Investigation of the Relationship between Surface Features, Protein Adsorption, and Osteoimmunomodulation: The Case of a Chemically Treated Titanium Alloy.

This paper deals with the combined effects of immune response and osseointegration because of the lack of comprehensive studies on this topic. An antibacterial Ti surface was considered because of the high risk of infection for titanium bone implants. A chemically treated Ti6Al4 V alloy [Ti64(Sr-Ag)] with a microporous and Sr-Ag doped surface was compared to a polished version (Ti64) regarding protein adsorption (albumin and fibronectin) and osteoimmunomodulation. Characterization via fluorescence microscopy and zeta potential showed a continuous fibronectin layer on Ti64(Sr-Ag), even with preadsorbed albumin, while it remained filamentous on Ti64. Macrophages (differentiated from THP-1 monocytes) were cultured on both surfaces, with viability and cytokine release analyzed. Differently from Ti64, Ti64(Sr-Ag) promoted early anti-inflammatory responses and significant downregulation of VEGF. Ti64(Sr-Ag) also enhanced human bone marrow mesenchymal cell differentiation toward osteoblasts, when a macrophage-conditioned medium was used, influencing ALP production. Surface properties in relation to protein adsorption and osteoimmunomodulation were discussed.

Scalable nanophotonic neural probes for multicolor and on-demand light delivery in brain tissue.

Neural probes arein vivobrain-invasive devices that record and manipulate neural circuits using electricity, light, or drugs. The capability to shine distinct wavelengths and control their respective output locations for activation or deactivation of specific groups of neurons is desirable but remains unachieved. Here, we discuss our probe's capability to deliver two independently controllable wavelengths (450 and 655 nm) in the location(s) of interest using nanophotonic directional couplers and ring resonators. These nanophotonics are scalable to dozens of outputs without significantly increasing the device's lateral dimensions. Furthermore, they are entirely passive and thus do not require electrical input that results in heat generation. Besides, we integrate a high number of electrodes for a simultaneous neural activity readout. Thus, we overcome the challenges associated with multicolor illumination for neural devices by exploiting the capability of miniaturizable, passive probes to deliver two different frequencies in several areas of interest. These devices open the path towards investigating thein vivoelectrical signal propagation under the individual or simultaneous activation or inhibition of distinct brain regions.

Resistive switching in sub-micrometric ZnO polycrystalline films.

Resistive switching (RS) devices are considered as the most promising alternative to conventional random access memories. They interestingly offer effective properties in terms of device scalability, low power-consumption, fast read/write operations, high endurance and state retention. Moreover, neuromorphic circuits and synapse-like devices are envisaged with RS modeled as memristors, opening the route toward beyond-Von Neumann computing architectures and intelligent systems. This work investigates how the RS properties of zinc oxide thin films are related to both sputtering deposition process and device configuration, i.e. valence change memory and electrochemical metallization memory (ECM). Different devices, with an oxide thickness ranging from 50-250 nm, are fabricated and deeply characterized. The electrical characterization evidences that, differently from typical nanoscale amorphous oxides employed for resistive RAMs (HfO x , WO x , etc), sub-micrometric thicknesses of polycrystalline ZnO layers with ECM configuration are needed to achieve the most reliable devices. The obtained results are deeply discussed, correlating the RS mechanism to material nanostructure.

Thermal evolution of MnxOy nanofibres as catalysts for the oxygen reduction reaction.

Manganese oxides (MnxOy) are considered as a promising catalyst alternative to platinum in fuel cell applications. In fact, a proper catalyst is needed in order to facilitate the oxygen reduction reaction (ORR) at the cathode, and platinum is considered the best material due to its low overpotential for this reaction. Contrary to platinum, MnxOy is inexpensive, environmentally friendly and can be shaped into several nanostructures; furthermore, most of them show significant electro-catalytic performance. Several strategies have been carried out in order to increase their efficiency, by preparing light and high-surface area materials. In this framework, nanofibres are among the most promising nanostructures that can be used for this purpose. In this work, a study of the thermal, morphological and catalytic behavior of MnxOy nanofibres obtained through the electrospinning technique is proposed. Emphasis is given to the thermal evolution of the precursors, proposing a possible crystallization mechanism of the different manganese oxides obtained. It turns out that manganese oxide nanofibres exhibit good catalytic performance for the ORR, comparable to those obtained by using Pt-based catalysts.

