Pulmonary embolism with migrating thrombus through patent foramen ovale: A case for a mixed pharmacological and percutaneous management.

A 61-year-old man, admitted to our hospital for bilateral pulmonary embolism, complicated by right renal ischemia and multiple splenic infarcts due to a mobile thrombus entrapped in a patent foramen ovale, has been successfully treated with apixaban 5 mg twice daily followed by transcatheter patent foramen ovale closure. .

Case report of a 65-year-old man with biatrial metastatic localisation from poorly differentiated cutaneous squamous cell carcinoma.

We report the case of an immunocompetent 65-year-old man affected by cutaneous squamous cell carcinoma (cSCC) with lung and biatrial metastatic localisation. In May 2018, the patient underwent lower limb amputation due to the finding of a large ulceration which upon biopsy was found to be a poorly differentiated squamous cell carcinoma (SCC), ulcerated, full-thickness infiltrating from the skin to the underlying bone tissue. After 1 month, a radiological restaging found multiple pulmonary localisations and a right-atrial metastatic localisation. The patient was then studied in-depth and a transesophageal echocardiogram found that the patient had two 2 and 5 cm metastatic localisations in the left atrium and a 3-cm metastatic localisation in the right atrium. Informed about the clinical situation and about the risks of a chemotherapeutic treatment, the patient decided not to start any treatment. This case represents, to our knowledge, the only case of a biatrial metastatic localisation from cSCC and is representative of how cardiac symptoms and signs in patients affected by this disease must be evaluated.

Apixaban-Induced Resolution of A Massive Left Atrial and Appendage Thrombosis in a Very Elderly Patient.

A 86-year-old woman with first diagnosed atrial fibrillation (AF) underwent mitral valve annuloplasty 10 years before was admitted to our Unit due to congestive heart failure. Trans-thoracic echocardiogram (TTE) revealed a large fluctuant echogenic mass in the posterior wall of the left atrium. Trans-esophageal echo (TEE) showed the origin of the mass within the left atrial appendage. An adjusted dose of the novel oral anticoagulant (NOAC) apixaban, was prescribed. A complete disappearance was appreciated by examination at 12 weeks after the first drug administration. Although apixaban, resulted superior to warfarin in preventing stroke and thrombo-embolic events in patients with non valvular AF, while causing less bleeding, few data are actually available regarding the efficacy and safety of this drug in left atrium and appendage thrombosis management. Our report shows that this NOAC could be a simple and useful option to manage huge atrial thrombosis in very elderly patients.

[Percutaneous implantation of a left ventricular restoration device [Parachute(TM)] for the treatment of ischemic heart failure]. / Trattamento della disfunzione ventricolare sinistra post-infartuale con impianto percutaneo di dispositivo ParachuteTM.

Congestive heart failure secondary to myocardial infarction is associated with significant morbidity and mortality despite currently available therapies. A novel catheter-based left ventricular partitioning device (ParachuteTM, CardioKinetix, Inc., Menlo Park, CA) is currently available for the treatment of patients with severe systolic dysfunction after antero-apical myocardial infarction with regional wall motion abnormalities. Preliminary clinical data showed that the ParachuteTM implantation could be associated with favorable clinical and left ventricular hemodynamic improvements post-implantation. Here, we present the case of a patient with symptomatic congestive heart failure after myocardial infarction implanted with the ParachuteTM device and we briefly review the current literature on this left ventricular partitioning system.

Nanoscale roughness affects the activity of enzymes adsorbed on cluster-assembled titania films.

In this study, we investigated how the adsorption properties governed by the nanometer-scale surface morphology of cluster-assembled titanium oxide films influence the catalytic activity of immobilized serine-protease trypsin. We developed an activity assay for the parallel detection of physisorbed enzyme activity and mass density of the adsorbed proteins in microarray format. The method combines a microarray-based technique and advanced quantitative confocal microscopy approaches based on fluorescent labeling of enzymes and covalent labeling of active sites of surface-bound enzymes. The observed diminishing trypsin binding affinity with increasing roughness, as opposed to the steep rise in its saturation uptake, was interpreted as heterogeneous nucleation-driven adsorption of trypsin at the rough nanoporous titania surface. The increase in relative activity of adsorbed trypsin is proportional to the fractional saturation of titania surfaces, expressed as percentage of saturation uptake. In turn, the specific activity, that is, the ratio of active proteins to the absolute number of adsorbed proteins, drops with growing saturation uptake and surface roughness, witnessing a reduction in the accessibility of enzyme active sites. Both geometrical constraints of titania nanopores and the clusterwise adsorption of trypsin were identified as the key factors underpinning the steric hindrance of the immobilized enzyme. These findings are relevant for the optimization of rough nanoporous surfaces as carriers of immobilized enzymes. The proposed activity assay is particularly advantageous in the screening of candidate materials for enzyme immobilization.

