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1.
Angew Chem Int Ed Engl ; 63(37): e202407131, 2024 Sep 09.
Artículo en Inglés | MEDLINE | ID: mdl-38935849

RESUMEN

Pancreatic cancer is one of the deadliest cancers worldwide, mainly due to late diagnosis. Therefore, there is an urgent need for novel diagnostic approaches to identify the disease as early as possible. We have developed a diagnostic assay for pancreatic cancer based on the detection of naturally occurring tumor associated autoantibodies against Mucin-1 (MUC1) using engineered glycopeptides on nanoparticle probes. We used a structure-guided approach to develop unnatural glycopeptides as model antigens for tumor-associated MUC1. We designed a collection of 13 glycopeptides to bind either SM3 or 5E5, two monoclonal antibodies with distinct epitopes known to recognize tumor associated MUC1. Glycopeptide binding to SM3 or 5E5 was confirmed by surface plasmon resonance and rationalized by molecular dynamics simulations. These model antigens were conjugated to gold nanoparticles and used in a dot-blot assay to detect autoantibodies in serum samples from pancreatic cancer patients and healthy volunteers. Nanoparticle probes with glycopeptides displaying the SM3 epitope did not have diagnostic potential. Instead, nanoparticle probes displaying glycopeptides with high affinity for 5E5 could discriminate between cancer patients and healthy controls. Remarkably, the best-discriminating probes show significantly better true and false positive rates than the current clinical biomarkers CA19-9 and carcinoembryonic antigen (CEA).


Asunto(s)
Autoanticuerpos , Glicopéptidos , Mucina-1 , Neoplasias Pancreáticas , Humanos , Neoplasias Pancreáticas/diagnóstico , Neoplasias Pancreáticas/inmunología , Neoplasias Pancreáticas/sangre , Mucina-1/inmunología , Mucina-1/sangre , Mucina-1/química , Glicopéptidos/inmunología , Glicopéptidos/química , Autoanticuerpos/sangre , Autoanticuerpos/inmunología , Autoanticuerpos/química , Nanopartículas del Metal/química , Oro/química , Anticuerpos Monoclonales/inmunología , Anticuerpos Monoclonales/química , Nanopartículas/química
2.
Clin Chim Acta ; 557: 117895, 2024 Apr 15.
Artículo en Inglés | MEDLINE | ID: mdl-38561063

RESUMEN

The discovery of new diagnostic tools for the early detection of diseases with poor prognosis such as pancreatic adenocarcinoma (PAC) is of high importance. The results from a control-case study (20 PAC patients, 19 healthy controls) for the search of new biomarkers of pancreatic cancer based in differences in the serum volatolome are presented in this work. Volatolomics were performed following a non-targeted HS-SPME-GC/MS approach, and a total of 433 volatile organic compounds (VOCs) was detected in the human serum samples. Of these, 125 VOC indexes showed a significant variation when controls and patients were compared (p-value < 0.05). Bonferroni corrected p-values < 0.05 were found for 40 features. PCA analysis showed the control-PAC discrimination capability of VOCs in serum, and PLS-DA was performed to select the best candidate biomarkers for the diagnosis of PAC. For the 40 selected VOCs, calculated areas under the curve (AUC) ranged from 0.98 to 0.85, and 11 of them were successfully validated using an independent set of samples (5 PAC patients, 5 healthy controls). Four of the proposed PAC biomarkers were identified as toluene, 2-ethyl-1-hexanol, pentylbenzene, and butoxymethylbenzene. Combinations of the identified PAC biomarkers were tested and showed AUC > 0.90, with the more promising candidate being butoxymethylbenzene (AUC = 0.98).


