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1.
Epileptic Disord ; 2020 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-32043469

RESUMO

Lacosamide (LCM) is a well-tolerated and increasingly used second-generation AED, and side effects such as atrial fibrillation are rare and poorly characterized. Supported by a literature review, we share our experience of the management of the first reported case of cardioembolic cerebral infarcts in the context of de novo atrial fibrillation, which appeared following a 200-mg intravenous infusion of LCM for the treatment of non-convulsive status epilepticus. Case report and literature review using search items including "atrial fibrillation OR atrial flutter AND LCM" in the thesaurus of Medline. We found three cases of atrial fibrillation/atrial flutter secondary to LCM, one following a 200-mg intravenous infusion. In one patient, previous risk factors for atrial fibrillation were reported and another was started on warfarin; all required suspension of LCM for cessation of atrial fibrillation. Previous risk factors for atrial fibrillation in our patient were older age, male gender, obesity, hypertension, valvular disease, first-degree atrioventricular block and left anterior fascicle block. Atrial fibrillation appeared at the end of the infusion and ceased after a loading dose of amiodarone and suspension of LCM. Apixaban was initiated indefinitely five days later, and MRI showed four acute silent infarctions. The appearance of atrial fibrillation has severe therapeutic and clinical implications and the use of LCM might be reconsidered within a context of increased predisposition to developing atrial fibrillation. If atrial fibrillation appears, the drug should be discontinued and anticoagulation should be considered according to embolic risk. Further investigation is needed in order to better categorize the risk profile of lacosamide regarding atrial fibrillation.

2.
Environ Sci Technol ; 54(3): 1740-1749, 2020 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-31944681

RESUMO

Phthalates are associated with several adverse health outcomes, but few studies have evaluated phthalate exposures in Mexican populations, particularly pregnant women. Between 2007 and 2011, 948 pregnant women from Mexico City were recruited as part of the PROGRESS cohort. We quantified 17 metabolites of phthalates and phthalate alternatives in urine samples collected during the second and third trimesters and examined temporal trends of metabolite concentrations, within-person reproducibility, and relations of individual metabolites with sociodemographic, lifestyle, and occupational factors. Concentrations of mono-2-ethyl-5-carboxypentyl terephthalate, a metabolite of the alternative phthalate di-2-ethylhexyl terephthalate, increased monotonically from 2007 to 2010 (31% per year; 95% confidence interval = 23 and 39%). We observed moderate to high correlations among metabolites collected at the same visit, but there was high variability between second and third trimester phthalate metabolite concentrations (intraclass correlation coefficients = 0.17-0.35). In general, higher socioeconomic status was associated with higher phthalate concentrations. Some metabolites were associated with maternal age and education, but no consistent patterns were observed. Women working in the home and those who worked in administration had higher concentrations of several phthalate metabolites relative to students, professionals, and those in customer service. Biomonitoring efforts are warranted to investigate present and future exposure trends and patterns.

3.
Reumatol Clin ; 16(1): 17-23, 2020.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-29530762

RESUMO

BACKGROUND AND OBJECTIVE: Diagnosis of lupus nephritis (LN) is usually based on renal biopsy, which is an invasive technique that involves multiple risks. Therefore, different biomarkers have emerged as alternatives for the diagnosis of LN. Nonetheless, studies regarding urinary biomarkers in Latin American patients are limited. The objective of this study was to assess the diagnostic value of urinary transferrin and ceruloplasmin to differentiate patients who have renal involvement from those who do not. MATERIALS AND METHODS: Systemic lupus erythematosus (SLE) patients that met the revised American College of Rheumatology (ACR) classification criteria were recruited. Patients with another autoimmune disease, active infection (urinary tract or systemic infection), renal replacement therapy, human immunodeficiency virus infection or pregnancy were excluded. A urine sample was collected from each patient. LN was diagnosed according to ACR criteria. The activity and chronicity of LN were measured using the Austin indices. Urinary transferrin and ceruloplasmin levels were measured using commercial enzyme-linked immunosorbent assay (ELISA) kits. Mann-Whitney U test and Student's t-test were used to compare data. Spearman's rank correlation was used to determine associations. Lastly, receiver operating characteristic (ROC) curves were created. RESULTS: The study involved 120 SLE patients. In all, 85% were female, 76% mestizo, the mean age was 32.8±12.1years and mean systemic lupus erythematosus disease activity index (SLEDAI) was 8.4±8.9; 64% had renal involvement. Urinary levels of the two biomarkers were significantly higher in patients with LN compared to those without LN. Similarly, urinary levels of both biomarkers were significantly higher in patients with active LN compared to those with inactive LN. Furthermore, urinary transferrin levels were significantly higher in Afro-Latin American patients. On the other hand, urinary transferrin levels correlated with SLEDAI and proteinuria, and transferrin and ceruloplasmin levels correlated with each other. The diagnostic value of ROC curves for these urinary biomarkers for LN were good. CONCLUSIONS: In our cohort of SLE patients, we found that transferrin and ceruloplasmin were potential biomarkers for LN, and can even differentiate active LN.

