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1.
Proc Biol Sci ; 291(2015): 20232292, 2024 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-38264783

RESUMO

Predator-prey interactions have been suggested as drivers of diversity in different lineages, and the presence of anti-predator defences in some clades is linked to higher rates of diversification. Warning signals are some of the most widespread defences in the animal world, and there is evidence of higher diversification rates in aposematic lineages. The mechanisms behind such species richness, however, are still unclear. Here, we test whether lineages that use aposematism as anti-predator defence exhibit higher levels of genetic differentiation between populations, leading to increased opportunities for divergence. We collated from the literature more than 3000 pairwise genetic differentiation values across more than 700 populations from over 60 amphibian species. We find evidence that over short geographical distances, populations of species of aposematic lineages exhibit greater genetic divergence relative to species that are not aposematic. Our results support a scenario where the use of warning signals could restrict gene flow, and suggest that anti-predator defences could impact divergence between populations and potentially have effects at a macro-evolutionary scale.


Assuntos
Anuros , Mimetismo Biológico , Animais , Deriva Genética , Evolução Biológica , Fluxo Gênico
2.
Eur J Clin Microbiol Infect Dis ; 42(4): 481-491, 2023 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-36820931

RESUMO

It is unclear whether norfloxacin predisposes to infections by multidrug-resistant organisms (MDROs). We aimed to evaluate if patients with cirrhosis receiving norfloxacin prophylaxis at the time of the diagnosis of bacterial infections were more likely to present a multidrug-resistant isolate than those without prophylaxis. This is a cross-sectional study of hospitalized patients with cirrhosis and bacterial infections from Argentina and Uruguay (NCT03919032) from September 2018 to December 2020. The outcome variable was a multidrug-resistant bacterial infection. We used inverse probability of treatment weighting to estimate the odds ratio (OR) of norfloxacin on infection caused by MDROs considering potential confounders. Among the 472 patients from 28 centers, 53 (11%) were receiving norfloxacin at the time of the bacterial infection. Patients receiving norfloxacin had higher MELD-sodium, were more likely to have ascites or encephalopathy, to receive rifaximin, beta-blockers, and proton-pump inhibitors, to have a nosocomial or health-care-associated infection, prior bacterial infections, admissions to critical care units or invasive procedures, and to be admitted in a liver transplant center. In addition, we found that 13 (24.5%) patients with norfloxacin and 90 (21.5%) of those not receiving it presented infections caused by MDROs (adjusted OR 1.55; 95% CI: 0.60-4.03; p = 0.360). The use of norfloxacin prophylaxis at the time of the diagnosis of bacterial infections was not associated with multidrug resistance. These results help empiric antibiotic selection and reassure the current indication of norfloxacin prophylaxis in well-selected patients.Study registration number: NCT03919032.


Assuntos
Infecções Bacterianas , Peritonite , Humanos , Norfloxacino/uso terapêutico , Estudos Transversais , Infecções Bacterianas/tratamento farmacológico , Infecções Bacterianas/prevenção & controle , Infecções Bacterianas/microbiologia , Antibacterianos/uso terapêutico , Cirrose Hepática/complicações , Cirrose Hepática/microbiologia , Peritonite/microbiologia , Resistência a Múltiplos Medicamentos , Antibioticoprofilaxia/efeitos adversos
3.
Ann Hepatol ; 28(4): 101110, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37100385

RESUMO

INTRODUCTION AND OBJECTIVES: With the advent of new therapeutic options for patients with hepatocellular carcinoma (HCC) for intermediate or advanced stages of the Barcelona Clinic Liver Cancer (BCLC), regional real-world data regarding prognostic survival factors are of significant importance. PATIENTS AND METHODS: A multicenter prospective cohort study was conducted in Latin America including BCLC B or C patients since 15th May 2018. We report here the second interim analysis focusing on prognostic variables and causes of treatment discontinuation. Cox proportional hazard survival analysis was performed, estimating hazard ratios (HR) and 95% confidence intervals (95% CI). RESULTS: Overall, 390 patients were included, 55.1% and 44.9% were BCLC B and C at the time of study enrollment. Cirrhosis was present in 89.5% of the cohort. Among the BCLC-B group, 42.3% were treated with TACE with a median survival since the first session of 41.9 months. Liver decompensation before TACE was independently associated with increased mortality [HR 3.22 (CI 1.64;6.33); P<.001]. Systemic treatment was initiated in 48.2% of the cohort (n=188), with a median survival of 15.7 months. Of these, 48.9% presented first-line treatment discontinuation (44.4% tumor progression, 29.3% liver decompensation, 18.5% symptomatic deterioration, and 7.8% intolerance), and only 28.7% received second-line systemic treatments. Liver decompensation [HR 2.9 (1.64;5.29); P<.0001], and symptomatic progression [HR 3.9 (1.53;9.78); P=0.004] were independently associated with mortality after first-line systemic treatment discontinuation. CONCLUSIONS: The complexity of these patients, with one-third presenting liver decompensation after systemic therapies, underlines the need for multidisciplinary team management and the central role of hepatologists.


