Micro/nanoscale patterning of nanostructured metal substrates for plasmonic applications.

The ability to precisely control the pattern of different metals at the micro- and nanoscale, along with their topology, has been demonstrated to be essential for many applications, ranging from material science to biomedical devices, electronics, and photonics. In this work, we show a novel approach, based on a combination of lithographic techniques and galvanic displacement reactions, to fabricate micro- and nanoscale patterns of different metals, with highly controlled surface roughness, onto a number of suitable substrates. We demonstrate the possibility to exploit such metal films to achieve significant fluorescence enhancement of nearby fluorophores, while maintaining accurate spatial control of the process, from submicron resolution to centimeter-sized features. These patterns may be also exploited for a wide range of applications, including SERS, solar cells, DNA microarray technology, hydrophobic/hydrophilic substrates, and magnetic devices

Microscale patterning of hydrophobic/hydrophilic surfaces by spatially controlled galvanic displacement reactions.

In this letter, we report the design and fabrication of different metal patterns for the realization of spatially controlled hydrophobic/hydrophilic regions with micrometer resolution. The fabrication procedure, based on a combination of lithographic techniques and wet-chemistry reactions (namely, spontaneous Galvanic displacement reactions) is reliable, undemanding, and highly versatile, allowing the achievement of precise spatial control along with the use of a wide variety of different materials

Mutagenic effects of gold nanoparticles induce aberrant phenotypes in Drosophila melanogaster

Abstract The peculiar physical/chemical characteristics of engineered nanomaterials have led to a rapid increase of nanotechnology-based applications in many fields. However, before exploiting their huge and wide potential, it is necessary to assess their effects upon interaction with living systems. In this context, the screening of nanomaterials to evaluate their possible toxicity and understand the underlying mechanisms currently represents a crucial opportunity to prevent severe harmful effects in the next future. In this work we show the in vivo toxicity of gold nanoparticles (Au NPs) in Drosophila melanogaster , highlighting significant genotoxic effects and, thus, revealing an unsettling aspect of the long-term outcome of the exposure to this nanomaterial. After the treatment with Au NPs, we observed dramatic phenotypic modifications in the subsequent generations of Drosophila , demonstrating their capability to induce mutagenic effects that may be transmitted to the descendants. Noteworthy, we were able to obtain the first nanomaterial-mutated organism, named NM-mut. Although these results sound alarming, they underline the importance of systematic and reliable toxicology characterizations of nanomaterials and the necessity of significant efforts by the nanoscience community in designing and testing suitable nanoscale surface engineering/coating to develop biocompatible nanomaterials with no hazardous effects for human health and environment. From the Clinical Editor While the clinical application of nanomedicine is still in its infancy, the rapid evolution of this field will undoubtedly result in a growing number of clinical trials and eventually in human applications. The interactions of nanoparticles with living organisms determine their toxicity and long-term safety, which must be properly understood prior to large-scale applications are considered. The paper by Dr. Pompa's team is the first ever demonstration of mutagenesis resulting in clearly observable phenotypic alterations and the generation of nano-mutants as a result of exposure to citrate-surfaced gold nanoparticles in drosophila. These groundbreaking results are alarming, but represent a true milestone in nanomedicine and serve as a a reminder and warning about the critical importance of "safety first" in biomedical science

Impact of nanoscale topography on genomics and proteomics of adherent bacteria.

Bacterial adhesion onto inorganic/nanoengineered surfaces is a key issue in biotechnology and medicine, because it is one of the first necessary steps to determine a general pathogenic event. Understanding the molecular mechanisms of bacteria−surface interaction represents a milestone for planning a new generation of devices with unanimously certified antibacterial characteristics. Here, we show how highly controlled nanostructured substrates impact the bacterial behavior in terms of morphological, genomic, and proteomic response. We observed by atomic force microscopy (AFM) and scanning electron microscopy (SEM) that type-1 fimbriae typically disappear in Escherichia coli adherent onto nanostructured substrates, as opposed to bacteria onto reference glass or flat gold surfaces. A genetic variation of the fimbrial operon regulation was consistently identified by real time qPCR in bacteria interacting with the nanorough substrates. To gain a deeper insight into the molecular basis of the interaction mechan..

Monodispersed and size-controlled multibranched gold nanoparticles with nanoscale tuning of surface morphology

A novel seed-mediated synthetic route to produce multibranched gold nanoparticles is reported, in which it is possible to precisely tune both their size and nanostructuration, while maintaining an accurate level of monodispersion. The nanoscale control of surface nanoroughness/branching, ranging from small bud-like features to elongated spikes, allows to obtain fine tuning of the nanoparticle optical properties, up to the red and near-IR region of the spectrum. Such anisotropic nanostructures were demonstrated to be excellent candidates for SERS applications, showing significantly higher signals with respect to the standard spherical nanoparticles

Room-temperature metal stamping by microfluidics

We show the possibility to fabricate highly controlled metal micropatterns on a variety of substrates, such as semiconducting or metallic materials, exploiting a combination of spontaneous galvanic displacement reactions with microfluidics. The process is reliable and quite versatile and allows the fabrication of complex patterns of different metals on a number of substrates in few minutes on a conventional laboratory bench

