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Cucullanus carettae Baylis, 1923 (Nematoda: Cucullanidae) is found worldwide in loggerhead turtles (Caretta caretta). Regarding the Mediterranean, C. carettae has been identified in the Tyrrhenian and the Ionian Sea and a unique description of a Cucullanus sp. specimen in loggerheads from the Adriatic Sea has been reported in the literature so far. In the framework of a bio-monitoring project of the Abruzzo and Molise coasts, a parasitological survey was performed on stranded and by-caught sea turtles, at the Istituto Zooprofilattico of Abruzzo and Molise "G. Caporale." During necropsy, the gastrointestinal system of 72 stranded loggerhead turtles was analyzed for the presence of endoparasites and fecal samples were collected for coprological examination. Adult C. carettae (n = 123) was found in the upper intestine of one loggerhead turtle, associated with chronic lymphoplasmocytic enteritis. Additionally, five stool samples (6.9%) were positive for Cucullanus sp. eggs. Molecular characterization of adult nematodes was carried out to study phylogenetic relationships among the Cucullanus species. To our knowledge, this is the first morphological and molecular identification of C. carettae in loggerhead turtles from the Adriatic Sea. Additional studies on the distribution of this parasite in the Mediterranean are encouraged.
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Ascaridoidea/isolamento & purificação , Intestinos/parasitologia , Spirurina/isolamento & purificação , Tartarugas/parasitologia , Animais , Ascaridoidea/classificação , Enterite/parasitologia , Fezes/parasitologia , Feminino , Masculino , Mar Mediterrâneo , Filogenia , Spirurina/classificaçãoRESUMO
Chemical and organoleptic properties of dairy products largely depend on the action of microorganisms that tend to be selected in cheese during ripening in response to the availability of specific substrates. The aim of this work was to evaluate the effects of a diet enriched with hemp seeds on the microbiota composition of fresh and ripened cheese produced from milk of lactating ewes. Thirty-two half-bred ewes were involved in the study, in which half (control group) received a standard diet, and the other half (experimental group) took a diet enriched with 5% hemp seeds (on a DM basis) for 35 d. The dietary supplementation significantly increased the lactose in milk, but no variations in total fat, proteins, caseins, and urea were observed. Likewise, no changes in total fat, proteins, or ash were detected in the derived cheeses. The metagenomic approach was used to characterize the microbiota of raw milk and cheese. The phyla Proteobacteria and Firmicutes were in equally high abundance in both control and experimental raw milk samples, whereas Bacteroidetes was less abundant. The scenario changed when considering the dairy products. In all cheese samples, Firmicutes was clearly predominant, with Streptococcaceae being the most abundant family in the experimental group. The reduction of taxa observed during ripening was in accordance with the increment (relative abundance) of the starter culture Lactococcus lactis and Streptococcus thermophilus, which together dominate the microbial community. The analysis of the volatile profile in ripened cheeses led to the identification of 3 major classes of compounds: free fatty acids, ketones, and aldehydes, which indicate a prevalence of lipolysis compared with the other biochemical mechanisms that characterize the cheese ripening.
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Cannabis/química , Queijo/análise , Suplementos Nutricionais/análise , Metagenoma , Sementes/química , Compostos Orgânicos Voláteis/análise , Ração Animal/análise , Animais , Dieta/veterinária , Feminino , Lactococcus lactis/fisiologia , Distribuição Aleatória , Sensação , Ovinos/fisiologia , Streptococcus thermophilus/fisiologiaRESUMO
BACKGROUND: As the epidemiology of human Q Fever generally reflects the spread of Coxiella burnetii in ruminant livestock, molecular characterization of strains is essential to prevent human outbreaks. In this study we report the genetic diversity of C. burnetii in central Italy accomplished by MST and MLVA-6 on biological samples from 20 goat, sheep and cow farms. RESULTS: Five MST and ten MLVA profiles emerged from the analysis establishing a part of C. burnetii strain world atlas. In particular, ST32 occurred on 12 farms (60%), prevalently in goat specimens, while ST12 (25%) was detected on 4 sheep and 1 goat samples. ST8 and a variant of this genotype were described on 2 different sheep farms, whereas ST55 was observed on a goat farm. Five complete MLVA profiles different from any other published genotypes were described in this study in addition to 15 MLVA incomplete panels. Despite this, polymorphic markers Ms23, Ms24 and Ms33 enabled the identification of samples sharing the same MST profile. CONCLUSIONS: Integration of such data in international databases can be of further help in the attempt of building a global phylogeny and epidemiology of Q fever in animals, with a "One Health" perspective.
