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El arte secuencial, cómic o historieta es un medio creativo de expresión que consiste en la disposición de dibujos o ilustraciones, compuestos por imágenes y palabras para contar una historia o escenificar una idea. Es una serie de ilustraciones yuxtapuestas que tienen el propósito de transmitir información y obtener una respuesta estética del lector. Esas ilustraciones, módulos o unidades narrativas se les conoce como viñetas. En ellas podemos encontrar además de las imágenes otros elementos que aportan y dan sentido a la historia y que forman todo un repertorio de unidades significantes que pueden ser objeto de varios estudios por separado. Entre estas unidades están las letras dibujadas que se utilizan cumpliendo diferentes funciones en ella. En este escrito se reflexiona así sobre estas capacidades significantes que se pueden encontrar en la letra dibujada o lettering de los comics, así como en la historia y particularidades de este oficio. También sobre las potencialidades y alternativas que una debida observación, consideración y reflexión de esta aplicación comunicacional de los textos graficados en el arte secuencial o cómic puede aportar en el quehacer de las disciplinas del diseño y la comunicación gráfica.

Antibiotic treatment of tuberculosis (TB) is complex, lengthy, and can be associated with various adverse effects. As a result, patient compliance often is poor, thus further enhancing the risk of selecting multi-drug resistant bacteria. Macrophage mannose receptor (MMR)-positive alveolar macrophages (AM) constitute a niche in which Mycobacterium tuberculosis replicates and survives. Therefore, we encapsulated levofloxacin in lipid nanocarriers functionalized with fucosyl residues that interact with the MMR. Indeed, such nanocarriers preferentially targeted MMR-positive myeloid cells, and in particular, AM. Intracellularly, fucosylated lipid nanocarriers favorably delivered their payload into endosomal compartments, where mycobacteria reside. In an in vitro setting using infected human primary macrophages as well as dendritic cells, the encapsulated antibiotic cleared the pathogen more efficiently than free levofloxacin. In conclusion, our results point towards carbohydrate-functionalized nanocarriers as a promising tool for improving TB treatment by targeted delivery of antibiotics.

Dendritic cells (DCs) translate local innate immune responses into long-lasting adaptive immunity by priming antigen-specific T cells. Accordingly, there is an ample interest in exploiting DCs for therapeutic purposes, e.g., in personalized immunotherapies. Despite recent advances in elucidating molecular pathways of antigen processing, in DCs the exact spatial organization of the underlying processes is largely unknown. Here, we unraveled the nanoscale organization of the transporter associated with antigen processing (TAP)-dependent peptide-loading machinery in human monocyte-derived DCs (moDC). We detected an unexpected accumulation of MHC I peptide-loading complexes (PLCs) and TAP-dependent peptide compartmentalization in protrusions of activated DCs. Using single-molecule localization microscopy we revealed that PLCs display homogeneously sized assemblies, independent of the DC activation status or cellular localization. Our data indicate that moDCs show augmentation of subcellular PLC density during DC maturation. We observed a twofold density increase in the cell body, while an even fourfold accumulation was detected in the tips of the protrusions at the mature DC stage in comparison to immature DCs. In these tip regions, PLC assemblies are found along highly compressed tubular ER networks. These findings provide novel insights into nanoscale organization of the antigen presentation machinery, and open new perspectives on the T cell stimulatory capacity of DCs.

Human cytomegalovirus (HCMV) is a widespread obligatory human pathogen causing life-threatening disease in immunocompromised hosts. Myeloid cells such as monocyte-derived dendritic cells (moDCs) are targets of HCMV. Here, we performed single-cell RNA sequencing, which revealed infection of most moDCs upon in vitro HCMV exposure, whereas only a fraction of them initiated viral gene expression. We identified three moDC subsets, of which CD1a−/CD86− cells showed the highest susceptibility. Upon HCMV entry, STING activation not only induced IFN-β, but also promoted viral gene expression. Upon progression of infection, IFN-β but not IFN-λ1 expression was inhibited. Similarly, ISG expression was initially induced and then shut off and thus allowed productive infection. Increased viral gene expression was associated with the induction of several pro- (RHOB, HSP1A1, DNAJB1) and anti-viral (RNF213, TNFSF10, IFI16) genes. Thus, moDC permissiveness to HCMV depends on complex interactions between virus sensing, regulation of IFNs/ISGs and viral gene expression.