Asunto(s)
Adenocarcinoma , Neoplasias Pancreáticas , Compuestos Orgánicos Volátiles , Humanos , Adenocarcinoma/diagnóstico , Biomarcadores , Neoplasias Pancreáticas/diagnóstico , Estudios de Casos Únicos como Asunto , Compuestos Orgánicos Volátiles/análisis , Estudios de Casos y Controles
3.
J Funct Biomater ; 14(9)2023 Aug 25.
Artículo en Inglés | MEDLINE | ID: mdl-37754854

RESUMEN

Prior studies demonstrated that encapsulation in poly(lactic-co-glycolic acid) (PLGA) nanoparticles (NPs) enhanced the delivery of enzymes used for replacement therapy (ERT) of lysosomal storage disorders (LSDs). This study examined how the copolymer lactide:glycolide ratio impacts encapsulation, physicochemical characteristics, stability, and release under lysosomal conditions. Hyaluronidase, deficient in mucopolysaccharidosis IX, was encapsulated in NPs synthesized using 50:50, 60:40, or 75:25 lactide:glycolide copolymers. All NPs had diameters compatible with cellular transport (≤168 nm) and polydispersity indexes (≤0.16) and ζ-potentials (≤-35 mV) compatible with colloidal stability. Yet, their encapsulation efficiency varied, with 75:25 NPs and 60:40 NPs having the lowest and highest EE, respectively (15% vs. 28%). Under lysosomal conditions, the 50:50 copolymer degraded fastest (41% in 1 week), as expected, and the presence of a targeting antibody coat did not alter this result. Additionally, 60:40 NPs destabilized fastest (<1 week) because of their smaller diameter, and 75:25 NPs did not destabilize in 4 weeks. All formulations presented burst release under lysosomal conditions (56-78% of the original load within 30 min), with 50:50 and 60:40 NPs releasing an additional small fraction after week 1. This provided 4 weeks of sustained catalytic activity, sufficient to fully degrade a substrate. Altogether, the 60:40 NP formulation is preferred given its higher EE, and 50:50 NPs represent a valid alternative, while the highest stability of 75:25 NPs may impair lysosomes. These results can guide future studies aiming to translate PLGA NP-based ERT for this and other LSDs.

4.
Mol Psychiatry ; 28(11): 4814-4822, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37644173

RESUMEN

Exposure to phthalates, used as plasticizers and solvents in consumer products, is ubiquitous. Despite growing concerns regarding their neurotoxicity, brain differences associated with gestational exposure to phthalates are understudied. We included 775 mother-child pairs from Generation R, a population-based pediatric neuroimaging study with prenatal recruitment, who had data on maternal gestational phthalate levels and T1-weighted magnetic resonance imaging in children at age 10 years. Maternal urinary concentrations of phthalate metabolites were measured at early, mid-, and late pregnancy. Child IQ was assessed at age 14 years. We investigated the extent to which prenatal exposure to phthalates is associated with brain volumetric measures and whether brain structural measures mediate the association of prenatal phthalate exposure with IQ. We found that higher maternal concentrations of monoethyl phthalate (mEP, averaged across pregnancy) were associated with smaller total gray matter volumes in offspring at age 10 years (ß per log10 increase in creatinine adjusted mEP = -10.7, 95%CI: -18.12, -3.28). Total gray matter volumes partially mediated the association between higher maternal mEP and lower child IQ (ß for mediated path =-0.31, 95%CI: -0.62, 0.01, p = 0.05, proportion mediated = 18%). An association of higher monoisobutyl phthalate (mIBP) and smaller cerebral white matter volumes was present only in girls, with cerebral white matter volumes mediating the association between higher maternal mIBP and lower IQ in girls. Our findings suggest the global impact of prenatal phthalate exposure on brain volumetric measures that extends into adolescence and underlies less optimal cognitive development.


Asunto(s)
Ácidos Ftálicos , Efectos Tardíos de la Exposición Prenatal , Femenino , Humanos , Niño , Embarazo , Adolescente , Estudios Longitudinales , Plastificantes , Ácidos Ftálicos/toxicidad , Ácidos Ftálicos/orina , Sustancia Gris , Exposición Materna
5.
Infect Control Hosp Epidemiol ; 44(11): 1801-1808, 2023 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-37138359