Assuntos
Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Humanos , Carcinoma Hepatocelular/patologia , Neoplasias Hepáticas/patologia , Prognóstico , Estudos Prospectivos , Quimioembolização Terapêutica/efeitos adversos , Estadiamento de Neoplasias , Estudos Retrospectivos , Resultado do Tratamento
4.
Mar Drugs ; 21(6)2023 Jun 10.
Artigo em Inglês | MEDLINE | ID: mdl-37367682

RESUMO

Marine organisms have gained considerable biotechnological interest in recent years due to their wide variety of bioactive compounds with potential applications. Mycosporine-like amino acids (MAAs) are UV-absorbing secondary metabolites with antioxidant and photoprotective capacity, mainly found in organisms living under stress conditions (e.g., cyanobacteria, red algae, or lichens). In this work, five MAAs were isolated from two red macroalgae (Pyropia columbina and Gelidium corneum) and one marine lichen (Lichina pygmaea) by high-performance countercurrent chromatography (HPCCC). The selected biphasic solvent system consisted of ethanol, acetonitrile, saturated ammonium sulphate solution, and water (1:1:0.5:1; v:v:v:v). The HPCCC process for P. columbina and G. corneum consisted of eight separation cycles (1 g and 200 mg of extract per cycle, respectively), whereas three cycles were performed for of L. pygmaea (1.2 g extract per cycle). The separation process resulted in fractions enriched with palythine (2.3 mg), asterina-330 (3.3 mg), shinorine (14.8 mg), porphyra-334 (203.5 mg) and mycosporine-serinol (46.6 mg), which were subsequently desalted by using precipitation with methanol and permeation on a Sephadex G-10 column. Target molecules were identified by HPLC, MS, and NMR.


Assuntos
Líquens , Rodófitas , Alga Marinha , Alga Marinha/química , Líquens/química , Distribuição Contracorrente , Aminoácidos/química , Rodófitas/química , Extratos Vegetais/metabolismo , Raios Ultravioleta
5.
Int J Mol Sci ; 24(4)2023 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-36834508

RESUMO

Cyclic AMP-dependent protein kinase A (PKA) is a ubiquitous enzymatic complex that is involved in a broad spectrum of intracellular receptor signaling. The activity of PKA depends on A-kinase anchoring proteins (AKAPs) that attach to PKAs close to their substrates to control signaling. Although the relevance of PKA-AKAP signaling in the immune system is evident in T cells, its relevance in B and other immune cells remains relatively unclear. In the last decade, lipopolysaccharide-responsive and beige-like anchor protein (LRBA) has emerged as an AKAP that is ubiquitously expressed in B and T cells, specifically after activation. A deficiency of LRBA leads to immune dysregulation and immunodeficiency. The cellular mechanisms regulated by LRBA have not yet been investigated. Therefore, this review summarizes the functions of PKA in immunity and provides the most recent information regarding LRBA deficiency to deepen our understanding of immune regulation and immunological diseases.


