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Taenia solium is the most common parasite infection of the brain, causing neurocysticercosis and typically found in rural communities with free-ranging pigs. Identification of transmission in rural areas is essential for its control. Risk factors and transmission of the parasite were evaluated in three rural Venezuelan communities (Valle del Rio and Potrero Largo, Cojedes state; and Palmarito, Portuguesa state) by a questionnaire (112 households) and coprological (492 samples) and serological (433 human and 230 porcine sera) analysis, respectively. Typical risk factors were found in all three communities: free-foraging pig husbandry, deficient sanitary conditions, high open defecation and ignorance of the parasite life cycle. Coprological examinations revealed a high level of soil-transmitted parasites. Importantly, two T. solium adult worm carriers were identified in each of the three communities. Anti-metacestode antibodies and the HP10 secreted metacestode glycoprotein were detected at significant levels in human and porcine sera in Valle del Rio, Potrero Largo and Palmarito. In conclusion, these communities may be considered to be endemic for taeniasis/cysticercosis, and the instigation of an appropriate control programme is recommended.
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Anticorpos Anti-Helmínticos/sangue , Cisticercose/epidemiologia , População Rural , Doenças dos Suínos/epidemiologia , Doenças dos Suínos/parasitologia , Teníase/epidemiologia , Adulto , Animais , Antígenos de Helmintos/análise , Cisticercose/imunologia , Características da Família , Fezes/parasitologia , Humanos , Fatores de Risco , Estudos Soroepidemiológicos , Suínos , Doenças dos Suínos/imunologia , Taenia solium/imunologia , Teníase/imunologia , VenezuelaRESUMO
ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February, who had been discharged or died, up to 29th April, 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV-2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) and cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345IU/L and age ≥65 years are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.
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Anticorpos Monoclonais Humanizados , Dessensibilização Imunológica , Mastocitose Sistêmica , Mieloma Múltiplo , Humanos , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/imunologia , Dessensibilização Imunológica/métodos , Mastocitose Sistêmica/tratamento farmacológico , Mastocitose Sistêmica/imunologia , Mastocitose Sistêmica/diagnóstico , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/efeitos adversosRESUMO
In 2019, Europe will adopt a no-discards policy in fisheries. This entails the landing of captured species unless strong evidence is provided supporting their survival and recovery after fishing. Thus, research on this topic is gaining momentum. Bottom-trawling, as a non-selective fishing method, is characterized by a high proportion of discards including vulnerable key species, such as demersal sharks. Their survival may also depend on capture depth. By paralleling onboard and laboratory experiments with the small-spotted catshark, Scyliorhinus canicula, we offer a robust experimental design to assess the survival of discarded sharks. Catsharks were captured by bottom-trawling at two depths (shallow ~89â¯m and deep ~479â¯m). Blood samples were collected following trawl capture and analyzed for stress biomarkers (lactate, osmolality, phosphate, urea). During recovery in onboard tanks, behavior was video-recorded and fish were re-sampled after 24â¯h. A second experiment was conducted in laboratory facilities to simulate air-exposure after trawling and to analyze the physiological recovery. Our results showed that 95.7% of the animals survived 24â¯h after trawling. We confirmed that trawling elicited acute stress responses in catshark but that they managed to recover. This was demonstrated by lactate concentrations that were 2.6â¯mM upon capture, but recovered to assumed baselines after 24â¯h (0.2â¯mM). Non-invasive video monitoring revealed behavioral differences with depth, whereby those captured at 89â¯m depth required longer to recover than those captured at 479â¯m depth. Implementation of standardized survival studies by fishery managers can benefit from holistic physiological approaches, such as the one proposed here.
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Pesqueiros , Tubarões/fisiologia , Animais , Humanos , Taxa de SobrevidaRESUMO
WHAT IS KNOWN AND OBJECTIVE: This study developed a population pharmacokinetic (PK) model of levetiracetam (LEV) for treating neonatal seizures (NS) and determined the influence of clinically relevant covariates to explain the interindividual variability and residual error. METHODS: Twenty newborns admitted to the Neonatal Intensive Care Unit at the Hospital Central "Dr. Ignacio Morones Prieto" were included. LEV doses were administered by intermittent infusion. Blood samples were drawn 3 times post-infusion. Levetiracetam was quantified by a chromatographic technique. NONMEM software was used to determine the population PK model of LEV in neonates and the influence of clinical covariates on drug disposition. RESULTS AND DISCUSSION: The LEV PK in neonates is described by a one-compartment open model with first-order elimination. The influence of creatinine clearance (CRCL) and body weight (BW) on clearance (CL[L/h] = 0.47*CRCL), as well as the volume of the distribution (Vd[L] = 0.65*BW) of LEV, were confirmed, considering interindividual variabilities of 36% and 22%, respectively, and a residual error of 13%. WHAT IS NEW AND CONCLUSION: Based on the PK of LEV in neonates and the influence of the final PK model, a priori dosing guidelines are proposed considering CRCL, BW and LEV plasma concentrations between 6 and 20 mg/L for NS treatment.
