RESUMEN
Perturbations in the gut microbiome have been associated with colorectal cancer (CRC), with the colonic overabundance of Fusobacterium nucleatum shown as the most consistent marker. Despite its significance in the promotion of CRC, genomic studies of Fusobacterium is limited. We enrolled 43 Vietnamese CRC patients and 25 participants with non-cancerous colorectal polyps to study the colonic microbiomes and genomic diversity of Fusobacterium in this population, using a combination of 16S rRNA gene profiling, anaerobic microbiology, and whole genome analysis. Oral bacteria, including F. nucleatum and Leptotrichia, were significantly more abundant in the tumour microbiomes. We obtained 53 Fusobacterium genomes, representing 26 strains, from the saliva, tumour and non-tumour tissues of six CRC patients. Isolates from the gut belonged to diverse F. nucleatum subspecies (nucleatum, animalis, vincentii, polymorphum) and a potential new subspecies of Fusobacterium periodonticum. The Fusobacterium population within each individual was distinct and in some cases diverse, with minimal intra-clonal variation. Phylogenetic analyses showed that within four individuals, tumour-associated Fusobacterium were clonal to those isolated from non-tumour tissues. Genes encoding major virulence factors (Fap2 and RadD) showed evidence of horizontal gene transfer. Our work provides a framework to understand the genomic diversity of Fusobacterium within the CRC patients, which can be exploited for the development of CRC diagnostic and therapeutic options targeting this oncobacterium.
Asunto(s)
Neoplasias Colorrectales , Microbiota , Humanos , ARN Ribosómico 16S/genética , Filogenia , Fusobacterium/genética , Genómica , Neoplasias Colorrectales/microbiología , Pueblo AsiaticoRESUMEN
Candida infections are a significant source of patient morbidity and mortality. Candida albicans is the most common pathogen causing Candida infections. Candida auris is a newly described pathogen that is associated with multi-drug-resistant candidiasis and candidaemia in humans. The antifungal effects of various essential oils and plant compounds have been demonstrated against human pathogenic fungi. In this study, the effect of cinnamon leaf and bark essential oils (CEOs) was determined against both C. albicans and C. auris. The disc diffusion (direct and vapour) and broth microdilution method was used to determine antifungal activity of the EOs against selected strains (C. albicans ATCC 10231, C. albicans ATCC 2091 and C. auris NCPF 8971) whilst the mode of action and haemolysin activity of the CEOs were determined using electron microscopy and light microscopy. Direct and vapour diffusion assays showed greater inhibitory activity of bark CEO in comparison with leaf CEO. The minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of bark CEO for all tested strains was below 0.03% (v/v), which was lower than the MICs of the leaf CEO (0.06-0.13%, v/v) dependent on the strain and the MFCs at 0.25% (v/v). In the morphological interference assays, damage to the cell membrane was observed and both CEOs inhibited hyphae formation. The haemolysin production assay showed that CEOs can reduce the haemolytic activity in the tested C. albicans and C. auris strains. At low concentrations, CEOs have potent antifungal and antihaemolytic activities in vitro against C. albicans and C. auris.Key points⢠Essential oils from Cinnamomum zeylanicum Blume bark and leaf (CBEO and CLEO) demonstrated fungicidal properties at very low concentrations.⢠The antifungal activity of CBEO was greater than that of CLEO consistent with other recent published literature.⢠The mode of action of CBEO and CLEO was damage to the membrane of C. albicans and C. auris.⢠Both CBEO and CLEO inhibited the formation of hyphae and reduced haemolysin production in C. albicans and C. auris. Graphical abstract.
