977 research outputs found
Heart rate variability and target organ damage in hypertensive patients
Background:
We evaluated the association between linear standard Heart Rate Variability (HRV) measures and vascular, renal and cardiac target organ damage (TOD).
Methods:
A retrospective analysis was performed including 200 patients registered in the Regione Campania network (aged 62.4 ± 12, male 64%). HRV analysis was performed by 24-h holter ECG. Renal damage was assessed by estimated glomerular filtration rate (eGFR), vascular damage by carotid intima-media thickness (IMT), and cardiac damage by left ventricular mass index.
Results:
Significantly lower values of the ratio of low to high frequency power (LF/HF) were found in the patients with moderate or severe eGFR (p-value < 0.001). Similarly, depressed values of indexes of the overall autonomic modulation on heart were found in patients with plaque compared to those with a normal IMT (p-value <0.05). These associations remained significant after adjustment for other factors known to contribute to the development of target organ damage, such as age. Moreover, depressed LF/HF was found also in patients with left ventricular hypertrophy but this association was not significant after adjustment for other factors.
Conclusions:
Depressed HRV appeared to be associated with vascular and renal TOD, suggesting the involvement of autonomic imbalance in the TOD. However, as the mechanisms by which abnormal autonomic balance may lead to TOD, and, particularly, to renal organ damage are not clearly known, further prospective studies with longitudinal design are needed to determine the association between HRV and the development of TOD
Nonlinear heart rate variability features for real-life stress detection. Case study : students under stress due to university examination
Background:
This study investigates the variations of Heart Rate Variability (HRV) due to a real-life stressor and proposes a classifier based on nonlinear features of HRV for automatic stress detection.
Methods:
42 students volunteered to participate to the study about HRV and stress. For each student, two recordings were performed: one during an on-going university examination, assumed as a real-life stressor, and one after holidays. Nonlinear analysis of HRV was performed by using Poincaré Plot, Approximate Entropy, Correlation dimension, Detrended Fluctuation Analysis, Recurrence Plot. For statistical comparison, we adopted the Wilcoxon Signed Rank test and for development of a classifier we adopted the Linear Discriminant Analysis (LDA).
Results:
Almost all HRV features measuring heart rate complexity were significantly decreased in the stress session. LDA generated a simple classifier based on the two Poincaré Plot parameters and Approximate Entropy, which enables stress detection with a total classification accuracy, a sensitivity and a specificity rate of 90%, 86%, and 95% respectively.
Conclusions:
The results of the current study suggest that nonlinear HRV analysis using short term ECG recording could be effective in automatically detecting real-life stress condition, such as a university examination
Mechanistic Multiscale Pharmacokinetic Model for the Anticancer Drug 2’,2’‐difluorodeoxycytidine (Gemcitabine) in Pancreatic Cancer
The aim of this work is to build a mechanistic multiscale pharmacokinetic model for the anticancer drug 2’, 2’-difluorodeoxycytidine
(gemcitabine, dFdC), able to describe the concentrations of dFdC metabolites in the pancreatic tumor tissue in dependence
of physiological and genetic patient characteristics, and, more in general, to explore the capabilities and limitations of this
kind of modeling strategy. A mechanistic model characterizing dFdC metabolic pathway (metabolic network) was developed
using in vitro literature data from two pancreatic cancer cell lines. The network was able to describe the time course of extracellular and intracellular dFdC metabolites concentrations. Moreover, a physiologically-based pharmacokinetic model was
developed to describe clinical dFdC profiles by using enzymatic and physiological information available in the literature. This
model was then coupled with the metabolic network to describe the dFdC active metabolite profile in the pancreatic tumor
tissue. Finally, global sensitivity analysis was performed to identify the parameters that mainly drive the interindividual variability for the area under the curve (AUC) of dFdC in plasma and of its active metabolite (dFdCTP) in tumor tissue. From this
analysis, cytidine deaminase (CDA) concentration was identified as the main driver of plasma dFdC AUC interindividual variability, whereas CDA and deoxycytidine kinase concentration mainly explained the tumor dFdCTP AUC variability. However,
the lack of in vitro and in vivo information needed to characterize key model parameters hampers the development of this
kind of mechanistic approach. Further studies to better characterize pancreatic cell lines and patient enzymes polymorphisms are encouraged to refine and validate the current model
A PBPK model for the study of Azathioprine pharmacokinetics in rats and prediction in humans
Grossi felini in cattività. Indagine sulla situazione in Italia: aspetti gestionali e di conservazione
We present the results of a survey in 11 Italian bodies hosting large felids, with the aim of highlighting their conditions in relation to management problems, particularly with regards to welfare and conservation issues.
