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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Amblyomma calcaratum parasitando tamanduá-bandeira (Myrmecophaga tridactyla) em Säo Paulo / Amblyomma calcaratum parasitizing giant anteater (Myrmecophaga tridactyla) in the State of Säo Paulo, Brazil

Ocurrence of Ambluomma calcaratum parasitizing giant anteater (Myrmecophaga tridactyla) is described in the State of Säo Paulo, Brazil

Contactless optoelectronic technique for monitoring epoxy cure.

We describe a novel noninvasive optical technique to monitor the refractive-index variation in an epoxy-based resin that is due to the polymerization process. This kind of resin is widely used in polymer matrix composites. It is well known that the process of fabricating a thermoset-based composite involves mass and heat transfer coupled with irreversible chemical reactions that induce physical changes. To improve the quality and the reliability of these materials, monitoring the cure and optimization of the manufacturing process are of key importance. We discuss the basic operating principles of an optical system based on angle deflection measurements and present typical cure-monitoring results obtained from optical characterization. The method provides a flexible, high-sensitivity, material-independent, low-cost, noninvasive tool for monitoring real-time refractive-index variation.

Effect of fabrication errors in channel waveguide Bragg gratings.

The spectral performances of nonideal rectangular Bragg gratings, integrated in a rib waveguide, are analyzed by a multilayer approach based on the effective-index method. The effects of errors on the photolithographic definition of the grating, that is, period and shape, and of errors on the control of etching depth are investigated. Also the influence of the stitching error, which is unavoidable when the grating is realized by means of electron-beam photolithography, is addressed. A novel analytical approach that extends coupled-mode theory to the analysis of real gratings is also presented.

Real-time measurement of transverse-mode-mixing effects in a Q-switched Nd:YAG laser.

We describe a novel apparatus for the real-time characterization of transverse-mode-mixing effects by monitoring the fluctuations of the M(2) factor defined by Siegman [Proc. Soc. Photo-Opt. Instrum. Eng. 1224, 2 (1990)]. A comparison between the results provided by our approach and those obtained by the use of a standard measurement apparatus has shown a satisfactory agreement within the experimental uncertainty.

Transverse mode analysis of a laser beam by near- and far-field intensity measurements.

A quantitative measurement of laser-beam quality can be performed by determination of the presence of multiple transverse modes of the laser oscillator and by calculation of their power content. Along this line of argument, we discuss a new approach that, starting from near-field and far-field intensity measurements, can evaluate the complex excitation coefficients of the transverse modes in a laser beam. The exploitation of near-field measurements sharply improves the performances of the technique in those cases in which only far-field measurements are used. The validity of the method is confirmed by several accurate numerical simulations and by some experimental results relative to a multimode Q-switched Nd:YAG laser.

Characterization of the transverse modes in a laser beam: analysis and application to a Q-switched Nd:YAG laser.

We have developed a numerical code that, starting from far-field intensity measurements, is able to evaluate the excitation coefficients of the transverse modes in a laser system.Both the coherent and incoherent mode cases are addressed, and, while the incoherent case is shown to be equivalent to a linear problem, the coherent case is discussed through its equivalence to the phase-retrieval problem. Problems arising from both ill posedness and the nonlinearity are discussed in detail.The validity of our approach is confirmed by several numerical simulations and some experimental results on the characterization of a Q-switched Nd:YAG laser.