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1.
Ann Hematol ; 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33409623

RESUMO

Among the different biomarkers predicting response in chronic lymphocytic leukemia (CLL), the most influential parameters are the mutational status of the IGHV genes and the presence of TP53 gene disruptions. Nevertheless, these important assessments are not readily available in most centers dealing with CLL patients. To provide this molecular testing across the country, the Spanish Cooperative Group on CLL (GELLC) established a network of four analytical reference centers. A total of 2153 samples from 256 centers were analyzed over a period of 30 months. In 9% of the patients, we found pathological mutations in the TP53 gene, whereas 48.96% were classified as IGHV unmutated. Results of the satisfaction survey of the program showed a Net Promoter Score of 85.15. Building a national network for molecular testing in CLL allowed the CLL population a broad access to complex biomarkers analysis that should translate into a more accurate and informed therapeutic decision-making.

2.
Int Orthop ; 2021 Jan 14.
Artigo em Inglês | MEDLINE | ID: mdl-33443596

RESUMO

PURPOSE: To evaluate prospectively the functional outcomes of tibiotalocalcaneal (TTC) arthrodesis with a contemporary retrograde intramedullary nail after a minimum follow-up of five years. METHODS: Sixty-one patients with a mean age of 51.3 (range, 18-79) years were included in the study. Functional outcome was assessed using the American Orthopaedic Foot and Ankle Society Ankle Hindfoot score (AOFAS), Short-Form 12-item Health Survey (SF12), and visual analog scales (VAS) for both pain and patient satisfaction. Radiographic evaluation was also assessed. RESULTS: The mean post-operative follow-up was 6.8 (range, 5-8) years. Mean AOFAS and SF12 scores significantly improved at the final follow-up (p < 0.001), and the mean VAS for pain significantly decreased (p < 0.001). At the final follow-up, only five (8.2%) patients gave an AOFAS score of less than 50, 52 (85.2%) were satisfied with their surgery, and 32 (52.4%) returned to their employment. There were two tibiotalar joint nonunions that required re-operations, and another patient required re-operation for screw removal. There was no deep infection. CONCLUSIONS: The retrograde intramedullary nail provided a stable TTC arthrodesis with a high union rate, acceptable functional outcomes, and a low severe complication rate. This procedure appears to offer a reliable salvage option for TTC arthrodesis in patients with severe ankle and hindfoot degeneration.

4.
BMJ Open Respir Res ; 7(1)2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-33268340

RESUMO

BACKGROUND: Global Asthma Network (GAN) was established in 2012 as a development to the International Study of Asthma and Allergies in Childhood to improve asthma care globally. OBJECTIVE: To survey asthma, allergic rhinitis and atopic dermatitis in primary and secondary school children and to investigate and evaluate its prevalence, severity, management and risk factors in Mexico. METHODS: GAN Phase I is a cross-sectional, multicentre survey carried out in 15 centres corresponding to 14 Mexican cities throughout 2016-2019 using the validated Spanish language version of the GAN Phase I questionnaires. The questionnaires were completed by parents of 6-7-year-old primary school pupils (school children) and by 13-14-year-old adolescents. RESULTS: A total of 35 780 school children and 41 399 adolescents participated. Wheezing ever prevalence was 26.2% (95% CI 25.8% to 26.7%) in school children and 23.9% (95% CI 23.4% to 24.3%) in adolescents. The corresponding frequencies for current wheeze were 10.2% (95% CI 9.9% to 10.5%) and 11.6% (95% CI 11.2% to 11.9%). In school children, the risk factors for current wheeze were rhinitis (OR 4.484; 95% CI 3.915% to 5.134%) and rash symptoms (OR 1.735; 95% CI 1.461% to 2.059%). For adolescents, rhinitis symptoms (OR 3.492; 95% CI 3.188% to 3.825%) and allergic rhinitis diagnosis (OR 2.144; 95% CI 1.787% to 2.572%) were the most significant. For both groups, there was a negative relation with centres' sea level altitude higher than 1500 m above mean sea level (p<0.005). CONCLUSIONS: The most important risk factors for asthma symptoms in both age groups were the presence of rhinitis and rash symptoms or diagnosis. On the other hand, sea level altitude higher than 1500 metres was a protective factor.