Enhanced fluorescence detection of miRNA-16 on a photonic crystal.

We report a novel sensing method for fluorescence-labelled microRNAs (miRNAs) spotted on an all-dielectric photonic structure. Such a photonic structure provides an enhanced excitation and a directional beaming of the emitted fluorescence, resulting in a significant improvement of the overall signal collected. As a result, the Limit of Detection (LoD) is demonstrated to decrease by a factor of about 50. A compact read-out system allows a wide-field imaging-based detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development for example in microarray-type bioassays.

Evaluation of the piezoelectric properties and voltage generation of flexible zinc oxide thin films.

Local piezoresponse and piezoelectric output voltage were evaluated on ZnO thin films deposited by radio-frequency magnetron sputtering on hard Si/Ti/Au and flexible Cu-coated polyimide substrates. Three different thicknesses of ZnO films were studied (285 nm, 710 nm, and 1380 nm), focusing on characteristics like crystallinity, grain size, surface roughness, and morphology. Independent of the nature of the metal layer and the substrate, our results show that thicker films presented a higher level of crystallinity and a preferential orientation along the c-axis direction, as well as a lower density of grain boundaries and larger crystal sizes. The improvement of the crystalline structure of the material directly enhances its piezoelectric properties, as confirmed by the local characterizations performed by piezoresponse force microscopy and by the evaluation of the output voltage generation under the application of a periodical mechanical deformation on the whole film. In particular, the highest value of the d33 coefficient obtained (8 pm V(-1)) and the highest generated output voltage (0.746 V) belong to the thickest films on hard and flexible substrates, respectively. These results envision the use of ZnO thin films--particularly on flexible substrates--as conformable, reliable, and efficient active materials for use in nanosensing, actuation, and piezoelectric nanogenerators.

EchoScopy in scanning abdominal diseases: initial clinical experience.

BACKGROUND AND AIMS: The introduction of a new type of small handheld ultrasound device brings greater portability and affordability. The basic ultrasound approach with these handheld devices has been defined by European Federation of Societies of Ultrasound in Medicine and Biology (EFSUMB) as "EchoScopy". The current study aimed to assess the image quality, indications and limitations of a portable pocket "EchoScope" compared with a high-end ultrasound system in abdominal diseases. METHODS: 231 consecutive patients were included in this study. Physician A performed ultrasound examinations with a high-end ultrasound system (HEUS), then physician B performed the same ultrasound examination using an EchoScope (Vscan™). In patients with focal lesions, physician B also measured the largest diameters and graded the vascularity by using colour Doppler imaging (CDI) within the lesion on the same plane with both ultrasound systems. Compared with the excellent image quality using HEUS, the image quality of the EchoScope was graded as good, sufficient or non-sufficient. RESULTS: Out of all 231 patients, 167 had focal lesions, 19 patients were found with diffuse pathological findings, six with ascites, six after liver puncture and 33 without any pathological findings. The image quality of the pocket device was considered as being good or sufficient to delineate the pathology in 225/231 (97.4 %). The detection rate of the EchoScope for abdominal focal lesion was 162/167 (97 %), only five superficially located lesions could not be detected. Both systems showed agreement in determination of the best positioning to perform abdominal paracentesis and assessing complications after intervention. CONCLUSIONS: The investigated EchoScope displays a sufficient image quality, in some indications such as detection of focal lesions > 20 mm, detection of ascites, hydronephrosis and other pathological findings with comparable results to HEUS. We conclude that pocket sized EchoScopy devices have a promising future but the indications have to be determined by a prospective study.

Measurement of shear wave velocity using acoustic radiation force impulse imaging is not hampered by previous use of ultrasound contrast agents.

