A compact evolved antenna for 5G communications.

Flexible and bendable electronics are gaining a lot of interest in these last years. In this scenario, compact antennas on flexible substrates represent a strategical technological step to pave the way to a new class of wearable systems. A crucial issue to overcome is represented by the poor radiation properties of compact antennas, especially in the case of flexible and thin substrates. In this paper, we propose an innovative design of a miniaturized evolved patch antenna whose radiation properties have been enhanced with a Split Ring Resonator (SRR) placed between the top and the ground plane. The antenna has been realized on a flexible and biocompatible substrate polyethylene naphthalate (PEN) of 250 µm by means of a new fabrication protocol that involves a three-layer 3D-inkjet printing and an alignment step. The antenna has been characterized in terms of the scattering parameter S11 and the radiation pattern showing a good agreement between simulations and measurements.

Wearable piezoelectric mass sensor based on pH sensitive hydrogels for sweat pH monitoring.

Colorimetric and electrochemical (bio)sensors are commonly employed in wearable platforms for sweat monitoring; nevertheless, they suffer from low stability of the sensitive element. In contrast, mass-(bio)sensors are commonly used for analyte detection at laboratory level only, due to their rigidity. To overcome these limitations, a flexible mass-(bio)sensor for sweat pH sensing is proposed. The device exploits the flexibility of piezoelectric AlN membranes fabricated on a polyimide substrate combined to the sensitive properties of a pH responsive hydrogel based on PEG-DA/CEA molecules. A resonant frequency shift is recorded due to the hydrogel swelling/shrinking at several pH. Our device shows a responsivity of about 12 kHz/pH unit when measured in artificial sweat formulation in the pH range 3-8. To the best of our knowledge, this is the first time that hydrogel mass variations are sensed by a flexible resonator, fostering the development of a new class of compliant and wearable devices.

Soft and flexible piezoelectric smart patch for vascular graft monitoring based on Aluminum Nitride thin film.

Vascular grafts are artificial conduits properly designed to substitute a diseased blood vessel. However prosthetic fail can occur without premonitory symptoms. Continuous monitoring of the system can provide useful information not only to extend the graft's life but also to optimize the patient's therapy. In this respect, various techniques have been used, but all of them affect the mechanical properties of the artificial vessel. To overcome these drawbacks, an ultrathin and flexible smart patch based on piezoelectric Aluminum Nitride (AlN) integrated on the extraluminal surface of the prosthesis is presented. The sensor can be conformally wrapped around the external surface of the prosthesis. Its design, mechanical properties and dimensions are properly characterized and optimized in order to maximize performances and to avoid any interference with the graft structure during its activity. The sensorized graft is tested in vitro using a pulsatile recirculating flow system that mimics the physiological and pathological blood flow conditions. In this way, the ability of the device to measure real-time variations of the hemodynamics parameters has been tested. The obtained high sensitivity of 0.012 V Pa-1 m-2, joint to the inherent biocompatibility and non-toxicity of the used materials, demonstrates that the device can successfully monitor the prosthesis functioning under different conditions, opening new perspectives for real-time vascular graft surveillance.

Characteristics of the case mix, organisation and delivery in cancer palliative care: a challenge for good-quality research.

OBJECTIVES: Palliative care (PC) services and patients differ across countries. Data on PC delivery paired with medical and self-reported data are seldom reported. Aims were to describe (1) PC organisation and services in participating centres and (2) characteristics of patients in PC programmes. METHODS: This was an international prospective multicentre study with a single web-based survey on PC organisation, services and academics and patients' self-reported symptoms collected at baseline and monthly thereafter, with concurrent registrations of medical data by healthcare providers. Participants were patients ≥18 enrolled in a PC programme. RESULTS: 30 centres in 12 countries participated; 24 hospitals, 4 hospices, 1 nursing home, 1 home-care service. 22 centres (73%) had PC in-house teams and inpatient and outpatient services. 20 centres (67%) had integral chemotherapy/radiotherapy services, and most (28/30) had access to general medical or oncology inpatient units. Physicians or nurses were present 24 hours/7 days in 50% and 60% of centres, respectively. 50 centres (50%) had professorships, and 12 centres (40%) had full-time/part-time research staff. Data were available on 1698 patients: 50% females; median age 66 (range 21-97); median Karnofsky score 70 (10-100); 1409 patients (83%) had metastatic/disseminated disease; tiredness and pain in the past 24 hours were most prominent. During follow-up, 1060 patients (62%) died; 450 (44%) <3 months from inclusion and 701 (68%) within 6 months. ANOVA and χ2 tests showed that hospice/nursing home patients were significantly older, had poorer performance status and had shorter survival compared with hospital-patients (p<.0.001). CONCLUSIONS: There is a wide variation in PC services and patients across Europe. Detailed characterisation is the first step in improving PC services and research. TRIAL REGISTRATION NUMBER: ClinicalTrials.gov Identifier: NCT01362816.