Robotic Upper Limb Rehabilitation after Acute Stroke by NeReBot: Evaluation of Treatment Costs

Stroke is the first cause of disability. Several robotic devices have been developed for stroke rehabilitation. Robot therapy by NeReBot is demonstrated to be an effective tool for the treatment of poststroke paretic upper limbs, able to improve the activities of daily living of stroke survivors when used both as additional treatment and in partial substitution of conventional rehabilitation therapy in the acute and subacute phases poststroke. This study presents the evaluation of the costs related to delivering such therapy, in comparison with conventional rehabilitation treatment. By comparing several NeReBot treatment protocols, made of different combinations of robotic and nonrobotic exercises, we show that robotic technology can be a valuable and economically sustainable aid in the management of poststroke patient rehabilitation

Framing the nano-biointeractions by proteomics

Knowledge of the molecular mechanisms underlying the interactions between nanomaterials and living systems is fundamental for providing more effective products for nanomedicine and drug delivery. Controlling the response of cells/bacteria (such as activation of inflammatory processes or apoptosis/necrosis in tumor cells or pathogenic bacteria) by tuning specific properties of the nanomaterials is ultimately the challenging goal. Notably, this may also provide crucial information in the assessment of any toxic risks induced by nanoparticles on humans. However, in studying the nano-biointeractions, it is imperative to take into account the dynamic evolutions of nanoparticles in the biological environments (in terms of protein corona formation, size and charge changes) in synergy with the dynamic events occurring in cells, including signal transduction, metabolic processes, homeostasis and membrane trafficking. In this context, we discuss the impact of analytical technologies, especially in the field of proteomics, which can provide major insights into the processes affecting the NPs surface as well as the cells and bacteria functionalities. In particular, we show that a precise control of the chemical-physical characteristics of the interacting nanoparticles or nanostructures may impact the cells by inducing changes in the proteomic profiles with direct consequences on their viability

Economic evaluation of two therapeutic sequences in the first-line treatment of moderate to severe active ulcerative rectocolitis in Italy

Background: Vedolizumab (VDZ) and infliximab are used to treat moderate to severe ulcerative colitis (UC). The choice of the drug to use at first-line is often based on a combination of clinical and economic factors. The cost of treatment pathway is rarely considered. Therefore, this cost-consequence analysis (CCA) investigated the overall costs of treatment pathway for vedolizumab followed by infliximab (VDZ → IFX) compared to infliximab followed by vedolizumab (IFX → VDZ). Methods: We used a published cost-consequence model (CCM), based on a targeted literature search reporting the time-on-treatment data for vedolizumab or infliximab in UC in first and second-line of treatment. CCM time horizon was defined by the length of treatment sequences. Considering the Italian hospital perspective, the CCA evaluated the biologic drugs acquisition costs, drug administration costs, hospitalization costs, switch costs, colectomy costs and third-line treatment costs. Third-line options included colectomy, tofacitinib, ustekinumab or dose escalation of second-line biologic. Results: Over the 5.2-year time horizon (duration of the longer VDZ → IFX pathway), the mean cost per patient of VDZ → IFX pathway was slightly lower than the mean cost per patient of IFX → VDZ pathway (€ 86,339 vs 89,636). The CCM predicted that using VDZ as first-line treatment delayed the time to costly third-line therapies compared to first-line using IFX (VDZ-first-line median time-on-treatment 3.6-years and IFX-second-line 1.6-years; IFX-first-line 1.4-years and VDZ-second-line 2.3-years and third-line 1.5-years). Conclusion: The CCA showed that a biologic treatment pathway that begins with first-line vedolizumab is not more expensive than one beginning with first-line infliximab and delayed the time to costly third-line

Trends in Net Survival from Vulvar Squamous Cell Carcinoma in Italy (1990–2015)

Objective: In many Western countries, survival from vulvar squamous cell carcinoma (VSCC) has been stagnating for decades or has increased insufficiently from a clinical perspective. In Italy, previous studies on cancer survival have not taken vulvar cancer into consideration or have pooled patients with vulvar and vaginal cancer. To bridge this knowledge gap, we report the trend in survival from vulvar cancer between 1990 and 2015. (2) Methods: Thirty-eight local cancer registries covering 49% of the national female population contributed the records of 6274 patients. Study endpoints included 1- and 2-year net survival (NS) calculated using the Pohar-Perme estimator and 5-year NS conditional on having survived two years (5|2-year CNS). The significance of survival trends was assessed with the Wald test on the coefficient of the period of diagnosis, entered as a continuous regressor in a Poisson regression model. (3) Results: The median patient age was stable at 76 years. One-year NS decreased from 83.9% in 1990–2001 to 81.9% in 2009–2015 and 2-year NS from 72.2% to 70.5%. Five|2-year CNS increased from 85.7% to 86.7%. These trends were not significant. In the age stratum 70–79 years, a weakly significant decrease in 2-year NS from 71.4% to 65.7% occurred. Multivariate analysis adjusting for age group at diagnosis and geographic area showed an excess risk of death at 5|2-years, of borderline significance, in 2003–2015 versus 1990–2002. (4) Conclusions: One- and 2-year NS and 5|2-year CNS showed no improvements. Current strategies for VSCC control need to be revised both in Italy and at the global level