RESUMEN

OBJECTIVE: To describe IMP-type carbapenemase-producing Pseudomonas aeruginosa outbreaks at Galdakao University Hospital between March 2021 to December 2021. DESIGN: Outbreak report. SETTING: Galdakao University Hospital is a tertiary-care hospital in the Basque Country (northern Spain). PATIENTS: All patients with a positive IMP-type carbapenemase producing Pseudomonas aeruginosa (IMP-PA) culture were included in this study, both colonization and infection cases. METHODS: An outbreak investigation was conducted, in which molecular epidemiology analysis [pulsed-field gel electrophoresis and whole-genome sequencing (WGS)] and environmental screenings were performed. RESULTS: Between March and December 2021, 21 cases of IMP-PA were detected in Galdakao University Hospital: 18 infection cases and 3 colonization cases. In total, 4 different pulsotypes were detected belonging to 4 clones according to WGS: ST175 (n = 14), ST633 (n = 3), ST179 (n = 3), and ST348 (n = 1). IMP-13 was detected in most isolates belonging to the ST175 clone and in all ST179 and ST348 clones, whereas IMP-29 was detected in isolates belonging to the ST633 clone. Clinical isolates belonging to the ST175 clone were isolated mainly from patients admitted to the respiratory ward, and isolates belonging to the ST633 clone from patients admitted to the ICU. Two environmental isolates belonging to the ST175 clone were detected in the respiratory ward. CONCLUSIONS: Molecular and genomic epidemiology revealed that there had been 2 independent IMP-PA outbreaks, one of long duration in the respiratory ward and the other more limited in the ICU.


Asunto(s)
Infecciones por Pseudomonas , Pseudomonas aeruginosa , Humanos , Pseudomonas aeruginosa/genética , Centros de Atención Terciaria , Infecciones por Pseudomonas/epidemiología , beta-Lactamasas/genética , Brotes de Enfermedades , Antibacterianos , Pruebas de Sensibilidad Microbiana
6.
Clin Nurs Res ; 32(1): 6-14, 2023 01.
Artículo en Inglés | MEDLINE | ID: mdl-36217959

RESUMEN

The aim of this study was to evaluate laboratory parameters for investigating their potential predictive ability to differentiate patients with fibromyalgia (FM) from healthy subjects. We carried out a case-control study with 79 FM patients and 20 controls to analyze complete blood count, serum chemistry profile, glycosylated hemoglobin (HbA1c), and erythrocyte sedimentation rate (ESR). The predictive value of these parameters was determined by receiver operating characteristic (ROC) analysis. We also examined the relationships with clinical parameters (functional capacity, pain, and physical and mental health status). Results showed significant differences in red blood cell count, hematocrit, mean corpuscular hemoglobin concentration, platelet count, creatinine, HbA1c, and ESR between groups. According to ROC analysis, all these parameters may assist in making FM diagnosis. Hematocrit and ESR values were correlated with FM clinical parameters. The determination of these routine laboratory parameters may be an uncomplicated means of facilitating FM diagnosis, together with the clinical data of the patient.


Asunto(s)
Fibromialgia , Humanos , Estudios de Casos y Controles , Fibromialgia/diagnóstico , Sedimentación Sanguínea
7.
Neurol Sci ; 44(4): 1235-1241, 2023 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-36547780

RESUMEN

BACKGROUND: So far, mutations in genes encoding lysosomal enzymes have been associated with Parkinson's disease (PD). Fabry disease (FD) is an X-linked lysosomal storage disease caused by alpha-galactosidase A (α-GAL) deficiency, leading to deposition of globotriaosylceramide in the nervous system and other organs. We aimed to screen for FD a case series of PD patients from Southern Italy and to review the literature. METHODS: One hundred and forty-four consecutive unrelated PD subjects were enrolled. The α-GAL activity was measured in all men and, in case of pathological values, subsequent determination of globotriaosylsphingosine (lyso-Gb3) and GLA gene sequencing were also performed. All the women underwent GLA gene sequencing. RESULTS: α-GAL levels resulted low in fifteen men, whereas lyso-Gb3 testing showed values within the reference range in all of them. GLA gene variants were not detected in any tested subjects. One pathological study, six case series, and five case reports are currently reported in literature. CONCLUSIONS: The few studies reviewed are heterogeneous, and the results are controversial. An unknown significance variant in GLA gene was detected in PD patients in one large study, whereas decreased α-GAL activity was observed in PD subjects in two other researches, but without confirmation by lyso-Gb3 assessment or genetic analysis. Vascular parkinsonism was associated to FD in five case reports. We found no association between PD and FD in our population. However, it is not possible to draw definitive conclusions due to limited sample size. Furthermore, controls would have been missing in case of a positive finding.