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Anticonvulsivantes/farmacocinética , Modelos Biológicos , Piracetam/análogos & derivados , Convulsões/tratamento farmacológico , Anticonvulsivantes/administração & dosagem , Creatinina/análise , Relação Dose-Resposta a Droga , Feminino , Humanos , Recém-Nascido , Levetiracetam , Masculino , Piracetam/administração & dosagem , Piracetam/farmacocinética , Estudos Prospectivos , Distribuição TecidualRESUMO
In euryhaline teleosts, the hypothalamus-pituitary-thyroid and hypothalamus-pituitary-interrenal axes (HPT and HPI, respectively) are regulated in response to environmental stimuli such as salinity changes. However, the molecular players participating in this physiological process in the gilthead seabream (Sparus aurata), a species of high value for aquaculture, are still not identified and/or fully characterized in terms of gene expression regulation. In this sense, this study identifies and isolates the thyrotropin-releasing hormone (trh) mRNA sequence from S. aurata, encoding prepro-Trh, the putative factor initiating the HPT cascade. In addition, the regulation of trh expression and of key brain genes in the HPI axis, i.e., corticotrophin-releasing hormone (crh) and corticotrophin-releasing hormone-binding protein (crhbp), was studied when the osmoregulatory status of S. aurata was challenged by exposure to different salinities. The deduced amino acid structure of trh showed 65-81% identity with its teleostean orthologs. Analysis of the tissue distribution of gene expression showed that trh mRNA is, though ubiquitously expressed, mainly found in brain. Subsequently, regulation of gene expression of trh, crh, and crhbp was characterized in fish acclimated to 5-, 15-, 40-, and 55-ppt salinities. In this regard, the brain gene expression pattern of trh mRNA was similar to that found for the crh gene, showing an upregulation of gene expression in seabream acclimated to the highest salinity tested. Conversely, crhbp did not change in any of the groups tested. Our results suggest that Trh and Crh play an important role in the acclimation of S. aurata to hypersaline environments.
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Encéfalo/metabolismo , Hormônio Liberador da Corticotropina/genética , Regulação da Expressão Gênica , Dourada/fisiologia , Hormônio Liberador de Tireotropina/genética , Sequência de Aminoácidos , Animais , Filogenia , Salinidade , Dourada/genética , Homologia de Sequência , Estresse FisiológicoRESUMO
BACKGROUND: Natural and industrial environments are dynamic with respect to substrate availability and other conditions like temperature and pH. Especially, metabolism is strongly affected by changes in the extracellular space. Here we study the dynamic flux of central carbon metabolism and storage carbohydrate metabolism under dynamic feast/famine conditions in Saccharomyces cerevisiae. RESULTS: The metabolic flux reacts fast and sensitive to cyclic perturbations in substrate availability. Compared to well-documented stimulus-response experiments using substrate pulses, different metabolic responses are observed. Especially, cells experiencing cyclic perturbations do not show a drop in ATP with the addition of glucose, but an immediate increase in energy charge. Although a high glycolytic flux of up to 5.4 mmol g DW-1 h-1 is observed, no overflow metabolites are detected. From famine to feast the glucose uptake rate increased from 170 to 4788 µmol g DW-1 h-1 in 24 s. Intracellularly, even more drastic changes were observed. Especially, the T6P synthesis rate increased more than 100-fold upon glucose addition. This response indicates that the storage metabolism is very sensitive to changes in glycolytic flux and counterbalances these rapid changes by diverting flux into large pools to prevent substrate accelerated death and potentially refill the central metabolism when substrates become scarce. Using 13C-tracer we found a dilution in the labeling of extracellular glucose, G6P, T6P and other metabolites, indicating an influx of unlabeled carbon. It is shown that glycogen and trehalose degradation via different routes could explain these observations. Based on the 13C labeling in average 15% of the carbon inflow is recycled via trehalose and glycogen. This average fraction is comparable to the steady-state turnover, but changes significantly during the cycle, indicating the relevance for dynamic regulation of the metabolic flux. CONCLUSIONS: Comparable to electric energy grids, metabolism seems to use storage units to buffer peaks and keep reserves to maintain a robust function. During the applied fast feast/famine conditions about 15% of the metabolized carbon were recycled in storage metabolism. Additionally, the resources were distributed different to steady-state conditions. Most remarkably is a fivefold increased flux towards PPP that generated a reversed flux of transaldolase and the F6P-producing transketolase reactions. Combined with slight changes in the biomass composition, the yield decrease of 5% can be explained.