A bio-inspired real-time capable artificial lateral line system for freestream flow measurements.

To enhance today's artificial flow sensing capabilities in aerial and underwater robotics, future robots could be equipped with a large number of miniaturized sensors distributed over the surface to provide high resolution measurement of the surrounding fluid flow. In this work we show a linear array of closely separated bio-inspired micro-electro-mechanical flow sensors whose sensing mechanism is based on a piezoresistive strain-gauge along a stress-driven cantilever beam, mimicking the biological superficial neuromasts found in the lateral line organ of fishes. Aiming to improve state-of-the-art flow sensing capability in autonomously flying and swimming robots, our artificial lateral line system was designed and developed to feature multi-parameter freestream flow measurements which provide information about (1) local flow velocities as measured by the signal amplitudes from the individual cantilevers as well as (2) propagation velocity, (3) linear forward/backward direction along the cantilever beam orientation and (4) periodicity of pulses or pulse trains determined by cross-correlating sensor signals. A real-time capable cross-correlation procedure was developed which makes it possible to extract freestream flow direction and velocity information from flow fluctuations. The computed flow velocities deviate from a commercial system by 0.09 m s(-1) at 0.5 m s(-1) and 0.15 m s(-1) at 1.0 m s(-1) flow velocity for a sampling rate of 240 Hz and a sensor distance of 38 mm. Although experiments were performed in air, the presented flow sensing system can be applied to underwater vehicles as well, once the sensors are embedded in a waterproof micro-electro-mechanical systems package.

Roles of autophagy induced by natural compounds in prostate cancer.

Autophagy is a homeostatic mechanism through which intracellular organelles and proteins are degraded and recycled in response to increased metabolic demand or stress. Autophagy dysfunction is often associated with many diseases, including cancer. Because of its role in tumorigenesis, autophagy can represent a new therapeutic target for cancer treatment. Prostate cancer (PCa) is one of the most common cancers in aged men. The evidence on alterations of autophagy related genes and/or protein levels in PCa cells suggests a potential implication of autophagy in PCa onset and progression. The use of natural compounds, characterized by low toxicity to normal tissue associated with specific anticancer effects at physiological levels in vivo, is receiving increasing attention for prevention and/or treatment of PCa. Understanding the mechanism of action of these compounds could be crucial for the development of new therapeutic or chemopreventive options. In this review we focus on the current evidence showing the capacity of natural compounds to exert their action through autophagy modulation in PCa cells.

Uncertainty quantification in MD simulations of concentration driven ionic flow through a silica nanopore. I. Sensitivity to physical parameters of the pore.

In this article, uncertainty quantification is applied to molecular dynamics (MD) simulations of concentration driven ionic flow through a silica nanopore. We consider a silica pore model connecting two reservoirs containing a solution of sodium (Na(+)) and chloride (Cl(-)) ions in water. An ad hoc concentration control algorithm is developed to simulate a concentration driven counter flow of ions through the pore, with the ionic flux being the main observable extracted from the MD system. We explore the sensitivity of the system to two physical parameters of the pore, namely, the pore diameter and the gating charge. First we conduct a quantitative analysis of the impact of the pore diameter on the ionic flux, and interpret the results in terms of the interplay between size effects and ion mobility. Second, we analyze the effect of gating charge by treating the charge density over the pore surface as an uncertain parameter in a forward propagation study. Polynomial chaos expansions and Bayesian inference are exploited to isolate the effect of intrinsic noise and quantify the impact of parametric uncertainty on the MD predictions. We highlight the challenges arising from the heterogeneous nature of the system, given the several components involved, and from the substantial effect of the intrinsic thermal noise.

Uncertainty quantification in MD simulations of concentration driven ionic flow through a silica nanopore. II. Uncertain potential parameters.