Asunto(s)
Enfermedad de Fabry , Enfermedad de Parkinson Secundaria , Enfermedad de Parkinson , Masculino , Humanos , Femenino , Enfermedad de Fabry/complicaciones , Enfermedad de Fabry/diagnóstico , Enfermedad de Fabry/genética , Enfermedad de Parkinson/complicaciones , Enfermedad de Parkinson/diagnóstico , Enfermedad de Parkinson/genética , alfa-Galactosidasa/genética , Mutación/genética
8.
EJVES Vasc Forum ; 56: 40, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36237733
10.
Int J Mol Sci ; 23(7)2022 Apr 06.
Artículo en Inglés | MEDLINE | ID: mdl-35409394

RESUMEN

Poly(lactide-co-glycolide) (PLGA) nanoparticles (NPs) enhance the delivery of therapeutic enzymes for replacement therapy of lysosomal storage disorders. Previous studies examined NPs encapsulating or coated with enzymes, but these formulations have never been compared. We examined this using hyaluronidase (HAse), deficient in mucopolysaccharidosis IX, and acid sphingomyelinase (ASM), deficient in types A−B Niemann−Pick disease. Initial screening of size, PDI, ζ potential, and loading resulted in the selection of the Lactel II co-polymer vs. Lactel I or Resomer, and Pluronic F68 surfactant vs. PVA or DMAB. Enzyme input and addition of carrier protein were evaluated, rendering NPs having, e.g., 181 nm diameter, 0.15 PDI, −36 mV ζ potential, and 538 HAse molecules encapsulated per NP. Similar NPs were coated with enzyme, which reduced loading (e.g., 292 HAse molecules/NP). NPs were coated with targeting antibodies (> 122 molecules/NP), lyophilized for storage without alterations, and acceptably stable at physiological conditions. NPs were internalized, trafficked to lysosomes, released active enzyme at lysosomal conditions, and targeted both peripheral organs and the brain after i.v. administration in mice. While both formulations enhanced enzyme delivery compared to free enzyme, encapsulating NPs surpassed coated counterparts (18.4- vs. 4.3-fold enhancement in cells and 6.2- vs. 3-fold enhancement in brains), providing guidance for future applications.


Asunto(s)
Terapia de Reemplazo Enzimático , Nanopartículas , Animales , Lisosomas/metabolismo , Ratones , Polímeros/metabolismo , Tensoactivos/metabolismo
11.
Anal Bioanal Chem ; 414(6): 2103-2116, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35013809

RESUMEN

Environmental chemical exposures have been associated with cancer, diabetes, hormonal and immunological disorders, and cardiovascular diseases. Some direct effects of chemical exposure that are precursors to adverse health outcomes, including oxidative stress, nitrative stress, hormonal imbalance, neutrophilia, and eosinophilia, can be assessed through the analysis of biomarkers in urine. In this study, we describe a novel methodology for the determination of 19 biomarkers of health effects: malondialdehyde (MDA), 8-isoprostaglandin-F2α (8-PGF2α), 11-ß-prostaglandin-F2α (11-PGF2α), 15-prostaglandin-F2α (15-PGF2α), 8-iso-15-prostaglandin-F2α (8,15-PGF2α), 8-hydroxy-2'-deoxyguanosine (8-OHdG), 8-hydroxyguanosine (8-HdG), 8-hydroxyguanine (8-HG), dityrosine (diY), allantoin (Alla), and two metabolic products of 4-hydroxynonenal (HNE), namely 4-hydroxy-2-nonenal glutathione (HNE-GSH) and 4-hydroxy-2-nonenal mercapturic acid (HNE-MA) (in total, 12 oxidative stress biomarkers, OSBs); 8-nitroguanosine (8-NdG), 8-nitroguanine (8-NG), and 3-nitrotyrosine (NY) (3 nitrative stress biomarkers, NSBs); chlorotyrosine (CY) and bromotyrosine (BY) (2 inflammatory biomarkers); and the advanced glycation end-products (AGEs) Nε-carboxymethyllysine (CML) and Nε-carboxyethyllysine (CEL) (2 metabolic disorder biomarkers). Since these biomarkers are trigged by a variety of environmental insults and produced by different biomolecular pathways, their selective and sensitive determination in urine would help broadly elucidate the pathogenesis of diseases mediated by environmental factors.