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Coxiella burnetii/genética , Febre Q/veterinária , Animais , Bovinos , Doenças dos Bovinos/microbiologia , Variação Genética/genética , Técnicas de Genotipagem/veterinária , Doenças das Cabras/microbiologia , Cabras , Itália , Febre Q/microbiologia , Ovinos , Doenças dos Ovinos/microbiologiaRESUMO
Fast real-time PCR TaqMan assays were developed and validated for species identification in dairy products. Based on the amplification of 12S rRNA and cytB partial genes of mitochondrial DNA, the methods were demonstrated to be sensitive, fast, and species-specific for Bos taurus, Ovis aries, Bubalus bubalis, and Capra hircus. The limit of detection calculated was lower than 1%, and the efficiency was reported to be higher than 96% in every assay. An internal amplification control was used to detect possible false negatives. The method was validated by means of laboratory-prepared samples mixing different species. Moreover, 18 commercial dairy samples were analyzed by both real-time PCR and isoelectric focusing, the official European Union reference method. The 4 TaqMan assays were confirmed to be a useful tool for milk and dairy product authentication.
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Laticínios/análise , Análise de Alimentos/métodos , Leite/química , Reação em Cadeia da Polimerase em Tempo Real/métodos , Animais , Búfalos , Bovinos , Cabras , Limite de Detecção , Sensibilidade e Especificidade , Carneiro Doméstico , Especificidade da EspécieRESUMO
Progress in medicine goes along with an exponential growth of the cost of drugs and devices. While any person has the right to obtain the best possible benefit from medical care, a state needs to strike a balance between granting the optimal personal benefit to each individual and the needs of the society as a whole. Health systems in all countries therefore are facing a huge problem of distributive justice, as while they should guarantee individual rights, among which the right to health in its broader sense, including physical, psychological and social well-being (therefore not limited to healing, but extending to compliance and quality of life), they must also grant equal access to the healthcare resources and keep the distribution system sustainable.
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Antivirais/administração & dosagem , Tratamento Farmacológico/métodos , Hepatite C Crônica/tratamento farmacológico , Feminino , Humanos , MasculinoRESUMO
Lower 25-hydroxyvitamin D [25(OH)D] serum levels have been associated with the severity of liver fibrosis in genotype 1 chronic hepatitis C patients (G1CHC). In addition, a recent genome-wide study identified genetic variants (rs12785878, near dehydrocholesterol reductase, DHCR7; rs10741657, near CYP2R1; and rs7041, near vitamin D-binding protein, GC) affecting 25(OH)D serum levels in healthy populations. We aimed to assess the association between vitamin D serum levels and its genetic determinants, with the severity of liver fibrosis. Two hundred and sixty patients with biopsy-proven G1CHC were consecutively evaluated. The 25(OH)D serum levels were measured by high-pressure liquid chromatography. All patients were genotyped for DHCR7 rs12785878, CYP2R1 rs10741657 and GC rs7041 single nucleotide polymorphisms. DHCR7 GG genotype (P = 0.003) and the severity of fibrosis (P = 0.03) were independent factors associated with lower 25(OH)D serum levels in multiple linear regression analysis. Interestingly, 53.8% (7/13) of patients with DHCR7 GG genotype had severe liver fibrosis, compared to 27.1% (67/247) of those with DHCR7 TT/TG genotype (P = 0.03). By multivariate logistic regression analysis, severe fibrosis was independently associated with older age (OR, 1.056; 95% CI, 1.023-1.089, P = 0.001), low cholesterol (OR, 0.984; 95% CI, 0.974-0.994, P = 0.002), high triglycerides (OR, 1.008; 95% CI, 1.002-1.015, P = 0.01), low 25(OH)D (OR, 0.958; 95% CI, 0.919-0.999, P = 0.04), DHCR7 GG genotype (OR, 4.222; 95% CI, 1.106-16.120; P = 0.03), moderate-severe steatosis (OR, 2.588; 95% CI, 1.355-4.943; P = 0.004) and moderate-severe necroinflammatory activity (grading) (OR, 2.437; 95% CI, 1.307-4.763; P = 0.001). No associations were found between liver fibrosis and both CYP2R1 and GC genotypes. In patients with G1CHC, GG homozygosis for DHCR7 gene and lower 25(OH)D levels are independently associated with the severity of liver fibrosis.
