. The difference between instruments after 5 minutes of adaptation was 2.53±1.62 mm Hg (P<0.001).Generalized estimating equations for performing linear regression multivariable analysis using atmospheric pressure, expressed as altitude, and age as covariates, shows that the difference between GAT and DCT increases by 1 mm Hg per 673 m of increase of altitude above sea level. Age was not a significant predictor. CONCLUSIONS: Acute changes in atmospheric pressure induce changes in IOP measurements for both GAT and DCT and in different directions. Despite the limitation of sample size, it may be postulated that the difference of IOP measurements between the 2 tonometers increases with lower atmospheric pressures.

16.
Nutrients ; 12(7)2020 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-32674463

RESUMO

Tools to assess diet in a reliable and efficient way are needed, particularly in children and adolescents. In this study, we assess the reproducibility and validity of a semiquantitative food frequency questionnaire (FFQ) among adolescents in Spain. We analyzed data of 51 male adolescents aged 15-17 years from a prospective birth cohort study. Participants answered the FFQ twice in a self-administered way over a 12-month period. Reproducibility was assessed by comparing nutrient and food intakes from the FFQs, and validity by comparing nutrient intakes from the average of two FFQs and the average of two 24-Hour Dietary Recalls obtained in the period. Pearson correlation coefficients were calculated. The average of reproducibility correlation coefficients for food group intakes was 0.33, with the highest correlation for vegetable intake (r = 0.81); and the average for nutrient intake was 0.32, with the highest coefficients for α- and ß-carotene (r = 0.65). Validity correlation coefficients ranged from 0.07 for carbohydrates to 0.53 for dietary fiber. The average of the validity correlation coefficients was r = 0.32. This study suggests that our FFQ may be a useful tool for assessing dietary intake of most nutrient and food groups among Spanish male adolescents in a self-administered way, despite reproducibility and, particularly validity, being low for some nutrients and food groups.

17.
Environ Health ; 19(1): 66, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32517692

RESUMO

Concerns about the effects of bisphenol A (BPA) on human brain and behavior are not novel; however, Grohs and colleagues have contributed groundbreaking data on this topic in a recent issue of Environmental Health. For the first time, associations were reported between prenatal BPA exposure and differences in children's brain microstructure, which appeared to mediate the association between this exposure and children's behavioral symptoms. Findings in numerous previous mother-child cohorts have pointed in a similar worrying direction, linking higher BPA exposure during pregnancy to more behavioral problems throughout childhood as assessed by neuropsychological questionnaires. Notwithstanding, this body of work has not been adequately considered in risk assessment. From a toxicological perspective, results are now available from the CLARITY-BPA consortium, designed to reconcile academic and regulatory toxicology findings. In fact, the brain has consistently emerged as one of the most sensitive organs disrupted by BPA, even at doses below those considered safe by regulatory agencies such as the European Food Safety Authority (EFSA). In this Commentary, we contextualize the results of Grohs et al. within the setting of previous epidemiologic and CLARITY-BPA data and express our disquiet about the "all-or-nothing" criterion adopted to select human data in a recent EFSA report on the appraisal methodology for their upcoming BPA risk assessment. We discuss the most relevant human studies, identify emerging patterns, and highlight the need for adequate assessment and interpretation of the increasing epidemiologic literature in this field in order to support decision-making. With the aim of avoiding a myopic or biased selection of a few studies in traditional risk assessment procedures, we propose a future reevaluation of BPA focused on neurotoxicity and based on a systematic and comprehensive integration of available mechanistic, animal, and human data. Taken together, the experimental and epidemiologic evidence converge in the same direction: BPA is a probable developmental neurotoxicant at low doses. Accordingly, the precautionary principle should be followed, progressively implementing stringent preventive policies worldwide, including the banning of BPA in food contact materials and thermal receipts, with a focus on the utilization of safer substitutes.