Asunto(s)
Enfermedades Metabólicas , Espectrometría de Masas en Tándem , Biomarcadores/orina , Cromatografía Liquida , Humanos , Inflamación , Estrés Oxidativo
12.
Environ Toxicol Pharmacol ; 90: 103814, 2022 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-35051617

RESUMEN

Sevoflurane is being repurposed as a topical analgesic for painful wounds. Providing pre-charged sevoflurane syringes to irrigate wounds implies a potential risk of accidental intravenous injections. We assessed the potential of two concentrations (33% and 50% v/v) of three anesthetics, isoflurane, desflurane and sevoflurane, to produce hemolysis in vitro. Spectrophotometric absorbance was read at 576 nm. For both concentrations, the percentage of hemolysis (mean ± SD) was higher for isoflurane (29.7 ± 3.4% and 39.5 ± 5.3%), mild for desflurane (8.0 ± 0.5% and 6.5 ± 0.9%) and negligible for sevoflurane (0.7 ± 0.0% and 0.6 ± 0.1%), respectively. In conclusion, in contrast to isoflurane and desflurane, sevoflurane did not display hemolytic potential in vitro. However, the use of syringes preloaded with sevoflurane may still be problematic if it increases the possibility of inadvertent intravenous administration through increased risk of gas embolism and severe central nervous system depression.


Asunto(s)
Desflurano/toxicidad , Hemólisis/efectos de los fármacos , Isoflurano/toxicidad , Sevoflurano/toxicidad , Analgésicos/toxicidad , Anestésicos por Inhalación/toxicidad , Hemoglobinas/análisis , Humanos
14.
Psicothema ; 33(4): 579-586, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34668472

RESUMEN

BACKGROUND: Adolescent attitudes towards bullying are determined by the interaction between individual characteristics and psychosocial development contexts such as the family environment. Our objective was to perform a psychosocial analysis of the differences in reported attitudes towards school bullying between peers according to a series of indicators of family social climate, such as perceived parental support and understanding, punishment and rejection, and disapproval. METHOD: 665 students (50.4% girls) aged 12-18 (M = 14.59, SD = 1.691) from Asturias (Spain) participated in the study.  Participants were selected by intentional sampling with simple random two-stage subsampling of secondary-school groups. RESULTS: The hypothesized positive relationship between the perception of parental support and increased resistance attitudes towards school bullying in the three attitudinal dimensions explored (cognitive, affective, and behavioural) was supported by our results. Notably, favourable attitudes towards bullying were associated to negative family climate perceptions.  Adolescents with permissive attitudes towards bullying reported higher use of physical and psychological violence, as well as corporal punishment by their parents. CONCLUSIONS: This study supports the importancer of family socialization practices in the construction of attitudes towards bullying.


Asunto(s)
Acoso Escolar , Víctimas de Crimen , Adolescente , Actitud , Femenino , Humanos , Masculino , Instituciones Académicas , Estudiantes , Violencia
15.
Environ Int ; 156: 106720, 2021 11.
Artículo en Inglés | MEDLINE | ID: mdl-34166875

RESUMEN

Polycyclic aromatic hydrocarbons (PAHs) are ubiquitous environmental pollutants. Urinary concentrations of mono-hydroxylated metabolites of PAHs (OH-PAHs) have been used as biomarkers of these chemicals' exposure in humans. Little is known, however, with regard to intra- and inter-individual variability in OH-PAH concentrations and their association with oxidative stress. We conducted a longitudinal study of measurement of urinary concentrations of 15 OH-PAHs and 7 oxidative stress biomarkers (OSBs) of DNA damage [8-hydroxy-2'-deoxyguanosine (8-OHdG)], lipid [malondialdehyde (MDA) and F2-isoprostanes (PGF2α)] and protein [o,o'-dityrosine (diY)] peroxidation in 19 individuals for 44 consecutive days. Metabolites of naphthalene (OHNap), fluorene (OHFlu), phenanthrene (OHPhe), and pyrene (OHPyr) were found in >70% of 515 urine samples analyzed, at sum concentrations (∑OH-PAH) measured in the range of 0.46-60 ng/mL. After adjusting for creatinine, OHNap and ∑OH-PAH concentrations exhibited moderate predictability, with intra-class correlation coefficients (ICCs) ranging from 0.359 to 0.760. However, ICC values were low (0.001-0.494) for OHFlu, OHPhe, and OHPyr, which suggested poor predictability for these PAH metabolites. Linear mixed-effects analysis revealed that an unit increase in ∑OH-PAH concentration corresponded to 4.5%, 5.3%, 20%, and 21% increase in respective urinary 8-OHdG, MDA, PGF2α, and diY concentrations, suggesting an association with oxidative damage to DNA, lipids, and proteins. The daily intakes of PAHs, calculated from urinary concentrations of OH-PAHs, were 10- to 100-fold below the current reference doses. This study provides valuable information to design sampling strategies in biomonitoring studies and in assigning exposure classifications of PAHs in epidemiologic studies.


