ABSTRACT
BACKGROUND/AIMS: Longitudinal studies assessing the impact of genetic polymorphisms on outcomes in patients with Type 2 Diabetes Mellitus (T2DM) and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) are scarce. This study aimed to evaluate the effect of PNPLA3 and TM6SF2 risk alleles on hepatic and extrahepatic outcomes in T2DM-MASLD individuals. METHODS: Patients' polymorphisms were analysed as follows: PNPLA3 CC, CG and GG; TM6SF2 CC and CT + TT; combined comparing no mutant allele, one allele G or T or ≥2 alleles G or T. Hierarchical models were built to assess associations between polymorphisms and outcomes, independently of confounding factors. Multivariate logistic regression was used for cirrhosis and its complications and extrahepatic cancer, and Cox regression for cardiovascular events (CVEs) and all-cause mortality. RESULTS: In total, 407 T2DM-MASLD patients (62.1 ± 10.5 years, 67.6% women) were followed for 11 (6-13) years. Having at least one G or T allele independently increased the risk of cirrhosis in the separate analysis of PNPLA3 and TM6SF2. Combined polymorphism analysis demonstrated an even higher risk of cirrhosis if two or more risk alleles were present (OR 18.48; 95% CI 6.15-55.58; p < .001). Regarding cirrhosis complications, the risk was higher in PNPLA3 GG and TM6SF2 CT + TT, also with an even higher risk when two or more risk alleles were present in the combined evaluation (OR 27.20; 95% CI 5.26-140.62; p < .001). There were no associations with CVEs or mortality outcomes. CONCLUSION: In T2DM, PNPLA3 and TM6SF2 polymorphisms, individually and additively, impact MASLD severity, with an increased risk of cirrhosis and its complications.
Subject(s)
Diabetes Mellitus, Type 2 , Fatty Liver , Non-alcoholic Fatty Liver Disease , Humans , Female , Male , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/genetics , Genetic Predisposition to Disease , Polymorphism, Single Nucleotide , Liver Cirrhosis/genetics , Fibrosis , Prognosis , Non-alcoholic Fatty Liver Disease/genetics , Genotype , Membrane Proteins/geneticsABSTRACT
BACKGROUND & AIMS: In non-alcoholic fatty liver disease (NAFLD), the influence of parental history of type 2 diabetes (T2D) allied to single nucleotide polymorphisms (SNPs) in the offspring is not known. We aimed to investigate the impact of the parental history of T2D, PNPLA3 and TM6SF2 polymorphisms in liver steatosis and fibrosis. METHODS: This was a case-control study involving the offspring of T2D patients and controls without a parental history of T2D. Participants underwent clinical and laboratory evaluation, transient elastography (TE) by Fibroscan® (Echosens, Fr) and genotyping for PNPLA3 and TM6SF2. Multivariate logistic regression evaluated the influence of parental history of T2D on liver steatosis and fibrosis, controlled for age, gender, metabolic traits and SNPs. RESULTS: 161 T2D offspring and 78 controls, 10-46 years old, were included. The offspring of T2D had higher prevalences of obesity, T2D, arterial hypertension and sedentarism. Parental history of T2D was associated with fibrosis ≥ F2 (OR 8.89, CI 95% 1.09-72.01, p = 0.041) after adjustment for age, gender, metabolic traits and SNPs. PNPLA3 GG genotype was independently associated with steatosis ≥ S1 (OR 8.15, CI 95% 1.93-34.38, p = 0.004) and fibrosis ≥ F2 (OR 4.31, CI 95% 1.11-16.61, p = 0.034). CONCLUSIONS: The offspring of T2D patients present a worse metabolic profile and the parental history of T2D confers an increased likelihood of hepatic fibrosis, independent of metabolic factors. PNPLA3 homozygous GG, but not TM6SF2 genotypes, also impacts on this phenotype.