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Colestanotriol 26-Mono-Oxigenase/genética , Hepatite C Crônica/patologia , Cirrose Hepática/patologia , Oxirredutases atuantes sobre Doadores de Grupo CH-CH/genética , Polimorfismo Genético , Proteína de Ligação a Vitamina D/genética , Vitamina D/sangue , Adulto , Cromatografia Líquida de Alta Pressão , Família 2 do Citocromo P450 , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepatite C Crônica/complicações , Hepatite C Crônica/virologia , Humanos , Cirrose Hepática/genética , Masculino , Pessoa de Meia-Idade , Soro/químicaRESUMO
Soluble CD36 (sCD36) plasma levels, a known marker of cardiometabolic disorders, are associated with surrogate markers of steatosis, while experimental and human studies show a link between CD36 expression in the liver and steatosis. In a cohort of patients with genotype 1 chronic hepatitis C (G1 CHC), we tested the association of sCD36 plasma levels with host and viral factors and sustained virological response (SVR). One hundred and seventy-five consecutive biopsy-proven patients were studied. sCD36 plasma levels were assessed by an in-house ELISA. All biopsies were scored by one pathologist for staging and grading (Scheuer) and graded for steatosis, which was considered moderate-severe if ≥20%. Patients underwent standard of care therapy with pegylated interferon and ribavirin. The severity of steatosis progressively increased according to sCD36 quartiles (P = 0.02); total and low-density lipoprotein (LDL) cholesterol levels were significantly higher in patients in the lower quartile compared to all the others. Gamma-glutamyl transferase (P = 0.02), homoeostasis model assessment (HOMA) score (P = 0.002) and sCD36 (P = 0.04) were independently associated with the severity of steatosis as continuous variable. Multivariate logistic regression analysis showed that HOMA (OR 1.243, 95% CI 1.04-1.484, P = 0.01) and sCD36 (OR 1.445, 95%CI 1.135-1.839, P = 0.003) were independently linked to steatosis ≥20%. No association was found between sCD36 and SVR. CD36 is linked to steatosis and insulin resistance in patients with G1 CHC, but does not predict response to treatment. The potential of sCD36 as a surrogate marker of steatosis should be further investigated.
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Biomarcadores/sangue , Antígenos CD36/sangue , Fígado Gorduroso/patologia , Hepatite C Crônica/patologia , Plasma/química , Adulto , Idoso , Antivirais/uso terapêutico , Biópsia , Ensaio de Imunoadsorção Enzimática , Fígado Gorduroso/diagnóstico , Feminino , Genótipo , Hepacivirus/genética , Hepacivirus/patogenicidade , Hepatite C Crônica/complicações , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferons/uso terapêutico , Fígado/patologia , Masculino , Pessoa de Meia-Idade , Ribavirina/uso terapêutico , Índice de Gravidade de DoençaRESUMO
Methylenetetrahydrofolate reductase status, homocysteine and lipoproteins levels have been associated with severity of disease and both rapid and sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C (CHC). We aimed to assess the association of homocysteine and MTHFR status with serum cholesterol levels and their potential links to both histological findings and virological response, in patients with genotype 1 hepatitis C virus (HCV). A total of 119 consecutive patients were evaluated by biopsy and metabolic measurements. A total of 103 healthy blood donors were used as controls. Serum homocysteine and MTHFR C677T mutation were also evaluated. All patients underwent antiviral therapy with PEG-IFN alfa-2a plus ribavirin. HCV-RNA was assessed at baseline, week 4, week 12, at the end of therapy and after 6 months of follow-up. Mean serum values of homocysteine were higher in patients than in controls (15.8 ± 5.8 µg/L vs 12.5 ± 5.8 µg/L; P < 0.001), with a similar CC, CT and TT MTHFR distribution (23.6%, 48.7% and 27.7% in G1-CHC vs 34%, 48.5% and 17.5% in controls; P = 0.14). In genotype 1, HCV MTHFR TT homozygosis was independently linked to higher LDL (OR 1.016; CI 1.002-1.031; P = 0.03), but not to homocysteine. No association were found between homocysteine, MTHFR and histological features or both rapid virological response (RVR) and SVR. Low cholesterol (OR 0.988, 95%CI 0.975-0.999, P = 0.04) was independently linked to severe fibrosis, and high LDL was the only independent positive predictors of both RVR and SVR (OR 1.036; 95%CI 1.017-1.055; P < 0.001; and OR 1.016; 95%CI 1.001-1.031; P = 0.04 respectively). In patients with genotype 1 hepatitis C, showing higher homocysteine serum levels than controls, MTHFR C677T homozygosis, via modulating cholesterol levels, could interfere with liver fibrosis and response to antiviral therapy.