PURPOSE: To assess the inter-observer reproducibility of acoustic radiation force impulse imaging (ARFI) between 2 skilled physicians and to evaluate if ultrasound contrast agents (UCA) affect the measurement of shear wave velocity (SWV) using ARFI. PATIENTS AND METHODS: 53 patients (29 males, 24 females, 59 ± 15 [22-84] years) who underwent contrast enhanced ultrasound (CEUS) examination were included. ARFI was performed on liver segment V by physicians A and B before CEUS, and by physician A within 4-6 minutes and 7-10 minutes after contrast injection. In a subgroup of 31 patients (15 males, 16 females, 57 ± 18 [22-84] years), ARFI was also performed on focal liver lesions (FLL) by physician A before CEUS, and within 4-6 minutes and 7-10 minutes after contrast injection. RESULTS: The SWV values obtained by physician A and B before CEUS yielded an intra-class correlation coefficient value of 0.913 (95% CI, 0.849-0.950). No significant differences were shown between the SWV values of liver segment V in all 53 patients and of FLL in the subgroup of 31 patients obtained before CEUS and that of within 4-6 minutes and 7-10 minutes after contrast injection (all P > 0.05). CONCLUSION: ARFI showed excellent inter-observer reproducibility between 2 skilled physicians. UCA did not affect the measurement of SWV in both liver parenchyma and FLL, at least when performed 4 minutes after the contrast injection. ARFI may become an additional tool in the differential diagnosis of FLL.

Pancreas mobile.

BACKGROUND AND AIM: Up to now, little is known about the mobility of the pancreas due to changes in posture. The present study was conducted to assess the position of the pancreas in the left recumbent posture (endoscopy posture), the pancreatic mobility during changes of the posture from supine to endoscopy posture and also evaluates the possible factors associated with pancreatic mobility. METHODS: 199 patients with (68) or without chronic pancreatitis were examined using conventional gray-scale transabdominal ultrasound to image the position and mobility of the pancreatic head with reference to the vertebral spine and aorta in the supine and left recumbent position. In a subgroup of 75 consecutive healthy subjects regarding the pancreas, the exact moving distance of the central line of the pancreatic head from the supine to left recumbent position was obtained regarding the central line of the spine as the reference. Besides the 199 patients, 50 patients without pancreatic pathology were evaluated by endoscopic ultrasound with radial transducers. RESULTS: On conventional ultrasound in supine (left lateral) position the percentage of patients with right-aortal, pre-aortal, left-aortal pancreatic head were 91.0 % (49 %), 8.0 % (31 %) and 1.0 % (20 %), respectively. Significant movement of the pancreatic head in relation to the aorta was observed in 48 % of patients. The moving distance was correlated to the age, sex and the presence of chronic pancreatitis. Pancreas mobility was more pronounced in young healthy females. No association was found between the moving distance and the body mass index (BMI) and splenic size. On endoscopic ultrasound, the orientation of the pancreas with a view of more (or equal) than 180o was observed in 48 % and less than 180o in 52 % of patients. CONCLUSION: Pancreas mobile is a common phenomenon (about 50 %) which has not often been recognized in daily routine. This phenomenon is more likely in healthy young females. This knowledge might be of importance for improved interpretation of endoscopic ultrasound imaging examinations in patients with and without peripancreatic infiltration.

The pancreatic head is larger than often assumed.

Reference values for B-mode abdominal ultrasound are controversially discussed in the literature mainly due to the lack of data and non-standardized examination techniques. A cohort of 100 patients was prospectively examined. Patients with hepatobiliary diseases including gallstones, acute or chronic pancreatitis (n = 13) and non-adequate visualization (n = 10) were excluded from statistical analysis. Therefore, 77 patients were analyzed including 52 female and 25 male healthy subjects regarding the biliopancreatic system (median age ± SD: 56 ± 18 years [minimum: 22 and maximum 93 years]). The mean value of the cranio-caudal diameter of the pancreatic head was 49 ± 10 [26 - 77] mm(mean ± SD [minimum - maximum]) which is larger than usually reported except in one study. The size of the pancreatic head is often larger than assumed which is of importance to know to exclude pancreatic pathology below the level of the common bile duct.

Expanding the product portfolio of carbon dioxide and hydrogen-based gas fermentation with an evolved strain of Clostridium carboxidivorans.