Subject(s)
Diabetes Mellitus, Type 2 , Non-alcoholic Fatty Liver Disease , Adolescent , Adult , Child , Humans , Middle Aged , Young Adult , Case-Control Studies , Diabetes Mellitus, Type 2/epidemiology , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Fibrosis , Genetic Predisposition to Disease , Genotype , Liver/pathology , Non-alcoholic Fatty Liver Disease/diagnostic imaging , Non-alcoholic Fatty Liver Disease/epidemiology , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single NucleotideABSTRACT
Nucleotide-binding leucine-rich repeat (NLR) plant immune receptors mediate the recognition and activation of defense signaling pathways in response to intra- and extracellular pathogens. Several NLR such as Tm-2 and Tm-22 have been introgressed into commercial solanaceous varieties to confer protection against different tobamoviruses. Particularly, Tm-22 was used during recent decades to confer resistance against tobacco mosaic virus, tomato mottle mosaic virus and tomato mosaic virus, which recognizes the viral movement protein (MP). However, tomato brown rugose fruit virus(ToBRFV), a novel tobamovirus, can avoid the protection conferred by Tm-22 due to the presence of key substitutions in the MP. The aim of this work was to identify the key amino acid residues involved in the interaction between Tm-22 and ToBRFV MP through bioinformatic analyses, and to identify potential Tm-22 mutations that could generate greater binding affinity. In silico 3D structure prediction, molecular docking, and computational affinity methods were performed. We predicted that R350, H384 and K385 Tm-22 residues are relevant for the interaction with MP, and two mutations (H384W and K385L) were identified as putative sites to increase the affinity of Tm-22 to the MP with the potential elicitation of resistance against ToBRFV.
ABSTRACT
Toxoplasma gondii, a protozoan parasite, is responsible for toxoplasmosis. The available therapy for patients with toxoplasmosis involves a combination of pyrimethamine and sulfadiazine, which have several adverse effects, including bone marrow suppression, megaloblastic anemia, leukopenia, and granulocytopenia. The development of therapeutic alternatives is essential for the management of toxoplasmosis, emphasizing the recent advances in nanomedicine. This study aimed to evaluate the in vitro effects of biogenic silver nanoparticles (AgNp-Bio) on tachyzoite forms and Leydig cells infected with T. gondii. We observed that the AgNp-Bio reduced the viability of the tachyzoites and did not exhibit cytotoxicity against Leydig cells at low concentrations. Additionally, treatment with AgNp-Bio reduced the rate of infection and proliferation of the parasite, and lowered the testosterone levels in the infected cells. It increased the levels of IL-6 and TNF-α and reduced the levels of IL- 10. Among the morphological and ultrastructural changes, AgNp-Bio induced a reduction in the number of intracellular tachyzoites and caused changes in the tachyzoites with accumulation of autophagic vacuoles and a decrease in the number of tachyzoites inside the parasitophorous vacuoles. Collectively, our data demonstrate that the AgNp-Bio affect T. gondii tachyzoites by activating microbicidal and inflammatory mechanisms and could be a potential alternative treatment for toxoplasmosis.
Subject(s)
Metal Nanoparticles , Toxoplasma , Toxoplasmosis , Humans , Interleukin-6 , Leydig Cells , Male , Metal Nanoparticles/therapeutic use , Metal Nanoparticles/toxicity , Silver/toxicity , Testosterone , Tumor Necrosis Factor-alphaABSTRACT
INTRODUCTION AND OBJECTIVES: PNPLA3 (rs738409) and TM6SF2 (rs58542926) variants, interindividual and ethnic differences may be risk factors for non-alcoholic fatty liver disease (NAFLD). The PNPLA3 G allele is associated with worse NAFLD evolution in Hispanics and Caucasians. TM6SF2 is associated with hypertriglyceridemia, NAFLD, and cardiovascular disease. We aimed to evaluate the association between genetic ancestry by Ancestry Informative Markers (AIM), PNPLA3 and TM6SF2 polymorphisms in patients with biopsy-proven NAFLD in an admixed population. METHODS: We included adults with biopsy-proven NAFLD and excluded patients with the presence of other chronic liver disease, alcohol intake >100g/week, HIV, drug-induced fatty liver disease, or liver transplantation. We classified NAFLD using the Non-Alcoholic Steatohepatitis Clinical Research Network (NASH-CRN) histological scoring system. The PNPLA3 (rs738409 c.444C>G) and TM6SF2 (rs58542926 c.449C>T) genotyping were performed by RT-PCR. Genetic ancestry was determined using 46 insertion-deletion AIM; α<0.05 was considered significant. RESULTS: A total of 248 patients with NAFLD were enrolled [34 with simple steatosis (NAFL); 214 with NASH]. Overall, we detected a greater European ancestry contribution (0.645), followed by African (0.173), Amerindian (0.095), and East Asian (0.087) ancestry contribution, without differences between NAFL and NASH patients. However, we found a higher African genetic ancestry contribution among patients with NAFL who had the PNPLA3 C/C genotype than those with the G allele (0.216 ± 0.205 versus 0.105 ± 0.101, respectively; p=0.047). Ancestry contributions did not differ among TM6SF2 genotypes. CONCLUSION: Among NAFL patients, greater African genetic ancestry was associated to a lower frequency of the PNPLA3 G allele, demonstrating a possible NASH ancestry-related protective factor.