4.
Int J Clin Pract ; : e13453, 2019 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-31769902

RESUMO

BACKGROUND: Insulin resistance (IR) precedes the diagnosis of many metabolic and non-metabolic illnesses, including type 2 diabetes mellitus (T2DM). Acanthosis nigricans (AN) is a clinical sign associated with IR. However, AN prevalence and diagnostic accuracy in middle-age adults before or at the time of prediabetes/diabetes diagnosis remain uncertain. METHODS: With the aim to define AN prevalence and diagnostic accuracy, adults between 40 and 60 years of age were consecutively invited to participate in the study. Participants were categorised into one of two main groups: individuals with normoglycaemia (group 1) and hyperglycaemia (group 2 [ie, prediabetes/diabetes]). Demographic, clinical, anthropometric characteristics, homeostasis model assessment of IR, homeostatic model assessment of ß-cell function, as well as the presence of AN on the neck, axillae, elbows and knuckles were assessed. RESULTS: A total of 320 consecutive participants with a mean age of 49.3 years (59.4% women) were included. Overall, AN prevalence was 46.3%, while AN in group 1 and group 2 was 36.3% and 49.6%, respectively (P = .04). The most common affected sites in group 1 (n = 80) were the knuckles (21.2%) and the neck (17.5%), while in group 2 (n = 240), the neck (29.6%) followed by the knuckles (26.7%). The specificity and positive predictive value of AN for IR were 0.85 and 0.86 in group 1 and 0.90 and 0.96 in group 2, respectively. CONCLUSIONS: In middle-age adults, within the entire spectrum of carbohydrate tolerance, AN is highly prevalent and specific. This finding supports its assessment as a reliable and convenient clinical sign of IR. The understanding of AN behaviour through different carbohydrate tolerance strata, and its different locations, could lead to early detection of individuals at high metabolic risk or help direct a more pathophysiological treatment approach in patients with T2DM.

5.
Med Sci Sports Exerc ; 2019 Oct 23.
Artigo em Inglês | MEDLINE | ID: mdl-31652236

RESUMO

INTRODUCTION/PURPOSE: Limited studies have examined the association of physical activity with reproductive hormones, DNA methylation, and pubertal status among adolescents. METHODS: Among 248 boys and 271 girls, we estimated daily physical activity levels based on 7 days of wrist-worn accelerometer data. We used an isotemporal substitution paradigm and sex-stratified regression models to examine the association of physical activity levels with 1) testosterone, cortisol, progesterone and androstenedione concentrations; 2) DNA methylation of long interspersed nucleotide (LINE-1) repeats, and the genes H19, hydroxysteroid (11-Beta) dehydrogenase 2 (HSD11B2) and peroxisome proliferator-activated receptor alpha (PPARA) from blood leukocytes; and 3) Tanner stages, adjusted for age, BMI and socioeconomic status. RESULTS: In boys, substituting 30 minutes of moderate physical activity for 30 minutes of sedentary behavior per day was associated with 29% (-49%, 0%) of lower testosterone, and 29% (4%, 61%) of higher progesterone. Substituting 30 minutes of light physical activity for sedentary behavior was associated with 13% (-22%, -2%) of lower progesterone. Among girls, 30 minutes of additional sedentary behavior was associated with 8% (-15%, 0%) of lower testosterone, and 24% (8%, 42%) of higher progesterone concentrations. Substituting 30 minutes of moderate physical activity for sedentary behavior was associated with 15% (0%, 31%) of higher cortisol, while substituting the same amount of light physical activity for sedentary behavior was associated with 22% (-39%, 0%) of lower progesterone. Substituting 30 minutes of vigorous physical activity for sedentary behavior per day was associated with almost six times higher levels (5.83 (1.79, 9.86)) of HSD11B2 methylation in boys. CONCLUSIONS: Accelerometer-measured daily physical activity was associated with reproductive hormones and HSD11B2 DNA methylation, differed by sex and activity intensity levels.

6.
Diabetes Ther ; 10(6): 2169-2181, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31599392

RESUMO

INTRODUCTION: Acanthosis nigricans (AN) is an early clinical sign of insulin resistance (IR) primarily in adults. The prevalence and association of AN and IR in infants, however, remains uncertain. We aimed to describe the prevalence of AN and its association with IR in a group of Latin-American infants. METHODS: We studied a random sample of 227 healthy infants between 9 and 24 months of age. After a complete clinical history was obtained and a physical examination was performed, fasting plasma glucose and serum insulin were measured. Three blinded evaluators assessed AN in each patient. Infants with AN were categorized as cases. The HOMA-IR index cutoffs of ≥ 90th and ≥ 95th percentiles were considered IR. RESULTS: There were 49 infants with AN (21.6%) (cases) and 178 without AN (78.4%) (controls). Cases had a significantly higher mean serum insulin, fasting plasma glucose, and HOMA-IR levels of 3.67 ± 2.56 µU/ml vs. 2.42 ± 1.45 µU/ml, P = 0.005; 84.2 ± 12.6 mg/dL vs. 77 ± SD 9.9 mg/dL, P ≤ 0.001; HOMA-IR 0.77 ± 0.54 vs. 0.46 ± 0.28, P ≤ 0.001, respectively. More cases than controls presented HOMA-IR levels ≥ 95th percentile (cases 18.4%; controls 0.5%, P ≤ 0.001) and ≥ 90th percentile (cases 32.7%; controls 1.6%, P ≤ 0.001). AN in the knuckles had a high sensitivity and a negative predictive value (NPV) for detecting patients with HOMA-IR levels above the 95th percentile (sensitivity 90%; NPV 99.4%) and above the 90th percentile (sensitivity 84.2%; NPV 98.3%). CONCLUSION: AN in the knuckles is a prevalent, non-invasive, costless, and reliable screening clinical tool that can be used for early detection of infants with IR and a high metabolic risk.