Resumen Una marca ciudad debe ayudar a una metrópoli a reposicionarse en diversos planos: cultural, social, económico, turístico, entre otros. La mayoría de las veces, estos planos tienen como función la proyección internacional; sin embargo, lo más importante debería conformarse desde una visión integradora e intercultural, constituyéndose así una marca ciudad que realmente traduzca la identidad con un objetivo desde y para sus ciudadanos; que muestre el corazón de la ciudad, y desde esta visión integradora, pueda entonces ser transferida a diversos campos e intereses. En este trabajo se analizan las aportaciones de dos equipos de trabajo en los que se plantearon proyectos para rediseñar y posicionar a las ciudades para una vida mejor. Estableciendo el papel del diseño desde una visión integradora, con un papel transdiciplinar e intercultural que pueda ser capaz de enriquecer, en el mejor de los casos, el entorno urbano y la vida cotidiana de los ciudadanos. Y se considerará cómo las malas decisiones y fallidas implementaciones de estos proyectos se traducen en ciudades en descomposición, sin identidad. Identidad que se muestra desfigurada, fragmentada y algunas veces, débil e incongruente con la riqueza cultural, caso de los países latinoamericanos. Abstract A City Branding can contribute to a metropolis to reposition itself in diverse planes: cultural, social, economic, tourist, among others. Most of the time, these plans have international projection as their function. However, the most important thing should be that they conform from an integrating and intercultural vision, thus constituting a City Branding that really translates the identity with a goal from and for its citizens; That shows the heart of the city, and from this integrating vision, it could then be transferred to different fields and interests. This paper analyzes the contributions of various work teams in which projects are proposed to redesign and position cities for a better life. Establishing the role of design from an integrating perspective, with a transdiciplinary and intercultural role that can be able to enrich the urban environment and the daily life of citizens, at best. And they will also consider how bad decisions and failed implementations of these projects are translated into cities in decomposition and with an identity that is shown disfigured, fragmented and in many cases weak and incongruent with cultural wealth: case of some Latin American countries. Resumo Uma Marca da Cidade pode contribuir para uma metrópole se reposicionar em diferentes planos; cultural, social, econômica, turismo, entre outros. Esses planos têm a projeção internacional na maior parte do tempo. No entanto, o mais importante deve ser baseado em uma visão integradora e intercultural, constituindo assim uma Marca da Cidade que realmente traduza a identidade com um objetivo de e para seus cidadãos; Ele mostra o coração da cidade e, a partir dessa visão integrada, pode ser transferido para diferentes campos e interesses. Este artigo analisa as contribuições de várias equipes de trabalho em que os projetos são propostos para redesenhar e posicionar as cidades para uma vida melhor. Estabelecer o papel do design a partir de uma visão integrada com um trasdiciplinar e papel intercultural para ser capaz de enriquecer o ambiente urbano e na vida quotidiana dos cidadãos, na melhor das hipóteses, e considerar como decisões e implementações fracassadas ruim desses projetos são traduzidos em cidades em decomposição, sem identidade. Identidade desfigurada, fragmentada e em muitos casos fraca e incongruente com a riqueza cultural, caso dos países latino-americanos.