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Isótopos de Carbono/análise , Saccharomyces cerevisiae/metabolismo , Isótopos de Carbono/metabolismo , Glucose/metabolismo , Glicogênio/metabolismo , Glicólise , Marcação por Isótopo , Saccharomyces cerevisiae/química , Saccharomyces cerevisiae/genética , Trealose/metabolismoRESUMO
Recent findings have shown that microbial nitrogen flow and digestible energy of diets are increased when urea is combined with a slow-release urea (SRU) in diets with a starch to acid detergent fibre ratio (S:F) 4:1. This affect is attributable to enhanced synchrony between ruminal N availability for microbial growth and carbohydrate degradation. To verify the magnitude of this effects on lamb performance, an experiment was conducted to evaluate the effects of combining urea and a SRU in diets containing S:F ratios of 3:1, 4:1, or 5:1 on performance, dietary energetics and carcass characteristics of finishing lambs. For that, 40 Pelibuey×Katahdin lambs (36.65±3 kg) were assigned to one of five weight groupings in 20 pens (5 repetition/treatments). The S:F ratio in the diet was manipulated by partially replacing the corn grain and dried distiller's grain with solubles by forage (wheat straw) and soybean meal to reach S:F ratios of 3:1, 4:1 or 5:1. An additional treatment of 4:1 S:F ratio with 0.8% urea as the sole source of non-protein nitrogen was used as a reference for comparing the effect of urea combination vs. conventional urea at the same S:F ratio. There were no treatment effects on dry matter intake (DMI). Compared the urea combination vs urea at the same S:F ratio, urea combination increased (p<0.01) average daily gain (ADG, 18.3%), gain for feed (G:F, 9.5%), and apparent energy retention per unit DMI (8.2%). Irrespective of the S:F ratio, the urea combination improved the observed-to-expected dietary ratio and apparent retention per unit DMI was maximal (quadratic effect, p≤0.03) at an S:F ratio of 4:1, while the conventional urea treatment did not modify the observed-to-expected net energy ratio nor the apparent retention per unit DMI at 4:1 S:F ratio. Urea combination group tended (3.8%, p = 0.08) to have heavier carcasses with no effects on the rest of carcass characteristics. As S:F ratio increased, ADG, G:F, dietary net energy, carcass weight, dressing percentage and longissimus thoracis (LM) area increased linearly (p≤0.02). Combining urea and a slow-release urea product results in positive effects on growth performance and dietary energetics, but the best responses are apparently observed when there is a certain proportion (S:F ratio = 4:1) of starch to acid detergent fibre in the diet.
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Haemolytic uraemic syndrome (HUS) is characterized by haemolytic anaemia, thrombocytopenia and acute renal failure. We studied the activation state of classical and alternative pathways of complement during the acute phase of Shiga toxin-associated HUS by performing a prospective study of 18 patients and 17 age-matched healthy controls to evaluate C3, C3c, C4, C4d, Bb and SC5b-9 levels. SC5b-9 levels were increased significantly in all patients at admission compared to healthy and end-stage renal disease controls, but were significantly higher in patients presenting with oliguria compared to those with preserved diuresis. C3 and C4 levels were elevated significantly at admission in the non-oliguric group when compared to controls. No significant differences were found for C4d values, whereas factor Bb was elevated in all patients and significantly higher in oliguric patients when compared to both controls and non-oliguric individuals. A positive and significant association was detected when Bb formation was plotted as a function of plasma SC5b-9 at admission. Bb levels declined rapidly during the first week, with values not significantly different from controls by days 3 and 5 for non-oligurics and oligurics, respectively. Our data demonstrate the activation of the alternative pathway of complement during the acute phase of Stx-associated HUS. This finding suggests that complement activation may represent an important trigger for the cell damage that occurs during the syndrome.
