Experimental Validation of Microwave Tomographywith the DBIM-TwIST Algorithm for Brain StrokeDetection and Classification.

We present an initial experimental validation of a microwave tomography (MWT) prototypefor brain stroke detection and classification using the distorted Born iterative method, two-stepiterative shrinkage thresholding (DBIM-TwIST) algorithm. The validation study consists of firstpreparing and characterizing gel phantoms which mimic the structure and the dielectric propertiesof a simplified brain model with a haemorrhagic or ischemic stroke target. Then, we measure theS-parameters of the phantoms in our experimental prototype and process the scattered signals from 0.5to 2.5 GHz using the DBIM-TwIST algorithm to estimate the dielectric properties of the reconstructiondomain. Our results demonstrate that we are able to detect the stroke target in scenarios where theinitial guess of the inverse problem is only an approximation of the true experimental phantom.Moreover, the prototype can differentiate between haemorrhagic and ischemic strokes based on theestimation of their dielectric properties.

Feasibility Study of Enhancing Microwave Brain Imaging Using Metamaterials.

We present an approach to enhance microwave brain imaging with an innovative metamaterial (MM) planar design based on a cross-shaped split-ring resonator (SRR-CS). The proposed metasurface is incorporated in different setups, and its interaction with EM waves is studied both experimentally and by using CST Microwave Studio® and is compared to a "no MM" case scenario. We show that the MM can enhance the penetration of the transmitted signals into the human head when placed in contact with skin tissue, acting as an impedance-matching layer. In addition, we show that the MM can improve the transceivers' ability to detect useful "weak" signals when incorporated in a headband scanner for brain imaging by increasing the signal difference from a blood-like dielectric target introduced into the brain volume. Our results suggest that the proposed MM film can be a powerful hardware advance towards the development of scanners for brain haemorrhage detection and monitoring.

Design and Experimental Validation of a Multiple-Frequency Microwave Tomography System Employing the DBIM-TwIST Algorithm.

We present a first prototype of a wideband microwave tomography system with potential application to medical imaging. The system relies on a compact and robust printed monopole antenna which can operate in the 1.0⁻3.0 GHz range when fully immersed in commonly used coupling liquids, such as glycerine⁻water solutions. By simulating the proposed imaging setup in CST Microwave Studio, we study the signal transmission levels and array sensitivity for different target and coupling liquid media. We then present the experimental prototype design and data acquisition process, and show good agreement between experimentally measured data and results from the CST simulations. We assess imaging performance by applying our previously proposed two-dimensional (2-D) DBIM TwIST-algorithm to both simulated and experimental datasets, and demonstrate that the system can reconstruct simple cylindrical targets at multiple frequencies.

Prognostic factors in patients presenting with pleural effusion revealing malignancy.

BACKGROUND: The survival of patients with malignant pleural effusion is considered generally poor. Most of the studies reporting results of prognostic factors are retrospective, using pleural thoracentesis for diagnosis. The objectives of our study were to reveal possible prognostic factors in patients initially presenting with undiagnosed pleural effusion proven to be malignant by diagnostic thoracoscopy. METHODS: Ninety consecutive patients, 48 of whom were male (53%), with a median age of 69 years (range 37-93) and a performance status (PS) of 0/1 (63%) and with initially undiagnosed pleural effusion that was proven to be malignant by thoracoscopy were evaluated. Survival time was defined as the time from thoracoscopic diagnosis to death or the last follow-up. A regression analysis was used to determine significant clinical and biological prognostic factors. RESULTS: Lung carcinoma (44.4%), breast carcinoma (24.4%), and mesothelioma (12.2%) were the most frequent tumors diagnosed. The median overall survival was 11 months (range 0.5-55). The survival of the patients was related to the following factors: histology of the primary tumor (p = 0.008), PS (p < 0.001), white blood cells (p = 0.018), and the blood neutrophil-to-lymphocyte (N/L) ratio (p = 0.002). Multiple regression showed PS, histology, and the N/L ratio. CONCLUSION: The factors affecting survival in our patients were PS, primary tumor histology, and the N/L ratio. These factors may help physicians select patients for treatment and/or interventional procedures.

Metasurface-Enhanced Antennas for Microwave Brain Imaging.