Asunto(s)
Candida albicans , Aceites Volátiles , Antifúngicos/farmacología , Candida , Cinnamomum zeylanicum , Humanos , Pruebas de Sensibilidad Microbiana , Aceites Volátiles/farmacología , Corteza de la Planta , Hojas de la PlantaRESUMEN
BACKGROUND: Establishing normal values and associated variations of three-dimensional speckle-tracking echocardiography- (3DSTE-) derived left ventricular (LV) strain is necessary for accurate interpretation and comparison of measurements. We aimed to perform a meta-analysis of normal ranges of LV global longitudinal strain (GLS), global circumferential strain (GCS), global radial strain (GRS), and global area strain (GAS) measurements derived by 3DSTE and to identify confounding factors that may contribute to variance in reported measures. METHODS: The authors searched four databases, PubMed, Scopus, Embase, and Cochrane Library, through January 2019 using the key terms "left ventricular/left ventricle/left ventricles", "strain/deformation/speckle tracking", and "three dimensional/three-dimensional/three-dimension/three dimension/3D". Studies were included if the articles reported LV strain using 3DSTE in healthy normal subjects, either in the control group or comprising the entire study cohort. The weighted mean was estimated by using the random effects model with a 95% CI. Heterogeneity across studies was assessed using the I2 test. Effects of demographic (age), clinical, and vendor variables were assessed in a metaregression. The National Institutes of Health tools were used to assess the quality of included articles. Publication bias was examined by Begg's funnel plot and Egger's regression test. RESULTS: The search yielded 895 articles. After abstract and full-text screening we included 33 data sets with 2,346 patients for meta-analysis. The reported normal mean values of GLS among the studies varied from -15.80% to -23.40% (mean, -19.05%; 95% CI, -18.18% to -19.93%; I2 = 99.0%), GCS varied from -15.50% to -39.50% (mean, -22.42%; 95% CI, -20.96% to -23.89%, I2 = 99.7%), GRS varied from 19.81% to 86.61% (mean, 47.48%; 95% CI, 41.50%-53.46%; I2 = 99.8%), and GAS varied from -27.40% to -50.80% (mean, -35.03%; 95% CI, -33.19% to -36.87%; I2 = 99.3%). Software for strain analysis was consistently associated with variations in normal strain values (GLS: P = .016; GCS: P < .001; GRS: P < .001; GAS: P < .001). CONCLUSIONS: Variations in the normal ranges across studies were significantly associated with the software used for strain analysis, emphasizing that this factor must be considered in the interpretation of strain data.
Asunto(s)
Ecocardiografía Tridimensional/métodos , Ventrículos Cardíacos/diagnóstico por imagen , Procesamiento de Imagen Asistido por Computador , Función Ventricular Izquierda/fisiología , Adulto , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Valores de Referencia , Reproducibilidad de los ResultadosRESUMEN
A newly reduced macrocyclic lactone antibiotic streptogramin A, 5,6-dihydrovirginiamycin M1 was created by feeding virginiamycin M1 into a culture of recombinant Streptomyces venezuelae. Its chemical structure was spectroscopically elucidated, and this streptogramin A analogue showed twofold higher antibacterial activities against methicillin-resistant Staphylococcus aureus (MRSA) compared with its parent molecule virginiamycin M1. Docking studies using the model of streptogramin A acetyltransferase (VatA) suggested that the newly generated analogue binds tighter with overall lower free energy compared with the parent molecule virginiamycin M1. This hypothesis was validated experimentally through the improvement of efficacy of the new analogue against MRSA strains. The biotransformation approach presented herein could have a broad application in the production of reduced macrocyclic molecules.
Asunto(s)
Antibacterianos/farmacología , Staphylococcus aureus Resistente a Meticilina/efectos de los fármacos , Estreptogramina A/análogos & derivados , Estreptogramina A/biosíntesis , Estreptogramina A/química , Estreptogramina A/farmacología , Virginiamicina/metabolismoRESUMEN
Between 1990 and 1998, we conducted a longitudinal study of 286 female twins aged 8 to 25 years at baseline (60 monozygotic (MZ) pairs, 44 dizygotic (DZ) pairs and 78 unpaired twins), measured on average 2.4 times (range 2-6) with an average of 1.8 years between measurements (range 0.7-6.7 years). Areal bone mineral density (ABMD) at the lumbar spine, total hip and femoral neck, total body bone mineral content (BMC), total body soft tissue composition (lean mass and fat mass) were measured by dual-energy X-ray absorptiometry, and height and menarchial status were also recorded. Median annual changes in height were negligible at 4 years post-menarche. During the 'linear growth' period up to 4 years post-menarche, ABMD at the lumbar spine, total hip and femoral neck increased with annual change in lean mass by 1.7 (S.E.0.1), 1.4 (0.1) and 1.0 (0.1) percent per kilogram per year, respectively (all p<0.001), independently of changes in fat mass or height. During the 'post-linear growth' period, ABMD at the total hip and femoral neck increased with annual change in fat mass by 0.3 (0.1) and 0.5 (0.1) percent per kilogram per year (all p < 0.01), independent of change in lean mass. Annual changes in total body BMC were associated with annual changes in lean mass (1.9 (0.2) percent per kilogram), in fat mass (1.3 (0.2) percent per kilogram) and in height (0.7) (0.2) percent per centimeter) during linear growth, and in fat mass (1.0 (0.1)) and lean mass (0.6 (0.1)) percent per kilogram post-linear growth (all p < 0.001). We conclude that changes in bone mineral measures are strongly associated with changes in lean mass during linear growth, while post-linear growth, changes in fat mass are the predominant, although weaker, predictor. These findings suggest that the strong cross-sectional association between bone mineral measures and lean mass is established during growth and development, and that fat mass emerges as a more powerful determinant of bone change in healthy adult females.