Subject(s)
Acyltransferases , Non-alcoholic Fatty Liver Disease , Phospholipases A2, Calcium-Independent , Adult , Humans , Alleles , Genetic Predisposition to Disease , Genotype , Liver/pathology , Membrane Proteins/genetics , Non-alcoholic Fatty Liver Disease/ethnology , Non-alcoholic Fatty Liver Disease/genetics , Polymorphism, Single Nucleotide , Black People/genetics , Acyltransferases/genetics , Phospholipases A2, Calcium-Independent/geneticsABSTRACT
Introducción: El hipotiroidismo congénito puede afectar el estado emocional, las relaciones sociales y el nivel de independencia del adolescente. Estos aspectos pueden influir en la percepción de su calidad de vida relacionada con la salud. Objetivo: Evaluar la calidad de vida relacionada con la salud en adolescentes con hipotiroidismo congénito permanente e identificar su posible relación con algunas características sociodemográficas y clínicas. Método: Se realizó un estudio observacional descriptivo de corte transversal en 40 adolescentes, varones y mujeres entre 10 y 19 años, registrados por el Programa Cubano de Diagnóstico Precoz de Hipotiroidismo Congénito, con el cuestionario genérico PedsQL TM ®, versión 4.0 para uso pediátrico. Resultados: Los mayores puntajes correspondieron a los adolescentes entre 10-14 años, del sexo masculino, nivel educacional primario, sin consumo de sustancias nocivas y que mostraron satisfacción con la vida familiar y un buen control de la enfermedad. Conclusiones: La mayoría de los adolescentes tienen una buena percepción de su calidad de vida relacionada con la salud. La dimensión y la función que más aportaron fueron la física y la social, respectivamente(AU)
Introduction: Congenital hypothyroidism can affect the emotional state, social relationships and the level of independence of adolescents. These aspects can influence the perception of their health-related quality of life. Objective: To evaluate the health-related quality of life of adolescents with permanent congenital hypothyroidism and to identify possible relationship with some sociodemographic and clinical characteristics. Methods: A cross-sectional descriptive observational study was carried out in 40 adolescents, male and female, between 10 and 19 years old, who were registered by the Cuban Program for Early Diagnosis, using the generic PedsQL TM ® questionnaire, version 4.0 for pediatric use, as an instrument. Results: The highest scores corresponded to adolescents between 10-14 years old, male, primary educational level, without harmful substance use and who showed satisfaction with family life and good control of the disease. Conclusions: Most adolescents have good perception of their health-related quality of life. The dimension and function that contributed the most were physical and social, respectively(AU)
Subject(s)
Humans , Male , Female , Adolescent , Personal Satisfaction , Quality of Life , Congenital Hypothyroidism , Early Diagnosis , Epidemiology, Descriptive , Cross-Sectional Studies , Observational Studies as TopicABSTRACT
El objetivo del presente estudio fue medir la curvatura vestíbulo-lingual de los conductos de las raíces mesiales de primeros molares inferiores en personas adultas del estado de Chihuahua, por medio de la técnica de tomografía computarizada de haz cónico (CBCT, por sus siglas en inglés) y usando el software de análisis 3D EndoTM (Dentsply/Sirona USA). Se llevó a cabo la medición por dos observadoras, empleando dos métodos diferentes, Schneider y 3D EndoTM (Dentsply/Sirona USA). Los resultados obtenidos tuvieron valores mayores a los 100 grados con la técnica 3D EndoTM y a los 20 grados con la técnica de Schneider. No se detectó una diferencia estadística significativa al comparar los diferentes conductos entre sí (AU)
The objective of the present study was to measure the vestibule-lingual curvature of the ducts of the mesial roots of lower first molars, of adults from the state of Chihuahua. Using the cone beam computed tomography (CBCT) technique and using the 3D analysis software EndoTM (Dentsply/Sirona USA). The measurement was carried out by two observers using two different methods, Schneider and 3D EndoTM (Dentsply/Sirona USA). The results obtained had values greater than 100 degrees with the 3D EndoTM technique and at 20 degrees with the Schneider technique. No statistically significant difference was detected when comparing the different ducts with each other (AU)
Subject(s)
Humans , Dental Pulp Cavity , Cone-Beam Computed Tomography , Molar , Software , Imaging, Three-Dimensional , MexicoABSTRACT
