Estimation of the cortical functional connectivity with the multimodal integration of high-resolution EEG and fMRI data by directed transfer function

Nowadays, several types of brain imaging device are available to provide images of the functional activity of the cerebral cortex based on hemodynamic, metabolic, or electromagnetic measurements. However, static images of brain regions activated during particular tasks do not convey the information of how these regions communicate with each other. In this study, advanced methods for the estimation of cortical connectivity from combined high-resolution electroencephalography (EEG) and functional magnetic resonance imaging (fMRI) data are presented. These methods include a subject's multicompartment head model (scalp, skull, dura mater, cortex) constructed from individual magnetic resonance images, multidipole source model, and regularized linear inverse source estimates of cortical current density. Determination of the priors in the resolution of the linear inverse problem was performed with the use of information from the hemodynamic responses of the cortical areas as revealed by block-designed (strength of activated voxels) fMRI. We estimate functional cortical connectivity by computing the directed transfer function (DTF) on the estimated cortical current density waveforms in regions of interest (ROIs) on the modeled cortical mantle. The proposed method was able to unveil the direction of the information flow between the cortical regions of interest, as it is directional in nature. Furthermore, this method allows to detect changes in the time course of information flow between cortical regions in different frequency bands. The reliability of these techniques was further demonstrated by elaboration of high-resolution EEG and fMRI signals collected during visually triggered finger movements in four healthy subjects. Connectivity patterns estimated for this task reveal an involvement of right parietal and bilateral premotor and prefrontal cortical areas. This cortical region involvement resembles that revealed in previous studies where visually triggered finger movements were analyzed with the use of separate EEG or fMRI measurements.     

Ambulatory blood pressure recording in diabetic patients with abnormal responses to cardiovascular autonomic function tests

The aim of our study was to analyse the 24-h periodic pattern of blood pressure (BP) in diabetic patients with abnormal responses to cardiovascular reflexes, in order to evaluate the extent of the initial autonomic damage. We studied 44 patients with diabetes mellitus (14 insulin-dependent, 30 non-insulin-dependent; mean duration of disease 6.5±1.8 years) in good metabolic control (fasting glycaemia <140 mg/dl, postprandial glycaemia <180 mg/dl, fructosamine <285 mg/dl), divided into two subgroups, containing 21 normotensives (13 males and 8 females aged 28–72 years) and 23 hypertensives (13 males and 10 females aged 32–70 years) respectively. All patients showed abnormal responses to at least two out of four tests: deep breathing, lying to standing, Valsalva manuvre and postural hypotension. Two sex-and age-matched control groups were recruited, comprising 20 normotensive and 20 hypertensive diabetic patients without dysautonomia, respectively. The reference group consisted of 248 normotensives (135 males and 113 females, aged 18–76 years) and 212 mild-moderate hypertensives (130 males and 82 females, aged 27–66 years). Each patient underwent ambulatory BP monitoring for at least 24 h, using an auscultatory automatic device. Data concerning biological rhythms were analysed by means of periodic functions. We limited the Fourier partial sums to the first three harmonics. In the diabetic normotensive groups, we observed that the absolute systolic and diastolic BP minima during the night occurred very rapidly and that the increase to the morning maximum was markedly slowed in patients with abnormal responses to cardiovascular tests in comparison with the controls (nocturnal BP decrease –5.8/–4.7 vs –3.8/–4.0 mm Hg/h; increase 4.7/3.6 vs 5.9/6.1 mm Hg/h). The same phenomenon was observed in both hypertensive groups but the differences were more marked (nocturnal BP decrase –7.7/–7.1 vs –4.3/–3.9 mm Hg/h; increase 3.2/2.1 vs 5.8/4.3 mm Hg/h). Diabetic patients without dysautonomia had similar patterns to those in the normotensive and hypertensive reference groups. Since alterations in circadian rhythm are preceded by an intermediate smoothed BP curve during the early morning, which is well defined by Fourier analysis and related speeds, this method makes it possible to quantify the extent of the initial autonomic damage.     