This article extends the uncertainty quantification analysis introduced in Paper I for molecular dynamics (MD) simulations of concentration driven ionic flow through a silica nanopore. Attention is now focused on characterizing, for a fixed pore diameter of D = 21 Å, the sensitivity of the system to the Lennard-Jones energy parameters, ɛ(Na(+)) and ɛ(Cl(-)), defining the depth of the potential well for the two ions Na(+) and Cl(-), respectively. A forward propagation analysis is applied to map the uncertainty in these parameters to the MD predictions of the ionic fluxes. Polynomial chaos expansions and Bayesian inference are exploited to isolate the effect of the intrinsic noise, stemming from thermal fluctuations of the atoms, and properly quantify the impact of parametric uncertainty on the target MD predictions. A Bayes factor analysis is then used to determine the most suitable regression model to represent the MD noisy data. The study shows that the response surface of the Na(+) conductance can be effectively inferred despite the substantial noise level, whereas the noise partially hides the underlying trend in the Cl(-) conductance data over the studied range. Finally, the dependence of the conductances on the uncertain potential parameters is analyzed in terms of correlations with key bulk transport coefficients, namely, viscosity and collective diffusivities, computed using Green-Kubo time correlations.

Clusterin (CLU) and lung cancer.

Lung cancer is the leading cause of cancer-related mortality. It is categorized into two histological groups that have distinct clinical behaviors, the nonsmall cell lung cancers (NSCLC) and the small cell lung cancer (SCLC). When identified at an early stage, NSCLC is treated by surgical resection. However, patients who undergo surgical resection still have a relative low survival rate, primarily for tumor recurrence. Unfortunately, advances in cytotoxic therapy have reached a plateau and new approaches to treatment are needed together with new and better parameters for more accurate prediction of the outcome and more precise indication of the efficacy of the treatment. Several in vitro studies have examined the role of Clusterin (CLU) in carcinogenesis, lung cancer progression, and response to chemo- and radiotherapy. Studies performed in lung cancer cell lines and animal models showed that CLU is upregulated after exposure to chemo- and radiotherapy. A potential role proposed for the protein is cytoprotective. In vitro, CLU silencing by antisense oligonucleotides (ASO) and small-interfering RNAs (siRNA) directed against CLU mRNA in CLU-rich lung cancer cell lines sensitized cells to chemotherapy and radiotherapy and decreased their metastatic potential. In vivo, a recent work analyzed the prognostic role of CLU in NSCLC, showing that CLU-positive patients with lung cancer had a better overall survival and disease-free survival than those with CLU-negative tumors. These data are contradictory to the promising in vitro results. From the results of these studies we may hypothesize that in early-stage lung cancers CLU represents a positive biomarker correlating with better overall survival. In advanced patients, already treated with chemo- and radiotherapy, the induction of CLU may confer resistance to the treatments. However, many studies are needed to better understand the role of CLU in early-stage and advanced lung cancers with the aim to discriminate patients and specific local conditions that could benefit for a CLU knocking down treatment.

Genetic inactivation of ApoJ/clusterin: effects on prostate tumourigenesis and metastatic spread.

ApoJ/Clusterin (CLU) is a heterodimeric protein localized in the nucleus, cytoplasm or secretory organelles and involved in cell survival and neoplastic transformation. Its function in human cancer is still highly controversial. In this study, we examined the prostate of mice in which CLU has been genetically inactivated. Surprisingly, we observed transformation of the prostate epithelium in the majority of CLU knockout mice. Either PIN (prostate intraepithelial neoplasia) or differentiated carcinoma was observed in 100 and 87% of mice with homozygous or heterozygous deletion of CLU, respectively. Crossing CLU knockout with TRAMP (prostate cancer prone) mice results in a strong enhancement of metastatic spread. Finally, CLU depletion causes tumourigenesis in female TRAMP mice, which are normally cancer free. Mechanistically, deletion of CLU induces activation of nuclear factor-kB, a potentially oncogenic transcription factor important for the proliferation and survival of prostate cells.

Molecular targets of (-)-epigallocatechin-3-gallate (EGCG): specificity and interaction with membrane lipid rafts.

Proteomic studies on anticancer activity of Green Tea Catechins (specifically EGCG) are suggesting a large set of protein targets that may directly interact with EGCG and alter the physiology of diseased cells, including cancer. Of notice, benign cells are usually left untouched. Lipid rafts have been recently recognized as signal processing hubs and suggested to be involved in drug uptake by means of endocytosis. These findings are suggesting new insights on the molecular mechanisms of anticancer drugs action. In the membrane, EGCG is hijacked by the laminin receptor (LamR), a lipid raft protein. Similar to aplidin and edelfosin, EGCG alters membrane domains composition also preventing EGF binding to EGFR, imerization of EGFR and relocation of phosphorylated EGFR to lipid rafts. In vitro studies have recently shown that EGCG also binds both DNA and RNA in GpC-rich regions. This event may importantly affect genes function. Moreover, EGCG was shown to inhibit telomerase, topoisomerase II and DNA methyltransferase 1 (DNMT1), thus ultimately affecting chromatin maintenance and remodeling. But another important alternative pathway besides interaction with specific proteins may play an important role in EGCG action: direct targeting of bioactive membrane platforms, lipid rafts. Structural alteration of the platforms deeply impact (and often inactivates) important pathways involving MAP kinases. The key issue is that, important and specific differences in lipid rafts composition have been found in transformed versus benign cells and apoptotic versus non-apoptotic cells. We suggest here that the anticancer activity of Green Tea Catechins against different kind of cancers may find an explanation in direct targeting of lipid rafts by EGCG.

