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In tissue engineering, the composition and the structural arrangement of molecular components within the extracellular matrix (ECM) determine the physical and biochemical features of a scaffold, which consequently modulate cell behavior and function. The microenvironment of the ECM plays a fundamental role in regulating angiogenesis. Numerous strategies in tissue engineering have attempted to control the spatial cues mimicking in vivo angiogenesis by using simplified systems. The aim of this study was to develop 3D porous crosslinked hydrogels with different spatial presentation of pro-angiogenic molecules to guide endothelial cell (EC) behavior. Hydrogels with pores and preformed microchannels were made with pharmaceutical-grade pullulan and dextran and functionalized with novel pro-angiogenic protein polymers (Caf1-YIGSR and Caf1-VEGF). Hydrogel functionalization was achieved by electrostatic interactions via incorporation of diethylaminoethyl (DEAE)–dextran. Spatial-controlled coating of hydrogels was realized through a combination of freeze-drying and physical absorption with Caf1 molecules. Cells in functionalized scaffolds survived, adhered, and proliferated over seven days. When incorporated alone, Caf1-YIGSR mainly induced cell adhesion and proliferation, whereas Caf1-VEGF promoted cell migration and sprouting. Most importantly, directed cell migration required the presence of both proteins in the microchannel and in the pores, highlighting the need for an adhesive substrate provided by Caf1-YIGSR for Caf1-VEGF to be effective. This study demonstrates the ability to guide EC behavior through spatial control of pro-angiogenic cues for the study of pro-angiogenic signals in 3D and to develop pro-angiogenic implantable materials.

Vascularization of 3D models represents a major challenge of tissue engineering and a key prerequisite for their clinical and industrial application. The use of prevascularized models built from dedicated materials could solve some of the actual limitations, such as suboptimal integration of the bioconstructs within the host tissue, and would provide more in vivo‐like perfusable tissue and organ‐specific platforms. In the last decade, the fabrication of vascularized physiologically relevant 3D constructs has been attempted by numerous tissue engineering strategies, which are classified here in microfluidic technology, 3D coculture models, namely, spheroids and organoids, and biofabrication. In this review, the recent advancements in prevascularization techniques and the increasing use of natural and synthetic materials to build physiological organ‐specific models are discussed. Current drawbacks of each technology, future perspectives, and translation of vascularized tissue constructs toward clinics, pharmaceutical field, and industry are also presented. By combining complementary strategies, these models are envisioned to be successfully used for regenerative medicine and drug development in a near future., Vascularization strategies of 3D tissue engineered models are reviewed in this article. The integration of a vascular network in vitro is fundamental to achieve tissue constructs with physiological relevance. Nowadays, numerous approaches have been developed to vascularize tissue and organ models, mainly by using microfluidic technology, 3D cell culture, and bioprinting. Recent advances and the combination of these strategies are promoting a rapid translation toward the clinical and industrials fields.

Purpose of Review The nitric oxide (NO)-soluble guanylate cyclase (sGC)-cyclic guanosine monophosphate (cGMP) pathway plays an important role in the regulation of cardiovascular function, and it is disrupted in heart failure (HF), resulting in decreased protection against myocardial injury. Impaired NO-sGC-cGMP signaling in HF is secondary to reduced NO bioavailability and altered redox state of sGC, which becomes less responsive to NO. The sGC activator cinaciguat increases cGMP levels by direct NO-independent activation of sGC and may be particularly effective in conditions of increased oxidative stress and endothelial dysfunction, and therefore reduced NO levels, at the expense of a greater risk of hypotension. Conversely, sGC stimulators (riociguat and vericiguat) enhance sGC sensitivity to endogenous NO, thus exerting a more physiological action. Recent Findings Clinical trials have suggested the benefit of vericiguat in patients with high-risk HF; in particular, a lower incidence of death from cardiovascular causes or HF hospitalization. Summary Adding vericiguat may be considered in individual patients with HF, and reduced left ventricular ejection fraction (HFrEF) particularly those at higher risk of HF hospitalization.

