RESUMO

Aim: Benznidazole (BNZ), a class-II drug, is the primary treatment for Chagas disease, but its low aqueous solubility presents challenges in formulation and efficacy. Nanosuspensions (NS) could potentially address these issues.Methods: BNZ-NS were prepared using a simple, organic solvents-free nano-milling approach. Physicochemical characterizations were conducted on both NS and lyophilized solid-state BNZ-nanocrystals (NC).Results: BNZ-NS exhibited particle size <500 nm, an acceptable polydispersity index (0.23), high Z-potential, and physical stability for at least 90 days. BNZ-NC showed tenfold higher solubility than pure BNZ. Dissolution assays revealed rapid BNZ-NS dissolution. BNZ-NC demonstrated biocompatibility on an eukaryotic cell and enhanced BNZ efficacy against trypomastigotes of Trypanosoma cruzi.Conclusion: BNZ-NS offers a promising alternative, overcoming limitations associated with BNZ for optimized pharmacotherapy.

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[Box: see text].

Assuntos

Doença de Chagas , Nanopartículas , Nitroimidazóis , Tamanho da Partícula , Solubilidade , Tripanossomicidas , Trypanosoma cruzi , Nitroimidazóis/química , Nitroimidazóis/administração & dosagem , Doença de Chagas/tratamento farmacológico , Trypanosoma cruzi/efeitos dos fármacos , Nanopartículas/química , Tripanossomicidas/administração & dosagem , Tripanossomicidas/química , Tripanossomicidas/farmacologia , Animais , Humanos , Suspensões , Estabilidade de Medicamentos , Química Farmacêutica/métodos , Solventes/química , Liofilização

RESUMO

New adjuvant strategies are needed to improve protein-based subunit vaccine immunogenicity. We examined the potential to use nanostructure of 6-O-ascorbyl palmitate to formulate ovalbumin (OVA) protein and an oligodeoxynucleotide (CpG-ODN) (OCC). In mice immunized with a single dose, OCC elicited an OVA-specific immune response superior to OVA/CpG-ODN solution (OC). Rheological studies demonstrated OCC's self-assembling viscoelastic properties. Biodistribution studies indicated that OCC prolonged OVA and CpG-ODN retention at injection site and lymph nodes, reducing systemic spread. Flow-cytometry assays demonstrated that OCC promoted OVA and CpG-ODN co-uptake by Ly6ChiCD11bhiCD11c+ monocytes. OCC and OC induced early IFN-γ in lymph nodes, but OCC led to higher concentration. Conversely, mice immunized with OC showed higher serum IFN-γ concentration compared to those immunized with OCC. In mice immunized with OCC, NK1.1+ cells were the IFN-γ major producers, and IFN-γ was essential for OVA-specific IgG2c switching. These findings illustrate how this nanostructure improves vaccine's response.

Assuntos

Nanoestruturas , Oligodesoxirribonucleotídeos , Ovalbumina , Vacinas de Subunidades Antigênicas , Animais , Nanoestruturas/química , Vacinas de Subunidades Antigênicas/imunologia , Vacinas de Subunidades Antigênicas/química , Vacinas de Subunidades Antigênicas/farmacocinética , Camundongos , Oligodesoxirribonucleotídeos/química , Oligodesoxirribonucleotídeos/farmacocinética , Ovalbumina/imunologia , Ovalbumina/química , Feminino , Camundongos Endogâmicos C57BL , Adjuvantes Imunológicos/química , Adjuvantes Imunológicos/farmacocinética , Interferon gama/metabolismo , Distribuição Tecidual , Ácido Ascórbico/análogos & derivados

RESUMO

Different efforts have been made to find better and less invasive methods for the diagnosis and prediction of oral cancer, such as the study of saliva as a source of biomarkers. The aim of this study was to perform a scoping review about salivary molecules that have been assessed as possible biomarkers for the diagnosis of oral squamous cell carcinoma (OSCC). A search was conducted using EBSCO, PubMed (MEDLINE), Scopus, and Web of Science. The research question was as follows: which molecules present in saliva have utility to be used as biomarkers for the early detection of oral cancer? Sixty-two studies were included. Over 100 molecules were assessed. Most of the markers were oriented towards the early diagnosis of OSCC and were classified based on their ability for detecting OSCC and oral potentially malignant disorders (OPMDs), OSCC outcome prediction, and the prediction of the malignant transformation of OPMDs. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 were the most studied, with almost all studies reporting high sensitivity and specificity values. TNF-α, IL-1ß, IL-6 IL-8, LDH, and MMP-9 are the most promising salivary biomarkers. However, more studies with larger cohorts are needed before translating the use of these biomarkers to clinical settings.