The obesity pandemic has been strongly associated with the Western diet, characterized by the consumption of ultra-processed foods. The Western lifestyle causes gut dysbiosis leading to impaired fatty acid metabolism. Therefore, this study aimed to evaluate shifts in gut microbiota and correlate these with serum fatty acid profiles in male Wistar rats fed a cafeteria diet. Ten male rats were fed with standard diet (CTL, n = 5) and cafeteria diet (CAF, n = 5) for fifteen weeks. Body weight and food intake were recorded once and three times per week, respectively. At the end of the study, fresh fecal samples were collected, tissues were removed, and serum samples were obtained for further analyses. Gut microbiota was analyzed by sequencing the V3-V4 region of 16S rRNA gene. Serum fatty acid profiles were fractioned and quantified via gas chromatography. The CAF diet induced an obese phenotype accompanied by impaired serum fatty acids, finding significantly higher proportions of total saturated fatty acids (SFAs) and C20:3 n-6, and lower C18:1 n-7 and C18:3 n-3 in the phospholipid (PL) fraction. Furthermore, circulating C10:0, total n-3 and n-7 decreased and total monounsaturated fatty acids (MUFAs), including oleic acid C18:1 n-9, increased in the cholesterol ester (CE) fraction. The obesity metabotype may be mediated by gut dysbiosis caused by a cafeteria diet rich in C16:0, C18:0, C18:1 n-9 and C18:2 n-6 fatty acids resulting in a 34:1 omega-6/omega-3 ratio. Therefore, circulating C10:0 was associated with several genera bacteria such as Prevotella (positive) and Anaerotruncus (negative). Two classes of Firmicutes, Bacilli and Erysipelotrichi, were positively correlated with PL- C20:3 n-6 and CE- 18:1 n-9, respectively. TM7 and Bacteroidetes were inversely correlated with PL-SFAs and CE- 18:2 n-6, respectively.
Subject(s)
Fatty Acids, Omega-3 , Gastrointestinal Microbiome , Humans , Rats , Male , Animals , Diet, Western/adverse effects , Gastrointestinal Microbiome/genetics , Lipidomics , Dysbiosis/complications , RNA, Ribosomal, 16S/genetics , Rats, Wistar , Obesity/metabolism , Fatty Acids/analysis , Diet, High-Fat/adverse effectsABSTRACT
All biological processes rely on the formation of protein-ligand, protein-peptide and protein-protein complexes. Studying the affinity, kinetics and thermodynamics of binding between these pairs is critical for understanding basic cellular mechanisms. Many different technologies have been designed for probing interactions between biomolecules, each based on measuring different signals (fluorescence, heat, thermophoresis, scattering and interference, among others). Evaluation of the data from binding experiments and their fitting is an essential step towards the quantification of binding affinities. Here, user-friendly online tools to analyze biophysical data from steady-state fluorescence spectroscopy, microscale thermophoresis and differential scanning fluorimetry experiments are presented. The modules of the data-analysis platform (https://spc.embl-hamburg.de/) contain classical thermodynamic models and clear user guidelines for the determination of equilibrium dissociation constants (Kd) and thermal unfolding parameters such as melting temperatures (Tm).
Subject(s)
Cyclic GMP-Dependent Protein Kinases/chemistry , Cyclic GMP-Dependent Protein Kinases/metabolism , Fluorescence , Mycobacterium tuberculosis/metabolism , Online Systems , Temperature , Thermodynamics , Kinetics , Ligands , Protein Binding , Spectrometry, FluorescenceABSTRACT
KMgF3 fluoroperovskite doped with thulium at different concentrations were synthesized by the solid-state reaction method. The phase composition and the thermal stability up to 600 °C of the polycrystals were analyzed by X-ray diffraction and thermogravimetric analysis, respectively. The KMgF3 at 1.0 mol% of Tm polycrystals showed the best thermal stability and did not present another phase. The gamma radiation (0.1-10 kGy) effect in thulium-doped KMgF3 produced the F color centers, and their aggregates such as F2, and F3 centers. The F centers, and the potassium vacancies (VK-) in the fluoroperosvkites were analyzed by the optical absorption and emission measurements. Optical absorption at 275 nm and 443 nm were assigned to F and F2, respectively, in undoped KMgF3. Tm-doped fluoroperovskite shows the optical absorption bands at 277, 393, 432, and 577 nm, which were ascribed to the F, F3, F2 and VK- centers, respectively. When the F band for undoped polycrystals was excited at 275 nm, a clear emission associated with F2 and F3 centers was observed. In the case of Tm-doped, an enhancement of the blue emission at 457 nm occurred and a UV band (354 nm) was observed upon exciting the F band. The blue emission of thulium was overlapped with the F3 color center band. The emission bands at 457 and 354 nm were ascribed to 1D2 - 3F4 and 1D2 - 3H6 transitions of Tm in KMgF3. The optical absorption and glow curves were investigated too. The glow curves were assisted by the color centers, vacancies, and thulium impurity. Thermal bleaching shows that the F center was the main participant to give rise to the TL intensity of the glow curves. Thulium acts as a deep electron trap in the bandgap of the KMgF3 fluoroperovskites forming TL peak at the higher temperature, from 430 to 408 °C. The absorption, emission, and thermoluminescence glow peaks of the undoped and Tm-doped KMgF3 were compared.