The use of chewing gum for postoperative ileus prevention in patients undergoing radical cystectomy

Does the postoperative use of chewing gum in patients undergoing radical cystectomy (RC) facilitate intestinal motility recovery, reduce intestinal recanalization times and decrease length of stay? Postoperative ileus is a temporary impairment of intestinal motility and a frequent complication after RC. It is characterized by abdominal distention and absence of bowel functions, with symptoms including nausea, vomiting, pain and cramps. This results in an increase in length of stay, patient discomfort and costs. Different studies investigated the efficacy of chewing gum use, as a form of simulated feeding, in accelerating the resolution of ileus after several abdominal surgical procedures. Considering the lack of specific studies, some other conducted in similar abdominal procedures were included in this literature review. Despite the diversity of type of surgery, all considered studies show for patients who received chewing gum, a significant reduction in the time of first flatus and faeces, a reduction in the time of first bowel movements; not all included studies instead have found a significant decreasing in morbidity and length of stay. The chewing gum use seems to be a simple and inexpensive way to enhance recovery of bowel function, although it is probably still a little known procedure. It is possible recommending the administration of chewing gum in patients after cystectomy, monitoring the effectiveness, upon the recognition of possible conditions that might contraindicate its use.     

Angiotensin II increases the release of endothelin-1 from human cultured endothelial cells but does not regulate its circulating levels

We investigated the effect of angiotensin II on endothelin-1 secretion in vitro and in vivo. In vivo, angiotensin II was given intravenously to 23 essential hypertensive and 8 control subjects according to different protocols: Study A, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 30 min each; Study B, 1.0 ng x min-1 x kg-1 and 3.0 ng x min-1 x kg-1 angiotensin II for 120 min each; Study C, 3.0 ng x min-1 x kg-1 angiotensin II for 30 min followed by a dose increment of 3.0 ng x min-1 x kg-1 every 30 min until mean blood pressure levels increased by 25 mmHg; Study D, 1.0 ng x min-1 x kg-1 followed by 3.0 ng x min-1 x kg-1 angiotensin II for 60 min each on two different NaCl diets (either 20 mmol NaCl/day or 220 mmol NaCl/day, both for 1 week). In all in vivo studies neither plasma nor urine endothelin-1 levels changed with angiotensin II infusion. In contrast, angiotensin II (10(-9), 10(-8), 10(-7) mol/l) stimulated endothelin-1 secretion from cultured human vascular endothelial cells derived from umbilical cord veins in a time- and dose-dependent manner. The in vitro angiotensin II effects were abolished by candesartan cilexetil, an inhibitor of the membrane-bound AT1 receptor, and also by actinomycin D, an RNA synthesis inhibitor, and cycloheximide, a protein synthesis inhibitor, indicating that endothelin-1 release depended on AT1 receptor subtype and de novo protein synthesis. Our findings indicate that angiotensin II regulates endothelin-1 release by cultured endothelial cells through an AT1 receptor-dependent pathway, but does not influence circulating endothelin-1 levels in vivo.     

The exploitation of Sentinel-1 images for vessel size estimation

In this article, a novel technique for fully automatic vessel size estimation using medium-to-high-resolution synthetic aperture radar (SAR) images is presented. Based on mathematical morphology, it aims at better delineating the vessel outline in the cluttered SAR image, thereby enabling the extraction of its actual dimensions. The technique has been tested on a set of 127 ships representing a range in lengths between 24 and 366 m in five Sentinel-1 images at 20 m multi-look resolution that have good quality ground truth available. It is found that the proposed algorithm produces very good length estimates (15% relative error/30 m absolute error) and reasonable width estimates (35%/11 m). The estimates are significantly better than those from a simpler automatic method that does not use mathematical morphology, and approach those from manual analysis by an expert.     

Bone metastatic disease: taking aim at new therapeutic targets

Conventional treatment for metastatic bone pain requires a multidisciplinary approach (medical therapy, surgery, and radiation), but is primarily palliative. Biphosphonates introduced the concept of disease-modifying therapy, by effectively reducing bone pain and skeletal related events in patients suffering from bone metastatic cancer. In the past decade, the growing knowledge of bone biology and our understanding of the molecular mechanisms at the basis of the interaction between cancer cells and bone matrix led to the identification of new therapeutic targets for innovative "smart drugs". The most investigated is the RANK/RANKL/OPG pathway, and denosumab, among novel targeted therapies, is the molecule that is in the most advanced development phase. Additional targets have been identified and potential novel therapeutic interventions, classified as inhibitors of bone resorption or stimulators of bone formation, are under preclinical and clinical evaluation. These promising targets include cathepsin K, the Src tyrosine kinases, integrins, chloride channels, the parathyroid hormone-related peptide, endotelin-1, sclerostin, and TGF-beta. Other pathways or molecules expressed by bone cells and cancer cells, such as CXCR4, GPNMB, EGF-family ligands, Wnt/DKK1, and MIP-1 alpha have recently emerged as potential targets. The aim of this review is to discuss the molecular mechanisms behind these emerging therapeutic targets in bone metastases and to give an overview of results from those in advanced clinical phases.