Asunto(s)
Hidrocarburos Policíclicos Aromáticos , Biomarcadores , Exposición a Riesgos Ambientales/análisis , F2-Isoprostanos , Humanos , Estudios Longitudinales , Estrés Oxidativo , Hidrocarburos Policíclicos Aromáticos/análisis , Hidrocarburos Policíclicos Aromáticos/toxicidad
16.
Environ Health ; 20(1): 60, 2021 05 15.
Artículo en Inglés | MEDLINE | ID: mdl-33992119

RESUMEN

BACKGROUND: Exposure to bisphenols may affect fetal growth and development. The trimester-specific effects of bisphenols on repeated measures of fetal growth remain unknown. Our objective was to assess the associations of maternal bisphenol urine concentrations with fetal growth measures and birth outcomes and identify potential critical exposure periods. METHODS: In a population-based prospective cohort study among 1379 pregnant women, we measured maternal bisphenol A, S and F urine concentrations in the first, second and third trimester. Fetal head circumference, length and weight were measured in the second and third trimester by ultrasound and at birth. RESULTS: An interquartile range increase in maternal pregnancy-averaged bisphenol S concentrations was associated with larger fetal head circumference (difference 0.18 (95% confidence interval (CI) 0.01 to 0.34) standard deviation scores (SDS), p-value< 0.05) across pregnancy. When focusing on specific critical exposure periods, any detection of first trimester bisphenol S was associated with larger second and third trimester fetal head circumference (difference 0.15 (95% CI 0.05 to 0.26) and 0.12 (95% CI 0.02 to 0.23) SDS, respectively) and fetal weight (difference 0.12 (95% CI 0.02 to 0.22) and 0.16 (95% CI 0.06 to 0.26) SDS, respectively). The other bisphenols were not consistently associated with fetal growth outcomes. Any detection of bisphenol S and bisphenol F in first trimester was also associated with a lower risk of being born small size for gestational age (Odds Ratio 0.56 (95% CI 0.38 to 0.74) and 0.55 (95% CI 0.36 to 0.85), respectively). Bisphenols were not associated with risk of preterm birth. CONCLUSIONS: Higher maternal bisphenol S urine concentrations, especially in the first trimester, seem to be related with larger fetal head circumference, higher weight and a lower risk of being small size for gestational age at birth.


Asunto(s)
Compuestos de Bencidrilo/orina , Disruptores Endocrinos/orina , Fenoles/orina , Sulfonas/orina , Adulto , Peso al Nacer , Femenino , Fémur/anatomía & histología , Fémur/crecimiento & desarrollo , Desarrollo Fetal , Cabeza/anatomía & histología , Cabeza/crecimiento & desarrollo , Humanos , Recién Nacido , Masculino , Embarazo , Estudios Prospectivos
17.
Environ Int ; 151: 106443, 2021 06.
Artículo en Inglés | MEDLINE | ID: mdl-33610054

