A stochastic delay differential model of cerebral autoregulation

Mathematical models of the cardiovascular system and of cerebral autoregulation (CAR) have been employed for several years in order to describe the time course of pressures and flows changes subsequent to postural changes. The assessment of the degree of efficiency of cerebral auto regulation has indeed importance in the prognosis of such conditions as cerebro-vascular accidents or Alzheimer. In the quest for a simple but realistic mathematical description of cardiovascular control, which may be fitted onto non-invasive experimental observations after postural changes, the present work proposes a first version of an empirical Stochastic Delay Differential Equations (SDDEs) model. The model consists of a total of four SDDEs and two ancillary algebraic equations, incorporates four distinct delayed controls from the brain onto different components of the circulation, and is able to accurately capture the time course of mean arterial pressure and cerebral blood flow velocity signals, reproducing observed auto-correlated error around the expected drift

Multi-Objective Optimization of a Vehicle Body by Combining Gradient-based Methods and Vehicle Concept Modelling

Abstract In the automotive field, size optimization procedures can be combined with concept modelling approaches, in order to design a vehicle Body-In-White (BIW) model with optimal static and dynamic performances already in the early design stages. However, this specific optimization problem, with hundreds of design variables, limited design space and often conflicting objectives, makes the choice of the appropriate optimization method really difficult. The aim of this paper is to show an industrial case study, where two different implementations of the classical gradient-based (GB) method are used in combination with a technique for vehicle body concept modelling to achieve a multi-objective BIW optimization of a passenger car

Synthesis and anticancer activity of CDDO and CDDO-me, two derivatives of natural triterpenoids

Triterpenoids are natural compounds synthesized by plants through cyclization of squalene, known for their weak anti-inflammatory activity. 2-cyano-3,12-dioxooleana-1,9(11)-dien-28-oic acid (CDDO), and its C28 modified derivative, methyl-ester (CDDO-Me, also known as bardoxolone methyl), are two synthetic derivatives of oleanolic acid, synthesized more than 20 years ago, in an attempt to enhance the anti-inflammatory behavior of the natural compound. These molecules have been extensively investigated for their strong ability to exert antiproliferative, antiangiogenic, and antimetastatic activities, and to induce apoptosis and differentiation in cancer cells. Here, we discuss the chemical properties of natural triterpenoids, the pathways of synthesis and the biological effects of CDDO and its derivative CDDO-Me. At nanomolar doses, CDDO and CDDO-Me have been shown to protect cells and tissues from oxidative stress by increasing the transcriptional activity of the nuclear factor (erythroid-derived 2)-like 2 (Nrf2). At doses higher than 100 nM, CDDO and CDDO-Me are able to modulate the differentiation of a variety of cell types, both tumor cell lines or primary culture cell, while at micromolar doses these compounds exert an anticancer effect in multiple manners; by inducing extrinsic or intrinsic apoptotic pathways, or autophagic cell death, by inhibiting telomerase activity, by disrupting mitochondrial functions through Lon protease inhibition, and by blocking the deubiquitylating enzyme USP7. CDDO-Me demonstrated its efficacy as anticancer drugs in different mouse models, and versus several types of cancer. Several clinical trials have been started in humans for evaluating CDDO-Me efficacy as anticancer and anti-inflammatory drug; despite promising results, significant increase in heart failure events represented an obstacle for the clinical use of CDDO-Me

Benign and Suspicious Ovarian Masses—MR Imaging Criteria for Characterization: Pictorial Review

Ovarian masses present a special diagnostic challenge when imaging findings cannot be categorized into benign or malignant pathology. Ultrasonography (US), Computed Tomography (CT), and Magnetic Resonance Imaging (MRI) are currently used to evaluate ovarian tumors. US is the first-line imaging investigation for suspected adnexal masses. Color Doppler US helps the diagnosis identifying vascularized components within the mass. CT is commonly performed in preoperative evaluation of a suspected ovarian malignancy, but it exposes patients to radiation. When US findings are nondiagnostic or equivocal, MRI can be a valuable problem solving tool, useful to give also surgical planning information. MRI is well known to provide accurate information about hemorrhage, fat, and collagen. It is able to identify different types of tissue contained in pelvic masses, distinguishing benign from malignant ovarian tumors. The knowledge of clinical syndromes and MRI features of these conditions is crucial in establishing an accurate diagnosis and determining appropriate treatment. The purpose of this paper is to illustrate MRI findings in neoplastic and non-neoplastic ovarian masses, which were assessed into three groups: cystic, solid, and solid/cystic lesions. MRI criteria for the correct diagnosis and characteristics for differentiating benign from malignant conditions are shown in this paper