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Ativação do Complemento/imunologia , Convertases de Complemento C3-C5 da Via Alternativa/imunologia , Complexo de Ataque à Membrana do Sistema Complemento/imunologia , Síndrome Hemolítico-Urêmica/imunologia , Adolescente , Adulto , Criança , Complemento C3/imunologia , Complemento C3c/imunologia , Complemento C4/imunologia , Complemento C4b/imunologia , Feminino , Humanos , Rim/imunologia , Rim/patologia , Masculino , Pessoa de Meia-Idade , Fragmentos de Peptídeos/sangue , Fragmentos de Peptídeos/imunologia , Estudos Prospectivos , Toxina Shiga/imunologia , Adulto JovemRESUMO
As a result of the cost of grains, the replacement of grains by co-products (i.e. DDGS) in feedlot diets is a common practice. This change produces diets that contain a lower amount of starch and greater amount of fibre. Hypothetically, combining feed grade urea (U) with slow release urea (Optigen) in this type of diet should elicit a better synchrony between starch (high-rate of digestion) and fibre (low-rate of digestion) promoting a better microbial protein synthesis and ruminal digestion with increasing the digestible energy of the diet. Four cannulated Holstein steers (213±4 kg) were used in a 4×4 Latin square design to examine the combination of Optigen and U in a finishing diet containing different starch:acid detergent fibre ratios (S:F) on the characteristics of digestive function. Three S:F ratios (3.0, 4.5, and 6.0) were tested using a combination of U (0.80%) and Optigen (1.0%). Additionally, a treatment of 4.5 S:F ratio with urea (0.80% in ration) as the sole source of non-protein nitrogen was used to compare the effect of urea combination at same S:F ratio. The S:F ratio of the diet was manipulated by replacing the corn grain by dried distillers grain with solubles and roughage. Urea combination did not affect ruminal pH. The S:F ratio did not affect ruminal pH at 0 and 2 h post-feeding but, at 4 and 6 h, the ruminal pH decreased as the S:F ratio increased (linear, p<0.05). Ruminal digestion of OM, starch and feed N were not affected by urea combination or S:F ratio. The urea combination did not affect ADF ruminal digestion. ADF ruminal digestion decreased linearly (p = 0.02) as the S:F ratio increased. Compared to the urea treatment (p<0.05) and within the urea combination treatment (quadratic, p<0.01), the flow of microbial nitrogen (MN) to the small intestine and ruminal microbial efficiency were greater for the urea combination at a S:F ratio of 4.5. Irrespective of the S:F ratio, the urea combination improved (2.8%, p = 0.02) postruminal N digestion. As S:F ratio increased, OM digestion increased, but ADF total tract digestion decreased. The combination of urea at 4.5 S:F improved (2%, p = 0.04) the digestible energy (DE) more than expected. Combining urea and Optigen resulted in positive effects on the MN flow and DE of the diet, but apparently these advantages are observed only when there is a certain proportion of starch:ADF in the diet.
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BACKGROUND: Anterior hairline measurements and their possible relationship with androgen levels, sebum production, and skin hydration have not been reported in white Spanish women. MATERIAL AND METHODS: This was a prospective descriptive and analytical observational study conducted on 103 healthy premenopausal white Spanish women recruited from the health staff of Hospital Universitario Virgen Macarena in Seville, Spain. Measurements were made of anterior hairline implantation, sebum levels, and the degree of hydration of the stratum corneum. Androgen levels were also determined in 50 volunteers from this group 3 to 5 days after the end of the menstrual cycle. RESULTS: The mean age of the women was 29.7 years. A widow's peak was observed in 94.17% of the group. The mean dimensions of the widow's peak were a height of 1.01 cm and width of 2.13 cm. The mean hormone levels were within normal limits for our hospital's laboratory with the exception of 17-hydroxyprogesterone, with a mean level of 1.39 ng/mL (range, 0.6-5.9ng/mL; normal limits, 0.15-1.10 ng/mL). The mean prostate specific antigen level was 0.04ng/mL (range 0.02-0.08ng/mL; normal limits, 0.00-0.02ng/mL). CONCLUSIONS: The hairline measurements of the white Spanish women in this study differ from those reported in American women. Knowledge of this normal pattern of anterior hairline implantation can be important in the evaluation of women with female androgenetic alopecia with male pattern, frontal fibrosing alopecia, or other established scarring alopecia seeking a surgical solution by hair transplantation.