CO2:H2-based gas fermentation with acetogenic Clostridium species are at an early stage of development. This work exploited the Adaptive Laboratory Evolution technique to improve the growth of C. carboxidivorans P7 on CO2 and H2. An adapted strain with decreased growth lag phase and improved biomass production was obtained. Genomic analysis revealed a conserved frameshift mutation in the catalytic subunit of the hexameric hydrogenase gene. The resulted truncated protein variant, most likely lacking its functionality, suggests that other hydrogenases might be more efficient for H2-based growth of this strain. Furthermore, the adapted strain generated hexanol as primary fermentation product. For the first time, hexanol was produced directly from CO2:H2 blend, achieving the highest maximum productivity reported so far via gas fermentation. Traces of valerate, pentanol, eptanol and octanol were observed in the fermentation broth. The adapted strain shows promising to enrich the product spectrum targetable by future gas fermentation processes.

Funneling Spontaneous Emission into Waveguides via Epsilon-Near-Zero Metamaterials.

In this work, we discuss the use of epsilon-near-zero (ENZ) metamaterials to efficiently couple light radiated by a dipolar source to an in-plane waveguide. We exploit both enhanced and directional emission provided by ENZ metamaterials to optimize the injection of light into the waveguide by tuning the metal fill factor. We show that a net increase in intensity injected into the waveguide with respect to the total power radiated by the isolated dipole can be achieved in experimentally feasible conditions. We think the proposed system may open up new opportunities for several optical applications and integrated technologies, especially for those limited by outcoupling efficiency and emission rate.

Numerical study of the effect of channel aspect ratio on particle focusing in acoustophoretic devices.

Acoustophoretic microfluidic devices are promising non-contact and high-throughput tools for particle manipulation. Although the effectiveness of this technique has been widely demonstrated for applications based on micrometer-sized particles, the manipulation and focusing of sub-micrometer ones is challenging due to the presence of acoustic streaming. In this article, our study has the aim to investigate and understand which geometrical parameters could be changed to limit the acoustic streaming effect. We numerically study the well-known rectangular cross section of a microfluidic channel and perform a parametric study of the aspect ratio for several particle sizes. The efficiency of the focusing, is explored for different sized particles in order to identify a trend for which the acoustic streaming does not drastically influence the focusing motion of the particles. The possibility to efficiently separate different solid components in liquid suspensions, i.e. the whole blood, is crucial for all applications that require a purified medium such as plasmapheresis or an increase of the concentration of specific subpopulation as the outcome, such as proteomics, cancer biomarker detections and extracellular vesicles separation.

Human obesity relationship with Ad36 adenovirus and insulin resistance.

OBJECTIVES: Infection with specific pathogens may lead to increased adiposity: a specific adiposity-promoting effect of Ad36 human adenovirus, without the involvement of neurological mechanisms, was reported. The aim of this study is to investigate whether non-diabetic patients with earlier Ad36 infection show greater degrees of overweight obesity, of Insulin Resistance (IR), assessed by homoeostasis-model assessment (HOMA), and/or of other related factors. Moreover, the relationship, if any, among these factors and an earlier Ad36 infection, and the hypothesis of a mechanism involving IR are investigated. SUBJECTS: Ad36 seropositivity is assessed in 68 obese and 135 non-obese subjects, along with body composition, HOMA and laboratory investigations. RESULTS: Age, body mass index (BMI), waist-hip ratio, blood pressure, insulin, HOMA and triglycerides are significantly greater in the Ad36 seropositive group. Ad36 seropositivity, along with HOMA and total cholesterol, explains BMI variance. No Ad36 seropositivity effect to HOMA could be envisaged by the same statistical model. CONCLUSION: A significant association of Ad36 seropositivity with obesity and with essential hypertension in human beings is suggested by our study; this association is mostly significant in women. Our results do not support that any Ad36 adipogenic adenovirus effect is operating in human obesity through an insulin-resistance-related mechanism. Ad36 seropositive status could also be a hallmark of a clinical-metabolic profile possibly preceding obesity and diabetes in non-obese patients.

Simple PDMS microdevice for biomedical applications.