Assuntos
Hepatite C Crônica/patologia , Lipoproteínas LDL/sangue , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Adulto , Biópsia , Feminino , Genótipo , Hepacivirus/classificação , Hepacivirus/genética , Hepacivirus/isolamento & purificação , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/virologia , Homozigoto , Humanos , Interferon-alfa/administração & dosagem , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis/administração & dosagem , RNA Viral/sangue , Proteínas Recombinantes/administração & dosagem , Ribavirina/administração & dosagem , Carga ViralRESUMO
Under-enrolment of women to randomized clinical trials, including chronic hepatitis C, has long been recognized. The aim of this study was to identify factors predictive of sustained virological response (SVR) to PEG IFN/Ribavirin antiviral therapy in relation to gender and reproductive status of female patients involved. Seven hundred and forty-six treatment-naïve patients (431 men, 315 women) treated with Peg-IFNα-2a (180 µg/week) or Peg-IFNα-2b (1.5 µg/kg/week) plus ribavirin (800-1400 mg/day) for 24 or 48 weeks were studied between 2006 and 2010. Differences in SVR rate, overall and by gender were assessed after adjustment and propensity score matching. SVR was obtained in 44.2% of Peg-IFNα-2a-treated patients and in 51.2% of Peg-IFNα-2b-treated patients (intention-to-treat; P = 0.139). Age, fibrosis stage and genotype 2 and 3 were independently associated with SVR by multivariate analysis. Analysing by gender, the difference in SVR between PEG-IFNα types was not significant in men but highly significant in women (Peg-IFNα-2a:39.1%vs Peg-IFNα-2b:54.4%, P = 0.007). This was attributable to a higher SVR rate with Peg-IFNα-2b in the difficult postmenopausal population (26.9% Peg-IFNα-2a vs 46.0% Peg-IFNα-2b, P = 0.040). In women, absence of menopause, genotype 2 hepatitis C virus infection and use of Peg-IFNα-2b were independently associated with SVR. In conclusion, predictive factors for SVR are different in men and women. Factors differing between genders are menopause, severe steatosis and peg-interferon used. The higher SVR rate with Peg-IFNα-2b in menopausal women is likely attributable to more favourable pharmacokinetics that allows Peg-IFNα-2b to reach visceral fat and oppose the increased cytokine production and enhanced inflammatory status in menopause.
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Antivirais/uso terapêutico , Hepatite C Crônica/tratamento farmacológico , Interferon-alfa/uso terapêutico , Menopausa , Polietilenoglicóis/uso terapêutico , Ribavirina/uso terapêutico , Adolescente , Adulto , Fatores Etários , Idoso , Quimioterapia Combinada/métodos , Feminino , Humanos , Interferon alfa-2 , Masculino , Pessoa de Meia-Idade , Proteínas Recombinantes/uso terapêutico , Fatores Sexuais , Resultado do Tratamento , Adulto JovemRESUMO
Campylobacter jejuni is considered as the main pathogen in human food-borne outbreaks worldwide. Over the past years, several studies have reported antimicrobial resistance (AMR) in C. jejuni strains. In Europe, the official monitoring of AMR comprises the testing of Campylobacter spp. from food-producing animals because this microorganism is responsible for human infections and usually predominant in poultry. Food-producing animals are considered to be a major source of campylobacteriosis through contamination of food products. Concerns are growing due to the current classification of C. jejuni by the WHO as a 'high priority pathogen' due to the emergence of resistance to multiple drugs such as those belonging to the fluoroquinolones, macrolides and other classes, which limits the treatment alternatives. Knowledge about the contributions of different food sources to gastrointestinal disease is fundamental to prioritise food safety interventions and to establish proper control strategies. Assessing the genetic diversity among Campylobacter species is essential to the understanding of their epidemiology and population structure. Using a population genetic approach and grouping the isolates into sequence types within different clonal complexes, it is possible to investigate the source of the human cases. The work programme was aimed for the fellow to assess the AMR of C. jejuni