ABSTRACT
The irreversible and progressive neurodegenerative Alzheimer's disease (AD) is characterized by cognitive decline, extracellular ß-amyloid peptide accumulation, and tau neurofibrillary tangles in the cortex and hippocampus. The triple-transgenic (3xTg) mouse model of AD presents memory impairment in several behavioral paradigms and histopathological alterations from 6 to 16 months old. Additionally, it seems that dysbiotic gut microbiota is present in both mouse models and patients of AD at the cognitive symptomatic stage. The present study aimed to assess spatial learning, memory retention, and gut microbiota alterations in an early adult stage of the 3xTg-AD mice as well as to explore its sexual dimorphism. We evaluated motor activity, novel-object localization training, and retention test as well as collected fecal samples to characterize relative abundance, alpha- and beta-diversity, and linear discriminant analysis (LDA) effect size (LEfSe) analysis in gut microbiota in both female and male 3xTg-AD mice, and controls [non-transgenic mice (NoTg)], at 3 and 5 months old. We found spatial memory deficits in female and male 3xTg-AD but no alteration neither during training nor in motor activity. Importantly, already at 3 months old, we observed decreased relative abundances of Actinobacteria and TM7 in 3xTg-AD compared to NoTg mice, while the beta diversity of gut microbiota was different in female and male 3xTg-AD mice in comparison to NoTg. Our results suggest that gut microbiota modifications in 3xTg-AD mice anticipate and thus could be causally related to cognitive decline already at the early adult age of AD. We propose that microbiota alterations may be used as an early and non-invasive diagnostic biomarker of AD.
ABSTRACT
Leydig cells play pivotal roles in eliciting male characteristics by producing testosterone and any damage to these cells can compromise male fertility Toxoplasma gondii (T. gondii) is an intracellular parasite capable to invade any nucleated cell, including cells from male reproductive system. Herein, we evaluated the capacity of RH strain of T. gondii to infect TM3 Leydig cells and the impact of this infection on testosterone and inflammatory mediators production. We first, by performing adherence, infection, and intracellular proliferation assays, we found a significant increase in the number of infected Leydig cells, peaking 48 h after the infection with T. gondii. Supernatants of TM3 infected cells exhibited, in a time-dependent manner, increased levels of testosterone as well as monocyte chemoattractant protein-1 (MCP-1) and interferon-γ (IFN-γ), which is correlated with the robust T. gondii infection. In conclusion, our study provides new insights regarding the harmful effects of T. gondii infection on male reproductive system.
Subject(s)
Leydig Cells/parasitology , Testosterone/biosynthesis , Toxoplasmosis/metabolism , Animals , Chemokine CCL2/biosynthesis , Interferon-gamma/biosynthesis , Male , Mice, Inbred BALB C , Time Factors , ToxoplasmaABSTRACT
Resumen La bacteriemia es una de las principales causas de muerte en todo el mundo y se asocia con alto costo. Los resultados rápidos obtenidos desde los hemocultivos positivos son una herramienta importante para la optimización temprana del tratamiento antimicrobiano. Los objetivos de este trabajo fueron evaluar el rendimiento del panel BCID del sistema FilmArrayTM y determinar su impacto en la adecuación del tratamiento antimicrobiano. Se analizaron 127 episodios de bacteriemia. Un porcentaje significativo de los tratamientos (45,8%) fueron cambiados en base a este resultado. La identificación global correcta fue del 89,2% y del 97,2% para los microorganismos incluidos en la base de datos, en tanto que la sensibilidad para la detección de los genes mecA y KPC fue del 100%. El panel BCID de FilmArrayTM es un método rápido y confiable para la detección de los microorganismos relacionados a bacteriemia y de alto impacto en la decisión terapéutica.