Assuntos

Carcinoma de Células Escamosas , Neoplasias de Cabeça e Pescoço , Neoplasias Bucais , Lesões Pré-Cancerosas , Humanos , Neoplasias Bucais/patologia , Metaloproteinase 9 da Matriz , Biomarcadores Tumorais , Interleucina-8 , Fator de Necrose Tumoral alfa , Interleucina-6 , Carcinoma de Células Escamosas/patologia , Biomarcadores , Carcinoma de Células Escamosas de Cabeça e Pescoço , Saliva , Interleucina-1beta

RESUMO

This work examines cellular immunity against SARS-CoV-2 in patients from Córdoba, Argentina, during two major waves characterized by different circulating viral variants and different social behavior. Using flow cytometry, we evaluated the main lymphocyte populations of peripheral blood from hospitalized patients with moderate and severe COVID-19 disease. Our results show disturbances in the cellular immune compartment, as previously reported in different cohorts worldwide. We observed an increased frequency of B cells and a significant decrease in the frequency of CD3+ T cells in COVID-19 patients compared to healthy donors (HD). We also found a reduction in Tregs, which was more pronounced in severe patients. During the first wave, the frequency of GZMB, CD107a, CD39, and PD-1-expressing conventional CD4+ T (T conv) cells was significantly higher in moderate and severe patients than in HD. During the second wave, only the GZMB+ T conv cells of moderate and severe patients increased significantly. In addition, these patients showed a decreased frequency in IL-2-producing T conv cells. Interestingly, we identified two subsets of circulating CD8+ T cells with low and high CD8 surface expression in both HD and COVID-19 patients. While the percentages of CD8hi and CD8lo T cells within the CD8+ population in HD are similar, a significant increase was observed in CD8lo T cell frequency in COVID-19 patients. CD8lo T cell populations from HD as well as from SARS-CoV-2 infected patients exhibited lower frequencies of the effector cytokine-producing cells, TNF, IL-2, and IFN-γ, than CD8hi T cells. Interestingly, the frequency of CD8lo T cells increased with disease severity, suggesting that this parameter could be a potential marker for disease progression. Indeed, the CD8hi/CD8lo index helped to significantly improve the patient's clinical stratification and disease outcome prediction. Our data support the addition of, at least, a CD8hi/CD8lo index into the panel of biomarkers commonly used in clinical labs, since its determination may be a useful tool with impact on the therapeutic management of the patients.

Assuntos

COVID-19 , Humanos , Linfócitos T CD8-Positivos , Interleucina-2/metabolismo , SARS-CoV-2 , Subpopulações de Linfócitos , Gravidade do Paciente

RESUMO

OBJECTIVE: Telomere length (TL) attrition is related to chronic disease risk. However, less is known on whether TL predicts infectious outcomes, especially in childhood. We examined whether leukocyte TL (LTL) was associated with subsequent infectious morbidity in schoolchildren. METHODS: We assessed LTL in 717 Colombian children 5-12 years-old at the beginning of a school year and followed them through the year for daily occurrence of common infection symptoms and doctor visits. We estimated adjusted incidence rate ratios (IRR) with 95% confidence intervals (CI) of gastrointestinal and respiratory syndromes for quartiles of standardized LTL Z score and per unit LTL Z score. RESULTS: A longer LTL was associated with increased incidence of all infectious morbidity syndromes considered. Adjusted IRR (95% CI) per unit LTL Z score were 1.55 (1.20, 2.00) for diarrhea with vomiting, 1.34 (1.13, 1.60) for cough with fever, 1.70 (1.28, 2.28) for ear infection, and 1.66 (1.36, 2.02) for doctor visits with symptoms. CONCLUSIONS: Longer LTL is related to increased incidence of common infectious morbidities in middle childhood.

RESUMO

BACKGROUND: The efficacy of cholecalciferol (vitamin D3) food fortification in low- and middle-income countries near the Equator is unknown. OBJECTIVES: We examined the effects of providing cholecalciferol-fortified skim milk to adolescents and their mothers on serum total 25(OH)D, free 25(OH)D, and vitamin D-binding protein (DBP) concentrations in a randomized controlled trial. METHODS: We randomly assigned 80 Colombian families each with a child aged 12-14.5 y and their mother 1 L of skim milk daily, either fortified with 2400 IU (60 µg) cholecalciferol or unfortified, for 6 wk. We prescribed 500 mL of milk daily to adolescents; mothers consumed the remainder ad libitum. We estimated intent-to-treat effects as the between-arm difference in the change in serum total and free 25(OH)D and DBP concentrations from baseline to the end of follow-up. Secondary analyses included stratification by baseline characteristics and per-protocol comparisons. RESULTS: Among adolescents, fortification effects (95% CI) on serum total 25(OH)D, free 25(OH)D, and DBP concentrations were 5.4 nmol/L (2.1, 8.8 nmol/L), 0.6 pmol/L (-0.2, 1.4 pmol/L), and -416 nmol/L (-944, 112 nmol/L), respectively. Effects on total 25(OH)D were stronger in adolescents with lower DBP concentrations, darker skin, less sunlight exposure, and higher compliance than in their respective counterparts. Fortification increased free 25(OH)D concentrations in high compliers. Among mothers, the effects (95% CI) on total 25(OH)D and DBP concentrations were 4.0 nmol/L (0.6, 7.5 nmol/L) and -128 nmol/L (-637, 381 nmol/L), respectively. There were no adverse events. CONCLUSIONS: Provision of cholecalciferol-fortified skim milk increases serum total 25(OH)D concentrations in Colombian adolescents and adult women.

