Long period grating working in transition mode as promising technological platform for label-free biosensing.

We present the development of a platform for label-free biosensing based on overlayered Long Period Gratings (LPGs) working in transition mode. Nano-scale layers of Polystyrene (PS) with different thicknesses were deposited onto the same LPG to test the performances of the device in different working points of its modified sensitivity characteristic. Adsorption dynamic of biotinylated bovine serum albumin (BBSA) onto the PS overlays was on-line monitored as well as a subsequent streptavidin (SA) binding dynamic on the biotinylated sites of the protein ad-layer. Experimental results show that overlayered LPGs are among the most sensitive refractive index transducers to be employed in label-free biochemical detection and that wide margins of further optimization exist.

Towards a patient-specific estimation of intra-operative femoral fracture risk.

Total Hip Arthroplasty requires pre-surgical evaluation between un-cemented and cemented prostheses. A Patient with intra-operative periprosthetic fracture and another with a successful outcome were recruited, and their finite element models were constructed by processing CT data, assuming elastic-plastic behavior of the bone as function of the local density. To resemble the insertion of the prosthesis into the femur, a fictitious thermal dilatation is applied to the broach volume. Strain-based fracture risk factor is estimated, depicting results in terms of the total mechanical strain expressed using a simple "traffic lights" color code to provide immediate, concise, and intelligible pre-operative information to surgeons.

Growth and in vivo stresses traced through tumor mechanics enriched with predator-prey cells dynamics.

Mechanical stress accumulating during growth in solid tumors plays a crucial role in the tumor mechanobiology. Stresses arise as a consequence of the spatially inhomogeneous tissue growth due to the different activity of healthy and cancer cells inhabiting the various districts of the tissue, an additional piling up effect, induced by stress transferring across the scales, contributing to determine the total stress occurring at the macroscopic level. The spatially inhomogeneous growth rates accompany nonuniform and time-propagating stress profiles, which constitute mechanical barriers to nutrient transport and influence the intratumoral interstitial flow, in this way deciding the starved/feeded regions, with direct aftereffects on necrosis, angiogenesis, cancer aggressiveness and overall tumor mass size. Despite their ascertained role in tumor mechanobiology, stresses cannot be directly appraised neither from overall tumor size nor through standard non-invasive measurements. To date, the sole way for qualitatively revealing their presence within solid tumors is ex vivo, by engraving the excised masses and then observing opening between the cut edges. Therefore, to contribute to unveil stresses and their implications in tumors, it is first proposed a multiscale model where Volterra-Lotka (predator/prey-like) equations describing the interspecific (environment-mediated) competitions among healthy and cancer cells are coupled with equations of nonlinear poroelasticity. Then, an experimental study on mice injected subcutaneously with a suspension of two different cancer cell lines (MiaPaCa-2 and MDA.MB231) was conducted to provide experimental evidences that gave qualitative and some new quantitative confirmations of the theoretical model predictions.

Micro-structured fiber Bragg gratings: optimization of the fabrication process.

This work has been devoted to present and demonstrate a novel approach for the fabrication of micro-structured fiber Bragg gratings (MSFBGs) with enhanced control of the geometric features and thus of the spectral properties of the final device. The investigated structure relies on the localized stripping of the cladding layer in a well defined region in the middle of the grating structure leading to the formation of a defect state in the spectral response. In order to fully explore the versatility of MSFBGs for sensing and communications applications, a technological assessment of the fabrication process aimed to provide high control of the geometrical features is required. To this aim, here, we demonstrate that the optimization of this device is possible by adopting a fabrication process based on polymeric coatings patterned by high resolution UV laser micromachining tools. The function of the polymeric coating is to act as mask for the HF based chemical etching process responsible for the cladding stripping. Whereas, UV laser micromachining provides a valuable method to accurately pattern the polymeric coating and thus obtain a selective stripping along the grating structure. Here, we experimentally demonstrate the potentiality of the proposed approach to realize reliable and cost efficient MSFBGs enabling the prototyping of advanced photonics devices based on this technology.

Near field behavior of SnO(2) particle-layer deposited on standard optical fiber by electrostatic spray pyrolysis method.

We report the emergent optical near field profiles from standard single mode optical fibers on the cleaved end of which were deposited particle layers of SnO(2). The layers, composed of micron and sub-micron sized particles, were deposited by means of Electrostatic Spray Pyrolysis (ESP) technique. Powerful analytical tools such as Atomic Force Microscopy (AFM) and Scanning Near-field Optical Microscopy (SNOM) were used to obtain simultaneously the SnO(2) layers topography and the related optical near field intensity distribution, when the fiber-substrate is illuminated by a light radiation in NIR range. We show that isolated microstructures, positioned in correspondence of the fiber core, reveal highly unusual capability of locally enhancing the collected optical near field. The observed phenomenon leads to new concepts of fiber optic chemical sensors and in fiber microsystems as well.

Microgel assisted Lab-on-Fiber Optrode.

