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Urbanization can negatively impact natural protected areas near or surrounded by cities, and such impacts include untreated wastewater discharge, leachates from dumpsters, e-waste, and road dust. In this research, we show that not only large cities with industry are prone to be polluted, but also young touristic cities with high population increase rate can suffer from urban contamination. We evaluated metal pollution in a natural protected area within a 50-year-old city without conventional industry that was likely contaminated by the urban sprawl around the protected area. We tested water, zooplankton, sediment and plant samples for metallic elements to evaluate their bioaccumulation in zooplankton, enrichment factors and geoaccumulation index values in sediments, and translocation factors in plants. Finally, we evaluated the ecological risk due to metal contamination. Metals at levels above our detection limit (20 µg/L) were not found in the water and zooplankton samples. The sediments and plants in the storm drain section of the protected area had a greater concentration of metals and wastewater indicators (coliforms) than those in the rest of the lagoon. Moreover, signs of Al, Cu, Ni, Zn, Cr, Pb, and Ti contamination were found in the plant tissues. We estimated that the ecological risk of this natural protected area surrounded by the city of Cancun (Mexico) ranged from mild to strong, with Zn being the metal of most concern. The results highlight that young touristic cities around the world will endure contamination from urban sources; signs or early warnings of contamination must be identified to prevent and resolve such issues.
Assuntos
Metais Pesados , Monitoramento Ambiental/métodos , Sedimentos Geológicos , Metais Pesados/análise , México , Águas Residuárias , ÁguaRESUMO
We evaluated the feasibility, reliability, and validity of a Spanish-language self-administered geriatric assessment (GA) in older (age ≥ 65) Spanish-speaking women with breast cancer in the United States. Eligible participants (n = 181) were recruited and randomized. Feasibility was defined as the participant's unassisted GA completion rate, completion time, and perception on ease of completion. Reliability and validity were assessed using Spearman's correlation coefficients. Two-sided p < 0.05 was considered significant. Ninety-eight percent of participants (n = 177) completed the GA at least once. Median age was 70 years (range: 65-95) and 55% had ≤8th grade education. Forty-one percent (n = 73) were unable to complete the GA unassisted, median completion time was 28 min (range 8-90), and 77% (n = 136) rated the GA as "easy"/"very easy". Patients with ≤8th grade education took longer to complete the GA (30 vs. 25 min, p = 0.0036) and needed more assistance (59% vs. 19%, p < 0.001) than those with ≥9th grade education. Test-retest reliability was high (≥0.82) for all domains except social activity (0.73). Validity among similar scales was found. The self-administered GA is a feasible, reliable, and valid tool for Spanish-speaking older women with breast cancer. Tailoring GA tools to the patients' educational level is important when implementing tools in multicultural environments.
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Protein arginine methylation regulates several cellular events, including epigenetics, splicing, translation, and stress response, among others. This posttranslational modification is catalyzed by protein arginine methyltransferases (PRMTs), which according to their products are classified from type I to type IV. The type I produces monomethyl arginine and asymmetric dimethyl arginine; in mammalian there are six families of this PRMT type (PRMT1, 2, 3, 4, 6, and 8). The protozoa parasite Entamoeba histolytica has four PRMTs related to type I; three of them are similar to PRMT1, but the other one does not show significant homology to be grouped in any known PRMT family, thus we called it as atypical PRMT (EhPRMTA). Here, we showed that EhPRMTA does not contain several of the canonical amino acid residues of type I PRMTs, confirming that it is an atypical PRMT. A specific antibody against EhPRMTA localized this protein in cytoplasm. The recombinant EhPRMTA displayed catalytic activity on commercial histones and the native enzyme modified its expression level during heat shock and erythrophagocytosis. Besides, the knockdown of EhPRMTA produced an increment in cell growth, and phagocytosis, but decreases cell migration and the survival of trophozoites submitted to heat shock, suggesting that this protein is involved in regulate negatively or positively these events, respectively. Thus, results suggest that this methyltransferase regulates some cellular functions related to virulence and cell surviving.