Selective modulation of cell response on engineered fractal silicon substrates.

A plethora of work has been dedicated to the analysis of cell behavior on substrates with ordered topographical features. However, the natural cell microenvironment is characterized by biomechanical cues organized over multiple scales. Here, randomly rough, self-affinefractal surfaces are generated out of silicon,where roughness Ra and fractal dimension Df are independently controlled. The proliferation rates, the formation of adhesion structures, and the morphology of 3T3 murine fibroblasts are monitored over six different substrates. The proliferation rate is maximized on surfaces with moderate roughness (Ra ~ 40 nm) and large fractal dimension (Df ~ 2.4); whereas adhesion structures are wider and more stable on substrates with higher roughness (Ra ~ 50 nm) and lower fractal dimension (Df ~ 2.2). Higher proliferation occurson substrates exhibiting densely packed and sharp peaks, whereas more regular ridges favor adhesion. These results suggest that randomly roughtopographies can selectively modulate cell behavior.

Quantitative characterization of the influence of the nanoscale morphology of nanostructured surfaces on bacterial adhesion and biofilm formation.

Bacterial infection of implants and prosthetic devices is one of the most common causes of implant failure. The nanostructured surface of biocompatible materials strongly influences the adhesion and proliferation of mammalian cells on solid substrates. The observation of this phenomenon has led to an increased effort to develop new strategies to prevent bacterial adhesion and biofilm formation, primarily through nanoengineering the topology of the materials used in implantable devices. While several studies have demonstrated the influence of nanoscale surface morphology on prokaryotic cell attachment, none have provided a quantitative understanding of this phenomenon. Using supersonic cluster beam deposition, we produced nanostructured titania thin films with controlled and reproducible nanoscale morphology respectively. We characterized the surface morphology; composition and wettability by means of atomic force microscopy, X-ray photoemission spectroscopy and contact angle measurements. We studied how protein adsorption is influenced by the physico-chemical surface parameters. Lastly, we characterized Escherichia coli and Staphylococcus aureus adhesion on nanostructured titania surfaces. Our results show that the increase in surface pore aspect ratio and volume, related to the increase of surface roughness, improves protein adsorption, which in turn downplays bacterial adhesion and biofilm formation. As roughness increases up to about 20 nm, bacterial adhesion and biofilm formation are enhanced; the further increase of roughness causes a significant decrease of bacterial adhesion and inhibits biofilm formation. We interpret the observed trend in bacterial adhesion as the combined effect of passivation and flattening effects induced by morphology-dependent protein adsorption. Our findings demonstrate that bacterial adhesion and biofilm formation on nanostructured titanium oxide surfaces are significantly influenced by nanoscale morphological features. The quantitative information, provided by this study about the relation between surface nanoscale morphology and bacterial adhesion points towards the rational design of implant surfaces that control or inhibit bacterial adhesion and biofilm formation.

High-throughput tools for the study of protein-nanostructured surface interaction.

The aim of this review is to describe and to analyze the ingredients that are necessary in order to develop a robust and effective experimental approach for the high-throughput characterization of protein-nanostructured surface interaction. In the first part of this paper we review the nanostructured surface synthesis methods that are potentially able to create nanostructured inorganic surface libraries. In the second part, we address another fundamental aspect consisting in the availability of high-throughput proteins detection methods. We describe in details new emerging analytical tools compatible with nanostructured surfaces, analyzing different possible strategies, depending on the objective of the experiment and on the library format.

The effect of surface nanometre-scale morphology on protein adsorption.