5.
Asia Pac Allergy ; 10(4): e40, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33178565

RESUMO

Background: Anaphylaxis is a life-threating hypersensitivity reaction. Epinephrine underuse in patients with anaphylaxis could lead to poor outcomes. There is evidence that the epinephrine use in such patients could be as low as 8%. Objective: To assess the percentage of physicians who know that epinephrine is the first-line treatment in anaphylaxis. The secondary objective was to assess knowledge gaps regarding anaphylaxis diagnosis and treatment that could lead to epinephrine underuse. Methods: We performed an online survey for physicians in Mexico City, using a 10-item questionnaire assessing anaphylaxis knowledge. We obtained measures of central tendency for statistical analysis, such as frequency, 95% confidence interval, as well as the chi-square test for comparing the groups. Results: A total of 196 surveys were considered for analysis. Of all the participants, 96.44% were able to correctly diagnose an anaphylaxis case with cutaneous, respiratory, and cardiovascular symptoms. Fifty-two percent correctly diagnosed anaphylaxis without cutaneous symptoms. The 72.4% of the respondents chose epinephrine as the first-line treatment, 42.3% correctly answered that there is no absolute contraindication to giving epinephrine, and 20.9% ignored whether there was any contraindication for its use. Only 38.3% of participants answered that during discharge they would prescribe an autoinjector. Regarding the administration route, 63.4% answered that the first dose of epinephrine is applied intramuscularly and 50% of the participants chose the correct dose of epinephrine. Only 2.6% of the participants answered all 10 questions correctly. Conclusion: There is still some difficulty recognizing anaphylaxis without cutaneous symptoms. Even though two-thirds of physicians identified that epinephrine is the treatment of choice, only 49.5% would have used intramuscular epinephrine as first-line treatment. We found a low percentage of epinephrine ampule prescription and knowledge of the correct dose. These findings can account for epinephrine underuse when dealing with anaphylaxis in the real clinical practice.

6.
Neurocirugia (Astur) ; 2020 Nov 11.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33189564

RESUMO

The purpose of the review is to collect the most relevant current literature on the mechanisms of normal sleep and sleep disorders associated with traumatic brain injury (TBI), to discuss the most frequent conditions and the evidence on their possible treatments and future research. Sleep disorders are extremely prevalent after TBI (30-84%). Insomnia and circadian rhythm disorders are the most frequent disorders among the population that has suffered mild TBI, while hypersomnolence disorders are more frequent in populations that have suffered moderate and severe TBI. The syndrome of obstructive sleep apnea and restless leg syndrome are also very frequent in these patients; and patients exposed to multiple TBIs (war veterans) are especially susceptible to sleep disorders. The treatment of these disorders requires taking into account the particularities of these patients. In conclusion, diagnosis and treatment of sleep disorders should become part of routine clinical practice and cease to be anecdotal (as it is today) in patients with TBI. In addition, it is necessary to continue carrying out research that reveals the best therapeutic approach to these patients.

7.
Rev Alerg Mex ; 67 Suppl 2: S1-S25, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-33017878

RESUMO

The fractional exhaled nitric oxide (FeNO) is related to the level of eosinophilic inflammation in the airways and the levels of interleukin-13, as such it could be a diagnostic and monitoring tool in asthma. A working group was convened between pulmonologists, respiratory physiology experts, and allergists to establish criteria for the use of FeNO in asthma in Mexico. Through a simplified Delphi method and group discussion, seven key points regarding the use of FeNO were agreed upon. We agree that the measurement of FeNO serves for the diagnosis of asthma in specialized clinics, both in children and adults, as well as to determine the level of corticosteroid treatment. In severe asthma, we recommend FeNO for endotyping, for detecting poor therapeutic adherence, undertreatment, and the risk of crisis. We suggest FeNO can be used to determine the level of corticosteroid treatment and to identify patients at risk of loss of lung function. We also recommend it in adults to improve the selection of biological therapy and, in this context, we only suggest it in selected cases for children.