7.
Am J Physiol Endocrinol Metab ; 317(5): E839-E851, 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31503514

RESUMO

Postnatal growth of lean mass is commonly blunted in preterm infants and may contribute to short- and long-term morbidities. To determine whether preterm birth alters the protein anabolic response to feeding, piglets were delivered at term or preterm, and fractional protein synthesis rates (Ks) were measured at 3 days of age while fasted or after an enteral meal. Activation of signaling pathways that regulate protein synthesis and degradation were determined. Relative body weight gain was lower in preterm than in term. Gestational age at birth (GAB) did not alter fasting plasma glucose or insulin, but when fed, plasma insulin and glucose rose more slowly, and reached peak value later, in preterm than in term. Feeding increased Ks in longissimus dorsi (LD) and gastrocnemius muscles, heart, pancreas, and kidney in both GAB groups, but the response was blunted in preterm. In diaphragm, lung, jejunum, and brain, feeding increased Ks regardless of GAB. Liver Ks was greater in preterm than term and increased with feeding regardless of GAB. In all tissues, changes in 4EBP1, S6K1, and PKB phosphorylation paralleled changes in Ks. In LD, eIF4E·eIF4G complex formation, phosphorylation of TSC2, mTOR, and rpS6, and association of mammalian target of rapamycin (mTOR1) complex with RagA, RagC, and Rheb were increased by feeding and blunted by prematurity. There were no differences among groups in LD protein degradation markers. Our results demonstrate that preterm birth reduces weight gain and the protein synthetic response to feeding in muscle, pancreas, and kidney, and this is associated with blunted insulin- and/or amino acid-induced translation initiation signaling.

8.
BMJ Open ; 9(8): e030427, 2019 Aug 26.
Artigo em Inglês | MEDLINE | ID: mdl-31455712

RESUMO

PURPOSE: The Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project is a mother-child pregnancy and birth cohort originally initiated in the mid-1990s to explore: (1) whether enhanced mobilisation of lead from maternal bone stores during pregnancy poses a risk to fetal and subsequent offspring neurodevelopment; and (2) whether maternal calcium supplementation during pregnancy and lactation can suppress bone lead mobilisation and mitigate the adverse effects of lead exposure on offspring health and development. Through utilisation of carefully archived biospecimens to measure other prenatal exposures, banking of DNA and rigorous measurement of a diverse array of outcomes, ELEMENT has since evolved into a major resource for research on early life exposures and developmental outcomes. PARTICIPANTS: n=1643 mother-child pairs sequentially recruited (between 1994 and 2003) during pregnancy or at delivery from maternity hospitals in Mexico City, Mexico. FINDINGS TO DATE: Maternal bone (eg, patella, tibia) is an endogenous source for fetal lead exposure due to mobilisation of stored lead into circulation during pregnancy and lactation, leading to increased risk of miscarriage, low birth weight and smaller head circumference, and transfer of lead into breastmilk. Daily supplementation with 1200 mg of elemental calcium during pregnancy and lactation reduces lead resorption from maternal bone and thereby, levels of circulating lead. Beyond perinatal outcomes, early life exposure to lead is associated with neurocognitive deficits, behavioural disorders, higher blood pressure and lower weight in offspring during childhood. Some of these relationships were modified by dietary factors; genetic polymorphisms specific for iron, folate and lipid metabolism; and timing of exposure. Research has also expanded to include findings published on other toxicants such as those associated with personal care products and plastics (eg, phthalates, bisphenol A), other metals (eg, mercury, manganese, cadmium), pesticides (organophosphates) and fluoride; other biomarkers (eg, toxicant levels in plasma, hair and teeth); other outcomes (eg, sexual maturation, metabolic syndrome, dental caries); and identification of novel mechanisms via epigenetic and metabolomics profiling. FUTURE PLANS: As the ELEMENT mothers and children age, we plan to (1) continue studying the long-term consequences of toxicant exposure during the perinatal period on adolescent and young adult outcomes as well as outcomes related to the original ELEMENT mothers, such as their metabolic and bone health during perimenopause; and (2) follow the third generation of participants (children of the children) to study intergenerational effects of in utero exposures. TRIAL REGISTRATION NUMBER: NCT00558623.