Stroke is a very frequent disorder and one of the major leading causes of death and disability worldwide. Timely detection of stroke is essential in order to select and perform the correct treatment strategy. Thus, the use of an efficient imaging method for an early diagnosis of this syndrome could result in an increased survival's rate. Nowadays, microwave imaging (MWI) for brain stroke detection and classification has attracted growing interest due to its non-invasive and non-ionising properties. In this paper, we present a feasibility study with the goal of enhancing MWI for stroke detection using metasurface (MTS) loaded antennas. In particular, three MTS-enhanced antennas integrated in different brain scanners are presented. For the first two antennas, which operate in a coupling medium, we show experimental measurements on an elliptical brain-mimicking gel phantom including cylindrical targets representing the bleeding in haemorrhagic stroke (h-stroke) and the not oxygenated tissue in ischaemic stroke (i-stroke). The reconstructed images and transmission and reflection parameter plots show that the MTS loadings improve the performance of our imaging prototype. Specifically, the signal transmitted across our head model is indeed increased by several dB's over the desired frequency range of 0.5-2.0 GHz, and an improvement in the quality of the reconstructed images is shown when the MTS is incorporated in the system. We also present a detailed simulation study on the performance of a new printed square monopole antenna (PSMA) operating in air, enhanced by a MTS superstrate loading. In particular, our previous developed brain scanner operating in an infinite lossy matching medium is compared to two tomographic systems operating in air: an 8-PSMA system and an 8-MTS-enhanced PSMA system. Our results show that our MTS superstrate enhances the antennas' return loss by around 5 dB and increases the signal difference due to the presence of a blood-mimicking target up to 25 dB, which leads to more accurate reconstructions. In conclusion, MTS structures may be a significant hardware advancement towards the development of functional and ergonomic MWI scanners for stroke detection.

Respiratory muscle strength and lung function in patients undergoing medical thoracoscopy.

BACKGROUND: Medical thoracoscopy (MT) is a procedure considered as minimally invasive. The safety of the procedure has been questioned recently in fragile patients, but no explanation of the pathophysiologic mechanism has been given. Although MT is applied by respiratory physicians who are also dealing with patients with impairment of lung function, it is surprising that there are no data concerning lung mechanics and function in this patient population. OBJECTIVES: To assess respiratory muscle strength and lung function in patients undergoing MT, with or without talc pleurodesis. METHODS: We measured prospectively the maximal inspiratory (MIP) and expiratory pressures (MEP) and lung function of 29 patients who underwent MT before (baseline) and on consecutive days following MT. RESULTS: 29 patients participated with a mean age of 63.6 +/- 13.8 (range 20-79) years. 15 of them underwent talc pleurodesis and 14 diagnostic thoracoscopy. Mean MIP and MEP values were significantly decreased on day (d) 1 after MT compared to baseline (p = 0.03 and p = 0.007, respectively) and recovered on d2. FEV(1) and FVC mean values were also found significantly decreased on d1 after MT compared to baseline (p < 0.0001 and p = 0.0003, respectively) and recovered on d2. Patients with pleurodesis presented with lower mean values of the studied parameters than those with diagnostic thoracoscopy. No significant complication was associated with the procedure. CONCLUSION: Respiratory muscles and lung function can be temporarily affected from MT. Physicians should be alert, especially in patients with already impaired lung function, where any further impairment could be detrimental.

Global impairment of CD4+CD25+FOXP3+ regulatory T cells in idiopathic pulmonary fibrosis.

RATIONALE: The implication of T cells in the pathogenesis of idiopathic pulmonary fibrosis (IPF) is controversial. CD4(+)CD25(+)FOXP3(+) regulatory T cells (Tregs) are pivotal in maintaining immune homeostasis, but their role in IPF pathophysiology has not yet been studied. OBJECTIVES: To explore Treg dynamics and function in IPF. METHODS: Treg levels and dynamics were analyzed by flow cytometry in the peripheral blood (PB) and bronchoalveolar lavage (BAL) of 21 patients with IPF, 35 patients with lung diseases other than IPF (patients without IPF), 20 patients with collagen vascular diseases with pulmonary parenchymal involvement (CVD-IP), and 28 healthy volunteers. The suppression of autologous CD4(+)CD25(-) cell-proliferative responses and cytokine release by magnetic bead-isolated Tregs was evaluated by proliferation assays and cytometric bead array. Correlations of Treg function and levels with lung function parameters were also performed. MEASUREMENTS AND MAIN RESULTS: In patients with IPF, both BAL and PB Tregs were reduced compared with those of healthy volunteers and patients without IPF, although not always significantly. Treg levels were not affected by the administration of low-dose prednisone in four nonresponding patients. The suppressor potential of BAL and PB Tregs was compromised in patients with IPF and patients with CVD-IP, compared with healthy volunteers and patients without IPF. Similarly, the Treg-induced suppression of helper T-cell type 1 and 2 cytokine secretion was impaired in the BAL of patients with IPF and patients with CVD-IP. Moreover, the defective function of BAL Tregs correlated highly with parameters of disease severity. CONCLUSIONS: This study provides the first evidence of global Treg impairment in IPF that strongly correlates with disease severity, suggesting a role for Tregs in the fibrotic process.

Down-regulation of the inhibitor of growth family member 4 (ING4) in different forms of pulmonary fibrosis.