Targeting Clusterin in prostate cancer.

The biological function of Clusterin has been puzzling researchers for a long time since its first discovery and characterization in the early 80's. CLU plays important roles nearly in all most important biological phenomena including cell proliferation and apoptosis, as well as in many diseases including cancer. Now we know that the CLU gene encodes at least three protein forms with different sub-cellular localization and diverse biological functions. The molecular mechanism of production of these protein isoforms remains unclear. Recent data show that many of the previous hypotheses based on preliminary observations are no longer true. For instance, while alternative splicing of CLU mRNA has never been confirmed, the complex transcriptional regulation of CLU gene is now recognized to produce two distinct transcripts resulting from two independent transcriptional start sites. CLU expression was found deregulated in many type of tumours, including prostate cancer. Considering that prostate cancer is one of the major threats in veterans' life, as well as one of the main causes of cancer related death in western countries, we will also specifically address whether targeting CLU might pave the way for a novel therapeutic intervention against prostate cancer.

Clinical relevance of the inhibitory effect of green tea catechins (GtCs) on prostate cancer progression in combination with molecular profiling of catechin-resistant tumors: an integrated view.

Prostate cancer (CaP) is a fast-growing health and social problem already representing the second leading cause of cancer-related death among men in Western countries. Lifestyle-related factors and diet are major contributors for CaP promotion. Because of unfavourable prognosis of extra-prostatic CaP, prevention is considered the best approach to fight it at present time. Green Tea Catechins (GTCs) were proven effective at inhibiting cancer growth in several laboratory studies. We recently performed a pilot clinical trial in HG-PIN subjects showing that only 1/30 tumour was diagnosed in subjects treated for 1 year with 600 mg/die GTCs, while 9/30 cancers were found in placebo-treated men. CaP is an elusive disease, whose biological behaviour is difficult to predict. We have recently described and validated a RT-qPCR method based on a 8-genes signature that significantly discriminated benign tissue from CaP in both humans and TRAMP mice spontaneously developing CaP. In the animal model, also GTCs-resistant CaP was significantly discriminated from GTCs-sensitive CaP, i.e. responding to GTCs administration. Preliminary experiments in our laboratory have shown that this method can be successfully applied to a single tissue needle biopsy specimen in humans. The combination of these results may be of particular significance on the field. In fact, GTCs treatment for men at high risk of CaP as first line prevention therapy in combination with the 8-genes signature profiling in tissue needle biopsies for real time monitoring of patient's response might importantly change, in the near future, the clinical managing of this highly diffuse malignancy.

Quantum cascade laser-based photoacoustic spectroscopy of volatile chemicals: application to hexamethyldisilazane.

The use of photoacoustic spectroscopy and mid-infrared quantum-cascade lasers (QCLs) for the detection of hexamethyldisilazane (HMDS) is reported. A detection limit of 200 parts in 10(9) is found using a Fabry-Perot QCL operated at 8.4 microm in pulsed mode and a photoacoustic cell equipped with four electret microphones. The laser multimode spectrum matches the range of the N-H bending absorption band of HMDS. Further improvements to reach lower detection limits are discussed.

Prognostic factors in multidisciplinary rehabilitation treatment in multiple sclerosis: an outcome study.