8.
World Allergy Organ J ; : 100476, 2020 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-33072240

RESUMO

Introduction: In the light of the current COVID-19 pandemic, during which the world is confronted with a new, highly contagious virus that suppresses innate immunity as one of its initial virulence mechanisms, thus escaping from the first-line human defense mechanisms, enhancing innate immunity seems a good preventive strategy. Methods: Without the intention to write an official systematic review, but more to give an overview of possible strategies, in this review article we discuss several interventions that might stimulate innate immunity and thus our defense against (viral) respiratory tract infections. Some of these interventions can also stimulate the adaptive T- and B-cell responses, but our main focus is on the innate part of immunity. We divide the reviewed interventions in: 1) lifestyle related (exercise, >7 hours sleep, forest walking, meditation/mindfulness, vitamin supplementation); 2) Non-specific immune stimulants (letting fever advance, bacterial vaccines, probiotics, dialyzable leukocyte extract, pidotimod) and 3) specific vaccines with heterologous effect (BCG vaccine, mumps-measles-rubeola vaccine, i.e.). Results: For each of these interventions we briefly comment on their definition, possible mechanisms and evidence of clinical efficacy or lack of it, especially focusing on respiratory tract infections, viral infections and eventually a reduced mortality in severe respiratory infections in the intensive care unit. At the end a summary table demonstrates the best trials supporting (or not) clinical evidence. Conclusion: Several interventions have some degree of evidence for enhancing the innate immune response and thus conveying possible benefit, but specific trials in COVID-19 should be conducted to support solid recommendations.

9.
Larenas-Linnemann, Désirée; Rodríguez-Pérez, Noel; Luna-Pech, Jorge A; Rodríguez-González, Mónica; Blandón-Vijil, María Virginia; Del-Río-Navarro, Blanca E; Costa-Domínguez, María Del Carmen; Navarrete-Rodríguez, Elsy Maureen; Macouzet-Sánchez, Carlos; Ortega-Martell, José Antonio; Pozo-Beltrán, César Fireth; Estrada-Cardona, Alan; Arias-Cruz, Alfredo; Rodríguez Galván, Karen Guadalupe; Brito-Díaz, Herson; Canseco-Raymundo, María Del Rosario; Castelán-Chávez, Enrique Emanuel; Escalante-Domínguez, Alberto José; Gálvez-Romero, José Luis; Gómez-Vera, Javier; González-Díaz, Sandra Nora; Guerrero-Núñez, María Gracia Belinda; Hernández-Colín, Dante Daniel; Macías-Weinmann, Alejandra; Mendoza-Hernández, David Alejandro; Meneses-Sánchez, Néstor Alejandro; Mogica-Martínez, María Dolores; Moncayo-Coello, Carol Vivian; Montiel-Herrera, Juan Manuel; O'Farril-Romanillos, Patricia María; Onuma-Takane, Ernesto; Ortega-Cisneros, Margarita; Rangel-Garza, Lorena; Stone-Aguilar, Héctor; Torres-Lozano, Carlos; Venegas-Montoya, Edna; Wakida-Kusunoki, Guillermo; Partida-Gaytán, Armando; López-García, Aída Inés; Macías-Robles, Ana Paola; Ambriz-Moreno, María de Jesús; Azamar-Jácome, Amyra Ali; Beltrán-De Paz, Claudia Yusdivia; Caballero-López, Chrystopherson; Fernández de Córdova-Aguirre, Juan Carlos; Fernández-Soto, José Roberto; Lozano-Sáenz, José Santos; Oyoqui-Flores, José Joel; Osorio-Escamilla, Roberto Efrain; Ramírez-Jiménez, Fernando.
World Allergy Organ J ; 13(8): 100444, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32884611