Tigers are the most represented species (79 individuals), followed by lions (51 individuals) and leopards (25 individuals). Both an internal and an external area were present in all the visited situations; the surface area available to the animals showed a great variation among different situation, but it was almost always in agreement with the suggested values for these species. The amount of feed offered to the animals was usually higher than the recommended values, the percentage of red meat was higher than that of white meat and usually no mineral or vitamin supplement was added to the diets. In most cases, vaccinations are performed only at birth; animals are treated against external parasites at seasonal changes. Haematological and faecal analysis are scarce.
Matings are not always performed in a rational way. In some cases, this important event is neglected, as animals of both sexes are kept in one group all year round, and therefore matings between related individuals are common.
This survey points out how the situation in most Italian zoos is still far from the standards at which the new legislation is aiming. However, efforts are been made in order to improve the situation and to solve the problems. To this aim, a strict collaboration among zoos, associations and research institutes, also at an international level, is strongly required in order to safeguard animal welfare and to improve conservation strategies for endangered species
Pupillometric analysis for assessment of gene therapy in Leber Congenital Amaurosis patients
Background:
Objective techniques to assess the amelioration of vision in patients with impaired visual function are needed to standardize efficacy assessment in gene therapy trials for ocular diseases. Pupillometry has been investigated in several diseases in order to provide objective information about the visual reflex pathway and has been adopted to quantify visual impairment in patients with Leber Congenital Amaurosis (LCA). In this paper, we describe detailed methods of pupillometric analysis and a case study on three Italian patients affected by Leber Congenital Amaurosis (LCA) involved in a gene therapy clinical trial at two follow-up time-points: 1 year and 3 years after therapy administration.
Methods:
Pupillary light reflexes (PLR) were measured in patients who had received a unilateral subretinal injection in a clinical gene therapy trial. Pupil images were recorded simultaneously in both eyes with a commercial pupillometer and related software. A program was generated with MATLAB software in order to enable enhanced pupil detection with revision of the acquired images (correcting aberrations due to the inability of these severely visually impaired patients to fixate), and computation of the pupillometric parameters for each stimulus. Pupil detection was performed through Hough Transform and a non-parametric paired statistical test was adopted for comparison.
Results:
The developed program provided correct pupil detection also for frames in which the pupil is not totally visible. Moreover, it provided an automatic computation of the pupillometric parameters for each stimulus and enabled semi-automatic revision of computerized detection, eliminating the need for the user to manually check frame by frame. With reference to the case study, the amplitude of pupillary constriction and the constriction velocity were increased in the right (treated eye) compared to the left (untreated) eye at both follow-up time-points, showing stability of the improved PLR in the treated eye.
Conclusions:
Our method streamlined the pupillometric analyses and allowed rapid statistical analysis of a range of parameters associated with PLR. The results confirm that pupillometry is a useful objective measure for the assessment of therapeutic effect of gene therapy in patients with LCA
A Two-Stages Global Sensitivity Analysis in presence of correlated inputs: Application on a Tumor-in-host-growth Inhibition model based on the Dynamic Energy Budget theory
Predicting Aqueous and Intrinsic Solubility of Pharmaceutical Molecules with Neural Networks
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