Assuntos
Proteínas de Ancoragem à Quinase A , Lipopolissacarídeos , Proteínas de Ancoragem à Quinase A/metabolismo , Transdução de Sinais , Proteínas Quinases Dependentes de AMP Cíclico/metabolismo , Linfócitos T/metabolismo
6.
Clin Infect Dis ; 75(1): e792-e804, 2022 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-34537835

RESUMO

BACKGROUND: The development of effective vaccines against coronavirus disease 2019 is a global priority. CoronaVac is an inactivated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccine with promising safety and immunogenicity profiles. This article reports safety and immunogenicity results obtained for healthy Chilean adults aged ≥18 years in a phase 3 clinical trial. METHODS: Volunteers randomly received 2 doses of CoronaVac or placebo, separated by 2 weeks. A total of 434 volunteers were enrolled, 397 aged 18-59 years and 37 aged ≥60 years. Solicited and unsolicited adverse reactions were registered from all volunteers. Blood samples were obtained from a subset of volunteers and analyzed for humoral and cellular measures of immunogenicity. RESULTS: The primary adverse reaction in the 434 volunteers was pain at the injection site, with a higher incidence in the vaccine than in the placebo arm. Adverse reactions observed were mostly mild and local. No severe adverse events were reported. The humoral evaluation was performed on 81 volunteers. Seroconversion rates for specific anti-S1-receptor binding domain (RBD) immunoglobulin G (IgG) were 82.22% and 84.44% in the 18-59 year age group and 62.69% and 70.37% in the ≥60 year age group, 2 and 4 weeks after the second dose, respectively. A significant increase in circulating neutralizing antibodies was detected 2 and 4 weeks after the second dose. The cellular evaluation was performed on 47 volunteers. We detected a significant induction of T-cell responses characterized by the secretion of interferon-γ (IFN-γ) upon stimulation with Mega Pools of peptides from SARS-CoV-2. CONCLUSIONS: Immunization with CoronaVac in a 0-14 schedule in Chilean adults aged ≥18 years is safe, induces anti-S1-RBD IgG with neutralizing capacity, activates T cells, and promotes the secretion of IFN-γ upon stimulation with SARS-CoV-2 antigens.


Assuntos
COVID-19 , Vacinas Virais , Adolescente , Adulto , Anticorpos Neutralizantes , Anticorpos Antivirais , COVID-19/prevenção & controle , Vacinas contra COVID-19/efeitos adversos , Chile , Método Duplo-Cego , Humanos , Imunogenicidade da Vacina , Imunoglobulina G , Pessoa de Meia-Idade , SARS-CoV-2 , Vacinas de Produtos Inativados/efeitos adversos , Adulto Jovem
7.
Ecol Lett ; 25(6): 1365-1375, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35343052

RESUMO

Nests are essential constructions that determine fitness, yet their structure can vary substantially across bird species. While there is evidence supporting a link between nest architecture and the habitat a species occupies, we still ignore what ecological and evolutionary processes are linked to different nest types. Using information on 3175 species of songbirds, we show that-after controlling for latitude and body size-species that build domed nests (i.e. nests with a roof) have smaller ranges, are less likely to colonise urban environments and have potentially higher extinction rates compared to species with open and cavity nests. Domed nests could be a costly specialisation, and we show that these nests take more time to be built, which could restrict breeding opportunities. These diverse strands of evidence suggest that the transition from domed to open nests in passerines could represent an important evolutionary innovation behind the success of the largest bird radiation.


Assuntos
Aves Canoras , Animais , Evolução Biológica , Tamanho Corporal , Ecossistema , Comportamento de Nidação
8.
Oecologia ; 199(3): 579-587, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35804249

RESUMO

One of the main aspects associated with the diversity in animal colour is the variation in melanization levels. In ectotherms, melanism can be advantageous in aiding thermoregulation through heat absorption. Darker bodies may also serve as a shield from harmful UV-B radiation. Melanism may also confer protection against parasites and predators through improving immunity responses and camouflage in regions with high precipitation, with complex and shaded vegetations and greater diversity of pathogens and parasites. We studied melanism evolution in the globally distributed ant genus Pheidole under the pressures of temperature, UV-B radiation and precipitation, while considering the effects of body size and nest habit, traits that are commonly overlooked. More importantly, we account for worker caste polymorphism, which is marked by distinct roles and behaviours. We revealed for the first time distinct evolutionary trajectories for each worker subcaste. As expected, major workers from species inhabiting locations with lower temperatures and higher precipitation tend to be more melanised. Curiously, we show a slight trend where minor workers of larger species also tend to have darker bodies when inhabiting regions with higher precipitation. Lastly, we did not find evidence for the effects of UV-B radiation and nest habit in the lightness variation of workers. Our paper explores the evolution of ant melanization considering a marked ant worker polymorphism and a wide range of ecological factors. We discuss our findings under the light of the Thermal Melanism Hypothesis, the Photoprotection Hypothesis and the Gloger's Rule.


