[18F](2S,4R)-4-Fluoroglutamine as a New Positron Emission Tomography Tracer in Myeloma

The high glycolytic activity of multiple myeloma (MM) cells is the rationale for use of Positron Emission Tomography (PET) with 18F-fluorodeoxyglucose ([18F]FDG) to detect both bone marrow (BM) and extramedullary disease. However, new tracers are actively searched because [18F]FDG-PET has some limitations and there is a portion of MM patients who are negative. Glutamine (Gln) addiction has been recently described as a typical metabolic feature of MM cells. Yet, the possible exploitation of Gln as a PET tracer in MM has never been assessed so far and is investigated in this study in preclinical models. Firstly, we have synthesized enantiopure (2S,4R)-4-fluoroglutamine (4-FGln) and validated it as a Gln transport analogue in human MM cell lines, comparing its uptake with that of 3H-labelled Gln. We then radiosynthesized [18F]4-FGln, tested its uptake in two different in vivo murine MM models, and checked the effect of Bortezomib, a proteasome inhibitor currently used in the treatment of MM. Both [18F]4-FGln and [18F]FDG clearly identified the spleen as site of MM cell colonization in C57BL/6 mice, challenged with syngeneic Vk12598 cells and assessed by PET. NOD.SCID mice, subcutaneously injected with human MM JJN3 cells, showed high values of both [18F]4-FGln and [18F]FDG uptake. Bortezomib significantly reduced the uptake of both radiopharmaceuticals in comparison with vehicle at post treatment PET. However, a reduction of glutaminolytic, but not of glycolytic, tumor volume was evident in mice showing the highest response to Bortezomib. Our data indicate that [18F](2S,4R)-4-FGln is a new PET tracer in preclinical MM models, yielding a rationale to design studies in MM patients

Comparison of anticoagulation quality between acenocoumarol and warfarin in patients with mechanical prosthetic heart valves: Insights from the nationwide PLECTRUM study

Vitamin K antagonists are indicated for the thromboprophylaxis in patients with mechanical prosthetic heart valves (MPHV). However, it is unclear whether some differences between acenocoumarol and warfarin in terms of anticoagulation quality do exist. We included 2111 MPHV patients included in the nationwide PLECTRUM registry. We evaluated anticoagulation quality by the time in therapeutic range (TiTR). Factors associated with acenocoumarol use and with low TiTR were investigated by multivariable logistic regression analysis. Mean age was 56.8 ± 12.3 years; 44.6% of patients were women and 395 patients were on acenocoumarol. A multivariable logistic regression analysis showed that patients on acenocoumarol had more comorbidities (i.e., ≥3, odds ratio (OR) 1.443, 95% confidence interval (CI) 1.081-1.927, p = 0.013). The mean TiTR was lower in the acenocoumarol than in the warfarin group (56.1 ± 19.2% vs. 61.6 ± 19.4%, p < 0.001). A higher prevalence of TiTR (<60%, <65%, or <70%) was found in acenocoumarol users than in warfarin ones (p < 0.001 for all comparisons). Acenocoumarol use was associated with low TiTR regardless of the cutoff used at multivariable analysis. A lower TiTR on acenocoumarol was found in all subgroups of patients analyzed according to sex, hypertension, diabetes, age, valve site, atrial fibrillation, and INR range. In conclusion, anticoagulation quality was consistently lower in MPHV patients on acenocoumarol compared to those on warfarin

Microbiota-driven interleukin-17-producing cells and eosinophils synergize to accelerate multiple myeloma progression

The gut microbiota has been causally linked to cancer, yet how intestinal microbes influence progression of extramucosal tumors is poorly understood. Here we provide evidence implying that Prevotella heparinolytica promotes the differentiation of Th17 cells colonizing the gut and migrating to the bone marrow (BM) of transgenic Vk*MYC mice, where they favor progression of multiple myeloma (MM). Lack of IL-17 in Vk*MYC mice, or disturbance of their microbiome delayed MM appearance. Similarly, in smoldering MM patients, higher levels of BM IL-17 predicted faster disease progression. IL-17 induced STAT3 phosphorylation in murine plasma cells, and activated eosinophils. Treatment of Vk*MYC mice with antibodies blocking IL-17, IL-17RA, and IL-5 reduced BM accumulation of Th17 cells and eosinophils and delayed disease progression. Thus, in Vk*MYC mice, commensal bacteria appear to unleash a paracrine signaling network between adaptive and innate immunity that accelerates progression to MM, and can be targeted by already available therapies