Abstract Bacteremia is one of the leading causes of death worldwide and is associated with high cost. The rapid results obtained from positive blood cultures are an important tool for early optimization of antimicrobial therapy. The objectives of this work were to evaluate the performance of the BCID panel of the FilmArrayTM system and determine its impact on the adequacy of the antimicrobial treatment. One hundred and twenty seven episodes of bacteremia were analyzed. A significant percentage of the treatments (45.8%) were changed based on this result. The correct global identification was 89.2% and 97.2% for the microorganisms included in the database, while the sensitivity for the detection of the mecA and KPC genes was 100%. The FilmArrayTM BCID panel is a fast and reliable method for the detection of microorganisms related to bacteremia and has a high impact on the therapeutic decision.
Resumo A bacteremia é uma das principais causas de morte no mundo e está associada a alto custo. Resultados rápidos obtidos de hemoculturas positivas são uma ferramenta importante para a otimização precoce da terapia antimicrobiana. Os objetivos deste trabalho foram avaliar o desempenho do painel BCID do sistema FilmArrayTM e determinar seu impacto na adequação do tratamento antimicrobiano. Foram analisados 127 episódios de bacteremia. Percentual significativo dos tratamentos (45,8%) foi alterado com base nesse resultado. A correta identificação global foi de 89,2% e 97,2% para os microrganismos incluídos na base de dados, enquanto a sensibilidade para detecção dos genes mecA e KPC foi de 100%. O painel FilmArrayTM BCID é um método rápido e confiável para a detecção de microrganismos relacionados à bacteremia e tem alto impacto na decisão terapêutica.
ABSTRACT
Several factors are associated with the progression of chronic hepatitis C: comorbidities, lifestyle, and pathogenic factors, including immune response, apoptosis and heredity. Single nucleotide polymorphisms (SNPs) in the PNPLA3 and TM6SF2 genes are more widely studied genetic risk factors, while CXCL9-11 chemokines produced by hepatocytes in the process of infection are less well studied. Our aim was to evaluate the influence of CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 in liver fibrosis when analysed together with PNPLA3 rs738409 and TM6SF2 rs58542926. The study included 219 patients with chronic hepatitis C. SNP genotyping was performed by real-time PCR. Univariate and multivariate analyses were used to detect the association between SNPs and advanced fibrosis in a recessive genetic model. All SNPs had a minimum allele frequency >5%, and CXCL9 rs10336, CXCL10 rs3921 and CXCL11 rs4619915 were in high linkage disequilibrium (D' ≥ 0.84). In the multivariate analysis, we observed that male gender (P = 0.000), older age (P = 0.025), moderate to intense inflammatory activity (P = 0.002), moderate to accentuated hepatic steatosis (P = 0.026) and the CT genotype of the TM6SF2 rs58542926 SNP (P = 0.014) presented significant associations with advanced fibrosis. Overall, the CXCL9 rs10336, CXCL10 rs3921, CXCL11 rs4619915 and PNPLA3 rs738409 SNPs did not influence liver fibrosis among patients with chronic hepatitis C.
Subject(s)
Chemokine CXCL10/genetics , Chemokine CXCL11/genetics , Chemokine CXCL9/genetics , Hepacivirus , Hepatitis C, Chronic/genetics , Liver Cirrhosis/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Alleles , Chemokine CXCL10/metabolism , Chemokine CXCL11/metabolism , Chemokine CXCL9/metabolism , Female , Genetic Predisposition to Disease , Genotype , Hepatitis C, Chronic/complications , Hepatitis C, Chronic/virology , Hepatocytes/metabolism , Humans , Lipase/genetics , Lipase/metabolism , Liver Cirrhosis/virology , Male , Membrane Proteins/genetics , Membrane Proteins/metabolism , Middle AgedABSTRACT
Vegetables are one of the most important components in the human diet, but despite their multiple nutritional components, studies have demonstrated the presence of trace metals in their edible parts. In Ecuador, two of the most consumed crops are tomato (Solanum lycopersicum) and lettuce (Lactuca sativa). The importance of these two crops in the Ecuadorian diet, especially in large and touristic locations like the Metropolitan District of Quito, implies food safety-related concerns for locals and visitors. However, no previous studies have quantified the cadmium and lead levels in these two vegetables using samples from Quito markets. Thus, the aim of this study was to determine the cadmium and lead content in both tomato and lettuce products from main nonorganic and organic markets in Quito using a graphite furnace atomic absorption spectrophotometer. The results showed that the cadmium levels were lower than 0.058 in tomatoes and 0.034 mg/kg in lettuce, which are under the respective threshold values (0.100 and 0.200 mg/kg). Regarding lead, levels lower than 0.066 mg/kg were detected in lettuce, which did not exceed the CXS 193-1995 threshold value, while levels in tomatoes were near or exceeded the threshold value (0.100 mg/kg) from four markets (0.209, 0.162, 0.110, 0.099 mg/kg), suggesting a possible risk from tomato consumption. In addition, most vegetables marketed as organic had higher metal content than those coming from nonorganic markets. Based on these results, local health and commercial control authorities should monitor contaminants in food products sold in Quito and other places in Ecuador to ensure their safety.