Assuntos
Formigas , Melanose , Animais , Tamanho Corporal , Clima , Temperatura
9.
Ann Hepatol ; 25: 100344, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33819695

RESUMO

INTRODUCTION AND OBJECTIVES: Failures at any step in the hepatocellular carcinoma (HCC) surveillance process can result in HCC diagnostic delays and associated worse prognosis. We aimed to estimate the prevalence of surveillance failure and its associated risk factors in patients with HCC in Argentina, considering three steps: 1) recognition of at-risk patients, 2) implementation of HCC surveillance, 3) success of HCC surveillance. METHODS: We performed a multi-center cross-sectional study of patients at-risk for HCC in Argentina seen between10.01.2018 and 10.30.2019. Multivariable logistic regression analysis was used to identify correlates of surveillance failure. RESULTS: Of 301 included patients, the majority were male (74.8%) with a mean age of 64 years old. At the time of HCC diagnosis, 75 (25%) patients were unaware of their diagnosis of chronic liver disease, and only 130 (43%) patients were under HCC surveillance. Receipt of HCC surveillance was significantly associated with follow-up by a hepatologist. Of 119 patients with complete surveillance, surveillance failure occurred in 30 (25%) patients. Surveillance failure was significantly associated with alpha fetoprotein ≥20 ng/mL (OR 4.0, CI 95% 1.43-11.55). CONCLUSIONS: HCC surveillance failure was frequent in all the evaluated steps. These data should help guide strategies to improve the implementation and results of HCC surveillance in our country.


Assuntos
Carcinoma Hepatocelular/diagnóstico , Detecção Precoce de Câncer , Neoplasias Hepáticas/diagnóstico , Idoso , Argentina , Carcinoma Hepatocelular/epidemiologia , Carcinoma Hepatocelular/terapia , Estudos Transversais , Diagnóstico Tardio , Feminino , Humanos , Neoplasias Hepáticas/epidemiologia , Neoplasias Hepáticas/terapia , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Prevalência , Fatores de Risco , Determinantes Sociais da Saúde , Falha de Tratamento , alfa-Fetoproteínas/metabolismo
10.
Int J Behav Med ; 28(3): 292-298, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32632745

RESUMO

BACKGROUND: Obesity is highly prevalent around the world, including in Chile. Although various psychological factors have been previously associated with obesity, there has been less attention on the role of weight stigma as a determinant of obesity in Chile. Therefore, the primary aim of this study was to examine the direct effect of weight stigma on obesity and determine whether chronic stress and unhealthy diet mediate the relationship between weight stigma and obesity. METHODS: Faculty and staff from a Chilean university enrolled in the Chilean Study of Psychological Predictors of Obesity and Metabolic Syndrome and completed anthropometric measurements and measures of weight stigma, chronic stress, and unhealthy diet. RESULTS: Three-hundred and eighty-three participants (Mage = 45 years old; 58% female) were included in the present analysis. Structural equation model analyses demonstrated a direct effect of weight stigma on obesity, chronic stress, and unhealthy diet. However, chronic stress and unhealthy diet did not mediate the relationship between weight stigma and obesity. CONCLUSIONS: Weight stigma is an important determinant of obesity and is associated with high levels of chronic stress and unhealthy diet in Chilean adults. Our results provide further support for the multifactorial nature of obesity and can inform future interventions aimed promoting weight loss in people with overweight and obesity.

11.
Mar Drugs ; 19(9)2021 Sep 11.
Artigo em Inglês | MEDLINE | ID: mdl-34564179

RESUMO

Phaeodactylum tricornutum is a rich source of fucoxanthin, a carotenoid with several health benefits. In the present study, high performance countercurrent chromatography (HPCCC) was used to isolate fucoxanthin from an extract of P. tricornutum. A multiple sequential injection HPCCC method was developed combining two elution modes (reverse phase and extrusion). The lower phase of a biphasic solvent system (n-heptane, ethyl acetate, ethanol and water, ratio 5/5/6/3, v/v/v/v) was used as the mobile phase, while the upper phase was the stationary phase. Ten consecutive sample injections (240 mg of extract each) were performed leading to the separation of 38 mg fucoxanthin with purity of 97% and a recovery of 98%. The process throughput was 0.189 g/h, while the efficiency per gram of fucoxanthin was 0.003 g/h. Environmental risk and general process evaluation factors were used for assessment of the developed separation method and compared with existing fucoxanthin liquid-liquid isolation methods. The isolated fucoxanthin retained its well-described ability to induce nuclear translocation of transcription factor FOXO3. Overall, the developed isolation method may represent a useful model to produce biologically active fucoxanthin from diatom biomass.