Polydimethylsiloxane (PDMS) is a well-known biocompatible polymer employed for many applications in the biomedical field. In this study, the biocompatibility and versatility of PDMS was tested setting up a microdevice devoted to the purification and analysis of nucleic acids. The PDMS microdevice was demonstrated to successfully fulfill all requirements of genetic analyses such as genotyping and pathogen DNA identification both in multiplex and real-time PCR, suggesting the possibility to carry out a molecular test directly on-chip. Moreover, the PDMS microdevice was successfully applied to the purification and detection of disease biomarkers, such as microRNAs related to cancer or heart disease. On-chip microRNA purification was demonstrated starting from clinically relevant samples, i.e. plasma, serum, tissue biopsies. Significantly, the purification and the transcription of microRNA into cDNA occur in the same PDMS chamber, saving time and labor for the overall analysis. Again, the PDMS microdevice was confirmed as a notable candidate for compact, rapid, easy-to-use molecular tests.

Smart detection of microRNAs through fluorescence enhancement on a photonic crystal.

The detection of low abundant biomarkers, such as circulating microRNAs, demands innovative detection methods with increased resolution, sensitivity and specificity. Here, a biofunctional surface was implemented for the selective capture of microRNAs, which were detected through fluorescence enhancement directly on a photonic crystal. To set up the optimal biofunctional surface, epoxy-coated commercially available microscope slides were spotted with specific anti-microRNA probes. The optimal concentration of probe as well as of passivating agent were selected and employed for titrating the microRNA hybridization. Cross-hybridization of different microRNAs was also tested, resulting negligible. Once optimized, the protocol was adapted to the photonic crystal surface, where fluorescent synthetic miR-16 was hybridized and imaged with a dedicated equipment. The photonic crystal consists of a dielectric multilayer patterned with a grating structure. In this way, it is possible to take advantage from both a resonant excitation of fluorophores and an angularly redirection of the emitted radiation. As a result, a significant fluorescence enhancement due to the resonant structure is collected from the patterned photonic crystal with respect to the outer non-structured surface. The dedicated read-out system is compact and based on a wide-field imaging detection, with little or no optical alignment issues, which makes this approach particularly interesting for further development such as for example in microarray-type bioassays.

On-chip purification and detection of hepatitis C virus RNA from human plasma.

Hepatitis C virus (HCV) is one of the main causes of chronic liver disease worldwide. The diagnosis and monitoring of HCV infection is a crucial need in the clinical management. The conventional diagnostic technologies are challenged when trying to address molecular diagnostics, especially because they require a complex and time-consuming sample preparation phase. Here, a new concept based on surface functionalization was applied to viral RNA purification: first of all polydimethylsiloxane (PDMS) flat surfaces were modified to hold RNA adsorption. After a careful chemical and morphological analysis of the modified surfaces, the functionalization protocols giving the best RNA adsorbing surfaces were applied to PDMS microdevices. The functionalized microdevices were then used for RNA purification from HCV infected human plasma samples. RNA purification and RT were successfully performed in the same microdevice chamber, saving time of analysis, reagents, and labor. The PCR protocol for HCV cDNA amplification was also implemented in the microdevice, demonstrating that the entire process of HCV analysis, from plasma to molecular readout, could be performed on-chip. Not only HCV but also other microdevice-based viral RNA detection could therefore result in a successful Point-of-Care (POC) diagnostics for resource-limited settings.

Nanostructural evolution of one-dimensional BaTiO3 structures by hydrothermal conversion of vertically aligned TiO2 nanotubes.

