Left ventricular diastolic indexes are influenced by several variables. In order to evaluate the relationship of these indexes to age, heart rate, sex and to standard echo parameters, 288 normal subjects aged from 20 to 80 years, divided into six age groups, underwent a two-dimensional colour Doppler examination. Doppler examination was performed from the apical four chamber view to evaluate transmitral flow; isovolumic relaxation time (IVRT) was measured from an apical five chamber view. In order to obtain a sufficient number of subjects for an adequate statistical analysis, seven hospitals were involved in the study. Univariate analysis showed that age influences the peak velocity of the E (r = -0.46) and A waves (r = 0.46), the E/A ratio (peak velocities) (r = -0.69), the A wave integral (r = 0.48) and the E/A integral ratio (r = -0.57), the early and late filling fractions (r = -0.48 and r = 0.51 respectively), and the E wave deceleration (r = -0.43) and deceleration time (r = 0.36). In subjects older than 70 years an inversion of the E/A wave ratio was observed. Multivariate analysis confirmed that age has an important influence on left ventricular diastolic indexes but also demonstrated that heart rate has a significant influence. Sex, ejection fraction (EF), and the dimensions of the mitral annulus and the left ventricular posterior wall had less influence on left ventricular diastolic indexes. The mean values of E and A wave acceleration, deceleration and peak velocity were used to depict left ventricular filling morphology in various age groups for three different heart rate values. The conclusions of the study, are: (1) normal left ventricular diastolic parameters were obtained as mean values at seven different hospitals (2) when evaluating left ventricular diastolic function parameters it is important to take into account age and heart rate; E/A inversion in older subjects should be considered the normal mitral flow pattern.

Background Inflammatory bowel disease (IBD), including Crohn disease (CD) and ulcerative colitis (UC), is a multifactorial disorder characterized by chronic inflammation and altered gut barrier function. Dysbiosis, a condition defined by dysregulation of the gut microbiome, has been reported in patients with IBD and in experimental models of colitis. Although several factors have been implicated in directly affecting gut microbial composition, the genetic determinants impacting intestinal dysbiosis in IBD remain relatively unknown. Methods We compared the microbiome of normal, uninflamed wild-type (WT) mice with that of a murine model of UC (ie, Winnie strain). Winnie mice possess a missense mutation in Muc2 that manifests in altered mucus production as early as 4 weeks of age, with ensuing colonic inflammation. To better address the potential role of mutant Muc2 in promoting dysbiosis in Winnie mice, we evaluated homozygous mutant mice (Winnie-/-) with their WT littermates that, after weaning from common mothers, were caged separately according to genotype. Histologic and inflammatory status were assessed over time, along with changes in their respective microbiome compositions. Results Dysbiosis in Winnie mice was already established at 4 weeks of age, before histologic evidence of gut inflammatory changes, in which microbial communities diverged from that derived from their mothers. Furthermore, dysbiosis persisted until 12 weeks of age, with peak differences in microbiome composition observed between Winnie and WT mice at 8 weeks of age. The relative abundance of Bacteroidetes was greater in Winnie compared with WT mice. Verrucomicrobia was detected at the highest relative levels in 4-week-old Winnie mice; in particular, Akkermansia muciniphila was among the most abundant species found at 4 weeks of age. Conclusions Our results demonstrate that mutant genetic determinants involved in the complex regulation of intestinal homeostasis, such as that observed in Winnie mice, are able to promote early gut dysbiosis that is independent from maternal microbial transfer, including breastfeeding. Our data provide evidence for intestinal dysbiosis attributed to a Muc2-driven mucus defect that leads to colonic inflammation and may represent an important target for the design of future interventional studies.

Inflammatory bowel diseases (IBD) are debilitating chronic inflammatory disorders that develop as a result of a defective immune response toward intestinal bacteria. Intestinal dysbiosis is associated with the onset of IBD and has been reported to persist even in patients in deep remission. We investigated the possibility of a dietary-induced switch to the gut microbiota composition using Winnie mice as a model of spontaneous ulcerative colitis and chow enriched with 1% Bronze tomato. We used the near isogenic tomato line strategy to investigate the effects of a diet enriched in polyphenols administered to mild but established chronic intestinal inflammation. The Bronze-enriched chow administered for two weeks was not able to produce any macroscopic effect on the IBD symptoms, although, at molecular level there was a significant induction of anti-inflammatory genes and intracellular staining of T cells revealed a mild decrease in IL17A and IFNγ production. Analysis of the microbial composition revealed that two weeks of Bronze enriched diet was sufficient to perturb the microbial composition of Winnie and control mice, suggesting that polyphenol-enriched diets may create unfavorable conditions for distinct bacterial species. In conclusion, dietary regimes enriched in polyphenols may efficiently support IBD remission affecting the intestinal dysbiosis.

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In order to find out the normal values and to evaluate the effects of age, heart rate, sex, and haemodynamic and standard echocardiographic parameters on pulmonary venous flow velocity obtained by the transthoracic approach. Doppler pulmonary venous flow parameters were measured in 143 healthy subjects aged from 20 to 80 years. Doppler pulmonary venous flow parameters which had the best correlation with age were: the peak velocity of the systolic wave (r = 0.39) and its integral (r = 0.5), the peak velocity of the diastolic wave (r = -0.6) and its integral (r = -0.44); the systolic (r = 0.68) and diastolic fractions (r = -0.68); the systolic/diastolic peak velocity ratio (r = 0.73) and the systolic/diastolic integral ratio (r = 0.7). The atrial reversal wave did not correlate with age; the atrial reversal wave was more difficult and probably less reliable to measure than the systolic and diastolic waves. The correlations of pulmonary venous flow parameters with mitral flow parameters were also examined. This study showed that, in healthy subjects, despite an increase in the early and atrial waves from the annulus to the tips of the mitral leaflets, there is a similar association between pulmonary venous flow and mitral flow measured at the annulus or at the tips of the mitral leaflets. The intra-observer reproducibility of all the pulmonary venous flow parameters considered were found to be excellent. Moderate inter-observer variability was observed for the systolic, diastolic and atrial reversal wave peak velocities and integrals; however, the systolic/diastolic ratio improved the precision of the measurements. Multivariate analysis showed that age is the principal determinant of the Doppler parameters of pulmonary venous flow: heart rate, sex, body surface area, the size of the left atrium in systole and the left ventricular ejection fraction all influence the Doppler parameters of pulmonary venous flow, even if only slightly.