Assuntos
Diatomáceas/química , Xantofilas/química , Animais , Cromatografia Líquida de Alta Pressão , Distribuição Contracorrente
12.
Rev Med Chil ; 149(8): 1134-1140, 2021 Aug.
Artigo em Espanhol | MEDLINE | ID: mdl-35319699

RESUMO

BACKGROUND: Several risk factors are associated with cognitive impairment in older people, but little attention has been paid to cardiometabolic variables, as well as how cognitive reserve can mediate this association. AIM: To determine the association of cardiometabolic risk factors with cognitive functioning and whether the cognitive reserve mediates this association. MATERIAL AND METHODS: A cross-sectional study with 300 participants with a median age of 56 years (53% male) was conducted. Participants had a cognitive functioning assessment. Fasting glucose, HDL-cholesterol, and blood pressure were measured. RESULTS: A Structural Equation Modeling, revealed a direct effect of cardiometabolic latent risk factors on both a cognitive functioning (ß = -.204; p = .056), and cognitive reserve factors (ß = -.236, p = .04). Cognitive reserve was directly associated with cognitive functioning (ß = .327, p = .01), but did not mediate the association between the cardiometabolic risk factors and cognitive functioning (ß = .077, p = .07). The overall goodness of fitness was excellent χ2 (50) = 58.357, p = .195, comparative fit index = .980, Tucker-Lewis Index = .974, root mean square error of approximation = .023 and Standardized Root Mean Square Residual = .041. CONCLUSIONS: A direct effect of cardiometabolic risk factors on cognitive functioning was observed.


Assuntos
Doenças Cardiovasculares , Disfunção Cognitiva , Reserva Cognitiva , Idoso , Doenças Cardiovasculares/etiologia , Cognição , Disfunção Cognitiva/etiologia , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
13.
Clin Gastroenterol Hepatol ; 18(11): 2554-2563.e3, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32113892

RESUMO

BACKGROUND & AIMS: Little is known about how a sustained virologic response (SVR) to treatment of hepatitis C virus infection with direct-acting antivirals (DAAs) affects patient mortality and development of new liver-related events. We aimed to evaluate the incidence of disease progression in patients treated with DAAs. METHODS: We performed a prospective multicenter cohort study of 1760 patients who received DAA treatment at 23 hospitals in Latin America, from May 1, 2016, through November 21, 2019. We excluded patients with a history of liver decompensation, hepatocellular carcinoma (HCC), or solid-organ transplantation. Disease progression after initiation of DAA therapy included any of the following new events: liver decompensation, HCC, liver transplantation, or death. Evaluation of variables associated with the primary outcome was conducted using a time-dependent Cox proportional hazards models. RESULTS: During a median follow-up period of 26.2 months (interquartile range, 15.3-37.5 mo), the overall cumulative incidence of disease progression was 4.1% (95% CI, 3.2%-5.1%), and after SVR assessment was 3.6% (95% CI, 2.7%-4.7%). Baseline variables associated with disease progression were advanced liver fibrosis (hazard ratio [HR], 3.4; 95% CI, 1.2-9.6), clinically significant portal hypertension (HR, 2.1; 95% CI, 1.2-3.8), and level of albumin less than 3.5 mg/dL (HR, 4.1; 95% CI, 2.3-7.6), adjusted for SVR achievement as a time covariable. Attaining an SVR reduced the risk of liver decompensation (HR, 0.3; 95% CI, 0.1-0.8; P = .016) and de novo HCC (HR, 0.2; 95% CI, 0.1%-0.8%; P = .02) in the overall cohort. CONCLUSIONS: Treatment of hepatitis C virus infection with DAAs significantly reduces the risk of new liver-related complications and should be offered to all patients, regardless of disease stage. Clinicaltrials.gov: NCT03775798.