9.
Acta biol. colomb ; 24(2): 322-330, May-ago. 2019. tab, graf
Artigo em Inglês | LILACS-Express | ID: biblio-1010860

RESUMO

ABSTRACT Endophyte microorganisms have great biotechnological interest, with features applicable to different areas and are potentially useful in agriculture. The current study determines the biotechnological potential of endophytic fungi, isolated from leaves of Sapindus saponaria, to control phytopathogenic fungi and evaluate their enzyme production. Molecular taxonomy was performed by sequencing of the ITS1-5.8S-ITS2 ribosomal DNA region, identifying the genera Phomopsis, Sordariomycetes, Diaporthe, and Colletotrichum. In vitro antagonism against phytopathogens showed better results against Fusarium solani and provided inhibition indices between 41.8 % and 67.5 %. The endophytic strain SS81 (Diaporthe citri) presented the highest antagonism index against the pathogen. Against Glomerella sp. and Moniliophthora perniciosa, inhibition rates ranged between 18.7 % and 57.4 % and between 38.3 % and 64.8 %, respectively. Enzyme assays revealed that strain SS65 (Diaporthe sp.) produced 1.16 UI μmol/min of amylase; strain SS77 (Diaporthe sp.) produced 2.74 UI μmol/min of pectinase, and strain SS08 (Diaporthe sp.) produced 1.51 UI μmol/min of cellulase. Thus, the current study shows evidence the importance of isolated endophytes with phytoprotective properties of plants with medicinal properties as alternatives for biological control and natural sources of products with biotechnological interest.


RESUMEN Los microorganismos endofíticos tienen gran interés biotecnológico, con características aplicables a diferentes áreas y potencialmente útiles en la agricultura. El presente estudio determinó el potencial biotecnológico de los hongos endofíticos, aislados de las hojas de Sapindus saponaria, en el control de hongos fitopatógenos y evaluación de su producción de enzimática. La taxonomía molecular fue realizada por la secuencia de la región ITS1-5.8S-ITS2 del ADN ribosomal, identificando los géneros Phomopsis, Sordariomycetes, Diaporthe y Colletotrichum. El antagonismo in vitro contra fitopatógenos mostró mejores resultados contra Fusarium solani y proporcionó índices de inhibición de entre el 41,8 % y el 67,5 %. El linaje endofítico SS81 (Diaporthe citri) presentó el mayor índice de antagonismo contra los patógenos. Contra Glomerella sp. y Moniliophthora perniciosa, las tasas de inhibición variaron entre el 18,7 % y el 57,4 % y entre el 38,3 % y el 64,8 %, respectivamente. El ensayo enzimático reveló que el linaje SS65 (Diaporthe sp.) produjo 1,16 UI μmol / min de amilasa; el linaje SS77 (Diaporthe sp.) produjo 2,74 UI μmol / min de pectinasa; y el linaje SS08 (Diaporthe sp.) produjo 1,51 UI μmol / min de celulasa. Así, el presente estudio evidencia la importancia de los endófitos aislados con propiedades fitoprotectoras como alternativas para el control biológico y como fuentes naturales de productos con interés biotecnológico.

10.
Nutrients ; 11(7)2019 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-31337124

RESUMO

Alterations in pubertal timing have been associated with long-term health outcomes. While a few reports have shown that dietary intake of selenium is associated with fertility and testosterone levels in men, no human studies have considered the association between selenium and pubertal development in children. We examined the cross-sectional association of childhood dietary intake of selenium with pubertal development among 274 girls and 245 boys aged 10-18 years in Mexico City. Multiple logistic and ordinal regression models were used to capture the association between energy-adjusted selenium intake (below Recommended Dietary Allowance (RDA) vs. above RDA) and stages of sexual maturity in children, adjusted for covariates. We found that boys with consumption of selenium below the RDA had lower odds of a higher stage for pubic hair growth (odds ratio (OR) = 0.51, 95% confidence interval (95% CI): 0.27-0.97) and genital development (OR = 0.53, 95% CI: 0.28-0.99) as well as a lower probability of having matured testicular volume (OR = 0.37, 95% CI: 0.15-0.88) compared with boys who had adequate daily dietary intake of selenium (above RDA). No associations were found in girls. According to our results, it is possible that inadequate consumption of selenium may be associated with later pubertal development in boys, suggesting a sex-specific pattern. Future work with a larger sample size and measures of selenium biomarkers is needed to confirm our findings and improve understanding of the role of this mineral in children's sexual development.