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Testa/anatomia & histologia , Cabelo , Adolescente , Adulto , Feminino , Hormônios/sangue , Humanos , Pessoa de Meia-Idade , Estudos Prospectivos , Espanha , População Branca , Adulto JovemRESUMO
The structures and associated functions of biological molecules are driven by noncovalent interactions, which have classically been dominated by the hydrogen bond (H-bond). Introduction of the σ-hole concept to describe the anisotropic distribution of electrostatic potential of covalently bonded elements from across the periodic table has opened a broad range of nonclassical noncovalent (ncNC) interactions for applications in chemistry and biochemistry. Here, we review how halogen bonds, chalcogen bonds and tetrel bonds, as they are found naturally or introduced synthetically, affect the structures, assemblies, and potential functions of peptides and proteins. This review intentionally focuses on examples that introduce or support principles of stability, assembly and catalysis that can potentially guide the design of new functional proteins. These three types of ncNC interactions have energies that are comparable to the H-bond and, therefore, are now significant concepts in molecular recognition and design. However, the recently described H-bond enhanced X-bond shows how synergism among ncNC interactions can be exploited as potential means to broaden the range of their applications to affect protein structures and functions.
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Halogênios , Proteínas , Modelos Moleculares , Proteínas/química , Halogênios/química , Ligação de Hidrogênio , Eletricidade EstáticaRESUMO
The use of porous phoxonic crystals with coupled optical and acoustic response has been proposed as a sensing device. Due to the porous nature of the crystal, each layer of the structure can be connected to the environment. As the optical and acoustic performances of the phoxonic crystal change when a gas permeates the pores due to modifications of the effective refractive index and density of the system, it results that these structures are suitable platforms for the detection of gases. The sensor designed following these premises can detect the composition of ternary gas mixtures through optical measurements, while an acoustic wave induces a structural oscillation. The amplified acoustic wave produces a mechanical deformation of the crystal layers that is maximized in the center a resonant microcavity. Therefore, under such experimental conditions, the sensitivity of the optical response is not only due to the optical property changes caused by the gas mixture in contact with the porous structure but also to changes in the mechanical deformations due to modifications of the acoustic properties. In this work, we discuss the device theoretical behavior as a multiparameter sensor that distinguishes the components and concentrations of a ternary gas mixture through the transfer matrix method. For a prototype combination of CO2-Air-CH4 mixture, the estimated resolution of the proposed device fabricated in porous silicon can be has high as 0.05% (500 ppm) in the concentration of each individual species.
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INTRODUCTION: Rafts are protein-lipid structural nanodomains involved in efficient signal transduction and the modulation of physiological processes of the cell plasma membrane. Raft disruption in the nervous system has been associated with a wide range of disorders. DEVELOPMENT: We review the concept of rafts, the nervous system processes in which they are involved, and their role in diseases such as Parkinson's disease, Alzheimer disease, and Huntington disease. CONCLUSIONS: Based on the available evidence, preservation and/or reconstitution of rafts is a promising treatment strategy for a wide range of neurological disorders.
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Doença de Alzheimer , Cavéolas , Humanos , Cavéolas/química , Cavéolas/metabolismo , Microdomínios da Membrana/química , Microdomínios da Membrana/metabolismo , Colesterol/análise , Colesterol/química , Colesterol/metabolismo , Membrana Celular/metabolismoRESUMO
A patient with chronic inflammatory demyelinating polyradiculoneuropathy and systemic lupus erythematosus arising after rubella vaccination was initially treated with plasmapheresis, corticosteroids and intravenous immunoglobulins, with partial response. After shift to rituximab, most clinical symptoms improved markedly, emphasizing the possible role of this monoclonal antibody in conventional therapy-resistant cases.