Assuntos
Carcinoma Hepatocelular , Hepatite C Crônica , Neoplasias Hepáticas , Antivirais/uso terapêutico , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/epidemiologia , Estudos de Coortes , Progressão da Doença , Hepacivirus , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Cirrose Hepática/tratamento farmacológico , Cirrose Hepática/epidemiologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/epidemiologia , Estudos Prospectivos , Fatores de Risco , Resposta Viral Sustentada
14.
Proc Biol Sci ; 287(1929): 20201011, 2020 06 24.
Artigo em Inglês | MEDLINE | ID: mdl-32576112

RESUMO

Many organisms use different antipredator strategies throughout their life, but little is known about the reasons or implications of such changes. For years, it has been suggested that selection by predators should favour uniformity in local warning signals. If this is the case, we would expect high resemblance in colour across life stages in aposematic animals where young and adults share similar morphology and habitat. In this study, we used shield bugs (Hemiptera: Pentatomoidea) to test whether colour and colour diversity evolve similarly at different life stages. Since many of these bugs are considered to be aposematic, we also combined multi-species analyses with predation experiments on the cotton harlequin bug to test whether there is evidence of selection for uniformity in colour across life stages. Overall, we show that the diversity of colours used by both life stages is comparable, but adults are more cryptic than nymphs. We also demonstrate that nymphs and adults of the same species do not tend to look alike. Experiments on our model system suggest that predators can generalise among life stages that look different, and exhibit strong neophobia. Altogether, our results show no evidence of selection favouring colour similarity between adults and nymphs in this speciose clade.


Assuntos
Heterópteros/fisiologia , Pigmentação , Animais , Evolução Biológica , Cor , Ninfa
15.
J Med Virol ; 92(12): 3545-3555, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32749710

RESUMO

INTRODUCTION: Although the effectiveness of direct-acting antivirals (DAAs) for the treatment of chronic hepatitis C virus (HCV) has been reported in real-world settings, predictive factors of treatment failure are lacking. Therefore, we sought to explore the baseline predictors of treatment response to DAAs. METHODS: This was a prospective multicenter cohort study from the Latin American Liver Research Educational and Awareness Network (LALREAN) including patients who received DAA treatment from May 2016 to April 2019. A multivariate logistic regression model was conducted to identify variables associated with unachieved sustained virological response (SVR), defined as treatment failure (odds ratios [OR] and 95% confidence intervals [CIs]). RESULTS: From 2167 patients (55.2% with cirrhosis) who initiated DAA therapy, 89.4% completed a full-course treatment (n = 1938). Median treatment duration was 12 weeks, and 50% received ribavirin. Definitive suspension due to intolerance or other causes was observed in only 1.0% cases (n = 20). Overall non-SVR12 was 4.5% (95% CI, 3.5-5.7). There were no significant differences in treatment failure according to HCV genotypes and the degree of fibrosis. Independently associated variables with DAA failure were liver function impairment according to the Child-Pugh score B OR, 2.09 (P = .06), Child-Pugh C OR, 11.7 (P < .0001); and liver transplant (LT) recipient OR, 3.75 (P = .01). CONCLUSION: In this real-life setting, higher DAA treatment failure rates were observed in patients with decompensated cirrhosis and in LT recipients. These predictive baseline factors should be addressed to individualize the appropriate time-point of DAA treatment (NCT03775798; www. CLINICALTRIALS: gov).