isolated from humans, poultry and birds from wild and urban Italian habitats. Given the public health concern represented by resistant pathogens in food-producing animals and the paucity of data about this topic in Italy, the aim was to identify correlations between phenotypic and genotypic AMR and comparing the origin of the isolates. The work programme allowed the fellow to acquire knowledge, skills and competencies on the web-based tools used by IZSAM to process the NGS data and perform bioinformatics analyses for the identification of epidemiological clusters, the study of AMR patterns in C. jejuni isolates, and the assessment of the human exposure to such AMR pathogens. Furthermore, the fellow became able to transfer the acquired knowledge through innovative web-based didactical tools applied to WGS and clustering of specific food-borne pathogens, with particular reference to C. jejuni. To achieve this objective, 2,734 C. jejuni strains isolated from domestic and wild animals and humans, during the period 2011-2021 were analysed. The resistance phenotypes of the isolates were determined using the microdilution method with EUCAST breakpoints, for the following antibiotics: nalidixic acid, ciprofloxacin, chloramphenicol, erythromycin, gentamicin, streptomycin, tetracycline. The data were complemented by WGS data for each strain, uploaded in the Italian information system for the collection and analysis of complete genome sequence of pathogens isolated from animal, food and environment (GENPAT) developed and maintained at IZSAM; information like clonal complex and sequence type to understand the phylogenetical distance between strains according to their origins were also considered. This work underlines that a better knowledge of the resistance levels of C. jejuni is necessary, and mandatory monitoring of Campylobacter species in the different animal productions is strongly suggested.
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This report describes the draft genomes of two Klebsiella pneumoniae strains that were isolated from two wild boars collected during epidemiological surveillance and monitoring of wild fauna in the Abruzzo and Molise regions. The strains belonged to sequence type 23 (ST23) and ST35, which are frequently reported in clinical cases.
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OBJECTIVES: Transient elastography (TE) is adequate for a diagnosis of cirrhosis, but its accuracy for milder stages of fibrosis is much less satisfactory. The objective of this study was to compare the performance and the discordance rate of acoustic radiation force impulse (ARFI) and TE with liver biopsy in a cohort of chronic hepatitis C (CHC) patients. METHODS: One hundred thirty-nine consecutive patients with CHC were enrolled in two tertiary centers, and evaluated for histological (Metavir score) and biochemical features. All patients underwent TE and ARFI. RESULTS: TE was unreliable in nine patients (6.5%), while in no cases (0%) were ARFI invalid measurements recorded (P=0.029). By area under receiver operating characteristic curve (AUROC), the best cutoff values for TE and ARFI for significant fibrosis (≥F2) were ≥6.5 kPa (AUROC: 0.78) and ≥1.3 m/s (AUROC: 0.86), respectively. For severe fibrosis (F3-F4), these cutoff values were 8.8 kPa (AUROC: 0.83) for TE and 1.7 m/s (AUROC: 0.94) for ARFI. For cirrhosis, TE had its best cutoff at ≥11 kPa (AUROC: 0.80) and ARFI at ≥2.0 m/s (AUROC: 0.89). By pairwise comparison of AUROC, ARFI was significantly more accurate than TE for a diagnosis of significant and severe fibrosis (P=0.024 and P=0.002, respectively), while this difference was only marginal for cirrhosis (P=0.09). By partial AUROC analysis, ARFI performance results significantly higher for all three stages of fibrosis. The average concordance rates of TE and ARFI vs. liver biopsy were 45.4 and 54.7%, respectively. By multivariate analysis, ARFI was not associated with alanine aminotransferase (ALT), body mass index, Metavir grade, and liver steatosis, while TE was significantly correlated with the ALT value (P=0.027). CONCLUSIONS: In a cohort of patients with CHC, ARFI imaging was more accurate than TE for the non-invasive staging of both significant and severe classes of liver fibrosis.