The aim of this outcome study was to evaluate the effectiveness and prognostic factors of inpatient multidisciplinary rehabilitation treatment in patients with multiple sclerosis (MS). We analysed 230 consecutive inpatients with MS admitted to an MS rehabilitation ward who followed an individualized, goal-oriented, multidisciplinary rehabilitation program. Every patient was submitted to a neurological examination and evaluated by means of Kurtzke's Expanded Disability Status Scale (EDSS), with its functional systems (FS), Barthel Index (BI) and the Rivermead Mobility Index (RMI). We observed an effectiveness (percentage of potential improvement achieved during rehabilitation) of nearly 16% on BI and 8% on RMI, corresponding to an improvement in 124 patients (54%) on BI and 113 patients (49%) on RMI. Basal EDSS (beta = -0.32, P <0.001), cognitive status (beta = -0.15, P <0.05) and disease duration (beta = -0.13, P <0.05) were negatively associated with effectiveness of treatment on BI (adjusted R2 = 0.176), whereas effectiveness on RMI was correlated only with the EDSS score (beta = -0.34, P <0.001, adjusted R2 = 0.113). In the logistic regression analysis, the absence of severe sphincteric disturbances was correlated with the probability of improvement on BI that was nearly twice as high (OR =2.25, 95% CI 1.24-4.08) as that of other patients. Moreover, patients without severe cognitive deficits showed a similar probability (OR =2.37, 95% CI 1.05-5.33) of improvement on RMI. The results of this study provide further evidence that intensive multidisciplinary rehabilitation in MS is effective in the majority of MS patients and that early treatment may favour functional recovery.

Post-stroke depression, antidepressant treatment and rehabilitation results. A case-control study.

The aim of this study was to assess the specific influence of poststroke depression (PSD) on both basal functional status and rehabilitation results. We performed a case-control study in 290 stroke inpatients, matched for age (+/-1 year) and onset admission interval (+/-3 days) and divided in two groups according to the presence (PSD+) or absence (PSD-) of PSD. All PSD+ patients were treated with antidepressants (AD), mainly with fluoxetine. PSD+ patients, despite similar severity of stroke, showed greater disability in coping with activities of daily living (ADL) on admission and greater disability both in ADL and mobility at discharge than PSD- patients. Although both groups exhibited similar average functional improvement during rehabilitation, PSD- patients were nearly twice as likely to show excellent recovery both on ADL and mobility as PSD+ patients (OR = 1.95, 95% CI = 1.01-3.75 and OR = 2.23, 95% CI = 1.14-4.35, respectively). All AD drugs improved depressive symptoms. Few relevant side effects were observed: fluoxetine was discontinued in 2 patients because of insomnia and in 2 patients because of nausea; paroxetine was stopped in 1 patient because of nausea and dry mouth. Our results confirm the unfavorable influence of PSD on functional outcome, despite pharmacological treatment.

Mobility status after inpatient stroke rehabilitation: 1-year follow-up and prognostic factors.

OBJECTIVES: To evaluate the stability of mobility status achieved by stroke patients during hospital rehabilitation treatment over time and to identify reliable prognostic factors associated with mobility changes. DESIGN: Follow-up evaluation in consecutive first-ever stroke patients 1 year after hospital discharge. Multiple logistic regressions were used to analyze increases and decreases in Rivermead Mobility Index (RMI) scores (dependent variables) between discharge and follow-up. Independent variables were medical, demographic, and social factors. SETTING: Rehabilitation hospital. PATIENTS: A cohort of 155 patients with sequelae of first stroke, with a final sample of 141. MAIN OUTCOME MEASURES: Mobility status at 1-year follow-up, as measured by the RMI, and odds ratios (OR) for improvement and decline in mobility. RESULTS: Functionally, 19.9% improved the mobility levels achieved during the inpatient rehabilitation treatment; levels of 42.6% worsened. Patients with global aphasia (OR = 5.66; 95% confidence interval [CI], 1.50-21.33), unilateral neglect (OR = 3.01; 95% CI, 1.21-7.50), and age 75 years or older (OR = 5.77; 95% CI, 1.42-23.34) had a higher probability of mobility decline than the remaining patients. Postdischarge rehabilitation treatment (PDT), received by 52.5% of the final sample, was significantly and positively associated with mobility improvement (OR = 5.86; 95% CI, 2.02-17.00). Absence of PDT was associated with a decline in mobility (OR = 3.73; 95% CI, 1.73-8.04). CONCLUSIONS: In most cases, mobility status had not yet stabilized at hospital discharge. PDT was useful in preventing a deterioration in mobility improvement achieved during inpatient treatment and in helping increase the likelihood of further mobility improvement.

In vitro micronucleus induction by polymethyl methacrylate bone cement in cultured human lymphocytes.

Human lymphocytes cultured in vitro were used to assess the ability of polymethyl methacrylate (PMMA), currently used in orthopaedic surgery as bone cement, to induce micronuclei in binucleated cells. The results of the study show a significant increase in the micronucleus frequency in treated cultures and therefore the genotoxic effect of PMMA bone cement or its ingredients (methyl methacrylate, dimethyl para-toluidine and hydroquinone) usually present in self-curing methacrylate bone cement and released in small quantities after polymerisation. This effect is evident during the stage immediately after the polymerisation process, and after a certain period of time (5 days in our experimental model).