Assuntos

Colecalciferol , Deficiência de Vitamina D , Adulto , Criança , Feminino , Adolescente , Humanos , Animais , Colecalciferol/farmacologia , Leite , Colômbia , Alimentos Fortificados , Vitamina D , Calcifediol , Suplementos Nutricionais , Deficiência de Vitamina D/prevenção & controle , Método Duplo-Cego

RESUMO

Background: COVID-19 severity has been linked to an increased production of inflammatory mediators called "cytokine storm". Available data is mainly restricted to the first international outbreak and reports highly variable results. This study compares demographic and clinical features of patients with COVID-19 from Córdoba, Argentina, during the first two waves of the pandemic and analyzes association between comorbidities and disease outcome with the "cytokine storm", offering added value to the field. Methods: We investigated serum concentration of thirteen soluble mediators, including cytokines and chemokines, in hospitalized patients with moderate and severe COVID-19, without previous rheumatic and autoimmune diseases, from the central region of Argentina during the first and second infection waves. Samples from healthy controls were also assayed. Clinical and biochemical parameters were collected. Results: Comparison between the two first COVID-19 waves in Argentina highlighted that patients recruited during the second wave were younger and showed less concurrent comorbidities than those from the first outbreak. We also recognized particularities in the signatures of systemic cytokines and chemokines in patients from both infection waves. We determined that concurrent pre-existing comorbidities did not have contribution to serum concentration of systemic cytokines and chemokines in COVID-19 patients. We also identified immunological and biochemical parameters associated to inflammation which can be used as prognostic markers. Thus, IL-6 concentration, C reactive protein level and platelet count allowed to discriminate between death and discharge in patients hospitalized with severe COVID-19 only during the first but not the second wave. Conclusions: Our data provide information that deepens our understanding of COVID-19 pathogenesis linking demographic features of a COVID-19 cohort with cytokines and chemokines systemic concentration, presence of comorbidities and different disease outcomes. Altogether, our findings provide information not only at local level by delineating inflammatory/anti-inflammatory response of patients but also at international level addressing the impact of comorbidities and the infection wave in the variability of cytokine and chemokine production upon SARS-CoV-2 infection.

Assuntos

COVID-19 , Humanos , Citocinas/metabolismo , SARS-CoV-2/metabolismo , Argentina , Quimiocinas , Síndrome da Liberação de Citocina , Pandemias

RESUMO

Leukocyte telomere length (LTL) is associated with obesity and may be involved in its aetiology, but few studies have focused on children and most have been cross-sectional. We assessed the relation of LTL with adiposity development in a prospective study of Colombian children. We quantified LTL at enrollment in 722 children aged 5-12 years and measured anthropometry annually for a median 6 years. Using mixed effects models, we estimated changes in adiposity measures including BMI and waist circumference (WC)-for-age z-scores in relation to baseline LTL z-score. In girls, longer LTL was linearly related to a lower increase in WC z-score from age 6 to 16 years. Every 1 SD LTL was associated with an adjusted 0.13 units lower increase in WC (95% CI: -0.23, -0.03; p = 0.01). In conclusion, longer LTL among girls in middle childhood is associated with smaller increases in WC, an indicator of abdominal adiposity.

Assuntos

Adiposidade , Obesidade , Telômero , Adiposidade/genética , Adolescente , Criança , Pré-Escolar , Colômbia , Estudos Transversais , Feminino , Humanos , Leucócitos , Masculino , Modelos Biológicos , Obesidade/genética , Estudos Prospectivos , Fatores Sexuais , Telômero/genética , Circunferência da Cintura/genética