‘Mosca de la bichera’ or simply ‘bichera’ are common names given in Uruguay and the region to the primary myiasis-causing species Cochliomyia hominivorax, the New World Screwworm (NWS) fly (Diptera: Calliphoridae). Myiasis happens when dipteran larvae infest live animals at least during some developmental phase to feed on host’s flesh and fluids. For the NWS fly it is mandatory that all three larvae phases develop on living tissues of warm-blooded vertebrates, including humans. Unsurprisingly, this parasitic behavior causes great profit losses to the livestock industry and is also considered a neglected public health issue. NWS is endemic from the tropics and subtropics of the Americas, but has been eradicated from North and Central America through a Sterile Insect Technique (SIT) based Area Wide – Integrated Pest Management (AW-IPM) program that lasted more than 50 years. Since 2004, a permanent barrier is actively maintained in Darien, along the Panama-Colombian border, by releasing 14 million sterile flies per week to avoid reintroductions. Due to its direct and indirect impact on the national economy, the logistic complexity and the cost of SIT control programs, much discussion is underway in Uruguay about NWS fly eradication. Direct economic losses due to myiasis in Uruguay oscillate between USD 40 and 154 million annually (i.e., between 2-8% of livestock Gross Domestic Product, GDP). Currently, the Food and Agriculture Organization of the UN/International Atomic Energy Agency (FAO/IAEA) and the US Department of Agriculture/Panama United States Commission for the Eradication and Prevention of Screwworm/ Ministry of Livestock, Agriculture and Fisheries (USDA/COPEG/MGAP) have been working on eradication proposals for Uruguay. Cost-benefit analysis of each group concluded that a net present value of around USD 98 million and USD 146 million could be achieved, respectively, supporting the positive impact of NWS fly eradication at local farmers and the whole livestock sector levels. The main challenge of this endeavor is to find a way to keep the myiasis-free status of Uruguay in case that its neighbors, Argentina and Brazil, do not engage in a similar program, at least for their southernmost region. Here we review the bulk of bibliography produced since the beginning of NWS eradication programs in North America during the 40s decade, its life cycle and parasitic lifestyle as well as many aspects of its population genetics and ecology. We further discuss promising biotechnological approaches under active development based on transgenesis and CRISPR/Cas genome-editing, that are considered the new avenue in insect-control strategies. Balance among innovation and regulation framework is considered based on lessons learned. Currently, a CRISPR/Cas gene editing strategy for gene drive is being investigated in Uruguay, a development conducted with national funds, what guarantees its complete control and local institutions, authorities and ultimately livestock producers can be the biotechnology owners. Finally, we highlight the know-how that will be generated opening the possibility to locally develop new genetic-based control strategies for other parasites and/or vector insects of high veterinary and public health relevance.

Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV-infected mice, mitochondrial antiviral-signaling protein (MAVS), the downstream adaptor of retinoic acid-inducible gene-I (RIG-I)-like receptor (RLR) signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To characterize the brain-resident cell subset that produces protective IFN-β in TBEV-infected mice, we isolated neurons, astrocytes, and microglia from mice and exposed these cell types to TBEV in vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN-β was not detectable, while infected astrocytes showed high and microglia low IFN-β expression. Transcriptome analyses of astrocytes implied that MAVS signaling was needed early after TBEV infection. Accordingly, MAVS-deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN-β responses. Nevertheless, at later time points, moderate amounts of IFN-β were detected in the SN of infected MAVS-deficient astrocytes. Transcriptome analyses indicated that MAVS deficiency negatively affected the induction of early anti-viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced only late IFN-β responses of TBEV-infected WT astrocytes and blocked entirely IFN-β responses of infected MAVS-deficient astrocytes. Thus, upon TBEV exposure of brain-resident cells, astrocytes are important IFN-β producers showing biphasic IFN-β induction that initially depends on MAVS and later on MyD88/TRIF signaling.

Targeting host factors exploited by multiple viruses could offer broad-spectrum solutions for pandemic preparedness. Seventeen candidates targeting diverse functions emerged in a screen of 4,413 compounds for SARS-CoV-2 inhibitors. We demonstrated that lapatinib and other approved inhibitors of the ErbB family receptor tyrosine kinases suppress replication of SARS-CoV-2, Venezuelan equine encephalitis virus (VEEV), and other emerging viruses with a high barrier to resistance. Lapatinib suppressed SARS-CoV-2 entry and later stages of the viral life cycle and showed synergistic effect with the direct-acting antiviral nirmatrelvir. We discovered that ErbB1, 2 and 4 bind SARS-CoV-2 S1 protein and regulate viral and ACE2 internalization, and they are required for VEEV infection. In human lung organoids, lapatinib protected from SARS-CoV-2-induced activation of ErbB-regulated pathways implicated in non-infectious lung injury, pro-inflammatory cytokine production, and epithelial barrier injury. Lapatinib suppressed VEEV replication, cytokine production and disruption of the blood-brain barrier integrity in microfluidic-based human neurovascular units, and reduced mortality in a lethal infection murine model. We validated lapatinib-mediated inhibition of ErbB activity as an important mechanism of antiviral action. These findings reveal regulation of viral replication, inflammation, and tissue injury via ErbBs and establish a proof-of-principle for a repurposed, ErbB-targeted approach to combat emerging viruses.