Sporadic and hereditary hemangioblastoma: The role of endothelial cells

Hemangioblastomas HBs are benign, highly vascularized tumors of the central nervous system. Approximately 75 of HBs are sporadic, while 25 are associated with von Hippel Lindau disease. HBs consist of two main components: A rich capillary network composed of vascular endothelia and pericytes, within large vacuolated stromal cells, which harbor the genetic defect

Age- and sex-related variations in platelet count in Italy: a proposal of reference ranges based on 40987 subjects' data

BACKGROUND AND OBJECTIVES: Although several studies demonstrated that platelet count is higher in women, decreases with age, and is influenced by genetic background, most clinical laboratories still use the reference interval 150-400×10(9) platelets/L for all subjects. The present study was to identify age- and sex-specific reference intervals for platelet count. METHODS: We analysed electronic records of subjects enrolled in three population-based studies that investigated inhabitants of seven Italian areas including six geographic isolates. After exclusion of patients with malignancies, liver diseases, or inherited thrombocytopenias, which could affect platelet count, reference intervals were estimated from 40,987 subjects with the non parametric method computing the 2.5° and 97.5° percentiles. RESULTS: Platelet count was similar in men and women until the age of 14, but subsequently women had steadily more platelets than men. The number of platelets decreases quickly in childhood, stabilizes in adulthood, and further decreases in oldness. The final result of this phenomenon is that platelet count in old age was reduced by 35% in men and by 25% in women compared with early infancy. Based on these findings, we estimated reference intervals for platelet count ×10(9)/L in children (176-452), adult men (141-362), adult women (156-405), old men (122-350) and, old women (140-379). Moreover, we calculated an extended reference interval that takes into account the differences in platelet count observed in different geographic areas. CONCLUSIONS: The age-, sex-, and origin-related variability of platelet count is very wide, and the patient-adapted reference intervals we propose change the thresholds for diagnosing both thrombocytopenia and thrombocytosis in Italy

Fibrinogen levels in relation to colorectal cancer onset: A nested case-cohort study from the Moli-sani cohort

Background: Patients with cancer are commonly characterized by abnormalities in laboratory coagulation tests, underlying a subclinical hypercoagulable condition. Due to the involvement of the hemostatic system in cancer patients, some of its biomarkers, such as fibrinogen, could be a useful tool in predicting cancer risk. We performed a case-cohort study to evaluate the relationship among fibrinogen levels and colorectal cancer (CRC). Methods: In the framework of Moli-sani Study (N = 24,325, enrolled 2005–2010) a subcohort of 1,290 individuals (55.0% women; mean age 55.0 ± 12.0 years) was selected and compared with 126 CRC cases identified during a follow-up of 4.3 years. Incident cases of colorectal cancer were ascertained by direct linkage with hospital discharge forms according to the International Classification of Disease (ICD-9-CM) codes: 153–154. Events were validated through medical records and confirmed by histological reports. Fibrinogen levels were measured in frozen citrated plasma samples. Hazard Ratio (HR) and 95% confidence interval (CI), adjusted by relevant covariates were estimated by a Cox regression model using Prentice method. Results: Individuals with levels of fibrinogen ≥400 mg/dL had a higher hazard to develop colorectal cancer when compared to those with lower levels after adjustment for sex and age (HR: 1.81; 95% CI 1.12–2.92). Additional adjustment for CRC family history, income, physical activity, diabetes medication and hypercholesterolemia did not modify the result (HR: 1.91; 95% CI 1.15–3.17). Analyses stratified by age and sex showed a most evident association in elderly (HR: 2.30; 95% CI: 1.10–4.81) and in women (HR: 2.28; 95% CI: 1.08–4.81). Sensitivity analyses confirmed the main findings, showing independence from a potential role of confounding by a large panel of biomarkers, including inflammation and hemostasis factors. Conclusion: Our results, based on a case-cohort study from a general adult population apparently free from any cancer during the recruitment, showed that fibrinogen levels ≥400 mg/dL were positively and independently associated with CRC, suggesting that this glycoprotein could be a potential biomarker for this type of cancer and supporting the “common soil hypothesis” in the pathophysiology of cardiovascular disease and tumors