ABSTRACT
Host single nucleotide polymorphisms (SNPs) in different genes can play a role in chronic hepatitis C virus (HCV) infection and influence the presence of hepatic fibrosis and comorbidities such as hepatic steatosis. We assessed the combined effect of SNPs in the PNPLA3, MTTP, TM6SF2, and IFNL3/IFNL4 genes in 288 Brazilian patients who were chronically infected with HCV. Hepatic fibrosis was observed in 246 (85.4%) patients and hepatic steatosis in 141 (49.0%) patients. PNPLA3 rs738409 (CG/GG) (Pâ¯=â¯0.044) and TM6SF2 rs58542926 (CT) (Pâ¯=â¯0.004) were alone associated with fibrosis, and PNPLA3 rs738409 (Pâ¯<â¯0.05, in distinct genetic models) was associated with steatosis. Multiple logistic regression of each SNP combined with HCV genotype 3 infection showed that MTTP rs1800591 (GT/TT) combined with HCV genotype 3 was associated with a 6.72-fold increased chance of hepatic steatosis (Pâ¯=â¯0.013). In the analysis of SNPs combined 2 by 2, no influence on hepatic fibrosis or steatosis was observed.
Subject(s)
Fatty Liver/genetics , Hepatitis C, Chronic/genetics , Liver Cirrhosis/genetics , Polymorphism, Single Nucleotide , Adult , Aged , Brazil , Carrier Proteins/genetics , Fatty Liver/virology , Female , Genetic Association Studies , Genotype , Hepacivirus/genetics , Hepacivirus/pathogenicity , Hepatitis C, Chronic/virology , Humans , Interferons/genetics , Lipase/genetics , Liver Cirrhosis/virology , Male , Membrane Proteins/genetics , Middle AgedABSTRACT
RESUMEN Introducción: las máscaras laríngeas son dispositivos supraglóticos utilizadas ampliamente en anestesia para el abordaje y mantenimiento de la vía respiratoria. Una de ellas, la Ambu® Aura 40TM, tiene un diseño que le permite ajustarse al entorno de la hipofaringe con su lumen dirigido a la apertura laríngea. Ha demostrado ser adecuada para procedimientos quirúrgicos donde no es necesaria la intubación endotraqueal. Objetivo: determinar la efectividad dicha máscara laríngea para anestesia general en cirugía ortopédica pediátrica. Materiales y métodos: se realizó un estudio descriptivo, prospectivo, transversal, en 135 pacientes intervenidos quirúrgicamente de forma electiva en el Hospital Pediátrico Eliseo Noel Caamaño, de Matanzas, en el periodo enero de 2015- junio 2017. Se tuvo en cuenta el número de intentos y el tiempo para insertar la máscara laríngea, la necesidad de reemplazarla por un tubo endotraqueal y las complicaciones relacionadas con su uso. Resultados: la ML Ambu® Aura 40TM fue efectiva en la mayoría de los pacientes ya que permitió realizar la cirugía sin necesidad de sustituirla por el tubo endotraqueal y la aparición de complicaciones relacionada con su uso fue baja. Conclusiones: la ML Ambu® Aura 40TM fue efectiva ya que en la mayoría de los pacientes fue insertada correctamente en el primer intento y un tiempo inferior a los 20 segundos. Solo una minoría necesitó que fuera reemplazada por el tubo endotraqueal, y la aparición de complicaciones relacionada con su uso fue baja (AU).