Asunto(s)
Composición Corporal/fisiología , Densidad Ósea/fisiología , Crecimiento/fisiología , Absorciometría de Fotón/métodos , Adolescente , Adulto , Estatura/fisiología , Peso Corporal/fisiología , Niño , Femenino , Cuello Femoral/fisiología , Humanos , Estudios Longitudinales , Vértebras Lumbares/fisiología , Minerales/metabolismo , Huesos Pélvicos/fisiologíaRESUMEN
Longitudinal data from twin pairs may be used to determine how the genetic effects influencing a quantitative trait change with age. Here a model for mixed longitudinal data of Huggins and Loesch [1998] on unrelated individuals is extended to twin studies. The model is fitted using robust statistical methods and a bootstrap procedure is proposed to estimate the percentiles. The method is applied to longitudinal twin data on body mass index in male and female twin pairs aged 5-18 years.
Asunto(s)
Estudios Longitudinales , Carácter Cuantitativo Heredable , Gemelos , Adolescente , Índice de Masa Corporal , Peso Corporal/genética , Niño , Preescolar , Ambiente , Femenino , Variación Genética , Humanos , Masculino , Modelos Genéticos , Modelos EstadísticosRESUMEN
Multivariate genetic models were fitted to data from 44 pairs of MZ and 42 pairs of DZ twin girls on weight, height, and skeletal maturation at the age of menarche, in order to obtain information on genetic relationships of those measures with the age of menarche. The relationships of all three physical measures with this age were largely genetically controlled, but a genetic system controlling skeletal maturity was identified as the only genetic determinant of menarcheal age, independent of those systems of the two remaining physical measures. Heritabilities of all individual traits considered in the study were uniformly high. Possible links of genetic information with hormonal functions determining menarche are discussed.
Asunto(s)
Menarquia/genética , Gemelos Dicigóticos/genética , Gemelos Monocigóticos/genética , Adolescente , Determinación de la Edad por el Esqueleto , Factores de Edad , Estatura , Peso Corporal , Niño , Estrógenos/fisiología , Femenino , Humanos , Menarquia/fisiología , Modelos Genéticos , Análisis MultivarianteRESUMEN
The effect of fragile X on growth in stature was estimated in individuals aged 5-20 years from 50 fragile X families. The multivariate normal model for pedigree analysis was applied to the mixed longitudinal data, which varied with regard to intervals between the measurements and their number in individual subjects, totalling 349 measurement data points from fragile X families, and 292 data points from unrelated normal subjects. The results of genetic and regression analysis showed that, in fragile X boys and girls, total pubertal height gain is impaired, whereas the rate of growth during the preadolescent period is increased, compared with the growth rate of nonfragile X subjects. Moreover, the growth parameters in fragile X males were found to be correlated with the size of CGG trinucleotide expansion. The hypothesis of premature activation of the hypothalamo-pituitary gonadal axis is postulated as the cause of growth impairment in fragile X boys and girls, which should be verified by data on the timing of pubertal stages, hormone levels, and bone maturation.
Asunto(s)
Síndrome del Cromosoma X Frágil/fisiopatología , Trastornos del Crecimiento/genética , Adolescente , Adulto , Estatura , Niño , Femenino , Humanos , Estudios Longitudinales , Masculino , LinajeRESUMEN
The plasma activity of plasminogen activator inhibitor 1 (PAI-1) was measured in 278 clinically healthy subjects (98 men, 180 women; mean age 26 [18-50] years). In 198 of them there were factors increasing the risk of thrombosis, such as smoking, over-weight and/or oral contraceptives. PAI-1 activity was within normal range (less than 4 U/ml) in male nonsmokers of normal weight and in female nonsmokers not taking oral contraceptives. In male smokers (5.76 +/- 1.93 U/ml) and in overweight subjects of both sexes (7.49 +/- 1.87 U/ml) PAI-1 was increased up to 10.6 U/ml as an indication of decreased fibrinolysis capacity. Nonsmoking females on oral contraceptives had lower PAI-1 levels (2.72 +/- 0.86 U/ml) than nonsmokers without hormonal intake (3.21 +/- 1.03 U/ml; P less than 0.001). Apparently the increased risk of thrombosis that occurs on oral contraceptives is not due to increased PAI-1 activity.