Assuntos
Dieta , Puberdade/efeitos dos fármacos , Puberdade/fisiologia , Selênio/administração & dosagem , Maturidade Sexual/efeitos dos fármacos , Adolescente , Criança , Estudos Transversais , Feminino , Humanos , Masculino , México , Recomendações Nutricionais , Selênio/deficiência , Fatores Sexuais , Maturidade Sexual/fisiologia
11.
Int J Rheum Dis ; 22(9): 1607-1615, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31328413

RESUMO

OBJECTIVE: We performed a systematic review and meta-analysis from randomized controlled trials to examine the efficacy and safety of avocado-soybean unsaponifiables (ASU) in patients with hip or knee osteoarthritis (OA). DATA SOURCES: Medline, SCOPUS, Web of Science, and Google Scholar databases were searched for randomized placebo-controlled trials. STUDY SELECTION: Original studies were randomized placebo-controlled trials evaluating the effect of orally administered ASU on knee or hip OA symptoms using the Lequesne index, visual analog scale (VAS) and/or joint space width (JSW). DATA EXTRACTION: Meta-analysis was conducted using a random-effects model and generic inverse variance method. Heterogeneity was tested using the I2 statistic index. DATA SYNTHESIS: Avocado-soybean unsaponifiables therapy had a significant reduction on pain by VAS assessment (weighted mean difference [WMD]: -9.64 mm, 95% CI: -17.43, -1.84; P = .02; I2  = 92%). A subanalysis according to the type of OA showed that ASU significantly decreased both VAS and Lequesne index in knee OA (WMD: -17.36, 95% CI: -25.91, -8.82; P < .0001; I2  = 87% and WMD: -2.33, 95% CI: -2.88, -1.78; P < .00001; I2  = 18%, respectively) but not in hip OA. Finally, ASU supplementation showed no significant differences for adverse events compared to placebo (relative risk: 1.02, 95% CI: 0.83, 1.25; P = .88; I2  = 0%). CONCLUSION: Results of this meta-analysis suggest a beneficial effect of ASU treatment in symptomatic knee OA but not in hip OA. Additionally, adverse events were similar in patients receiving ASU therapy or placebo.

12.
Front Public Health ; 7: 162, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31275917

RESUMO

Phthalates are a class of endocrine disrupting chemicals with near ubiquitous exposure to populations around the world. Phthalates have been associated with children's adiposity in previous studies, though discrepancies exist across studies that may be due to timing of exposure or outcome assessment and population differences (i.e., genetics, other confounders). DNA methylation, an epigenetic modification involved in gene regulation, may mediate the effects of early life phthalate exposures on health outcomes. This study aims to evaluate the mediating effect of DNA methylation at growth-related genes on the association between phthalate exposure and repeat measures of adiposity (BMI-for-age z-score, waist circumference, and skinfolds thickness) in Mexican children. Urinary phthalate metabolite concentrations were quantified in mothers at each of the three trimesters of pregnancy and in children at the first peri-adolescent study visit. Blood leukocyte DNA methylation at H19 and HSD11B2 was quantified during the first peri-adolescent visit, and adiposity was measured at the first visit and again ~3 years later among participants (n = 109 boys, 114 girls) from the Early Life Exposure in Mexico to Environmental Toxicants (ELEMENT) project. Associations between phthalates or DNA methylation and repeat outcome measures were assessed separately in boys and girls using generalized estimating equation models including covariates (urinary specific gravity, maternal education, and child's age). Sobel tests were used to assess DNA methylation as a mediator in models adjusting for the same covariates. Associations between phthalates and adiposity varied by phthalate and timing of exposure. Early gestation MBP, MIBP, and MBzP were associated with adiposity among girls. For example, among girls first trimester maternal urine concentrations of MIBP were associated with increases in skinfold thickness, BMI-for-age, and waist circumference (p < 0.01). Second trimester and adolescent MBzP were associated with adiposity among boys in opposite directions. In girls, H19 methylation was positively associated with skinfold thickness. No significant mediation of phthalate exposure on adiposity by DNA methylation of H19 or HSD11B2 was observed (Sobel p > 0.05). However, the mediation analysis was underpowered to detect small to medium effect sizes, and the role of DNA methylation as a mediator between phthalates and outcomes merits further study.

13.
Front Immunol ; 10: 1129, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31191521

RESUMO

Over the past several decades there has been an increasing interest in the role of environmental factors in the etiology of neuropsychiatric and neurodevelopmental disorders. Epidemiologic studies have shifted from an exclusive focus on the identification of genetic risk alleles for such disorders to recognizing and understanding the contribution of xenobiotic exposures, infections, and the maternal immune system during the prenatal and early post-natal periods. In this review we discuss the growing literature regarding the effects of maternal brain-reactive antibodies on fetal brain development and their contribution to the development of neuropsychiatric and neurodevelopmental disorders. Autoimmune diseases primarily affect women and are more prevalent in mothers of children with neurodevelopmental disorders. For example, mothers of children with Autism Spectrum Disorder (ASD) are significantly more likely to have an autoimmune disease than women of neurotypically developing children. Moreover, they are four to five times more likely to harbor brain-reactive antibodies than unselected women of childbearing age. Many of these women exhibit no apparent clinical consequence of harboring these antibodies, presumably because the antibodies never access brain tissue. Nevertheless, these maternal brain-reactive antibodies can access the fetal brain, and some may be capable of altering brain development when present during pregnancy. Several animal models have provided evidence that in utero exposure to maternal brain-reactive antibodies can permanently alter brain anatomy and cause persistent behavioral or cognitive phenotypes. Although this evidence supports a contribution of maternal brain-reactive antibodies to neurodevelopmental disorders, an interplay between antibodies, genetics, and other environmental factors is likely to determine the specific neurodevelopmental phenotypes and their severity. Additional modulating factors likely also include the microbiome, sex chromosomes, and gonadal hormones. These interactions may help to explain the sex-bias observed in neurodevelopmental disorders. Studies on this topic provide a unique opportunity to learn how to identify and protect at risk pregnancies while also deciphering critical pathways in neurodevelopment.