Precision medicine is continuously demanding for novel point of care systems, potentially exploitable also for in-vivo analysis. Biosensing probes based on Lab-On-Fiber Technology have been recently developed to meet these challenges. However, devices exploiting standard label-free approaches (based on ligand/target molecule interaction) suffer from low sensitivity in all cases where the detection of small molecules at low concentrations is needed. Here we report on a platform developed through the combination of Lab-On-Fiber probes with microgels, which are directly integrated onto the resonant plasmonic nanostructure realized on the fiber tip. In response to binding events, the microgel network concentrates the target molecule and amplifies the optical response, leading to remarkable sensitivity enhancement. Moreover, by acting on the microgel degrees of freedom such as concentration and operating temperature, it is possible to control the limit of detection, tune the working range as well as the response time of the probe. These unique characteristics pave the way for advanced label-free biosensing platforms, suitably reconfigurable depending on the specific application.

Mode transition in high refractive index coated long period gratings.

In this work, the numerical and experimental investigation of the cladding modes re-organization in high refractive index (HRI) coated Long Period Gratings (LPGs) is reported. Moreover, the effects of the cladding modes re-organization on the sensitivity to the surrounding medium refractive index (SRI) have been outlined. When azimuthally symmetric nano-scale HRI coatings are deposited along LPGs devices, a significant modification of the cladding modes distribution occurs, depending on the layer features (refractive index and thickness) and on the SRI. In particular, if layer parameters are properly chosen, the transition of the lowest order cladding mode into an overlay mode occurs. As a consequence, a cladding modes re-organization can be observed leading to relevant improvements in the SRI sensitivity in terms of wavelength shift and amplitude variations of the LPGs attenuation bands.

Novel Approaches for the Treatment of Familial Hypercholesterolemia.

Familial hypercholesterolemia (FH) is an autosomal disorder characterized by increased levels of total cholesterol and low density lipoprotein (LDL) cholesterol.The extent of underdiagnosis and undertreatment of individuals with FH is largely unknown.The LDL-lowering capacity of statins in combination with other lipid-lowering drugs is maximally around 50-60%. FH patients have a strongly elevated LDL-C and in most cases maximal current treatment is not sufficient to reach the desired LDL targets.Therefore, FH patients have a large residual cardiovascular risk despite the use of statins and there is a medical need for new additional drugs to further lower LDL-C in patients with FH to improve their prognosis.PCSK9 inhibitors have shown great efficacy in lowering lipids with very few side effects. No synergism between statins and PCSK9 inhibition was observed in many trials, allowing clinicians to select a statin dose before considering the initiation of PCSK9-inhibitor therapy.In patients with FH, who are at risk for markedly accelerated atherosclerosis and premature cardiovascular death, also treatment with lomitapide or mipomersen has the potential to reduce the risk of atherosclerotic cardiovascular disease and premature mortality.These new drugs will be probably reserved for the most severely affected FH patients and could help clinicians to reduce their residual cardiovascular risk.

Disputes in the Treatment of Diabetic Nephropathy: The Dual Blockade of Renin-Angiotensin System.

The prevention and the treatment with drugs interacting with the renin-angiotensin system (RAAS) are one of the greatest successes of the pharmacological research in the last years. Many trials demonstrated the efficacy of ARBs and ACEi in preventing or reducing the progression of albuminuria, the loss of kidney function and the mortality in diabetic population.The rationale for applying a dual RAAS blockade is based on data showing that ACEi mono-therapy produces an incomplete RAAS blockade with angiotensin I and renin accumulation and the subsequent angiotensin II 'escape' production by non-ACE pathways. The use of ARBs and ACEi in combination could lead to a stronger RAAS block and consequently to a more effective nephroprotection. Years ago, some studies performed in small groups of patients with diabetic nephropathy confirmed the effectiveness of this pharmacological approach.In contrast recent important trials, like ONTARGET, ALTITUDE and VA NEPHRON-D failed to demonstrate the effectiveness of this therapeutic strategy, suggesting that probably not all the diabetic patients with nephropathy should be considered equal as regard the response to this therapy. These 3 long-term studies showed that the dual blockade of RAAS may bring cardiovascular and renal adverse events, even in presence of a reduction of albuminuria. Dual blockade of RAAS is not currently feasible in patients with diabetic nephropathy, but we consider that the effort to try to apply a complete RAAS blockade should be pursued and that probably through an accurate selection of patients in the future we could reconsider this kind of therapy.

The role of viscoelasticity and stress gradients on the outcome of conductive keratoplasty.

A mechanical analysis of the conductive keratoplasty on hyperopic eyes has been carried out, and the attention has been focused on incorporating the actual viscoelastic properties of the human corneal tissue and on the stress gradients induced by the intervention. By avoiding unnecessary complications which may obscure the essential behaviour of the model, the results are in very good agreement with the clinical and experimental findings and suggest that the major role in the commonly observed decrease of the initial degree of the refractive correction might be played by the stress gradients at the intervention spots, which are likely to influence the wound-healing. The study aims to contribute some firm mechanical roots to the predictability of the outcome of an increasingly popular technique that, notwithstanding several advantages with respect to ablative interventions, at present cannot be considered completely satisfactory.

Topological optimization in hip prosthesis design.