16.
Immunology ; 158(4): 322-339, 2019 12.
Artigo em Inglês | MEDLINE | ID: mdl-31509246

RESUMO

Current treatments for systemic autoimmune diseases partially improve the health of patients displaying low pharmacological efficacy and systemic immunosuppression. Here, the therapeutic potential of transferring tolerogenic dendritic cells (tolDCs) generated with heme-oxygenase inductor cobalt (III) protoporphyrin IX (CoPP), dexamethasone and rosiglitazone for the treatment of systemic autoimmunity was evaluated in two murine models of systemic lupus erythematosus (SLE), MRL-Faslpr and NZM2410 mice. Dendritic cells treated ex vivo with these drugs showed a stable tolerogenic profile after lipopolysaccharide stimulation. Regular doses of tolDCs were administered to anti-nuclear antibody-positive mice throughout 60-70 days, and the clinical score was evaluated. Long-term treatment with these tolDCs was well tolerated and effective to improve the clinical score on MRL-Faslpr lupus-prone mice. Additionally, decreased levels of anti-nuclear antibodies in NZM2410 mice were observed. Although tolDC treatment increased regulatory T cells, no significant reduction of renal damage or glomerulonephritis could be found. In conclusion, these results suggest that the transfer of histone-loaded tolDCs could improve only some SLE symptoms and reduced anti-nuclear antibodies. This is the first study to evaluate antigen-specific tolDC administration to treat SLE. Our report strengthens the clinical relevance of tolDC generation with CoPP, dexamethasone and rosiglitazone and the use of these modified cells as a therapy for systemic autoimmunity.


Assuntos
Células Dendríticas/imunologia , Imunoterapia Adotiva/métodos , Rim/patologia , Lúpus Eritematoso Sistêmico/terapia , Linfócitos T Reguladores/imunologia , Animais , Anticorpos Antinucleares/sangue , Diferenciação Celular , Células Cultivadas , Células Dendríticas/transplante , Dexametasona/metabolismo , Modelos Animais de Doenças , Humanos , Tolerância Imunológica , Lúpus Eritematoso Sistêmico/imunologia , Ativação Linfocitária , Camundongos , Camundongos Endogâmicos MRL lpr , Pirazinas/metabolismo , Pirróis/metabolismo , Rosiglitazona/metabolismo
17.
J Viral Hepat ; 26(11): 1284-1292, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31273860

RESUMO

The ECHO model was developed to expand access to medical care for populations with HCV infection in underserved areas. We aimed to compare HCV treatment outcomes in community-based clinics with the Austral University Hospital (AUH) and to assess improvement in physician knowledge and skills. In October 2015, we established an HCV ECHO clinic at the AUH in Buenos Aires. To evaluate the impact of this programme, we conducted a prospective cohort study comparing treatment for HCV infection at the AUH with healthcare providers from different Argentinean provinces. A survey evaluating skills and competence in HCV care was administered, and results were compared. The primary endpoint was sustained virologic response (SVR) and under direct-acting antivirals. Since the implementation of ECHO clinics, a total of 25 physicians participated in at least one session (median 10.0; IQR 3.0-18.0). SVR rates (n = 437 patients) were 94.2% (95% CI 90.4-96.8) in patients treated at AUH clinic (n = 227/242) and 96.4% (95% CI 92.7-98.5) in those treated at ECHO sites (n = 188/195), with a nonsignificant difference between sites, 2.2% SVR difference (95% CI -0.24-0.06; P = 0.4). We also found a significant improvement in all the evaluated skills and abilities. Replicating the ECHO model helped to improve participants' skills in the management of HCV achieving similar SVR rates. ECHO model was demonstrated to be an effective intervention able to multiply and expand HCV treatment, a critical barrier to access to care that needs to be solved if we are committed with WHO goals to eliminate HCV by 2030.


Assuntos
Competência Clínica , Hepatite C/epidemiologia , Assistência ao Paciente , Padrões de Prática Médica , Telemedicina , Adulto , Idoso , Antivirais/uso terapêutico , Argentina/epidemiologia , Quimioterapia Combinada , Feminino , Geografia , Hepatite C/diagnóstico , Hepatite C/terapia , Hepatite C/virologia , Humanos , Masculino , Pessoa de Meia-Idade , Modelos Teóricos , Resposta Viral Sustentada , Telemedicina/métodos
18.
Liver Int ; 39(6): 1033-1043, 2019 06.
Artigo em Inglês | MEDLINE | ID: mdl-30636361