14.
Sleep ; 2019 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-31181146

RESUMO

STUDY OBJECTIVES: Sleep deprivation and low sleep quality are widespread among adolescents, and associate with obesity risk. Plausible mediators include diet and physical activity. Another potential interrelated pathway, as yet unexplored in adolescents, could involve epigenetic modification of metabolism genes. METHODS: In a cohort of 351 Mexico City adolescents (47% male; mean [SD] age = 14 [2] years), 7-day actigraphy was used to assess average sleep duration, sleep fragmentation, and movement index. DNA isolated from blood leukocytes was bisulfite-converted, amplified, and pyrosequenced at four candidate regions. Linear mixed models evaluated sex-stratified associations between sleep characteristics (split into quartiles [Q]) and DNA methylation of each region, adjusted for potential confounders. RESULTS: Mean sleep duration was 8.5 [0.8] hours for boys and 8.7 [1] hours for girls. There were sex-specific associations between sleep duration and LINE-1 (long interspersed nuclear element) methylation. Boys with longer sleep duration (Q4) had lower LINE-1 methylation than boys in the 3rd quartile reference category, while girls with both longer and shorter sleep duration had higher LINE-1 methylation compared to Q3. Longer sleep duration was associated with higher H19 methylation among girls (comparing highest to third quartile, -0.9% [-2.2, 0.5]; p, trend = 0.047). Sleep fragmentation was inversely associated with peroxisome proliferator-activated receptor alpha (PPARA) methylation among girls (comparing highest to lowest fragmentation quartile, 0.9% [0.1 to 1.8]). Girls also showed an inverse association between sleep fragmentation and hydroxysteroid (11-beta) dehydrogenase 2 (HSD11B2; Q4 to Q1, 0.6% [-1.2%, 0%]). CONCLUSIONS: Sleep duration and fragmentation in adolescents show sex-specific associations with leukocyte DNA methylation patterns of metabolism genes.

15.
Rev. iberoam. micol ; 36(2): 90-92, abr.-jun. 2019. ilus
Artigo em Inglês | IBECS | ID: ibc-185483

RESUMO

Background: Phaeoacremonium parasiticum is considered a rare infectious agent that is part of a heterogeneous group of fungi causing phaeohyphomycosis. This organism is capable of producing subcutaneous infections, eumycetomas, osteomyelitis, arthritis, myositis and also disseminated diseases, such as fungemia and endocarditis. Case report: We describe a case of cutaneous infection by P. parasiticum in a kidney transplant patient. The identification of this microorganism was performed by microbiological and histopathological studies and confirmed with the sequence of the gene encoding β-tubulin and a real time panfungal PCR targeting 18S ribosomal RNA gene. The microorganism was correctly identified by phenotypic and molecular methods. The patient was treated with oral antifungal therapy and a debulking surgery and evolved without any complication. Conclusions: The diagnosis of this infection is difficult and usually affects kidney transplant patients, but the reasons of this association are still unknown


Antecedentes: Phaeoacremonium parasiticum es considerado un agente infeccioso poco común que forma parte de un grupo heterogéneo de hongos causantes de feohifomicosis. Este microorganismo es capaz de producir infección cutánea, eumicetoma, osteomielitis, artritis, miositis e incluso enfermedad diseminada como fungemia y endocarditis. Caso clínico: Se describe un caso de infección cutánea por P. parasiticum en un paciente trasplantado renal. Para la identificación del microorganismo se realizaron pruebas microbiológicas e histopatológicas, y se confirmó la identificación con la secuenciación del gen de la β-tubulina y una PCR a tiempo real para la detección del gen 18S rRNA. El microorganismo fue identificado correctamente por métodos fenotípicos y moleculares. El paciente recibió tratamiento con antifúngicos orales y citorreducción quirúrgica, y evolucionó sin ninguna complicación. Conclusiones: El diagnóstico de esta infección es difícil y se presenta habitualmente en pacientes trasplantados renales. Sin embargo, la asociación de esta infección con este tipo de pacientes no ha sido aún explicada


Assuntos
Humanos , Masculino , Idoso , Ascomicetos/isolamento & purificação , Dermatomicoses/microbiologia , Rim , Feoifomicose/microbiologia , Transplantados , Ascomicetos/genética , Dermatomicoses/terapia , Hospedeiro Imunocomprometido , Feoifomicose/terapia , Fenótipo , RNA Ribossômico 18S/genética , Tubulina (Proteína)/genética
16.
Rev Panam Salud Publica ; 43: e38, 2019.
Artigo em Espanhol | MEDLINE | ID: mdl-31093262