Background In the last years prognosis of cancer patients (pts) has been improved, but the develop of cardiotoxicity (CTX) in pts with low CV risk treated with cumulative doses of Anthracycline (ANT) considered safe, led to investigate the possible role of the genetic profile in the onset of CTX. Purpose To study the role of some single nucleotide polymorphisms (SNPs) as predictive genetic markers of individual susceptibility to CTX induced by anticancer treatment. Methods We have enrolled women with non-metastatic breast cancer who had to start a therapy with ANT. The presence of a known heart disease, a previous mediastinal irradiation and a previous treatment with ANT, were the main exclusion criteria. All pts underwent complete cardiological evaluation (ECG, echo) before the beginning of the therapy (T0), after each ANT cycle and every 3 months up to 1 year of follow-up after the end of treatment. During each visit, we performed the determination of troponin I (TnI) and NT-proBNP. The genetic profile of each pts was also investigated, analyzing 6 SNPs belonging to 3 different genes (two for each genes) coding for enzymes or enzyme systems involved in the metabolism of ANT. DNA extraction from blood samples was performed using the QIAamp DNA Mini kit (QIAGEN). The DNA extracted was genotyped (by performing TaqMan SNP Genotyping assays) identifying 3 possible variants for each SNPs: homozygosity for the protective and “at risk” variant and heterozygosity. Results 179 pts finished the follow-up and from the analysis of the trend of biomarkers we found that 53 pts (30%) showed a significant increase in TnI (>0.04ng/mL) or less than this cut-off but persistently >0.015ng/mL in at least 2 measurements (“TnI+ group”), in the remaining 126 pts the TnI remained non-measurable (“TnI− group”); 76 pts (43%) showed NT-proBNP values ≥125 ng/L in at least two consecutive determinations (“NT-proBNP + group”),in the remaining 57% of pts this increase was not detected (“NT-proBNP - group”). Comparing “TnI+ group” to “TnI− group” we observed that only the genotyping of the SNPs rs1149222 (G/T) belonging to the ABCB4 gene is distributed differently in the two groups, in particular the homozygosity for the “at risk” variant (G/G) was present in 13% of the pts of the “TnI+ group” vs 5% in the “TnI− group” (p 0.06). The results of the comparison of “NT-proBNP+ group” vs “NT-proBNP− group”, showed that the genotyping of the SNPs rs6759892 (G/T) belonging to the UGT1A6 gene was distributed differently, the homozygosity for the “at risk” variant (G/G) was present in 28% of the “NT-proBNP+ group” vs 17% in the “NT-proBNP− group” (p 0.07). Conclusion Together with the baseline clinical evaluation, genetic markers could contribute to the early identification of pts at high risk of developing CTX especially following treatment with ANT and they could support future therapeutic decisions and the planning of taylored strategies for the prevention of the CTX development. Funding Acknowledgement Type of funding source: None

Leveraging the advantageous material properties of recently developed softthermoplastic elastomer materials, this work presents the facile and rapid fabrication of compositemembrane-integrated microfluidic devices consisting of FlexdymTMpolymer and commerciallyavailable porous polycarbonate membranes. The three-layer devices can be fabricated in under2.5 h, consisting of a 2-min hot embossing cycle, conformal contact between device layersand a low-temperature baking step. The strength of the FlexdymTM-polycarbonate seal wascharacterized using a specialized microfluidic delamination device and an automated pressurecontroller configuration, offering a standardized and high-throughput method of microfluidic bursttesting. Given a minimum bonding distance of 200μm, the materials showed bonding that reliablywithstood pressures of 500 mbar and above, which is sufficient for most microfluidic cell cultureapplications. Bonding was also stable when subjected to long term pressurization (10 h) and repeateduse (10,000 pressure cycles). Cell culture trials confirmed good cell adhesion and sustained cultureof human dermal fibroblasts on a polycarbonate membrane inside the device channels over thecourse of one week. In comparison to existing porous membrane-based microfluidic platforms of thisconfiguration, most often made of polydimethylsiloxane (PDMS), these devices offer a streamlinedfabrication methodology with materials having favourable properties for cell culture applicationsand the potential for implementation in barrier model organ-on-chips.

We hereby report a puzzling case of multiple sclerosis (MS) relapse presenting as Takotsubo syndrome (TTS). Female, 42-years old, who presented herself to the Emergency Room of University Hospital “ASST Spedali Civili” of Brescia, Italy, for a severe headache and a non-ST-segment elevation acute coronary syndrome. Coronary angiogram showed no signs of coronary atherosclerosis. Upon further neurological evaluation, a diagnosis of MS relapse, related to TTS, was made, and treatment was started accordingly. The patient was discharged after 12 days after the admission, free of symptoms, and without signs of neurological and cardiological active disease. A hallmark of TTS is its association with a preceding stressful event. It may also be connected to a wide variety of diseases, including neurological ones, such as stroke, intracranial bleeding, head trauma, migraine, and seizures. However, up to our knowledge, only few cases of MS-induced TTS were previously described. Whether it is plausible to consider TTS as an uncommon extra-neurological manifestation of MS is still debated, however all the evidence points in that direction, considering the central role of catecholamines in TTS pathogenesis. With this case report the authors hope to encourage research on this field and on the intricate topic of brain-heart connections.