With particular interest on total hip arthroplasty (THA), optimization of orthopedic prostheses is employed in this work to minimize the probability of implant failure or maximize prosthesis reliability. This goal is often identified with the reduction of stress concentrations at the interface between bone and these devices. However, aseptic loosening of the implant is mainly influenced by bone resorption phenomena revealed in some regions of the femur when a prosthesis is introduced. As a consequence, bone resorption appears due to stress shielding, that is to say the decrease of the stress level in the implanted femur caused by the significant load carrying of the prosthesis due to its higher stiffness. A maximum stiffness topological optimization-based (TO) strategy is utilized for non-linear static finite element (FE) analyses of the femur-implant assembly, with the goal of reducing stress shielding in the femur and to furnish guidelines for re-designing hip prostheses. This is accomplished by employing an extreme accuracy for both the three- dimensional reconstruction of the femur geometry and the material properties maps assigned as explicit functions of the local densities.

Performance of a real time PCR for leishmaniasis dignosis using a L. (L.) infantum hypothetical protein as target in canine samples

Visceral leishmaniasis represents an important public health issue in different parts of the world, requiring that measures be put in place to control the spread of the disease worldwide. The canine leishmaniasis diagnosis is not easy based on clinical signs, since dogs may not develop the infection with recognizable signs. Thus, the laboratorial diagnosis is essential to ascertain the incidence and prevalence of canine leishmaniasis especially in areas with major control efforts. Although, the diagnosis can be performed by the use of different approaches, the molecular methods such as PCR have become an indispensable tool for leishmaniases diagnosis. A TaqMan assay for real-time PCR (Linj31-qPCR) was developed to determine the parasite occurrence in clinical cases of leishmaniasis. The assay targets an L. (L.) infantum hypothetical protein region. The specificity of the assay was verified by using Leishmania World Health Organization reference strains including parasites belonging to subgenus L. (Leishmania), subgenus L. (Viannia), other Leishmania species and Trypanosoma cruzi. The sensitivity was verified by using isolates of L. (L.) amazonensis and L. (L.) infantum. The usefulness of the assay for diagnosis was ascertained by testing 277 samples from dogs in regions endemic for visceral and/or cutaneous leishmaniasis and from regions in which leishmaniasis was not endemic in São Paulo State, Brazil. Diagnosis of canine visceral leishmaniasis (CVL) was determined on these animals by conventional PCR and three serological tests. The dog samples were divided into four groups. I, dogs with CVL (n = 101); II, dogs with other diseases and without CVL (n = 97); III, dogs with American cutaneous leishmaniasis (n = 7), and, IV, dogs without CVL (n = 72) from areas where leishmaniasis was not endemic as control group. Results indicated that Linj31-qPCR was able to identify parasites belonging to subgenus L. (Leishmania) with no cross-amplification with other parasite subgenera. The Linj31-qPCR detected Leishmania parasites DNA in 98% of samples from Group I. In conclusion this methodology can be used as routine diagnostic tools to detect parasites from subgenus Leishmania.

Immediate- and late-hemodynamic coronary effects of tadalafil in men with erectile dysfunction and coronary artery disease.

We investigated whether coronary flow reserve (CFR) can be modified by tadalafil, a long-acting phosphodiesterase 5 (PDE5) inhibitor, in patients with documented coronary artery disease (CAD). CFR was non-invasively evaluated in 12 men with a positive history for erectile dysfunction (ED) and angiographically documented CAD, in the distal portion of the left anterior descending coronary artery, free from critical stenosis, with contrast enhanced echocardiography at time zero (T0). Then, after 20 mg tadalafil was orally administered CFR measurement was repeated after 2 h (T1) and after 24 h (T2). Doppler curves suitable for the analysis were obtained in all patients (CFR feasibility: 100%). The peak diastolic velocity after adenosine infusion increased from 71.3+/-14.3 cm/s at T0 to 82.5+/-24.0 at T1 (P=NS) and to 89.5+/-21.1 at T2 (P=0.0010). CFR after tadalafil increased significantly from 2.6+/-0.3 at T0 to 3.1+/-0.7 at T1 (P=0.0078) and a further increment was found at T2 (3.5+/-0.9; P=0.0010 vs T0). Our study shows that oral administration of tadalafil exerts a long standing, potentially beneficial effect on coronary microvasculature in patients with ED.

Alignment and performance of almost concentric resonators for low gain free-electron lasers.

The propagation of mismatched and misaligned laser beams bouncing back and forth between the mirrors of an almost concentric resonator is investigated with reference to the alignment of the cavities used for low gain free-electron lasers. In addition, the excitation of the cavity modes by the spontaneous radiation of a linear undulator is analyzed by considering the reduction of their coupling factors due to the misadjustment of the optical cavity with respect to the axis and the center of the undulator. In particular, analytical expressions are given for the coupling coefficients of two misaligned sets of Gauss-Laguerre or Gauss-Hermite modes and for the coupling factors between the cavity modes and the spontaneous radiation.

Tunable electrooptic intracavity filter for sideband suppression in free electron lasers.

We describe a tunable intracavity filter, which, taking advantage on the electrooptic effect, limits the growth of the sidebands in a free electron laser and even suppresses them in some cases.