RESUMO

Introduction: Half of the Colombian households experience some degree of food insecurity. Food insecurity has been associated with malnutrition, which could result in micronutrient deficiencies in children; however, the evidence is not conclusive. Objective: To examine the associations between food insecurity and blood concentrations of hemoglobin, ferritin, vitamin A, vitamin B12, folate, and zinc in school-age children from Bogotá, Colombia. Materials and methods: We conducted a cross-sectional study among 2,660 children aged 5-12 from Bogotá's public schools. We assessed their household food insecurity level with the Spanish version of the Household Food Security Survey Module (HFSSM), a validated scale, and quantified blood biomarkers of iron, vitamin A, folate, vitamin B12, and zinc status. We examined the associations between food insecurity, severe hunger, and micronutrient status biomarkers using propensity scores. Results: Three-quarters of households had some degree of food insecurity and 12 % had food insecurity and severe hunger. Prevalence of marginal vitamin B12 status and vitamin A and zinc deficiencies were, respectively, 17%, 14%, and 1.4%. Compared with children from households without severe hunger, those exposed to it had lower adjusted mean concentrations of vitamin A, vitamin B12, and folate, but these differences were not statistically significant. Conclusion: Food insecurity with severe hunger was not associated with micronutrient status biomarkers in Colombian school-age children. The HFSSM may adequately measure hardship in food acquisition due to lack of resources, but it does not yield an index that is associated with micronutrient status biomarkers.

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Introducción. La mitad de los hogares colombianos padecen inseguridad alimentaria. Esta se ha asociado con malnutrición, la que, según algunos estudios, podría reflejarse en un déficit de micronutrientes en los niños, aunque los datos no son concluyentes. Objetivo. Establecer la asociación entre la inseguridad alimentaria y los niveles de hemoglobina, hierro, vitamina A, vitamina B12, folato y cinc, en escolares de Bogotá. Materiales y métodos. Se hizo un estudio de corte transversal. Se aplicó la escala del Household Food Security Survey Module (HFSSM) validada en español en una muestra de hogares de escolares de Bogotá, para establecer la prevalencia de inseguridad alimentaria. Utilizando el índice de propensión, se exploró la asociación entre la inseguridad alimentaria, el hambre grave y las concentraciones de hierro, vitamina A, folato, vitamina B12 y cinc, estimadas en muestras de suero provenientes de los escolares. Resultados. Se incluyeron 2.660 escolares. En el 76 % de los hogares había inseguridad alimentaria, de los cuales el 11,6 % se clasificaba como inseguridad alimentaria con hambre grave. La deficiencia marginal de vitamina B12 fue del 17 % y las de vitamina A y cinc, de 14 y 1,4 %, respectivamente. Aunque se encontraron niveles promedios más bajos de vitamina A (-0,009 µmol/L; IC95% -0,13 - 0,03 µmol/L), vitamina B12 (-19,57 pmol/L; IC95% -72,55 - 29,94 pmol/L) y folato (-9,25 nmol/L; IC95% -29,55 - 18,66 nmol/L) en los niños expuestos a inseguridad alimentaria con hambre grave, al compararlos con los de los no expuestos, las diferencias no fueron estadísticamente significativas. Conclusiones. La inseguridad alimentaria con hambre grave no se asoció los valores de micronutrientes o sus deficiencias en los escolares. La escala del HFSSM mide adecuadamente la dificultad en la adquisición de alimentos por falta de recursos, pero no permite establecer una asociación con las concentraciones de micronutrientes.

Assuntos

Insegurança Alimentar , Micronutrientes , Biomarcadores , Criança , Colômbia/epidemiologia , Estudos Transversais , Abastecimento de Alimentos , Humanos , Estado Nutricional , Instituições Acadêmicas

RESUMO

Resumen Introducción. La mitad de los hogares colombianos padecen inseguridad alimentaria. Esta se ha asociado con malnutrición, la que, según algunos estudios, podría reflejarse en un déficit de micronutrientes en los niños, aunque los datos no son concluyentes. Objetivo. Establecer la asociación entre la inseguridad alimentaria y los niveles de hemoglobina, hierro, vitamina A, vitamina B12, folato y cinc, en escolares de Bogotá. Materiales y métodos. Se hizo un estudio de corte transversal. Se aplicó la escala del Household Food Security Survey Module (HFSSM) validada en español en una muestra de hogares de escolares de Bogotá, para establecer la prevalencia de inseguridad alimentaria. Utilizando el índice de propensión, se exploró la asociación entre la inseguridad alimentaria, el hambre grave y las concentraciones de hierro, vitamina A, folato, vitamina B12 y cinc, estimadas en muestras de suero provenientes de los escolares. Resultados. Se incluyeron 2.660 escolares. En el 76 % de los hogares había inseguridad alimentaria, de los cuales el 11,6 % se clasificaba como inseguridad alimentaria con hambre grave. La deficiencia marginal de vitamina B12 fue del 17 % y las de vitamina A y cinc, de 14 y 1,4 %, respectivamente. Aunque se encontraron niveles promedios más bajos de vitamina A (-0,009 µmol/L; IC95% -0,13 - 0,03 µmol/L), vitamina B12 (-19,57 pmol/L; IC95% -72,55 - 29,94 pmol/L) y folato (-9,25 nmol/L; IC95% -29,55 - 18,66 nmol/L) en los niños expuestos a inseguridad alimentaria con hambre grave, al compararlos con los de los no expuestos, las diferencias no fueron estadísticamente significativas. Conclusiones. La inseguridad alimentaria con hambre grave no se asoció los valores de micronutrientes o sus deficiencias en los escolares. La escala del HFSSM mide adecuadamente la dificultad en la adquisición de alimentos por falta de recursos, pero no permite establecer una asociación con las concentraciones de micronutrientes.