Assuntos
Entamoeba histolytica/enzimologia , Entamoeba histolytica/patogenicidade , Proteína-Arginina N-Metiltransferases/metabolismo , Sequência de Aminoácidos , Movimento Celular , Proliferação de Células/fisiologia , Sequência Conservada , Entamoeba histolytica/citologia , Entamoeba histolytica/metabolismo , Eritrócitos/metabolismo , Regulação Enzimológica da Expressão Gênica , Técnicas de Silenciamento de Genes , Resposta ao Choque Térmico/fisiologia , Fagocitose , Processamento de Proteína Pós-Traducional/fisiologia , Proteína-Arginina N-Metiltransferases/classificação , Proteína-Arginina N-Metiltransferases/genética , VirulênciaRESUMO
Circulating biological markers, such as miRNAs, hold the greatest possibilities to complement tissue biopsy and clinical diagnostic tests. The objective of this study was to evaluate the relative abundance of three circulating miRNAs in serum from 17 HPV16-positive patients with early cervical lesions known as Low-Grade Squamous Intraepithelial Lesions (LSILs). The expression of circulating microRNAs miR-15b, miR-34a and miR-218 in patients with LSILs was compared to 23 HPV-negative individuals showing normal cervical epithelium (healthy women) and 23 Squamous Cell Carcinoma (SCC) samples. The expression levels of miR-15b remained unchanged while those of miRNAs 34a and 218 were relatively high in serum obtained from LSIL patients in comparison with healthy women (results were statistically significant with a p of < 0.01 or < 0.001). According to previous findings, miR-15b was overexpressed and miRNAs 34a and 218 were underexpressed in serum from SCC patients. Additionally, the mRNA expression levels of some selected gene targets were determined [Cyclin D1 (CCND1), Cyclin E1 (CCNE1), B-cell lymphoma 2 (Bcl-2) and MutS homolog 2 (MSH-2)]. All serum results correlated with tissue samples from the same patients. We propose that circulating microRNAs can be valuable as molecular markers for the early follow-up of cervical carcinogenesis risk.
Assuntos
MicroRNA Circulante/sangue , MicroRNAs/sangue , Displasia do Colo do Útero/genética , Neoplasias do Colo do Útero/genética , Adulto , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Carcinogênese/genética , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Colo do Útero/patologia , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Genótipo , Papillomavirus Humano 16/genética , Papillomavirus Humano 16/isolamento & purificação , Humanos , MicroRNAs/genética , Pessoa de Meia-Idade , Infecções por Papillomavirus/genética , Neoplasias do Colo do Útero/sangue , Adulto Jovem , Displasia do Colo do Útero/sangueRESUMO
Around 25% of patients with systemic lupus erythematosus (SLE) could be refractory to conventional therapies. P-glycoprotein expression on cell surface has been implied on drug resistance, however, to date, it is unknown if P-gp serum levels are associated with SLE disease activity. Evaluate the association of serum P-gp levels and SLE with disease activity despite treatment. A cross-sectional study was conducted on 93 female SLE patients, all receiving glucocorticoids at stable doses for the previous 6 months before to baseline. SLE patients were classified into two groups: (a) patients with active disease [SLE disease activity index (SLEDAI) ≥ 3] despite treatment, and (b) patients with inactive disease (SLEDAI < 3) after treatment. Forty-three healthy females comprised the control group. Serum P-gp, anti-DNA, and both anti-nucleosome antibody levels were measured using ELISA. Active-SLE patients despite treatment had higher P-gp levels compared with inactive-SLE after treatment (78.02 ng/mL ± 114.11 vs. 33.75 ng/mL ± 41.11; p = 0.018) or versus reference group subjects (30.56 ng/mL ± 28.92; p = 0.011). P-gp levels correlated with the scores of SLEDAI (r = 0.26; p = 0.01), Mexican-SLEDAI (MEX-SLEDAI) (r = 0.32; p = 0.002), SLICC/ACR damage index (r = 0.47; p < 0.001), and with prednisone doses (r = 0.33; p = 0.001). In the multivariate model, the high P-gp levels were associated with SLICC/ACR score (p = 0.001), and SLEDAI score (p = 0.014). Our findings support a relationship between serum P-gp levels and SLE with disease activity despite treatment, but it requires further validation in longitudinal studies.
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Membro 1 da Subfamília B de Cassetes de Ligação de ATP/sangue , Glucocorticoides/administração & dosagem , Imunossupressores/administração & dosagem , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/patologia , Soro/química , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Anticorpos Antinucleares/sangue , Estudos Transversais , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Pessoa de Meia-Idade , Índice de Gravidade de Doença , Voluntários , Adulto JovemRESUMO
Congenital myasthenic syndromes (CMS) are neuromuscular transmission disorders caused by mutations in genes encoding neuromuscular junction proteins. A 61-year-old female and her older sister showed bilateral ptosis, facial and proximal limb weakness, and scoliosis since childhood. Another female sibling had milder signs, while other family members were asymptomatic. Facial nerve repetitive stimulation in the proband showed decrement of muscle responses. Single fiber EMG revealed increased jitter and blocking. Muscle biopsy showed type 2-fiber atrophy, without tubular aggregates. Mutational analysis in the three affected siblings revealed two compound heterozygous mutations in DOK7: c.1457delC, that predicts p.Pro486Argfs*13 and truncates the protein C-terminal domain, and c.473G>A, that predicts p.Arg158Gln and disruption of the dok7-MuSK interaction in the phosphotyrosine binding (PTB) domain. Unaffected family members carried only one or neither mutation. Discussion: Two of the affected sisters showed marked improvement with salbutamol treatment, which illustrates the benefits of a correct diagnosis and treatment of DOK7-CMS.