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Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/tratamento farmacológico , Corticosteroides/uso terapêutico , Adulto , Feminino , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lúpus Eritematoso Sistêmico/complicações , Polirradiculoneuropatia Desmielinizante Inflamatória Crônica/complicações , Retratamento , Rituximab , Resultado do TratamentoRESUMO
Background: Nonalcoholic fatty liver disease (NAFLD) is a major nonacquired immune deficiency syndrome-defining condition for persons with human immunodeficiency virus (PWH). We aimed to validate noninvasive tests for the diagnosis of NAFLD in PWH. Methods: This is a cross-sectional study of PWH on stable antiretroviral therapy with persistently elevated transaminases and no known liver disease. The area under the receiver operating characteristic curve (AUROC) was calculated to compare the diagnostic accuracy of liver biopsy with abdominal ultrasound, transient elastography (TE) (including controlled attenuation parameter [CAP]), and noninvasive markers of steatosis (triglyceride and glucose index [TyG], hepatic steatosis index [HSI], fatty liver index [FLI]) and fibrosis ([FIB]-4, aminotransferase-to-platelet ratio index [APRI], NAFLD fibrosis score). We developed a diagnostic algorithm with serial combinations of markers. Results: Of 146 patients with increased transaminase levels, 69 underwent liver biopsy (90% steatosis, 61% steatohepatitis, and 4% F ≥3). The AUROC for steatosis was as follows: ultrasound, 0.90 (0.75-1); CAP, 0.94 (0.88-1); FLI, 0.81 (0.58-1); HSI, 0.74 (0.62-0.87); and TyG, 0.75 (0.49-1). For liver fibrosis ≥F3, the AUROC for TE, APRI, FIB-4, and NAFLD fibrosis score was 0.92 (0.82-1), 0.96 (0.90-1), 0.97 (0.93-1), and 0.85 (0.68-1). Optimal diagnostic performance for liver steatosis was for 2 noninvasive combined models of tests with TyG and FLI/HSI as the first tests and ultrasound or CAP as the second tests: AUROC = 0.99 (0.97-1, P < .001) and 0.92 (0.77-1, P < .001). Conclusions: Ultrasound and CAP performed best in diagnosing liver steatosis, and FLI, TyG, and HSI performed well. We propose an easy-to-implement algorithm with TyG or FLI as the first test and ultrasound or CAP as the second test to accurately diagnose or exclude NAFLD.
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BACKGROUND AND AIMS: Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. METHODS: Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson's trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. RESULTS: Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. CONCLUSIONS: Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.
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Resistência à Insulina , MicroRNAs , Moringa oleifera , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Animais , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Epigênese Genética , Insulina/metabolismo , Leptina , Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Moringa oleifera/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Resistina/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Extratos Vegetais/farmacologiaRESUMO
INTRODUCTION: Rafts are function-structural cell membrane nano-domains. They contribute to explain the efficiency of signal transduction at the low physiological membrane concentrations of the signaling partners by their clustering inside specialized signaling domains. DEVELOPMENT: In this article, we review the current model of the membrane rafts and their physio-pathological relevance in the nervous system, including their role in Parkinson, Alzheimer, and Huntington diseases. CONCLUSIONS: Rafts disruption/dysfunction has been shown to relate diverse neurological diseases. Therefore, it has been suggested that preservation of membrane rafts may represent a strategy to prevent or delay neuronal dysfunctions in several diseases.
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ANTECEDENTS AND OBJECTIVE: To describe clinical features, comorbidity, and prognostic factors associated with in-hospital mortality in a cohort of COVID-19 admitted to a general hospital. MATERIAL AND METHODS: Retrospective cohort study of patients with COVID-19 admitted from 26th February 2020, who had been discharged or died up to 29th April 2020. A descriptive study and an analysis of factors associated with intrahospital mortality were performed. RESULTS: Out of the 101 patients, 96 were analysed. Of these, 79 (82%) recovered and were discharged, and 17 (18%) died in the hospital. Diagnosis of COVID-19 was confirmed by polymerase chain reaction to SARS-CoV2 in 92 (92.5%). The mean age was 63 years, and 66% were male. The most frequent comorbidities were hypertension (40%), diabetes mellitus (16%) y cardiopathy (14%). Patients who died were older (mean 77 vs 60 years), had higher prevalence of hypertension (71% vs 33%), and cardiopathy (47% vs 6%), and higher levels of lactate dehydrogenase (LDH) and reactive C protein (mean 662 vs 335 UI/L, and 193 vs 121mg/L respectively) on admission. In a multivariant analysis the variables significantly associated to mortality were the presence of cardiopathy (CI 95% OR 2,58-67,07), levels of LDH≥345 IU/L (CI 95% OR 1,52-46,00), and age≥65 years (CI 95% OR 1,23-44,62). CONCLUSIONS: The presence of cardiopathy, levels of LDH≥345 IU/L and age≥65 years, are associated with a higher risk of death during hospital stay for COVID-19. This model should be validated in prospective cohorts.