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Abstract Introduction: Half of the Colombian households experience some degree of food insecurity. Food insecurity has been associated with malnutrition, which could result in micronutrient deficiencies in children; however, the evidence is not conclusive. Objective: To examine the associations between food insecurity and blood concentrations of hemoglobin, ferritin, vitamin A, vitamin B12, folate, and zinc in school-age children from Bogotá, Colombia. Materials and methods: We conducted a cross-sectional study among 2,660 children aged 5-12 from Bogotá's public schools. We assessed their household food insecurity level with the Spanish version of the Household Food Security Survey Module (HFSSM), a validated scale, and quantified blood biomarkers of iron, vitamin A, folate, vitamin B12, and zinc status. We examined the associations between food insecurity, severe hunger, and micronutrient status biomarkers using propensity scores. Results: Three-quarters of households had some degree of food insecurity and 12 % had food insecurity and severe hunger. Prevalence of marginal vitamin B12 status and vitamin A and zinc deficiencies were, respectively, 17%, 14%, and 1.4%. Compared with children from households without severe hunger, those exposed to it had lower adjusted mean concentrations of vitamin A, vitamin B12, and folate, but these differences were not statistically significant. Conclusion: Food insecurity with severe hunger was not associated with micronutrient status biomarkers in Colombian school-age children. The HFSSM may adequately measure hardship in food acquisition due to lack of resources, but it does not yield an index that is associated with micronutrient status biomarkers.

Assuntos

Criança , Micronutrientes , Abastecimento de Alimentos , Estudantes , Colômbia

RESUMO

BACKGROUND: Xerostomia or dry mouth sensation corresponds to a common clinical problem that can significantly impair the oral health related quality of life (OHRQoL). Currently, there is a large variety of local agents available for the treatment of xerostomia, but there is a lack robust evidence supporting the use of one treatment over another. We aimed to compare the effectiveness of a 1% malic acid salivary stimulant spray with a 1.33% betaine-based saliva substitute mouthwash in the improvement of xerostomia. MATERIAL AND METHODS: Fifty-one participants with drug induced or idiopathic xerostomia were randomly allocated into three groups, two intervention and one control group (placebo). OHRQoL and severity of xerostomia were assessed with the OHIP-14sp questionnaire and a visual analogue scale (VAS) respectively. Stimulated and non-stimulated salivary flow rates before and after treatments were also measured. RESULTS: All three groups reported a significantly improvement in the dry mouth sensation and non-stimulated salivary flow rates, but only the malic acid spray and the betaine-based mouthwash significantly improved the OHRQoL. There were no significant differences between both intervention groups. CONCLUSIONS: This study provides evidence that both tested agents are comparable in improving the dry mouth sensation and OHRQoL of patients with drug induced and idiopathic xerostomia. Key words:Xerostomia, dry mouth, malic acid, betaine, oral-health related quality of life.

RESUMO

OBJECTIVE: The aim of this study was to report the clinicopathologic features of 62 cases of central odontogenic fibroma (COdF). STUDY DESIGN: Clinical and radiographic data were collected from the records of 13 oral pathology laboratories. All cases were microscopically reviewed, considering the current World Health Organization classification of tumors and were classified according to histopathologic features. RESULTS: There were 43 females and 19 males (average age 33.9 years; range 8-63 years). Clinically, COdF lesions appeared as asymptomatic swellings, occurring similarly in the maxilla (n = 33) and the mandible (n = 29); 9 cases exhibited palatal depression. Imaging revealed well-defined, interradicular unilocular (n = 27), and multilocular (n = 12) radiolucencies, with displacement of contiguous teeth (55%) and root resorption (46.4%). Microscopically, classic features of epithelial-rich (n = 33), amyloid (n = 10), associated giant cell lesion (n = 7), ossifying (n = 6), epithelial-poor (n = 3), and granular cell (n = 3) variants were seen. Langerhans cells were highlighted by CD1a staining in 17 cases. Most patients underwent conservative surgical treatments, with 1 patient experiencing recurrence. CONCLUSIONS: To the best of our knowledge, this study represents the largest clinicopathologic study of COdF. Most cases appeared as locally aggressive lesions located in tooth-bearing areas in middle-aged women. Inactive-appearing odontogenic epithelium is usually observed within a fibrous/fibromyxoid stroma, occasionally exhibiting amyloid deposits, multinucleated giant cells, or granular cells.