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BACKGROUND: There is limited information about the factors related with the development of long-term permanent work disability (PWD) in rheumatoid arthritis (RA) treated with a combination of conventional synthetic disease-modifying antirheumatic drugs (cs-DMARDs). OBJECTIVE: The aim of this study was to evaluate incidence and factors associated with the development of PWD in RA treated with combination therapy using conventional synthetic cs-DMARDs. METHODS: We assessed in multivariate models the effect of clinical and demographic factors in the development of PWD in a long-term retrospective cohort of 180 workers with RA who were treated with a combination of cs-DMARDs. RESULTS: Incidence rates of PWD were 2.2% at 1 year, 7.7% at 5 years, 24.9% at 10 years, 34.9% at 15 years, and 45% at 20 years. In the adjusted Cox regression analysis, factors associated with PWD development were the first failure with combination of cs-DMARDs (hazard ratio [HR], 2.4; 95% confidence interval [CI], 1.05-5.46; P = 0.03), poor functioning at time of cohort onset (HR, 2.2; 95% CI, 1.05-4.70; P = 0.03), and requirement for joint replacement (HR, 3.3; 95% CI, 1.28-8.79; P = 0.01). CONCLUSIONS: Around 25% of workers with combination therapy with cs-DMARDs developed PWD in 10 years following the diagnosis of RA. Some factors increase the risk of disability. Permanent work disability generates a relevant society burden and increases health care costs. Therefore, indicators predicting failure of combination therapies with cs-DMARDs might provide clinicians of useful tools for modifying treatments avoiding the disease progression.
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Antirreumáticos , Artrite Reumatoide , Efeitos Psicossociais da Doença , Licença Médica/estatística & dados numéricos , Adulto , Antirreumáticos/classificação , Antirreumáticos/uso terapêutico , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/economia , Artrite Reumatoide/fisiopatologia , Avaliação da Deficiência , Quimioterapia Combinada/métodos , Feminino , Custos de Cuidados de Saúde , Humanos , Masculino , México , Pessoa de Meia-Idade , Prognóstico , Estatística como AssuntoRESUMO
The goal of the present study was to determine whether peptidylarginine deiminase PAD2 and PAD4 enzymes are present in Balb/c mouse salivary glands and whether they are able to citrullinate Ro and La ribonucleoproteins. Salivary glands from Balb/c mice were cultured in DMEM and supplemented with one of the following stimulants: ATP, LPS, TNF, IFNγ, or IL-6. A control group without stimulant was also evaluated. PAD2, PAD4, citrullinated peptides, Ro60, and La were detected by immunohistochemistry and double immunofluorescence. PAD2 and PAD4 mRNAs and protein expression were detected by qPCR and Western blot analysis. PAD activity was assessed using an antigen capture enzyme-linked immunosorbent assay. LPS, ATP, and TNF triggered PAD2 and PAD4 expression; in contrast, no expression was detected in the control group (p < 0.001). PAD transcription slightly increased in response to stimulation. Additionally, PAD2/4 activity modified the arginine residues of a reporter protein (fibrinogen) in vitro. PADs citrullinated Ro60 and La ribonucleoproteins in vivo. Molecular stimulants induced apoptosis in ductal cells and the externalization of Ro60 and La ribonucleoproteins onto apoptotic membranes. PAD enzymes citrullinate Ro and La ribonucleoproteins, and this experimental approach may facilitate our understanding of the role of posttranslational modifications in the pathophysiology of Sjögren's syndrome.