BACKGROUND: Recent evidence has underscored the role of hypoxia and angiogenesis in the pathogenesis of idiopathic fibrotic lung disease. Inhibitor of growth family member 4 (ING4) has recently attracted much attention as a tumor suppressor gene, due to its ability to inhibit cancer cell proliferation, migration and angiogenesis. The aim of our study was to investigate the role of ING4 in the pathogenesis of pulmonary fibrosis both in the bleomycin (BLM)-model and in two different types of human pulmonary fibrosis, including idiopathic pulmonary fibrosis (IPF) and cryptogenic organizing pneumonia (COP). METHODS: Experimental model of pulmonary fibrosis was induced by a single tail vein injection of bleomycin in 6- to 8-wk-old C57BL/6mice. Tissue microarrays coupled with qRT-PCR and immunohistochemistry were applied in whole lung samples and paraffin-embedded tissue sections of 30 patients with IPF, 20 with COP and 20 control subjects. RESULTS: A gradual decline of ING4 expression in both mRNA and protein levels was reported in the BLM-model. ING4 was also found down-regulated in IPF patients compared to COP and control subjects. Immunolocalization analyses revealed increased expression in areas of normal epithelium and in alveolar epithelium surrounding Masson bodies, in COP lung, whereas showed no expression within areas of active fibrosis within IPF and COP lung. In addition, ING4 expression levels were negatively correlated with pulmonary function parameters in IPF patients. CONCLUSION: Our data suggest a potential role for ING4 in lung fibrogenesis. ING4 down-regulation may facilitate aberrant vascular remodelling and fibroblast proliferation and migration leading to progressive disease.

Plasma visfatin levels in severe obstructive sleep apnea-hypopnea syndrome.

BACKGROUND: Obstructive sleep apnea syndrome (OSAS) is associated with obesity and insulin resistance. Visfatin is an insulin-mimicking adipokine, which is considered a link between obesity and insulin resistance. Aim of this study was to evaluate levels of plasma visfatin in patients with severe OSAS and examine their potential correlation with sleep characteristics and several biochemical parameters. METHODS: Nondiabetic patients with severe OSAS (Apnea Hypopnea Index > 30/h, n = 32) and healthy controls (Apnea Hypopnea Index < 5/h, n = 12), examined with polysomnography, underwent a biochemical analysis to estimate fasting levels of visfatin, glucose, insulin, C-peptide, and lipid profile. RESULTS: The two groups were matched for age and body mass index (BMI). OSAS patients had significantly higher fasting insulin levels (p = 0.045), but no difference was shown in visfatin between patients and controls (p = 0.585). In OSAS patients, visfatin levels correlated positively with sleep latency (r = 0.539, p = 0.01) and triglyceride levels (r = 0.584, p = 0.036) and negatively with total sleep time, percentage of stage 2 and REM sleep, and LDL-cholesterol levels (r = -0.659 and p = 0.001; r = -0.496 and p = 0.019; r = -0.577 and p = 0.005; r = -0.804 and p = 0.003, respectively). No association was found, however, between visfatin levels and HOMA index or indices of nocturnal hypoxia. CONCLUSIONS: In patients with severe OSAS, visfatin levels are associated with characteristics of sleep architecture. However, there is no correlation between visfatin and insulin resistance or nocturnal hypoxia.

Pharmacotherapy in smoking cessation: Corticotropin Releasing Factor receptors as emerging intervention targets.

Smoking represents perhaps the single most important health risk factor and a global contributor to mortality that can unquestionably be prevented. Smoking is responsible for many diseases, including various types of cancer, chronic obstructive pulmonary disease, coronary heart disease, peripheral vascular disease and peptic ulcer, while it adversely affects fetal formation and development. Since smoking habit duration is a critical factor for mortality, the goal of treatment should be its timely cessation and relapse prevention. Drug intervention therapy is an important ally in smoking cessation. Significant positive steps have been achieved in the last few years in the development of supportive compounds. In the present review, we analyze reports studying the role of Corticotropin Releasing Factor (CRF), the principle neuroendocrine mediator of the stress response and its two receptors (CRF1 and CRF2) in the withdrawal phase as well as in the abstinence from nicotine use. Although still in pre-clinical evaluation, therapeutic implications of these data were investigated in order to highlight potential pharmaceutical interventions.

A Glucose Sensing System Based on Transmission Measurements at Millimetre Waves using Micro strip Patch Antennas.

We present a sensing system operating at millimetre (mm) waves in transmission mode that can measure glucose level changes based on the complex permittivity changes across the signal path. The permittivity of a sample can change significantly as the concentration of one of its substances varies: for example, blood permittivity depends on the blood glucose levels. The proposed sensing system uses two facing microstrip patch antennas operating at 60 GHz, which are placed across interrogated samples. The measured transmission coefficient depends on the permittivity change along the signal path, which can be correlated to the change in concentration of a substance. Along with theoretical estimations, we experimentally demonstrate the sensing performance of the system using controlled laboratory samples, such as water-based glucose-loaded liquid samples. We also present results of successful glucose spike detection in humans during an in-vivo Intravenous Glucose Tolerance Test (IVGTT). The system could eventually be developed into a non-invasive glucose monitor for continuous monitoring of glucose levels for people living with diabetes, as it can detect as small as 1.33 mmol/l (0.025 wt%) glucose concentrations in the controlled water-based samples satisfactorily, which is well below the typical human glucose levels of 4 mmol/l.