Assuntos
Técnicas de Imagem por Elasticidade/métodos , Hepatite C Crônica/classificação , Cirrose Hepática/classificação , Adulto , Idoso , Biópsia , Estudos de Coortes , Feminino , Hepacivirus/genética , Hepatite C Crônica/patologia , Humanos , Cirrose Hepática/patologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , RNA Viral/sangue , Curva ROC , Reprodutibilidade dos TestesRESUMO
The triglycerides × glucose (TyG) index is a recently proposed surrogate marker of insulin resistance (IR), calculated from fasting plasma triglyceride and glucose concentrations. We tested the host and viral factors associated with Tyg and homeostasis model assessment (HOMA) scores, comparing their associations with histological features and with sustained virological response (SVR) in patients with genotype 1 chronic hepatitis C(G1CHC). Three hundred and forty consecutive patients with G1CHC were considered. All had a liver biopsy scored by one pathologist for staging and grading (Scheuer), and graded for steatosis, which was considered moderate-severe if ≥30%. Anthropometric and metabolic measurements, including IR measured by both HOMA and TyG, were registered. By linear regression analysis, TyG was independently associated with waist circumference (WC), total cholesterol, presence of arterial hypertension, Log10 HCV-RNA and steatosis. Similarly, WC and steatosis were significantly associated with HOMA. Older age (OR, 1.036; 95%CI, 1.004-1.070, P = 0.02), higher WC (1.031; 1.004-1.060; P = 0.02) and higher TyG (11.496; 3.163-41.784; P < 0.001) were linked to moderate-to-severe steatosis (≥30%) by multiple logistic regression analysis. When TyG was replaced by HOMA-IR in the model, the latter remained significantly associated with steatosis ≥30% (1.237; 1.058-1.448; P = 0.008). Receiver operating characteristic curves showed a similar performance of TyG (AUC 0.682) and HOMA-IR (AUC 0.699) in predicting moderate-severe steatosis. No independent associations were found between both TyG and HOMA and fibrosis or SVR. In patients with G1CHC , TyG, an easy-to-calculate and low-cost surrogate marker of IR, is linked to liver steatosis and shows an independent association with viral load.
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Glicemia , Hepatite C Crônica/sangue , Hepatite C Crônica/virologia , Homeostase , Resistência à Insulina , Triglicerídeos/sangue , Adulto , Idoso , Antivirais/uso terapêutico , Índice de Massa Corporal , Quimioterapia Combinada , Fígado Gorduroso , Feminino , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Humanos , Interferon-alfa , Masculino , Pessoa de Meia-Idade , Polietilenoglicóis , RNA Viral/sangue , Proteínas Recombinantes , Ribavirina , Resultado do Tratamento , Carga ViralRESUMO
In chronic hepatitis C, transient elastography (TE) accurately identifies cirrhosis, but its ability to assess significant fibrosis (Metavir > or = F2) is variable. Constitutional and liver disease-related factors may influence TE and here we examined the variables associated with differences. Three hundred consecutive hepatitis C virus (HCV)-RNA positive patients had biochemical tests, TE and a biopsy performed on the same day. The Dale model was used to identify the variables associated with discordance between biopsy and elastography results. In 97 patients (34.2%), TE and histological assessment were discordant. Seventy-six of 286 (26.6%) had stage > or =F2 and TE < 7.1 kPa (false negative); 21 of 286 (7.3%) had stage
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Biópsia , Técnicas de Imagem por Elasticidade , Hepatite C Crônica/complicações , Cirrose Hepática/diagnóstico , Cirrose Hepática/patologia , Índice de Gravidade de Doença , Adulto , Erros de Diagnóstico , Feminino , Histocitoquímica , Humanos , Masculino , Pessoa de Meia-Idade , Curva ROC , Transaminases/sangueRESUMO
Epithelial-mesenchymal transition (EMT) is a complex biological program between physiology and pathology. Here, amniotic epithelial cells (AEC) were used as in vitro model of transiently inducible EMT in order to evaluate the transcriptional insights underlying this process. Therefore, RNA-seq was used to identify the differentially expressed genes and enrichment analyses were carried out to assess the intracellular pathways involved. As a result, molecules exclusively expressed in AEC that experienced EMT (GSTA1-1 and GSTM3) or when this process is inhibited (KLHL14 and KCNE3) were identified. Lastly, the network theory was used to obtain a computational model able to recognize putative controller genes involved in the induction and in the prevention of EMT. The results suggested an opposite role of lysophosphatidic acid (LPA) synthesis and degradation enzymes in the regulation of EMT process. In conclusion, these molecules may represent novel EMT regulators and also targets for developing new therapeutic strategies.