Assuntos

Fibroma , Tumores Odontogênicos , Adolescente , Adulto , Criança , Feminino , Fibroma/diagnóstico por imagem , Fibroma/cirurgia , Humanos , Masculino , Mandíbula , Maxila , Pessoa de Meia-Idade , Recidiva Local de Neoplasia , Tumores Odontogênicos/diagnóstico por imagem , Tumores Odontogênicos/cirurgia , Adulto Jovem

RESUMO

Purpose: To perform a comprehensive and systematic critical appraisal of the genetic alterations reported to be present in adenomatoid odontogenic tumor (AOT) compared to ameloblastoma (AM), to aid in the understanding in their development and different behavior. Methods: An electronic search was conducted in PubMed, Scopus, and Web of Science during March 2021. Eligibility criteria included publications on humans which included genetic analysis of AOT or AM. Results: A total of 43 articles reporting 59 AOTs and 680 AMs were included. Different genomic techniques were used, including whole-exome sequencing, direct sequencing, targeted next-generation sequencing panels and TaqMan allele-specific qPCR. Somatic mutations affecting KRAS were identified in 75.9% of all AOTs, mainly G12V; whereas a 71% of the AMs harbored BRAF mutations, mainly V600E. Conclusions: The available genetic data reports that AOTs and AM harbor somatic mutations in well-known oncogenes, being KRAS G12V/R and BRAFV600E mutations the most common, respectively. The relatively high frequency of ameloblastoma compared to other odontogenic tumors, such as AOT, has facilitated the performance of different sequencing techniques, allowing the discovery of different mutational signatures. On the contrary, the low frequency of AOTs is an important limitation for this. The number of studies that have a assessed the genetic landscape of AOT is still very limited, not providing enough evidence to draw a conclusion regarding the relationship between the genomic alterations and its clinical behavior. Thus, the presence of other mutational signatures with clinical impact, co-occurring with background KRAS mutations or in wild-type KRAS cases, cannot be ruled out. Since BRAF and RAS are in the same MAPK pathway, it is interesting that ameloblastomas, frequently associated with BRAFV600E mutation have aggressive clinical behavior, but in contrast, AOTs, frequently associated with RAS mutations have indolent behavior. Functional studies might be required to solve this question.

RESUMO

PURPOSE: Leukocyte telomere length (LTL) is a biomarker of inflammation and oxidative stress that predicts chronic disease risk. Nutritional factors are related to LTL in adulthood, but these associations are not well characterized in children. We examined whether micronutrient status biomarkers were associated with LTL in school-age children. METHODS: We conducted a cross-sectional study of 330 boys and 393 girls aged 5-12 years from Bogotá, Colombia. We quantified blood concentrations of hemoglobin, ferritin, zinc, vitamin A, folate, and vitamin B-12; and measured LTL using qPCR in DNA extracted from buffy coat. We estimated mean differences in LTL by quartiles of micronutrient status biomarkers and categories of relevant sociodemographic and anthropometric covariates with the use of linear regression. RESULTS: In girls, plasma vitamin B-12 was positively associated with LTL (adjusted LTL difference between extreme vitamin B-12 quartiles = 0.11; P, trend = 0.02). LTL was also positively associated with birth order in girls (P, trend = 0.02). In boys, LTL was not related to the micronutrient status biomarkers but, unexpectedly, it was positively associated with birth weight (P = 0.02), height-for-age Z score (P, trend = 0.01), and serum C-reactive protein (P, trend = 0.01). CONCLUSIONS: LTL is associated with vitamin B-12 status among girls. LTL is also associated with birth weight, height, and C-reactive protein in boys.

Assuntos

Leucócitos , Micronutrientes/sangue , Inquéritos Nutricionais/métodos , Inquéritos Nutricionais/estatística & dados numéricos , Telômero , Biomarcadores/sangue , Criança , Pré-Escolar , Colômbia , Estudos Transversais , Feminino , Humanos , Masculino , Fatores Sexuais