O objetivo dessa pesquisa é demonstrar como um restaurante de alta gastronomia cria experiências com base na construção da imagem midiática de um chef celebridade, e como essa construção ocorre no contexto do capitalismo comunicativo. Utilizamos o método de análise de conteúdo de reportagens da Revista Prazeres da Mesa no período de 2008 a 2018 para demonstrar, a partir da trajetória do chef Alex Atala, a influência da construção midiática na experiência de consumo no D.O.M., um restaurante contemporâneo de cozinha autoral, que explora sabores de ingredientes tipicamente brasileiros e que hoje é premiado e reconhecido pela crítica mundial. O estudo foi estruturado de forma a responder à pergunta: qual o papel da comunicação midiática na construção e gestão de experiências de consumo, tornando-as centrais na cultura do consumo contemporânea? E pretende ressaltar a importância de se estudar o consumo de forma integrada à produção, além de relacionar o papel da comunicação midiática com a produção de experiências, contribuindo, assim, para a diminuição de uma lacuna encontrada na literatura dos Estudos Organizacionais. The objective of this research is to demonstrate how an haute cuisine restaurant creates experiences based on the production of the media image of a celebrity chef, and how this production occurs in the context of communicative capitalism. The content analysis method of articles from Prazeres da Mesa magazine from 2008 to 2018 was used to demonstrate, based on the story of Chef Alex Atala, the influence of media construction in the consumer experience at D.O.M., a contemporary creative cuisine restaurant, which explores the flavor of typical Brazilian ingredients, and which boasts worldwide acclaim and international awards. This study was structured to answer the following research question: what is the role of media communication in the production and management of consumption experiences, making them central to the contemporary consumer culture? This research seeks to highlight the importance of the study of consumption integrated with production. Additionally, this research relates the role of media communication to the production of experiences, thereby contributing to the reduction of an existing gap in Organizational Studies literature.

Silks have been widely used as biomaterials due to their biocompatibility, biodegradability, and excellent mechanical properties. In the present work, native spider silk was used as organic template for controlled nucleation of hydroxyapatite (HA) nano-coating that can act as biomimetic interface. Different bio-inspired neutralization methods and process parameters were evaluated to optimize the silk functionalization. The morphology and chemical composition were investigated by scanning electron microscopy, energy-dispersive X-ray spectroscopy, Fourier transform infrared spectroscopy, and X-ray diffraction analysis and mechanical properties were studied through tensile tests. Results showed that the optimized protocol enabled a controlled and homogeneous nucleation of apatite nano-crystals while maintaining silk mechanical performances after mineralization. This study reports the optimization of a simple and effective bio-inspired nucleation process for precise nucleation of HA onto spider silk templates, suitable to develop high-performance hybrid interfaces for bone tissue engineering. (c) 2019 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2019, 137, 48739.

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior - CAPES In the history of mathematics some problems had special significance for the influence they exerted in this development. Among these, we mention the classical Greek problems related to construction with a non-graduated ruler and compass. In this work we will discuss these problems, giving special focus to the trisection of the angle. These problems challenged the intellectual power of many mathematicians and intellectuals for a long time, and it was only in the nineteenth century that the impossibility of this construction, using only a non-graduated ruler and compass, was demonstrated. The objective of this work is to present these problems, to discuss their impossibility of resolution and to present, in the special case of the trisection problem, possible resolutions using other instruments. We also present a technique to approach the problem of angle trisection through Origami, which can be used in the classroom. Na história da matemática alguns problemas tiveram um significado especial pela influência que exerceram no seu desenvolvimento. Dentre esses, citamos os problemas clássicos gregos relacionados à construção com régua não graduada e compasso. Neste trabalho discutiremos esses problemas, dando enfoque especial ao da trissecção do ângulo. Esses problemas desafiaram o poder intelectual de vários matemáticos e intelectuais durante muito tempo, e somente no século XIX demonstrou-se a impossibilidade dessa construção utilizando-se apenas régua não graduada e compasso. O objetivo deste trabalho é apresentar esses problemas, discutir sua impossibilidade de resolução e apresentar, no caso especial do problema da trissecção, resoluções possíveis utilizando-se outros instrumentos. Apresentamos também uma técnica de abordagem do problema da trissecção do ângulo através do Origami, que pode ser utilizada em sala de aula.