RESUMO

Objective: The Zika outbreak affected several tropical countries in 2015 and 2016, requiring the creation of intensified surveillance strategies for microcephaly and other neurological syndromes. The effect of the Zika outbreak on the reporting of birth defects in Colombia was evaluated from the perspective of the national surveillance system. Methods: National reporting of newborns with different birth defects was analyzed; variations in reporting attributed to the epidemic were determined through difference in differences (DID), a semiparametric model. Results: During the period of study, 18,234 cases of birth defects were reported in Colombia. The majority were congenital malformations (91.9%), and 82.3% was confirmed by clinical diagnosis or epidemiological link. In the case of microcephaly, eight new cases per epidemiological week were reported (coefficient of case reporting [D] = 8.8; P = 0.000) and 32 cases from other congenital anatomical malformations (D = 32.0; P = 0.000). The absolute value of the difference in differences estimator attributed to the Zika outbreak increased weekly case reporting of microcephaly (DID = |-5.0|; P = 0.008) and congenital malformations (DID = |-12.0|; P = 0.111). Conclusions: The Zika outbreak increased reporting of newborns with microcephaly, but caused no significant variation in reporting of other malformations and functional birth defects of sensory or metabolic origin in the surveillance system.

17.
Artigo em Espanhol | PAHO-IRIS | ID: phr-50937

RESUMO

[RESUMEN]. Objetivo. El brote por virus del Zika afectó a varios países tropicales durante 2015 y 2016. Esto obligó a crear estrategias de vigilancia intensificada de microcefalia y otros síndromes neurológicos. Se evaluó el efecto del brote por virus del Zika en la notificación de defectos congénitos en Colombia desde la perspectiva del sistema nacional de vigilancia. Métodos. Se analizó la notificación nacional de recién nacidos con diferentes defectos congénitos y se determinaron las variaciones en la notificación atribuidas a la epidemia mediante un modelo semiparamétrico denominado “diferencia en diferencias” (DID). Resultados. Un total de 18 234 casos por defectos congénitos fueron notificados en Colombia durante el período de estudio. La mayoría eran malformaciones congénitas (91,9%). El 82,3% se confirmó por diagnóstico clínico o nexo epidemiológico. En el caso de la microcefalia, se notificaron ocho casos nuevos por semana epidemiológica (coeficiente de notificación de casos [D] = 8,8; P = 0,000) y 32 casos por otras malformaciones congénitas anatómicas (D = 32,0; P = 0,000). El valor absoluto del estimador de diferencia en diferencias atribuido al brote por virus del Zika incrementó la notificación semanal de casos de microcefalia (DID = |-5,0|; P = 0,008) y malformaciones congénitas (DID = |-12,0|; P = 0,111). Conclusiones. El brote por virus del Zika incrementó la notificación de recién nacidos con microcefalia, pero sin ninguna variación significativa en la notificación de otras malformaciones y defectos congénitos funcionales de origen sensorial o metabólico en el sistema de vigilancia.


[ABSTRACT]. Objective. The Zika outbreak affected several tropical countries in 2015 and 2016, requiring the creation of intensified surveillance strategies for microcephaly and other neurological syndromes. The effect of the Zika outbreak on the reporting of birth defects in Colombia was evaluated from the perspective of the national surveillance system. Methods. National reporting of newborns with different birth defects was analyzed; variations in reporting attributed to the epidemic were determined through difference in differences (DID), a semiparametric model. Results. During the period of study, 18,234 cases of birth defects were reported in Colombia. The majority were congenital malformations (91.9%), and 82.3% was confirmed by clinical diagnosis or epidemiological link. In the case of microcephaly, eight new cases per epidemiological week were reported (coefficient of case reporting [D] = 8.8; P = 0.000) and 32 cases from other congenital anatomical malformations (D = 32.0; P = 0.000). The absolute value of the difference in differences estimator attributed to the Zika outbreak increased weekly case reporting of microcephaly (DID = |-5.0|; P = 0.008) and congenital malformations (DID = |-12.0|; P = 0.111). Conclusions. The Zika outbreak increased reporting of newborns with microcephaly, but caused no significant variation in reporting of other malformations and functional birth defects of sensory or metabolic origin in the surveillance system.


[RESUMO]. Objetivo. O surto de vírus zika afetou vários países tropicais de 2015 a 2016. Fez-se necessário elaborar estratégias de vigilância intensificada da microcefalia e outras síndromes neurológicas. O presente estudo avaliou o impacto do surto de vírus zika na notificação de defeitos congênitos no sistema nacional de vigilância da Colômbia. Métodos. A notificação nacional de recém-nascidos com defeitos congênitos foi analisada e a variação na notificação atribuída à epidemia de zika foi determinada com o uso de um modelo semiparamétrico de diferença em diferenças (DD). Resultados. Ao todo, 18.234 casos de defeitos congênitos foram notificados na Colômbia no período considerado. Os casos, na sua maioria, foram de malformações congênitas (91,9%), sendo 82,3% confirmados por diagnóstico clínico ou nexo epidemiológico. Foram notificados oito casos novos de microcefalia por semana epidemiológica (coeficiente de notificação de casos [D] = 8,8; P = 0,000) e 32 casos de outras malformações congênitas anatômicas (D = 32,0; P = 0,000). O valor absoluto do estimador do método de diferença em diferenças atribuído ao surto de vírus zika indicou um aumento na notificação semanal de casos de microcefalia (DD = |–5,0|; P = 0,008) e malformações congênitas (DD = |–12,0|; P = 0,111). Conclusões. O surto de vírus zika ocasionou um aumento na notificação de recém-nascidos com microcefalia, mas não houve variação significativa na notificação de outras malformações e defeitos congénitos funcionais de origem sensorial ou metabólica no sistema de vigilância.