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Autoantígenos/metabolismo , Hidrolases/metabolismo , Desiminases de Arginina em Proteínas/metabolismo , Ribonucleoproteínas/metabolismo , Glândulas Salivares/fisiologia , Síndrome de Sjogren/metabolismo , Trifosfato de Adenosina/imunologia , Animais , Apoptose , Células Cultivadas , Citrulinação , Citocinas/metabolismo , Ativação Enzimática , Fibrinogênio/metabolismo , Regulação da Expressão Gênica , Humanos , Hidrolases/genética , Mediadores da Inflamação/metabolismo , Lipopolissacarídeos/imunologia , Camundongos , Camundongos Endogâmicos BALB C , Proteína-Arginina Desiminase do Tipo 2 , Proteína-Arginina Desiminase do Tipo 4 , Desiminases de Arginina em Proteínas/genética , Antígeno SS-BRESUMO
Si bien las mujeres rurales poseen mayor riesgo de morir por causas relacionadas con el embarazo, el parto y puerperio, los estudios que abordan el tema suelen prestar escasa atención a la variable 'ruralidad'. Se realizó un estudio comparativo de tres casos apoyado en un abordaje cualitativo orientado a identificar, describir y analizar las barreras de orden geográfico, económico y administrativo que limitan el acceso de mujeres rurales al sistema público de salud en el ámbito de la salud materna. Se seleccionaron tres territorios de diferentes provincias del norte argentino: el municipio de Goya (provincia de Corrientes), el municipio de Dos Arroyos (provincia de Misiones) y la comuna de Ranchillos (provincia de Tucumán). En cada caso se realizaron 15 entrevistas, en su mayoría a mujeres rurales y a profesionales que atienden en el ámbito de la salud materna. Las entrevistas fueron transcriptas y los textos categorizados a partir de ejes temáticos expresados en los objetivos de la investigación. Se concluye que existen importantes barreras de accesibilidad que articulan problemas de nivel geográfico, económico y administrativo en ámbitos rurales.
Abstract Despite rural women's increased risk of dying due to pregnancy, childbirth and puerperium related causes, investigations usually only pay scarce attention to the variable 'rurality'. Thus, we conducted a qualitative research comparing three case studies aiming to identify, describe and analyse geographical, economic and administrative barriers that limit the access of rural women to public maternal health care. Three territories located in different provinces in the northern region of Argentina were selected: the municipality of Goya (province of Corrientes), the municipality of Dos Arroyos (province of Misiones) and the commune of Ranchillos (province of Tucumán). Fifteen interviews were carried out in each case study, mainly with rural women and physicians that provide maternal health care to them. The interviews were typed and their text categorized using the topics expressed in the objectives of this research. We conclude that there are a set of interrelated geographical, economic and administrative barriers limiting maternal health care accessibility in rural areas.
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Humanos , Feminino , Bem-Estar Materno , Complicações do Trabalho de Parto , Localização Geográfica de Risco , Mortalidade Materna , População Rural , Saúde da Mulher , Serviços de Saúde Materna , Acessibilidade aos Serviços de Saúde , Pessoal de Saúde , Sistemas de SaúdeRESUMO
BACKGROUND: In eukaryotes, histone arginine methylation associates with both active and repressed chromatin states depending on the residues involved and the status of methylation. Even when the amino-terminus of Entamoeba histolytica histones diverge from metazoan sequences, these regions contain arginine residues that are potential targets for methylation. However, histone arginine methylation as well as the activity of arginine methyltransferases (PRMTs) has not been studied in this parasite. The aim of this work was to examine the dimethylation of arginine 3 of H4 histone (H4R3me2) and to identify the parasite PRMT that could be responsible for this modification (EhPRMT1). METHODS: To examine the presence of H4R3me2 in E histolytica, we performed Western blot and immunofluorescence assays on trophozoites using an antibody against this epigenetic mark. To recognize the PRMT1 enzyme of this parasite that possibly perform that modification, we first performed a phylogenetic analysis of E. histolytica and human PRMTs. RT-PCR assays were carried out to analyze the expression of the putative PRMT1 genes. One of these genes was cloned and expressed in Escherichia coli. The recombinant protein was tested by its recognition by an antibody against human PRMT1 and in its ability to form homodimers and to methylate commercial histones. RESULTS: The arginine 3 of human H4, which is subjected to post translational methylation, was aligned with the arginine 8 of E. histolytica H4, suggesting that this residue could be methylated. The recognition of an 18 kDa nuclear protein of E. histolytica by an antibody against H4R3me2 confirmed this assumption. We found that this parasite expresses three phylogenetic and structural proteins related to PRMT1. Antibodies against the human PRMT1 detected E. histolytica proteins in cytoplasm and nuclei and recognized a recombinant PRMT1 of this parasite. The recombinant protein was able to form homodimers and homotetramers and displayed methyltransferase activity on arginine 3 of chicken H4. CONCLUSION: All these results suggest that E. histolytica contains as a minimum one structural and functional protein ortholog to PRMT1, enzyme that potentially dimethylates H4R8. This modification may play an important role in the gene expression regulation of this microorganism.