RESUMO

Background: Allergen immunotherapy (AIT) has a longstanding history and still remains the only disease-changing treatment for allergic rhinitis and asthma. Over the years 2 different schools have developed their strategies: the United States (US) and the European. Allergen extracts available in these regions are adapted to local practice. In other parts of the world, extracts from both regions and local ones are commercialized, as in Mexico. Here, local experts developed a national AIT guideline (GUIMIT 2019) searching for compromises between both schools. Methods: Using ADAPTE methodology for transculturizing guidelines and AGREE-II for evaluating guideline quality, GUIMIT selected 3 high-quality Main Reference Guidelines (MRGs): the European Academy of Allergy, Asthma and Immunology (EAACI) guideines, the S2k guideline of various German-speaking medical societies (2014), and the US Practice Parameters on Allergen Immunotherapy 2011. We formulated clinical questions and based responses on the fused evidence available in the MRGs, combined with local possibilities, patient's preference, and costs. We came across several issues on which the MRGs disagreed. These are presented here along with arguments of GUIMIT members to resolve them. GUIMIT (for a complete English version, Supplementary data) concluded the following. Results: Related to the diagnosis of IgE-mediated respiratory allergy, apart from skin prick testing complementary tests (challenges, in vitro testing and molecular such as species-specific allergens) might be useful in selected cases to inform AIT composition. AIT is indicated in allergic rhinitis and suggested in allergic asthma (once controlled) and IgE-mediated atopic dermatitis. Concerning the correct subcutaneous AIT dose for compounding vials according to the US school: dosing tables and formula are given; up to 4 non-related allergens can be mixed, refraining from mixing high with low protease extracts. When using European extracts: the manufacturer's indications should be followed; in multi-allergic patients 2 simultaneous injections can be given (100% consensus); mixing is discouraged. In Mexico only allergoid tablets are available; based on doses used in all sublingual immunotherapy (SLIT) publications referenced in MRGs, GUIMIT suggests a probable effective dose related to subcutaneous immunotherapy (SCIT) might be: 50-200% of the monthly SCIT dose given daily, maximum mixing 4 allergens. Also, a table with practical suggestions on non-evidence-existing issues, developed with a simplified Delphi method, is added. Finally, dissemination and implementation of guidelines is briefly discussed, explaining how we used online tools for this in Mexico. Conclusions: Countries where European and American AIT extracts are available should adjust AIT according to which school is followed.

10.
Rev Alerg Mex ; 67(2): 199-201, 2020.
Artigo em Espanhol | MEDLINE | ID: mdl-32892535
11.
Med Hypotheses ; 144: 109935, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32795834

RESUMO

Coronavirus disease 2019 (COVID-19) was declared a pandemic and international health emergency by the World Health Organization. Patients with obesity with COVID-19 are 7 times more likely to need invasive mechanical ventilation than are patients without obesity (OR 7.36; 95% CI: 1.63-33.14, p = 0.021). Acute respiratory distress syndrome (ARDS) is one of the main causes of death related to COVID-19 and is triggered by a cytokine storm that damages the respiratory epithelium. Interleukins that cause the chronic low-grade inflammatory state of obesity, such as interleukin (IL)-1ß, IL-6, monocyte chemoattractant peptide (MCP)-1, and, in particular, IL-17A and tumour necrosis factor alpha (TNF-α), also play very important roles in lung damage in ARDS. Therefore, obesity is associated with an immune state favourable to a cytokine storm. Our hypothesis is that serum concentrations of TNF-α and IL-17A are more elevated in patients with obesity and COVID-19, and consequently, they have a greater probability of developing ARDS and death. The immunobiology of IL-17A and TNF-α opens a new fascinating field of research for COVID-19.