Assuntos
Zika virus , Anormalidades Congênitas , Vigilância Sanitária , Saúde Pública , Colômbia , Zika virus , Anormalidades Congênitas , Vigilância Sanitária , Saúde Pública , Anormalidades Congênitas , Vigilância Sanitária , Saúde Pública , Colômbia
19.
Front Public Health ; 7: 61, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31032242

RESUMO

Introduction: Cadmium is a pervasive toxic metal that remains a public health concern and exposure in early life has been associated with growth deficits in infancy and childhood. Growth during adolescence also may be sensitive to effects of cadmium exposure, given the changes in distribution of lean and adipose tissue that vary by sex during puberty. This study examines whether prenatal and concurrent cadmium exposures are associated with adiposity measures at ages 8-15 years in a well-characterized birth cohort. Methods: The sample included 185 participants from the ELEMENT birth cohorts in Mexico City with complete data on urinary cadmium exposures, anthropometry and covariates [child age and sex, household socioeconomic status, and maternal smoking history and body mass index (BMI)]. Maternal third trimester and adolescent urines were analyzed for cadmium using an Inductively Coupled Plasma Mass Spectrometer. Trained personnel obtained anthropometry including height, weight, waist circumference and subscapular, suprailiac, and triceps skinfold thickness. BMI z-scores for age and sex were calculated using the World Health Organization's reference standard. Linear regression models were used to estimate the association of prenatal and concurrent urinary cadmium levels with adolescent anthropometry, adjusting for covariates. Results: Among 87 males and 98 females, median age was 10 years (IQR 9 -11 years). Pregnant women and children had median urinary cadmium concentrations of 0.19 µg/L (IQR 0.12- 0.27 µg/L) and 0.14 µg/L (IQR 0.11- 0.18 µg/L), respectively. Regression models showed inverse relationships between prenatal cadmium exposure and adolescent adiposity. An IQR increase in prenatal cadmium was associated with percent decreases in BMI z-score (-27%, p = 0.01), waist circumference (-3%, p = 0.01), and subscapular (-11%, p = 0.01), suprailiac (-11%, p = 0.02), and triceps (-8%, p < 0.01) skinfold thickness. When stratified by sex, these relationships remained statistically significant in females but not males. Conclusions: Prenatal cadmium exposure was negatively associated with measures of both abdominal and peripheral adiposity in girls, but not in boys. These results emphasize the sex-dependent effects of in utero cadmium exposure on adiposity in adolescence.

20.
Lipids Health Dis ; 18(1): 88, 2019 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-30954082

RESUMO

OBJECTIVE: The aim of this meta-analysis of randomized placebo-controlled trials was to examine whether ursodeoxycholic acid treatment is an effective lipid-lowering agent. METHODS: PubMed-Medline, SCOPUS, Web of Science and Google Scholar databases were searched in order to find randomized controlled trials evaluating the effect of ursodeoxycholic acid on lipid profile. A random-effect model and the generic inverse variance weighting method were used for quantitative data synthesis. Sensitivity analysis was conducted using the leave-one-out method. A random-effects meta-regression model was performed to explore the association between potential confounders and the estimated effect size on plasma lipid concentrations. RESULTS: Meta-analysis of 20 treatment arms revealed a significant reduction of total cholesterol following ursodeoxycholic acid treatment (WMD: - 13.85 mg/dL, 95% CI: -21.45, - 6.25, p < 0.001). Nonetheless, LDL-C (WMD: -6.66 mg/dL, 95% CI: -13.99, 0.67, p = 0.075), triglycerides (WMD: - 1.42 mg/dL, 95% CI: -7.51, 4.67, p = 0.648) and HDL-C (WMD: -0.18 mg/dL, 95% CI: -5.23, 4.87, p = 0.944) were not found to be significantly altered by ursodeoxycholic acid administration. In the subgroup of patients with primary biliary cirrhosis, ursodeoxycholic acid reduced total cholesterol (WMD: - 29.86 mg/dL, 95% CI: -47.39, - 12.33, p = 0.001) and LDL-C (WMD: -37.27 mg/dL, 95% CI: -54.16, - 20.38, p < 0.001) concentrations without affecting TG and HDL-C. CONCLUSION: This meta-analysis suggests that ursodeoxycholic acid therapy might be associated with significant total cholesterol lowering particularly in patients with primary biliary cirrhosis.


Assuntos
Hipolipemiantes/uso terapêutico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/sangue , Ácido Ursodesoxicólico/uso terapêutico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Humanos , Ensaios Clínicos Controlados Aleatórios como Assunto , Triglicerídeos/sangue
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