RESUMO

There is a need for new vaccine adjuvant strategies that offer both vigorous antibody and T-cell mediated protection to combat difficult intracellular pathogens and cancer. To this aim, we formulated class-B synthetic oligodeoxynucleotide containing unmethylated cytosine-guanine motifs (CpG-ODN) with a nanostructure (Coa-ASC16 or coagel) formed by self-assembly of 6-0-ascorbyl palmitate ester. Our previous results demonstrated that mice immunized with ovalbumin (OVA) and CpG-ODN formulated with Coa-ASC16 (OVA/CpG-ODN/Coa-ASC16) elicited strong antibodies (IgG1 and IgG2a) and Th1/Th17 cellular responses without toxic systemic effects. These responses were superior to those induced by a solution of OVA with CpG-ODN or OVA/CpG-ODN formulated with aluminum salts. In this study, we investigated the capacity of this adjuvant strategy (CpG-ODN/Coa-ASC16) to elicit CD8+ T-cell response and some of the underlying cellular and molecular mechanisms involved in adaptive response. We also analyzed whether this adjuvant strategy allows a switch from an immunization scheme of three-doses to one of single-dose. Our results demonstrated that vaccination with OVA/CpG-ODN/Coa-ASC16 elicited an antigen-specific long-lasting humoral response and importantly-high quality CD8+ T-cell immunity with a single-dose immunization. Moreover, Coa-ASC16 promoted co-uptake of OVA and CpG-ODN by dendritic cells. The CD8+ T-cell response induced by OVA/CpG-ODN/Coa-ASC16 was dependent of type I interferons and independent of CD4+ T-cells, and showed polyfunctionality and efficiency against an intracellular pathogen. Furthermore, the cellular and humoral responses elicited by the nanostructured formulation were IL-6-independent. This system provides a simple and inexpensive adjuvant strategy with great potential for future rationally designed vaccines.

Assuntos

Antígenos/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T CD8-Positivos/imunologia , Linfócitos T CD8-Positivos/metabolismo , Interferon Tipo I/metabolismo , Oligodesoxirribonucleotídeos/imunologia , Adjuvantes Imunológicos , Animais , Antígenos/química , Citocinas/metabolismo , Humanos , Imunidade Humoral , Camundongos , Camundongos Knockout , Nanoestruturas , Oligodesoxirribonucleotídeos/química , Ovalbumina/imunologia , Transdução de Sinais , Subpopulações de Linfócitos T/imunologia , Subpopulações de Linfócitos T/metabolismo

RESUMO

BACKGROUND: Iron deficiency (ID) in infancy is related to subsequent behavior problems. The effects of micronutrient status in middle childhood are uncertain. OBJECTIVE: The aim of the study was to examine the associations of micronutrient status biomarkers in middle childhood with externalizing and internalizing behavior problems in adolescence. METHODS: We assessed whether ID (ferritin <15 µg/L), anemia (hemoglobin <12.7 g/dL), or blood concentrations of zinc, vitamins A and B-12, and folate at ages 5-12 y were associated with externalizing or internalizing behavior problems in adolescence in 1042 schoolchildren from Bogotá, Colombia. Behavior problems were assessed with the Youth Self-Report questionnaire after a median 6.2 y of follow-up. Mean problem score differences with 95% CIs were estimated between categories of micronutrient status biomarkers with the use of multivariable linear regression. RESULTS: Mean ± SD externalizing and internalizing problems scores were 52.6 ± 9.6 and 53.8 ± 9.9, respectively. Among boys, middle-childhood ID, anemia, and low plasma vitamin B-12 were associated with 5.9 (95% CI: 1.0, 10.7), 6.6 (95% CI: 1.9, 11.3), and 2.7 (95% CI: 0.4, 4.9) units higher mean externalizing problems scores in adolescence, respectively-after adjustment for baseline age, time spent watching television or playing video games, mother's height, and socioeconomic status. Also in boys, ID was related to an adjusted 6.4 (95% CI: 1.2, 11.6) units higher mean internalizing problems score. There were no associations among girls. Other micronutrient status biomarkers were not associated with behavior problems. CONCLUSIONS: ID, anemia, and low vitamin B-12 in middle childhood are related to behavior problems in adolescent boys.This study was registered at clinicaltrials.gov as NCT03297970.

Assuntos

Comportamento do Adolescente/fisiologia , Anemia/psicologia , Deficiências de Ferro , Transtornos Mentais/sangue , Transtornos Mentais/etiologia , Deficiência de Vitamina B 12/psicologia , Adolescente , Comportamento do Adolescente/psicologia , Anemia/sangue , Biomarcadores/sangue , Criança , Colômbia , Feminino , Ferritinas/sangue , Ácido Fólico/sangue , Humanos , Ferro/sangue , Modelos Lineares , Masculino , Transtornos Mentais/psicologia , Micronutrientes/sangue , Estado Nutricional , Autorrelato , Estudantes/psicologia , Vitamina A/sangue , Vitamina B 12/sangue , Zinco/sangue