The use of TiO2 nanotube (NT) arrays as templates for hydrothermal conversion of one-dimensional barium titanate (BaTiO3) structures is considered a promising synthesis approach, even though the formation mechanisms are not yet fully understood. Herein we report a nanostructural study by means of XRD and (HR)TEM of high aspect ratio TiO2-NTs hydrothermally converted into BaTiO3. The nanostructure shows two different and well-defined regions: at the top the conversion involves complete dissolution of NTs and subsequent precipitation of BaTiO3 crystals by homogeneous nucleation, followed by the growth of dendritic structures by aggregation and oriented attachment mechanisms. Instead, at the bottom, the low liquid/solid ratio, due to the limited amount of Ba solution that infiltrates the NTs, leads to the rapid crystallization of such a solution into BaTiO3, thus allowing the NTs to act as a template for the formation of highly oriented one-dimensional nanostructures. The in-depth analysis of the structural transformations that take place during the formation of the rod-like arrays of BaTiO3 could help elucidate the conversion mechanism, thus paving the way for the optimization of the synthesis process in view of new applications in energy harvesting devices, where easy and low temperature processing, controlled composition, morphology and functional properties are required.

Non-alcoholic fatty liver disease (NAFLD) and MTHFR 1298A > C gene polymorphism.

INTRODUCTION: Non-Alcoholic Fatty Liver Disease (NAFLD) is related to unhealthy habits, mainly to unfavorable dietary profiles. MTHFR gene encodes MethyleneTetraHydroFolate Reductase, a regulatory enzyme whose polymorphisms are associated with hyperhomocysteinemia. Among polymorphisms, C677T, a thermolabile form, but not A1298C, thermostable, was associated with fatty liver and insulin resistance. AIM: to investigate if NAFLD, in subjects referred for nutritional assessment and counselling, has any difference of prevalence and severity when associated with isolated MTHFR A1298C polymorphism and hyperhomocysteinemia. PATIENTS AND METHODS: 94 subjects, age 55.65 ± 15.43 years, BMI 27.88 ± 5.17 kg/m2, 26 with MTHFR Wild type genotype (1298AA) and 68 with MTHFRA1298C single polymorphism were studied: of them, 35 were homozygous (MTHFR1298CC), 33 were heterozygous (MHTFR 1298AC). Insulin resistance was assessed by HOMA-IR, NAFLD by UltraSound Brigh-Liver-Score (BLS). RESULTS: MTHFR subgroups (wild and A1298C single polymorphism) were not different for age, gender, dietary profile and BMI. In NAFLD, MTHFR 1298AC (heterozygous) vs. homozygous wild genotype (MTHFR 1298AA) patients had more severe NAFLD (BLS: 1.12 ± 1.14 vs. 0.54 ± 0.76, p < 0.029), greater insulin resistance (HOMA 3.20±2.35 vs. 2.12 ± 1.12; p < 0.036), higher AST and gammaGT. CONCLUSIONS: MTHFR1298AC gene heterozygous polymorphisms can be weakly predictive for NAFLD severity. This mutation occurs frequently in populations with low prevalence of overall mortality and of atherosclerosis-associated disease: it could have maintained and maintain its persistence by an heterozygosis advantage mechanism, within significant adherence to healthy nutritional profiles. Interactions of nutrition, genetics and health are a part of the aging process throughout the life span and a greater consideration to the genetic characteristics of populations and individuals is warranted.

Room-temperature ferromagnetism of all-epitaxial ß-Fe-Ge/diamond-Ge/ß-Fe-Ge trilayers.

We report on the first all-epitaxial ferromagnet/inorganic semiconductor/ferromagnet hybrid heterostructure that exhibits (i) a Ge barrier of diamond crystal structure, (ii) room-temperature ferromagnetic electrodes and (iii) very smooth interfaces. Both bottom- and top-Fe-Ge electrodes exhibit tiny in-plane magnetic anisotropies dominated by a magnetocrystalline contribution of six-fold symmetry originating from the hexagonal symmetry of the B82 (Ni2In) ß-Fe-Ge phase. A key result is the absence of any magnetic coupling between these soft-magnetic electrodes for Ge barrier thickness as low as ~2.5 nm, which allows us to easily tune the parallel and antiparallel magnetic alignments by applying suitably small magnetic fields. This confirms the beneficial use of H-surfactant in order to drastically reduce the roughness of the Ge barrier, as revealed by our scanning tunneling microscopy and transmission electron microscopy measurements. This new all-epitaxial ferromagnet/semiconductor hybrid system appears, therefore, to be a promising candidate for the realization of magnetic tunnel junctions with a single crystal semiconductor barrier that are fully compatible with Si-based technology.