Dynamic Landscapes, Emerging Territories

As a result of the pressing environmental and technological conditions dominant today, new frontiers for architectural production are emerging. Fueled by accelerated change and increased connectivity, these trajectories operate across multiple scales and domains. The evolving relationship between place, technology, and occupancy formulates a complex active structure that tends to have fluctuating levels of activity and impact. These conditions are giving way to hybridized settings where the interdependence of digital and analog is altering the very politics of place and identity. In response to the prevalence of amalgamated settings, the paradigm of “Dynamic Landscapes, Emerging Territories” is presented. Dynamic Landscapes have definitions and presence in multiple locations simultaneously, requiring new methods of documentation and assessment in order to conceive appropriate design responses. The paper uses the Syrian Refugee Crisis as a case study for deciphering the implications inherent in displacement in the context of dynamic landscapes. Furthermore, it presents an opportunity to think of new architectural trajectories rooted and driven by the animation of such sites. Inherently dynamic, forced displacement presents rich emerging territories where design carries significant impact and facilitates a tangible reassessment of a refugee’s narrative. Supported by robust information networks and active feedback loops, displaced landscapes as such can learn from their residents and inform their imminent futures specifically, as well as our collective human occupancy at large. Within constantly changing milieus, architecture’s premises and processes are being challenged to respond to fluctuating contexts and provide for transient occupancies. While some may see this as a loss of spatial agency when it comes to design, these conditions present an opportunity to think of new architectural trajectories that are rooted and driven by the dynamism of multilayered landscapes and new approaches towards practice

Real-time visualization of the Forum of Pompei

This paper describes the process to create a single realistic 3D digital model of a wide archeological site, to be used for virtual reality application. The incoming data are texturized models coming from an accurate 3D survey of the entire area: the ground, buildings and finds were acquired with active and passive sensors and converted into polygonal models. Afterwards, the models were assembled in a single virtual scene that reproduces the Forum as it would actually appear to a tourist. The scene can be visualized by means of stereoscopic devices to increase the feeling of immersion. During the data conversion process we had to face three main kind of problems: the database optimization, the correction of digital objects position into the scene and the realism of the displayed model. The real time rendered model of the Forum was displayed on a large screen with stereoscopic technology, as a support for archeological studies

An unusual case of acute periorbital swelling.

Periorbital swelling is frequently encountered in ear, nose, and throat practices and, as it may be secondary to acute sinusitis, delayed diagnosis may lead to significant morbidity. We describe the case of a 24-year-old man with acute ethmoid-maxillary sinusitis and ipsilateral facial swelling particularly involving the periorbital area. We also discuss the workup that led to the formulation of an unusual diagnosi

Tools and Methods to Assist the Product Customization in the Field of Furniture Design

Abstract: The design-to-customer pipeline in companies operating in the high-end furniture market is pretty complex and fragmented, mainly because during the last years fundamental requirements have become: • to suggest the customer not only a single piece of furniture, but a whole interior design solution, building and communicating a ‘brand atmosphere’ with a strong semantic coherence; • to provide an increasing level of customization of the product, which turns into the problem of controlling variety and variability. For these reasons the sale process requires wide spaces, filled with many physical products, and the use of sophisticated images of furnished scenes in communication tools, to suggest the customer not only the functional performance of products, but also a ‘mood’ linked with immaterial brand values. Unfortunately, photographic sets and physical showrooms are resource demanding, and do not allow a fast time-to-market. Moreover, it’s practically impossible to have the full range of each product in a showroom, with all the configurations, accessories and finishing variants (i.e. the swivel sofa AMOENUS in Maxalto collection has more than 430 variants). In this context a first goal for companies is to have a significantly more structured design process, compressing time, optimizing resources, building a simpler and faster communication process. In this paper we present a new framework to assist the product customization in the furniture sector using digital methods, 3D virtual models, and high quality real-time rendering solutions. The paper is organized in 4 sections: a. Furniture customization problem characterization; b. B&B Italia Case study explanation; c. New design process pipeline using 3D models description; d. New ‘virtual furniture’ framework, adopting new visualization and project management solutions developed to support product customization, combining virtual modeling with photorealistic visualization depiction