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Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Lisofosfolipídeos/metabolismo , Canais de Potássio de Abertura Dependente da Tensão da Membrana/metabolismo , Transcriptoma/genética , Biologia Computacional , Simulação por Computador , Epistasia Genética/genética , Epistasia Genética/fisiologia , Transição Epitelial-Mesenquimal/genética , Transição Epitelial-Mesenquimal/fisiologia , Glutationa Transferase/genética , Glutationa Transferase/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , RNA-Seq , Reação em Cadeia da Polimerase em Tempo RealRESUMO
Mycoplasma mycoides subsp. mycoides is the etiological agent of contagious bovine pleuropneumonia (CBPP). While several findings on CBPP prevalence in Nigeria were documented, no data were reported about the genomic characterization of Nigerian M. mycoides subsp. mycoides strains. Here, we present the draft genome sequences of two novel M. mycoides subsp. mycoides strains isolated in Nigeria.
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Eosinophilic infiltrate of liver tissue is described in primary cholestatic diseases, hepatic allograft rejection and drug-induced liver injury, but its significance and its implications in chronic hepatitis C are unknown. The aim of this study was to investigate the clinical significance of eosinophilic liver infiltrate in patients with chronic hepatitis C. We retrospectively evaluated 147 patients with chronic hepatitis C. The presence of eosinophilic infiltrate was investigated in liver biopsies, and a numeric count of eosinophilic leucocytes in every portal tract was assessed. An eosinophilic infiltrate of liver tissue (> or =3 cells evaluated in the portal / periportal spaces) was observed in 46 patients (31%), and patients who consumed drugs had an odds ratio (OR) of 4.02 (95% CI: 1.62-9.96) to have an eosinophilic infiltrate in liver biopsy. By logistic regression analysis, the presence of steatosis was independently associated with eosinophilic infiltrate (OR 5.86; 95% CI: 2.46-13.96) and homeostasis model assessment-score (OR 1.18; 95% CI: 1.00-1.39). Logistic regression analysis also showed that fibrosis staging > or = 2 by Scheuer score was associated with grading >1 by Scheuer score (OR 6.82; 95% CI 2.46-18.80) and eosinophilic infiltrate (OR 4.00; 95% CI 1.23-12.91). In conclusion, we observed that the eosinophilic infiltrate of liver tissue was significantly more frequent in patients who assumed drugs, and found a significant association between eosinophilic infiltrate, liver steatosis and liver fibrosis. These preliminary data could lead to a constant assumption of drugs as a co-factor of eosinophils-mediated liver injury in chronic hepatitis C.
Assuntos
Eosinofilia/patologia , Hepatite C Crônica/patologia , Eosinófilos , Fígado Gorduroso/etiologia , Feminino , Hepatite C Crônica/imunologia , Hepatite C Crônica/fisiopatologia , Humanos , Fígado/patologia , Fígado/virologia , Cirrose Hepática/etiologia , Masculino , Estudos RetrospectivosRESUMO
BACKGROUND: Sarcopenia recognises insulin resistance and obesity as risk factors, and is frequently associated with cardiometabolic disorders, including non-alcoholic fatty liver disease (NAFLD). AIM: To test the prevalence of sarcopenia and its relation with the severity of fibrosis (main outcome) and the entire spectrum of liver histology in patients with NAFLD. METHODS: We considered 225 consecutive patients with histological diagnosis of NAFLD (Kleiner score). The skeletal muscle index (%) (total appendicular skeletal muscle mass (kg)/weight (kg) × 100), a validated measure of sarcopenia, was assessed by bioelectrical impedance analysis. Sarcopenia was defined as a skeletal muscle mass index ≤37 in males and ≤28 in females. RESULTS: The prevalence of sarcopenia showed a linear increase with the severity of fibrosis, and severe fibrosis (F3-F4) was more than doubled in sarcopenia (48.3% vs. 20.4% in fibrosis ≤F2, P < 0.001). After adjusting for confounders, the association of sarcopenia with severe fibrosis was maintained (OR 2.36, CI 1.16-4.77, P = 0.01), together with age > 50 (OR 6.53, CI 2.95-14.4, P < 0.001), IFG/Diabetes (OR 2.14, CI 1.05-4.35, P = 0.03) and NASH (OR 13.3, CI 1.64-108.1, P = 0.01). Similarly, a significant association was found between sarcopenia and NASH (P = 0.01), steatosis severity (P = 0.006), and ballooning (P = 0.01), but only the association with severe steatosis was maintained (OR 2.02, CI 1.06-3.83, P = 0.03) after adjusting for confounders. CONCLUSIONS: In Western patients with NAFLD, with high prevalence of metabolic disorders and advanced liver disease, sarcopenia was associated with the severity of fibrosis and steatosis, independently of hepatic and metabolic risk factors. Studies are needed to assess the impact of interventions to reduce sarcopenia on NAFLD progression.