12.
Nanomaterials (Basel) ; 10(5)2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32455643

RESUMO

Nanostructured composite materials based on noble mono-(Pd) or bi-metallic (Ag/Pd) particles supported on mixed iron oxides (II/III) with bulk magnetite structure (Fe3O4) have been developed in order to assess their potential for heterogeneous catalysis applications in methane partial oxidation. Advancing the direct transformation of methane into value-added chemicals is consensually accepted as the key to ensuring sustainable development in the forthcoming future. On the one hand, nanosized Fe3O4 particles with spherical morphology were synthesized by an aqueous-based reflux method employing different Fe (II)/Fe (III) molar ratios (2 or 4) and reflux temperatures (80, 95 or 110 °C). The solids obtained from a Fe (II)/Fe (III) nominal molar ratio of 4 showed higher specific surface areas which were also found to increase on lowering the reflux temperature. The starting 80 m2 g-1 was enhanced up to 140 m2 g-1 for the resulting optimized Fe3O4-based solid consisting of nanoparticles with a 15 nm average diameter. On the other hand, Pd or Pd-Ag were incorporated post-synthesis, by impregnation on the highest surface Fe3O4 nanostructured substrate, using 1-3 wt.% metal load range and maintaining a constant Pd:Ag ratio of 8:2 in the bimetallic sample. The prepared nanocomposite materials were investigated by different physicochemical techniques, such as X-ray diffraction, thermogravimetry (TG) in air or H2, as well as several compositions and structural aspects using field emission scanning and scanning transmission electron microscopy techniques coupled to energy-dispersive X-ray spectroscopy (EDS). Finally, the catalytic results from a preliminary reactivity study confirmed the potential of magnetite-supported (Ag)Pd catalysts for CH4 partial oxidation into formaldehyde, with low reaction rates, methane conversion starting at 200 °C, far below temperatures reported in the literature up to now; and very high selectivity to formaldehyde, above 95%, for Fe3O4 samples with 3 wt.% metal, either Pd or Pd-Ag.

13.
J Sci Food Agric ; 100(7): 3228-3235, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32108339

RESUMO

BACKGROUND: Protein glycation by Maillard reaction is commonly used to improve the functional and bioactive properties of food proteins. It is also known that this glycation method can be accelerated by heat without the need for chemical reagents that could be harmful to health. In this study, glycoconjugates were obtained from a mixture of connective tissue proteins (CTP) from jumbo squid (Dosidicus gigas) and two different sugars, dextran (DEX; 10 kDa) and glucose (GLU), using protein-to-carbohydrate ratios of 1:2 and 1:3, in solution at 50 °C for 6 h. The glycation products were characterized by means of their physicochemical properties and cytotoxic effect. RESULTS: The intensity of the browning measured at A420nm and A294nm in glycoconjugates showed no significant difference (P < 0.05). CTP-DEX (1:2) and CTP-DEX (1:3) were those products with the greatest fluorescence related to the intermediate stage in the Maillard reaction, and also with the highest degree of glycation, which was confirmed using o-phthaldialdehyde assay and Fourier transform infrared analysis. The values of cellular viability for CTP-GLU (1:3), CTP-DEX (1:2, 1:3) as well as CTP (0, 6 h) were around 92-103%. CONCLUSIONS: The operational parameters used in the glycation process achieved the formation of glycoconjugates from proteins of D. gigas, showing no cytotoxic effect on the HaCaT cell line. This research proposes an alternative for the modification of proteins and opens the way to future investigations regarding the bioactivity of these macromolecules to have applications for the use of byproducts in food science and technology. © 2020 Society of Chemical Industry.