BACKGROUND: Protein adsorption is the first of a complex series of events that regulates many phenomena at the nano-bio interface, e.g. cell adhesion and differentiation, in vivo inflammatory responses and protein crystallization. A quantitative understanding of how nanoscale morphology influences protein adsorption is strategic for providing insight into all of these processes, however this understanding has been lacking until now. METHODOLOGY/PRINCIPAL FINDINGS: Here we introduce novel methods for quantitative high-throughput characterization of protein-surface interaction and we apply them in an integrated experimental strategy, to study the adsorption of a panel of proteins on nanostructured surfaces. We show that the increase of nanoscale roughness (from 15 nm to 30 nm) induces a decrease of protein binding affinity (

Direct microfabrication of topographical and chemical cues for the guided growth of neural cell networks on polyamidoamine hydrogels.

Cell patterning is an important tool for organizing cells in surfaces and to reproduce in a simple way the tissue hierarchy and complexity of pluri-cellular life. The control of cell growth, proliferation and differentiation on solid surfaces is consequently important for prosthetics, biosensors, cell-based arrays, stem cell therapy and cell-based drug discovery concepts. We present a new electron beam lithography method for the direct and simultaneous fabrication of sub-micron topographical and chemical patterns, on a biocompatible and biodegradable PAA hydrogel. The localized e-beam modification of a hydrogel surface makes the pattern able to adsorb proteins in contrast with the anti-fouling surface. By also exploiting the selective attachment, growth and differentiation of PC12 cells, we fabricated a neural network of single cells connected by neuritis extending along microchannels. E-beam microlithography on PAA hydrogels opens up the opportunity of producing multifunctional microdevices incorporating complex topographies, allowing precise control of the growth and organization of individual cells.

Life-threatening left main stenosis induced by compression from a dilated pulmonary artery.

On a rare occasion, pulmonary artery dilatation can be complicated by an extrinsic compression of the left main coronary artery (LMCA) whose effects are immediately evident, whereas a delayed presentation is unusual. We report the uncommon case of a delayed acute coronary syndrome caused by the extrinsic compression of the LMCA due to pulmonary artery enlargement and the potential problems related to its management. An 82-year-old woman with a history of severe chronic obstructive pulmonary disease, a previous episode of deep venous thrombosis and a computed tomography-documented pulmonary artery dilatation was referred to the emergency room for worsening dyspnoea and chest pain. Five days after admission to the coronary care unit, the patient developed a cardiogenic shock with consecutive episodes of ventricular fibrillation. Urgent coronary angiography showed severe LMCA stenosis caused by extrinsic compression from the pulmonary artery with no other lesions in the coronary arteries; coronary angioplasty was successfully performed with a direct drug-eluting stent implantation that led to a significant improvement of the haemodynamic conditions in the following days. Planned control angiography performed 10 days later showed the recurrence of the LMCA stenosis together with a forward displacement of the previously implanted drug-eluting stent, which was managed with a further direct implantation of a bare metal stent. The immediate good results of this second procedure were confirmed by follow-up angiography performed 2 months later and by the 6-month follow-up clinical examination.

Adsorption and stability of streptavidin on cluster-assembled nanostructured TiOx films.

The study of the adsorption of proteins on nanostructured surfaces is of fundamental importance to understand and control cell-surface interactions and, notably, cell adhesion and proliferation; it can also play a strategic role in the design and fabrication of nanostructured devices for postgenomic and proteomic applications. We have recently demonstrated that cluster-assembled nanostructured TiO x films produced by supersonic cluster beam deposition possess excellent biocompatibility and that these films can be functionalized with streptavidin, allowing the immobilization of biotinylated retroviral particles and the realization of living-cell microarrays for phenotype screening. Here we present a multitechnique investigation of the adsorption mechanisms of streptavidin on cluster-assembled TiO x films. We show that this nanostructured surface provides an optimal balance between adsorption efficacy and protein functionality. By using low-resolution protein arrays, we demonstrate that a layer of adsorbed streptavidin can be stably maintained on a cluster-assembled TiO x surface under cell culture conditions and that streptavidin retains its biological activity in the adsorbed layer. The adsorption mechanisms are investigated by atomic force microscopy in force spectroscopy mode and by valence-band photoemission spectroscopy, highlighting the potential role of the interaction of the exposed carboxyl groups on streptavidin with the titanium atoms of the nanostructured surface.