Assuntos
Compostos Benzidrílicos , Fenóis , Animais , Compostos Benzidrílicos/toxicidade , Encéfalo , Criança , Pré-Escolar , Feminino , Humanos , Fenóis/toxicidade , Gravidez , Medição de Risco
18.
Integr Cancer Ther ; 19: 1534735420924757, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32462950

RESUMO

Background: Integrative oncology has proven to be a useful approach to control cancer symptoms and improve the quality of life (QoL) and overall health of patients, delivering integrated patient care at both physical and emotional levels. The objective of this randomized trial was to evaluate the effects of a triple intervention program on the QoL and lifestyle of women with breast cancer. Methods: Seventy-five survivors of stage IIA-IIB breast cancer were randomized into 2 groups. The intervention group (IG) received a 6-month dietary, exercise, and mindfulness program that was not offered to the control group (CG). Data were gathered at baseline and at 6 months postintervention on QoL and adherence to Mediterranean diet using clinical markers and validated questionnaires. Between-group differences at baseline and 3 months postintervention were analyzed using Student's t test for related samples and the Wilcoxon and Mann-Whitney U tests. Results: At 6 months postintervention, the IG showed significant improvements versus CG in physical functioning (p = .027), role functioning (p = .028), and Mediterranean diet adherence (p = .02) and a significant reduction in body mass index (p = .04) and weight (p = .05), with a mean weight loss of 0.7 kg versus a gain of 0.55 kg by the CG (p = .05). Dyspnea symptoms were also increased in the CG versus IG (p = .066). Conclusions: These results demonstrate that an integrative dietary, physical activity, and mindfulness program enhances the QoL and healthy lifestyle of stage IIA-IIB breast cancer survivors. Cancer symptoms may be better managed by the implementation of multimodal rather than isolated interventions.

19.
Artigo em Inglês | MEDLINE | ID: mdl-32455625

RESUMO

Bisphenols, particularly bisphenol A (4,4'-(hexafluoroisopropylidene)-diphenol) (BPA), are suspected of inducing oxidative stress in humans, which may be associated with adverse health outcomes. We investigated the associations between exposure to bisphenols and biomarkers of oxidative stress in human studies over the last 12 years (2008‒2019) related to six health endpoints and evaluated their suitability as effect biomarkers. PubMed database searches identified 27 relevant articles that were used for data extraction. In all studies, BPA exposure was reported, whereas some studies also reported other bisphenols. More than a dozen different biomarkers were measured. The most frequently measured biomarkers were 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoprostane) and malondialdehyde (MDA), which almost always were positively associated with BPA. Methodological issues were reported for MDA, mainly the need to handle samples with caution to avoid artefact formation and its measurements using a chromatographic step to distinguish it from similar aldehydes, making some of the MDA results less reliable. Urinary 8-OHdG and 8-isoprostane can be considered the most reliable biomarkers of oxidative stress associated with BPA exposure. Although none of the biomarkers are considered BPA- or organ-specific, the biomarkers can be assessed repeatedly and non-invasively in urine and could help to understand causal relationships.


Assuntos
Compostos Benzidrílicos , Estresse Oxidativo , Fenóis , 8-Hidroxi-2'-Desoxiguanosina/urina , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Compostos Benzidrílicos/toxicidade , Biomarcadores/urina , Criança , Estudos Transversais , Dinoprosta/análogos & derivados , Dinoprosta/urina , Feminino , Seguimentos , Humanos , Recém-Nascido , Masculino , Fenóis/toxicidade , Gravidez , Estudos Prospectivos , Método Simples-Cego , Adulto Jovem
20.
Pathogens ; 9(5)2020 May 20.
Artigo em Inglês | MEDLINE | ID: mdl-32443925

RESUMO

The threadworm, Strongyloides stercoralis, is endemic in tropical and subtropical areas. Data on the prevalence and distribution of infection with this parasite species is scarce in many critical regions. We conducted a seroprevalence study of S. stercoralis infection in 13 locations in the Gran Chaco and Yungas regions of Argentina and Bolivia during the period 2010-2016. A total of 2803 human serum samples were analyzed by ELISA-NIE which has a sensitivity of 75% and specificity of 95%. Results showed that 551 (19.6%) of those samples were positive. The adjusted prevalence was 20.9%, (95% confidence interval (CI) 19.4%-22.4%). The distribution of cases was similar between females and males with an increase of prevalence with age. The prevalence in the different locations ranged from 7.75% in Pampa del Indio to 44.55% in Santa Victoria Este in the triple border between Argentina, Bolivia, and Paraguay in the Chaco region. Our results show that S. stercoralis is highly prevalent in the Chaco and Yungas regions, which should prompt prospective surveys to confirm our findings and the design and deployment of control measures.

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