14.
Clin Chem ; 66(3): 463-473, 2020 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-32068788

RESUMO

BACKGROUND: The specific characteristics of copy number variations (CNVs) require specific methods of detection and characterization. We developed the Easy One-Step Amplification and Labeling procedure for CNV detection (EOSAL-CNV), a new method based on proportional amplification and labeling of amplicons in 1 PCR. METHODS: We used tailed primers for specific amplification and a pair of labeling probes (only 1 labeled) for amplification and labeling of all amplicons in just 1 reaction. Products were loaded directly onto a capillary DNA sequencer for fragment sizing and quantification. Data obtained could be analyzed by Microsoft Excel spreadsheet or EOSAL-CNV analysis software. We developed the protocol using the LDLR (low density lipoprotein receptor) gene including 23 samples with 8 different CNVs. After optimizing the protocol, it was used for genes in the following multiplexes: BRCA1 (BRCA1 DNA repair associated), BRCA2 (BRCA2 DNA repair associated), CHEK2 (checkpoint kinase 2), MLH1 (mutL homolog 1) plus MSH6 (mutS homolog 6), MSH2 (mutS homolog 2) plus EPCAM (epithelial cell adhesion molecule) and chromosome 17 (especially the TP53 [tumor protein 53] gene). We compared our procedure with multiplex ligation-dependent probe amplification (MLPA). RESULTS: The simple procedure for CNV detection required 150 min, with <10 min of handwork. After analyzing >240 samples, EOSAL-CNV excluded the presence of CNVs in all controls, and in all cases, results were identical using MLPA and EOSAL-CNV. Analysis of the 17p region in tumor samples showed 100% similarity between fluorescent in situ hybridization and EOSAL-CNV. CONCLUSIONS: EOSAL-CNV allowed reliable, fast, easy detection and characterization of CNVs. It provides an alternative to targeted analysis methods such as MLPA.


Assuntos
Variações do Número de Cópias de DNA , Reação em Cadeia da Polimerase/métodos , Receptores de LDL/genética , Sondas de DNA/química , Sondas de DNA/metabolismo , Corantes Fluorescentes/química , Humanos , Hibridização in Situ Fluorescente , Reação em Cadeia da Polimerase Multiplex , Análise de Sequência de DNA
15.
J Clin Immunol ; 40(3): 475-493, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32040803

RESUMO

PURPOSE: Chronic granulomatous disease (CGD) is a primary immunodeficiency characterized by an inability of phagocytes to produce reactive oxygen species, impairing their killing of various bacteria and fungi. We summarize here the 93 cases of CGD diagnosed in Mexico from 2011 to 2019. METHODS: Thirteen Mexican hospitals participated in this study. We describe the genetic, immunological, and clinical features of the 93 CGD patients from 78 unrelated kindreds. RESULTS: Eighty-two of the patients (88%) were male. All patients developed bacterial infections and 30% suffered from some kind of fungal infection. Fifty-four BCG-vaccinated patients (58%) presented infectious complications of BCG vaccine. Tuberculosis occurred in 29%. Granulomas were found in 56% of the patients. Autoimmune and inflammatory diseases were present in 15% of patients. A biological diagnosis of CGD was made in 89/93 patients, on the basis of NBT assay (n = 6), DHR (n = 27), and NBT plus DHR (n = 56). The deficiency was complete in all patients. The median age of biological diagnosis was 17 months (range, 0-186 months). A genetic diagnosis was made in 83/93 patients (when material was available), corresponding to CYBB (n = 64), NCF1 (n = 7), NCF2 (n = 7), and CYBA (n = 5) mutations. CONCLUSIONS: The clinical manifestations in these Mexican CGD patients were similar to those in patients elsewhere. This cohort is the largest in Latin America. Mycobacterial infections are an important cause of morbidity in Mexico, as in other countries in which tuberculosis is endemic and infants are vaccinated with BCG. X-linked CGD accounted for most of the cases in Mexico, as in other Latin American countries. However, a significant number of CYBA and NCF2 mutations were identified, expanding the spectrum of known causal mutations.

16.
World Allergy Organ J ; 13(1): 100092, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31934263

RESUMO

Background: According to the International Study of Asthma and Allergies in Childhood (ISAAC) methodology, in 2003, the prevalence of asthma symptoms in children 6-7 years old and adolescents 13-14 years old was 11.6% and 13.7%, respectively. Since then, the number of asthma cases has increased worldwide. The study was conducted in several districts in northern Mexico City to evaluate the prevalence of asthma in these age groups and examine possible risk factors. The data were compared to the 2003 results from the same area. Methods: This was a comparative cross-sectional study following the official Global Asthma Network (GAN) methodology. The parents or guardians of participants completed a questionnaire that explored demographics, asthma symptoms, diagnoses, and possible risk factors. Central tendency measurements were determined for statistical analysis and chi-squared distribution for possible risk factors. Results: A total of 2515 children aged 6-7 years and 3375 adolescents aged 13-14 years participated in the study. Compared to the ISAAC results, we found a greater prevalence of wheezing in both children (at some time in life, 19.2% vs. 27.1%; over the last year, 6.8% vs. 10.6%) and adolescents (at some time in life, 16.9% vs. 19.7%), and for children with an asthma diagnosis (4.5% vs. 5.1%). For both groups, the most common risk factor associated with wheezing was the presence of rhinitis symptoms. Conclusions: Asthma symptoms are highly prevalent in Mexico City, occurring in almost 20% of adolescents. Compared to a decade ago, there was a 7.9% increase in the prevalence of asthma symptoms in children. Almost half of the children and adolescents presenting with symptoms had experienced more than four episodes per year. However, less than 50% of children and adolescents with asthma symptoms had been diagnosed with this disorder, suggesting under-diagnosis.