RESUMEN

IMPORTANCE: Exposure to phthalates may affect fetal growth, but previous studies are inconsistent and have not explored the trimester-specific effects of phthalates on repeated measures of fetal growth. OBJECTIVE: To assess the associations of maternal phthalate metabolites urine concentrations with fetal growth measures and birth outcomes and identify potential windows of vulnerability to exposure. DESIGN: Population-based prospective cohort study, the Generation R Study (2002-2006). Data analysis was performed from November 2019 to June 2020. SETTING: Rotterdam, the Netherlands. PARTICIPANTS: 1379 pregnant women. EXPOSURES: Maternal phthalate metabolites urine concentrations in first, second and third trimester. MAIN OUTCOMES AND MEASURES: Fetal head circumference, length and weight measured in the second and third trimester by ultrasound and at birth and preterm birth and small size for gestational age at birth. RESULTS: Higher pregnancy-averaged phthalic acid, low molecular weight phthalate (LMWP), high molecular weight phthalate (HMWP) and di-2-ethylhexylphthalate (DEHP) concentrations tended to be associated with lower fetal weight SDS across gestation. The associations of phthalic acid and LMWP with fetal weight became stronger as pregnancy progressed (differences -0.08 (95% CI -0.14 to -0.02) SDS and -0.09 (95% CI -0.16 to -0.02) SDS at 40 weeks per interquartile range increase in phthalic acid and LMWP, respectively). Higher concentrations of specific LMWP, HMWP and DEHP metabolites were also associated with smaller head circumference and lower length SDS at birth and an increased risk of preterm birth and small size for gestational age at birth (p-values < 0.05). We observed differences by timing of exposure in these associations. CONCLUSIONS AND RELEVANCE: Higher maternal phthalate metabolites urine concentrations seem to be related with fetal growth restriction and preterm birth. Phthalates may have trimester specific effects on fetal growth and birth outcomes. Further studies are needed to explore the underlying mechanisms and long-term consequences.


Asunto(s)
Ácidos Ftálicos , Nacimiento Prematuro , Estudios de Cohortes , Femenino , Desarrollo Fetal , Humanos , Recién Nacido , Exposición Materna , Países Bajos , Embarazo , Estudios Prospectivos
18.
J Am Med Dir Assoc ; 22(2): 245-252.e2, 2021 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-33417840

RESUMEN

OBJECTIVES: To describe the clinical characteristics, 30-day mortality, and associated factors of patients living in nursing homes (NH) with COVID-19, from March 20 to June 1, 2020. DESIGN: This is a retrospective study. A geriatric hospital-based team acted as a consultant and coordinated the care of older people living in NHs from the hospital. SETTING AND PARTICIPANTS: A total of 630 patients aged 70 and older with Coronavirus Disease 2019 COVID-19 living in 55 NHs. METHODS: A logistic regression was performed to analyze the factors associated with mortality. In addition, Kaplan-Meier curves were applied according to mortality and its associated factors using the log-rank Mantel-Cox test. RESULTS: The diagnosis of COVID-19 was mainly made by clinical compatibility (N = 430). Median age was 87 years, 64.6% were women and 45.9% were transferred to be cared for at the hospital. A total of 282 patients died (44.7%) within the 30 days of first attention by the team. A severe form of COVID-19 occurred in 473 patients, and the most frequent symptoms were dyspnea (n = 332) and altered level of consciousness (n = 301). According to multiple logistic regression, male sex (P = .019), the Clinical Frailty Score (CFS) ≥6 (P = .004), dementia (P = .012), dyspnea (P < .001), and having a severe form of COVID-19 (P = .001), were associated with mortality, whereas age and care setting were not. CONCLUSIONS AND IMPLICATIONS: Mortality of the residents living in NHs with COVID-19 was almost 45%. The altered level of consciousness as an atypical presentation of COVID-19 should be considered in this population. A severe form of the disease, present in more than three-quarters of patients, was associated with mortality, apart from the male sex, CFS ≥6, dementia, and dyspnea, whereas age and care setting were not. These findings may also help to recognize patients in which the Advance Care Planning process is especially urgent to assist in the decisions about their care.