Assuntos
Cirrose Hepática/diagnóstico , Cirrose Hepática/epidemiologia , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Sarcopenia/diagnóstico , Sarcopenia/epidemiologia , Adulto , Idoso , Estudos Transversais , Progressão da Doença , Feminino , Humanos , Resistência à Insulina/fisiologia , Cirrose Hepática/sangue , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/sangue , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Estudos Prospectivos , Fatores de Risco , Sarcopenia/sangue , Índice de Gravidade de DoençaRESUMO
BACKGROUND: The accuracy of available non-invasive tools for staging severe fibrosis in patients with nonalcoholic fatty liver disease (NAFLD) is still limited. AIM: To assess the diagnostic performance of paired or serial combination of non-invasive tools in NAFLD patients. METHODS: We analysed data from 741 patients with a histological diagnosis of NAFLD. The GGT/PLT, APRI, AST/ALT, BARD, FIB-4, and NAFLD Fibrosis Score (NFS) scores were calculated according to published algorithms. Liver stiffness measurement (LSM) was performed by FibroScan. RESULTS: LSM, NFS and FIB-4 were the best non-invasive tools for staging F3-F4 fibrosis (AUC 0.863, 0.774, and 0.792, respectively), with LSM having the highest sensitivity (90%), and the highest NPV (94%), and NFS and FIB-4 the highest specificity (97% and 93%, respectively), and the highest PPV (73% and 79%, respectively). The paired combination of LSM or NFS with FIB-4 strongly reduced the likelihood of wrongly classified patients (ranging from 2.7% to 2.6%), at the price of a high uncertainty area (ranging from 54.1% to 58.2%), and of a low overall accuracy (ranging from 43% to 39.1%). The serial combination with the second test used in patients in the grey area of the first test and in those with high LSM values (>9.6 KPa) or low NFS or FIB-4 values (<-1.455 and <1.30, respectively) overall increased the diagnostic performance generating an accuracy ranging from 69.8% to 70.1%, an uncertainty area ranging from 18.9% to 20.4% and a rate of wrong classification ranging from 9.2% to 11.3%. CONCLUSION: The serial combination of LSM with FIB-4/NFS has a good diagnostic accuracy for the non-invasive diagnosis of severe fibrosis in NAFLD.
Assuntos
Cirrose Hepática/diagnóstico , Hepatopatia Gordurosa não Alcoólica/diagnóstico , Adulto , Idoso , Algoritmos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/patologia , Sensibilidade e EspecificidadeRESUMO
BACKGROUND: In HCV-infected cirrhotic patients with successfully treated early hepatocellular carcinoma (HCC), the time to HCC recurrence and the effects of sustained viral eradication (SVR) by interferon (IFN)-based or IFN-free regimens on HCC recurrence remain unclear. AIM: To perform an indirect comparison of time to recurrence (TTR) in patients with successfully treated early HCC and active HCV infection with those of patients with SVR by IFN-based and by IFN-free regimens. METHODS: We evaluated 443 patients with HCV-related cirrhosis and Barcelona Clinic Liver Cancer Stage A/0 HCC who had a complete radiological response after curative resection or ablation. Active HCV infection was present in 328, selected from the Italian Liver Cancer group cohort; 58 patients had SVR achieved by IFN-free regimens after HCC cure, and 57 patients had SVR achieved by IFN-based regimens after HCC cure. Individual data of patients in the last two groups were extracted from available publications. RESULTS: TTR by Kaplan-Meier curve was significantly lower in patients with active HCV infection compared with those with SVR both by IFN-free (P = 0.02) and by IFN-based (P < 0.001) treatments. TTR was similar in patients with SVR by IFN-free or by IFN-based (P = 0.49) strategies. CONCLUSION: In HCV-infected, successfully treated patients with early HCC, SVR obtained by IFN-based or IFN-free regimens significantly reduce tumour recurrence without differences related to the anti-viral strategy used.