17.
Gut Microbes ; 11(4): 900-917, 2020 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-31973685

RESUMO

BACKGROUND: Gut microbiota, by influencing multiple metabolic processes in the host, is an important determinant of human health and disease. However, gut dysbiosis associated with metabolic complications shows inconsistent patterns. This is likely driven by factors shaping gut microbial composition that have largely been under-evaluated, at a population level, in school-age children, especially from developing countries. RESULTS: Through characterization, by 16S sequencing, of the largest gut microbial population-based school-aged children cohort in Latin America (ORSMEC, N = 926, aged 6-12 y), we identified associations of 14 clinical and environmental covariates (PFDR<0.1), collectively explaining 15.7% of the inter-individual gut microbial variation. Extrinsic factors such as markers of socioeconomic status showed a major influence in the most abundant taxa and in the enterotypes' distribution. Age was positively correlated with higher diversity, but only in normal-weight children (rho = 0.138, P =2 × 10-3). In contrast, this correlation although not significant, was negative in overweight and obese children (rho = -0.125, P = 0.104 and rho = -0.058, P = 0.409, respectively). Finally, co-abundance groups (CAGs) were associated with the presence of metabolic complications. CONCLUSIONS: Our study offers evidence that the presence of overweight and obesity could impair the microbial diversity maturation associated with age. Furthermore, it provides novel results toward a better understanding of gut microbiota in the pediatric population that will ultimately help to develop therapeutic approaches to improve metabolic status.

18.
Ann Hematol ; 99(3): 527-537, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31989250

RESUMO

Azacitidine (AZA) is a DNA hypomethylation agent administered in myeloid neoplasms; however, there is still a lack of established predictors of response. We studied 113 patients with myelodysplastic syndromes (n = 85) or acute myeloid leukemia (n = 28) who received AZA to assess the predictive value on response of clinical features, cytogenetics, and molecular markers. Overall, 46 patients (41%) responded to AZA. Platelet doubling after the first AZA cycle was associated with a better response (68% vs. 32% responders, P = 0.041). Co-occurrence of chromosome 7 abnormalities and 17p deletion was associated with a worse response (P = 0.039). Pre-treatment genetic mutations were detected in 98 patients (87%) and methylation of CDKN2B and DLC-1 promoters were detected in 50 (44%) and 37 patients (33%), respectively. Patients with SF3B1 mutations showed a better response to AZA (68% vs. 35% responders, P = 0.008). In contrast, subjects with mutations in transcription factors (RUNX1, SETBP1, NPM1) showed a worse response (20% vs. 47% responders, P = 0.014). DLC-1 methylation pre-treatment was associated with poor clinical features and its reduction post-treatment resulted in a better response to AZA in MDS patients (P = 0.037). In conclusion, we have identified several predictors of response to AZA that could help select the best candidates for this treatment.