RESUMO

BACKGROUND & AIMS: Data from Europe and North America have been published regarding the risk of developing hepatocellular carcinoma (HCC) after treatment with direct antiviral agents (DAA). We proposed to evaluate cumulative incidence and associated risk factors for de novo HCC. METHODS: This was a prospective multicentre cohort study from Latin America including 1400 F1-F4-treated patients with DAAs (F3-F4 n = 1017). Cox proportional regression models (hazard ratios, HR and 95% CI) were used to evaluate independent associated variables with HCC. Further adjustment with competing risk regression and propensity score matching was carried out. RESULTS: During a median follow-up of 16 months (IQR 8.9-23.4 months) since DAAs initiation, overall cumulative incidence of HCC was 0.02 (CI 0.01; 0.03) at 12 months and 0.04 (CI 0.03; 0.06) at 24 months. Cumulative incidence of HCC in cirrhotic patients (n = 784) was 0.03 (CI 0.02-0.05) at 12 months and 0.06 (CI 0.04-0.08) at 24 months of follow-up. Failure to achieve SVR was independently associated with de novo HCC with a HR of 4.9 (CI 1.44; 17.32), after adjusting for diabetes mellitus, previous interferon non-responder, Child-Pugh and clinically significant portal hypertension. SVR presented an overall relative risk reduction for de novo HCC of 73% (CI 15%-91%), 17 patients were needed to be treated to prevent one case of de novo HCC in this cohort. CONCLUSIONS: Achieving SVR with DAA regimens was associated with a significant risk reduction in HCC. However, this risk remained high in patients with advanced fibrosis, thus demanding continuous surveillance strategies in this population.


Assuntos
Antivirais/uso terapêutico , Carcinoma Hepatocelular/epidemiologia , Hepatite C Crônica/tratamento farmacológico , Cirrose Hepática/complicações , Neoplasias Hepáticas/epidemiologia , Idoso , Carcinoma Hepatocelular/virologia , Feminino , Hepacivirus/efeitos dos fármacos , Hepatite C Crônica/complicações , Humanos , Incidência , América Latina/epidemiologia , Cirrose Hepática/virologia , Neoplasias Hepáticas/virologia , Masculino , Pessoa de Meia-Idade , Pontuação de Propensão , Modelos de Riscos Proporcionais , Estudos Prospectivos , Fatores de Risco , Resposta Viral Sustentada
19.
Rev Med Chil ; 147(3): 314-321, 2019 Mar.
Artigo em Espanhol | MEDLINE | ID: mdl-31344168

RESUMO

BACKGROUND: Weight-based stigmatization is frequent among overweight and obese people. AIM: To determine the association between weight-based stigmatization, psychological stress, cortisol, negative emotions, and eating behavior in a sample of middle-aged women. MATERIAL AND METHODS: Eighty-two women aged 45 ± 8 years, 55% with overweight or obesity, were randomly allocated to watch a video called "Stigma: the human cost of obesity" or a control video about planet earth. The effect of watching either video on calorie consumption, psychological stress and cortisol reactivity was assessed. Cortisol was measured on four salivary samples. Psychological stress and negative emotions were self-reported. RESULTS: Among women who watched the stigmatizing video, there was a direct association between psychological stress and calorie intake, but negative emotions did not mediate this association. Moreover, psychological stress moderated the association between watching the stigmatizing video and the cortisol output (ß = 0.32; p = 0.005). CONCLUSIONS: Women with high psychological stress have a greater intake of calories. After watching the stigmatizing video, a greater psychological stress is associated with greater cortisol output.


Assuntos
Ingestão de Energia , Obesidade/psicologia , Sobrepeso/psicologia , Estigma Social , Estereotipagem , Estresse Psicológico/psicologia , Adulto , Peso Corporal , Comportamento Alimentar/psicologia , Feminino , Humanos , Pessoa de Meia-Idade , Obesidade/metabolismo , Sobrepeso/metabolismo
20.
Rev Med Chil ; 145(9): 1160-1164, 2017 Sep.
Artigo em Espanhol | MEDLINE | ID: mdl-29424403

RESUMO

Weight stigmatization is defined as the devaluation of others based on weight, a visible and specific characteristic that cannot be hidden. The consequences of weight stigmatization have been studied in victims and healthcare providers. This narrative literature review describes the consequences of weight stigmatization in victims and healthcare practitioners. According to several studies, high levels of psychological dysfunction in victims coexist with negative stereotypes in healthcare professionals, since the latter are exposed to the same negative media messages about obesity. Thus, weight stigmatization contributes to increase the burden of obesity, since when obese patients perceive that they are discriminated by healthcare professionals, their unhealthy behaviors persist and they have a low adherence to obesity treatment and medical recommendations.


Assuntos
Atitude do Pessoal de Saúde , Obesidade/psicologia , Estigma Social , Humanos , Discriminação Social/psicologia
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