RESUMO

OBJECTIVE: To determine if processed and ultra-processed foods consumed by children in Colombia are associated with lower-quality nutrition profiles than less processed foods. DESIGN: We obtained information on sociodemographic and anthropometric variables and dietary information through dietary records and 24 h recalls from a convenience sample of the Bogotá School Children Cohort. Foods were classified into three categories: (i) unprocessed and minimally processed foods, (ii) processed culinary ingredients and (iii) processed and ultra-processed foods. We also examined the combination of unprocessed foods and processed culinary ingredients. SETTING: Representative sample of children from low- to middle-income families in Bogotá, Colombia. SUBJECTS: Children aged 5-12 years in 2011 Bogotá School Children Cohort. RESULTS: We found that processed and ultra-processed foods are of lower dietary quality in general. Nutrients that were lower in processed and ultra-processed foods following adjustment for total energy intake included: n-3 PUFA, vitamins A, B12, C and E, Ca and Zn. Nutrients that were higher in energy-adjusted processed and ultra-processed foods compared with unprocessed foods included: Na, sugar and trans-fatty acids, although we also found that some healthy nutrients, including folate and Fe, were higher in processed and ultra-processed foods compared with unprocessed and minimally processed foods. CONCLUSIONS: Processed and ultra-processed foods generally have unhealthy nutrition profiles. Our findings suggest the categorization of foods based on processing characteristics is promising for understanding the influence of food processing on children's dietary quality. More studies accounting for the type and degree of food processing are needed.

Assuntos

Dieta , Fast Foods , Valor Nutritivo , Índice de Massa Corporal , Criança , Pré-Escolar , Estudos de Coortes , Colômbia , Gorduras na Dieta/administração & dosagem , Fibras na Dieta/administração & dosagem , Proteínas Alimentares/administração & dosagem , Características da Família , Ácidos Graxos/administração & dosagem , Feminino , Manipulação de Alimentos , Humanos , Masculino , Micronutrientes/administração & dosagem , Mães , Fatores Socioeconômicos

RESUMO

Childhood intake of animal foods is associated with age at first menstrual period (menarche). It is unknown whether the micronutrients present in these foods could explain this association. Our objective was to investigate the associations of micronutrient status biomarkers in middle childhood with age at menarche. We quantified circulating Hb, ferritin, mean corpuscular volume, Zn, vitamin B12, erythrocyte folate and retinol in 1464 pre-menarcheal girls aged 5-12 years in Bogotá, Colombia, and followed them for a median 5·7 years for the occurrence and date of menarche. We estimated median age at menarche and hazard ratios (HR) with 95 % CI by levels of each biomarker with use of Kaplan-Meier survival probabilities and Cox regression, respectively. Median age at menarche was 12·4 years. Middle childhood Hb was inversely related to age at menarche whereas plasma ferritin was positively associated with this outcome in a linear manner. HR of menarche for every 1 sd of Hb (11 g/l) and ferritin (23·2 µg/l) were 1·11 (95 % CI 1·04, 1·18; P=0·001) and 0·94 (95 % CI 0·88, 0·99; P=0·02), respectively, after adjustment for baseline age, C-reactive protein concentration, maternal age at menarche and parity and socioeconomic status. The association with ferritin was stronger in girls aged 9-10 years at baseline. Additional adjustment for baseline height- and BMI-for-age did not change the results. We conclude that higher Fe status in middle childhood is related to later age at menarche whereas Hb concentrations are inversely associated with age at onset of menses.

Assuntos

Menarca/sangue , Micronutrientes/sangue , Biomarcadores/sangue , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , Criança , Colômbia/epidemiologia , Eritrócitos/metabolismo , Feminino , Ferritinas/sangue , Ácido Fólico/sangue , Seguimentos , Hemoglobinas/metabolismo , Humanos , Estudos Longitudinais , Micronutrientes/deficiência , Estado Nutricional , Modelos de Riscos Proporcionais , Fatores Socioeconômicos , Vitamina A/sangue , Vitamina B 12/sangue , Zinco/sangue

RESUMO

Morphea, or localized scleroderma, is an inflammatory disease that leads to sclerosis of the skin and underlying tissues due to excessive collagen deposition. Oral involvement is unusual and it may produce white linear fibrotic areas with a scar-like appearance, atrophy of tongue papillae, gingival recession and alveolar bone resorption. We report a case of a 13-year-old girl who consulted for progressive recession on the attached gingiva of her upper left incisors. She also presented a hypopigmented line on the left side skin of her upper lip, which continued through the vermilion and the lip mucosa, including the gingiva of the affected teeth. Clinical examination, blood tests, computerized axial tomography, echo-Doppler ultrasound and histopathological evaluation confirmed the diagnosis of morphea. Treatment with methotrexate and systemic corticosteroids was conducted. After 24 months, no other lesions appeared. No adverse side effects have been reported so far. Key words:Localized scleroderma, oral morphea, linear scleroderma, oral involvement, intraoral lesions.