Assuntos
Azacitidina/administração & dosagem , Inibidor de Quinase Dependente de Ciclina p15 , Metilação de DNA/efeitos dos fármacos , DNA de Neoplasias , Proteínas Ativadoras de GTPase , Síndromes Mielodisplásicas , Regiões Promotoras Genéticas , Proteínas Supressoras de Tumor , Idoso , Idoso de 80 Anos ou mais , Deleção Cromossômica , Cromossomos Humanos Par 7/genética , Cromossomos Humanos Par 7/metabolismo , Inibidor de Quinase Dependente de Ciclina p15/genética , Inibidor de Quinase Dependente de Ciclina p15/metabolismo , DNA de Neoplasias/genética , DNA de Neoplasias/metabolismo , Intervalo Livre de Doença , Feminino , Proteínas Ativadoras de GTPase/genética , Proteínas Ativadoras de GTPase/metabolismo , Humanos , Leucemia Mieloide Aguda/tratamento farmacológico , Leucemia Mieloide Aguda/genética , Leucemia Mieloide Aguda/metabolismo , Leucemia Mieloide Aguda/mortalidade , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/tratamento farmacológico , Síndromes Mielodisplásicas/genética , Síndromes Mielodisplásicas/metabolismo , Síndromes Mielodisplásicas/mortalidade , Taxa de Sobrevida , Proteínas Supressoras de Tumor/genética , Proteínas Supressoras de Tumor/metabolismo
19.
Med Hypotheses ; 134: 109527, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31877441

RESUMO

Obesity is a serious public health problem worldwide and has been associated in epidemiological studies with a unique type of non-atopic asthma, although the causal association of asthma and obesity has certain criteria, such as the strength of association, consistency, specificity, temporality, biological gradient, coherence, analogy and experimentation; nevertheless, the biological plausibility of this association remains uncertain. Various mechanisms have been postulated, such as immunological, hormonal, mechanical, environmental, genetic and epigenetic mechanisms. Our hypothesis favours immunological mechanisms because some cytokines, such as tumour necrosis factor alpha (TNF-α) and interleukin (IL)-17A, are responsible for orchestrating low-grade systemic inflammation associated with obesity; however, these cytokines are regulated by epigenetic mechanisms, such as gene promoter methylation.


Assuntos
Asma/etiologia , Metilação de DNA , Interleucina-17/genética , Modelos Imunológicos , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Obesidade/complicações , Regiões Promotoras Genéticas , Células Th17/metabolismo , Fator de Necrose Tumoral alfa/genética , Tecido Adiposo/metabolismo , Adolescente , Adulto , Animais , Asma/genética , Asma/imunologia , Causalidade , Criança , Feminino , Regulação da Expressão Gênica , Humanos , Inflamação , Interleucina-23/fisiologia , Macrófagos/metabolismo , Masculino , Metanálise como Assunto , Camundongos , Pessoa de Meia-Idade , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/fisiologia , Obesidade/imunologia , Fator de Necrose Tumoral alfa/fisiologia
20.
Anticancer Res ; 39(9): 4757-4766, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31519576

RESUMO

BACKGROUND/AIM: Azacitidine (AZA) is a hypomethylating agent used in myeloid neoplasms, however, approximately half of patients show treatment failure or relapse. This in vitro study investigated the effect of the combination of AZA with the natural compound curcumin (CUR) in increasing its efficacy. MATERIALS AND METHODS: We analyzed the effects of AZA plus CUR on proliferation, apoptosis, cell cycle and differentiation in myeloid leukemic cell lines (U-937, HL-60, K-562, and OCI-AML3) and bone marrow samples of patients. RESULTS: The results showed a synergy between AZA and CUR in all leukemic lines and in most leukemic samples, with a decrease in proliferation and an increase in apoptosis compared to the activity of each drug separately. In addition, AZA plus CUR showed low cytotoxicity in healthy samples. CONCLUSION: A remarkable antioncogenic effect of the combination of AZA plus CUR was shown, providing a basis for future studies analyzing the clinical efficacy of these drugs.


Assuntos
Antineoplásicos/farmacologia , Azacitidina/farmacologia , Curcumina/farmacologia , Idoso , Idoso de 80 Anos ou mais , Apoptose/efeitos dos fármacos , Ciclo Celular/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Sinergismo Farmacológico , Feminino , Humanos , Leucemia Mieloide/genética , Masculino , Síndromes Mielodisplásicas/genética
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