Asunto(s)
COVID-19/mortalidad , Anciano Frágil , Casas de Salud , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Estimación de Kaplan-Meier , Masculino , Pandemias , Estudios Retrospectivos , SARS-CoV-2 , España/epidemiología
19.
Obesity (Silver Spring) ; 29(2): 409-417, 2021 02.
Artículo en Inglés | MEDLINE | ID: mdl-33491307

RESUMEN

OBJECTIVE: The purpose of this study was to investigate the associations of urinary phthalates and bisphenols at age 6 years old with body fat and cardiovascular risk factors at 6 and 10 years and with the change from 6 to 10 years. METHODS: Among 471 Dutch children, the phthalates and bisphenols urinary concentrations at 6 years and BMI, fat mass index, android fat mass, blood pressure, glucose, insulin, and lipids blood concentrations at 6 and 10 years were measured. RESULTS: An interquartile range increase in di-n-octyl phthalate (DNOP) metabolites concentrations at 6 years was associated with an increased risk of overweight at 6 and 10 years (odds ratio: 1.44; 95% CI: 1.11-1.87, and 1.43; 95% CI: 1.09-1.86, respectively). Also, higher DNOP metabolites concentrations were associated with higher fat mass index at 6 years, higher systolic blood pressure at 10 years, a decrease in high-density lipoprotein cholesterol, and an increase in triglycerides concentrations from 6 to 10 years (P < 0.05). Higher total bisphenols and bisphenol A concentrations were associated with a decrease in BMI from 6 to 10 years (P < 0.01). CONCLUSIONS: DNOP metabolites are associated with overweight and an adverse cardiovascular profile in childhood. Total bisphenols and bisphenol A are associated with a decrease in BMI from 6 to 10 years.


Asunto(s)
Tejido Adiposo/química , Compuestos de Bencidrilo/orina , Índice de Masa Corporal , Fenoles/orina , Ácidos Ftálicos/orina , Glucemia/análisis , Presión Sanguínea/fisiología , Niño , Factores de Riesgo de Enfermedad Cardiaca , Humanos , Países Bajos , Sobrepeso/epidemiología
20.
Psicothema (Oviedo) ; 33(4): 579-586, 2021. tab
Artículo en Inglés | IBECS | ID: ibc-225855

RESUMEN

Background: Adolescent attitudes towards bullying are determined by the interaction between individual characteristics and psychosocial development contexts such as the family environment. Our objective was to perform a psychosocial analysis of the differences in reported attitudes towards school bullying between peers according to a series of indicators of family social climate, such as perceived parental support and understanding, punishment and rejection, and disapproval. Method: 665 students (50.4% girls) aged 12-18 (M = 14.59, SD = 1.691) from Asturias (Spain) participated in the study. Participants were selected by intentional sampling with simple random two-stage subsampling of secondary-school groups. Results: The hypothesized positive relationship between the perception of parental support and increased resistance attitudes towards school bullying in the three attitudinal dimensions explored (cognitive, affective, and behavioural) was supported by our results. Notably, favourable attitudes towards bullying were associated to negative family climate perceptions. Adolescents with permissive attitudes towards bullying reported higher use of physical and psychological violence, as well as corporal punishment by their parents. Conclusions: This study supports the importancer of family socialization practices in the construction of attitudes towards bullying. (AU)


Antecedentes: las actitudes de los adolescentes hacia el bullying están determinadas por la interacción entre las características individuales y diversos contextos de desarrollo, como el familiar. El objetivo de este estudio es realizar un análisis psicosocial de las diferencias reportadas según las actitudes percibidas frente al bullying en indicadores como apoyo y comprensión, castigo y rechazo, así como reprobación paterna. Método: participaron en el estudio 665 estudiantes (50,4% chicas) de 12 a 18 años (M = 14.59; DT = 1.691) del Principado de Asturias (España) que han sido seleccionados mediante un muestreo intencional con submuestreo bietápico aleatorio simple de los grupos escolares. Resultados: se ha hallado una relación positiva entre la percepción de apoyo de los padres y las actitudes de rechazo ante el bullying en las tres dimensiones actitudinales exploradas (cognitiva, afectiva y conductual). A su vez, las percepciones del clima familiar son más negativas en quienes presentan actitudes más favorables. Los adolescentes con actitudes permisivas reportan un mayor uso de violencia física, castigo corporal y violencia psicológica por parte de sus padres. Conclusiones: se apoya la relevancia de las prácticas de socialización familiar en la construcción de las actitudes hacia el bullying. (AU)


Asunto(s)
Humanos , Masculino , Femenino , Adolescente , Ciencias de la Salud , Acoso Escolar/psicología , Relaciones Familiares/psicología , Actitud , Salud de la Familia , España
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