ABSTRACT Introduction: laryngeal mask are supra glottal devices widely used in anesthetics for approaching and maintaining the airway. One of them, the Ambu® Aura 40TM, has a design allowing to adjust to the surroundings of hypo-pharynx with its lumen directed to the pharyngeal opening. It has demonstrated to be adequate for surgical procedures when there is no need of endotracheal intubation. Objective: to determine the effectiveness of that laryngeal mask for general anesthetic in pediatric orthopedic surgery. Materials and methods: a cross-sectional, prospective, descriptive study was carried out in 135 patients who underwent elective surgical intervention in the Pediatric Hospital ?Eliseo Noel Caamaño?, of Matanzas, in the period January 2015- June 2017. The number of attempts and the time needed to insert laryngeal mask, the necessity of changing it for an endotracheal tube, and complications related to its usage were taking into account. Results: Ambu® Aura 40TM laryngeal mask was effective in most patients, due to it allowed to perform the surgery without need of changing it for an endotracheal tube, and the low appearance of complications related to its use. Conclusions: Ambu® Aura 40TM laryngeal mask was effective because it was inserted correctly at the first attempt, in a time less than 20 seconds. Only a minority needed to replace it by endotracheal tube, and the appearance of complications related to its use were low (AU).
Subject(s)
Humans , Child, Preschool , Child , Adolescent , Pediatrics , Effectiveness , Laryngeal Masks/statistics & numerical data , Orthopedic Procedures , Anesthesia, General/instrumentation , Epidemiology, Descriptive , Cross-Sectional Studies , Prospective Studies , Laryngeal Masks/adverse effects , Hospitals, PediatricABSTRACT
The fungal cell wall building processes are the ultimate determinants of hyphal shape. In Neurospora crassa the main cell wall components, ß-1,3-glucan and chitin, are synthesized by enzymes conveyed by specialized vesicles to the hyphal tip. These vesicles follow different secretory routes, which are delicately coordinated by cargo-specific Rab GTPases until their accumulation at the Spitzenkörper. From there, the exocyst mediates the docking of secretory vesicles to the plasma membrane, where they ultimately get fused. Although significant progress has been done on the cellular mechanisms that carry cell wall synthesizing enzymes from the endoplasmic reticulum to hyphal tips, a lot of information is still missing. Here, the current knowledge on N. crassa cell wall composition and biosynthesis is presented with an emphasis on the underlying molecular and cellular secretory processes.
ABSTRACT
The aim of the study was to evaluate the food intake of pregnant women with gestational diabetes mellitus (GDM) according to two methods of dietary guidance. A randomised controlled clinical trial was conducted by appointment with a nutritionist and by using data from hospital records (2011-2014). The study population comprised adult women diagnosed with GDM treated in a public maternity hospital in Rio de Janeiro, Brazil. The control group (CG) received nutritional advice by the traditional method and the intervention group (IG) were instructed on carbohydrate counting. The analysis of food intake and the consumption of processed foods (PF) and ultra-processed foods (UPF) were evaluated in the second and third trimester. A total of 286 pregnant women were initially assessed (145 in the CG and 141 in the IG). It was observed that 89/120 (74·2 %) and 183/229 (79·9 %) consumed PF daily in the second and third trimesters, respectively, whereas 117/120 (97·5 %) and 225/231 (97·4 %) consumed UPF daily in the second and third trimesters, respectively. When analysing the intake of macronutrients (%) by quartiles, women who had fat intake in the third quartile had the highest average postprandial blood glucose compared with those who consumed fat in the second quartile (P=0·02). The consumption of PF and UPF was high and dietary intake was similar in both groups, regardless of dietary guidance method deployed, suggesting that both methods tested in the study can be used for monitoring the nutritional status of pregnant women with GDM.
Subject(s)
Diabetes, Gestational/diet therapy , Eating , Nutrition Therapy/methods , Adult , Brazil , Counseling , Diet , Dietary Carbohydrates/administration & dosage , Female , Gestational Age , Humans , Nutrition Assessment , Pregnancy , Single-Blind MethodABSTRACT
This study aimed to develop community educational activities in Brazilian primary health care settings. A randomized controlled community trial was conducted to encourage fruit and vegetable consumption (FV-RCT) in a representative sample of consumers aged 20 years or older in a Brazilian city. The fruit and vegetable consumption was classified according to the transtheoretical model's stages of change, reflecting different degrees of readiness for change. The educational activities were based on the transtheoretical model and a problematizing-dialogic pedagogy, planned by an interdisciplinary team, using information collected in a qualitative pilot study. The actions were conducted over seven months, and baseline data were collected from 1483 participants. The educational strategies included workshops interspersed with motivational messages conveyed via postcard, interactive environment-based activities, and informative material. In the workshops, different techniques were used - conversation circles, image theatre, self-portraits, cooking and art as experience. The applied intervention based on the chosen theories implied in a refinement of the intervention, but, nevertheless, proved to be feasible for large population groups and to the scenario of health services. Thus, this interdisciplinary FV-RCT study represents an effort to advance methodological issues and provide theoretical subsidies for actions.