With the goal of improving public policy design and to better achieve institutional goals, the Ministry of Livestock, Agriculture and Fisheries (MGAP) of Uruguay allocated re-sources towards strengthening the evaluation of its agricultural policies. To this end, the Agricultural Policy Evaluation Area was created within the Office of the Agricultural Programming and Policy Office (OPYPA). This multidisciplinary team is specialized in impact evaluations of public interventions combining econometric techniques with qualitative methods and theoretical analysis. This document presents the main results and lessons learned in this process, in three sections. The first section summarizes the goals for the impact evaluation of MGAP policies and the basis for the institutional arrangement. Then, the progress made in mainstreaming policy evaluation within MGAP is discussed. Finally, the main results and the lessons learned from the application of evaluations in evidence-based decision making are presented.

Tick-borne encephalitis virus (TBEV), a member of the Flaviviridae family, is typically transmitted upon tick bite and can cause meningitis and encephalitis in humans. In TBEV infected mice, mitochondrial antiviral signaling protein (MAVS), the downstream adaptor of retinoic acid inducible gene I-like receptor (RLR)-signaling, is needed to induce early type I interferon (IFN) responses and to confer protection. To identify the brain resident cell subset that produces protective IFN-β in TBEV infected mice, we isolated neurons, astrocytes and microglia and exposed these cells to TBEV in vitro. Under such conditions, neurons showed the highest percentage of infected cells, whereas astrocytes and microglia were infected to a lesser extent. In the supernatant (SN) of infected neurons, IFN-β was not detectable, while infected astrocytes showed very high and microglia low IFN-β production. Transcriptome analyses of astrocytes implied that MAVS-signaling was needed early after TBEV infection. Accordingly, MAVS-deficient astrocytes showed enhanced TBEV infection and significantly reduced early IFN-β responses. At later time points, moderate amounts of IFN-β were detected in the SN of infected MAVS-deficient astrocytes. Transcriptome analyses indicated that MAVS-deficiency negatively affected the induction of early anti-viral responses, which resulted in significantly increased TBEV replication. Treatment with MyD88 and TRIF inhibiting peptides reduced late IFN-β responses of TBEV infected WT astrocytes and entirely blocked IFN-β responses of infected MAVS-deficient astrocytes. Thus, upon TBEV exposure of brain-resident cells, astrocytes are important IFN-β producers that show biphasic IFN-β induction that initially depends on MAVS- and later on MyD88/TRIF-signaling.

Tuberculosis is the infectious disease with the worldwide largest disease burden and there remains a great need for better diagnostic biomarkers to detect latent and active M. tuberculosis infection. RNA molecules hold great promise in this regard, as their levels of expression may differ considerably between infected and uninfected subjects. We have measured expression changes in the four major classes of small noncoding RNAs in blood samples from patients with different stages of TB infection. We found that, in addition to miRNAs (which are known to be highly regulated in blood cells from TB patients), expression of piRNA and snoRNA is greatly altered in both latent and active TB, yielding promising biomarkers. Even though the functions of many sncRNA other than miRNA are still poorly understood, our results strongly suggest that at least piRNA and snoRNA populations may represent hitherto underappreciated players in the different stages of TB infection., In tuberculosis (TB), as in other infectious diseases, studies of small noncoding RNAs (sncRNA) in peripheral blood have focused on microRNAs (miRNAs) but have neglected the other major sncRNA classes in spite of their potential functions in host gene regulation. Using RNA sequencing of whole blood, we have therefore determined expression of miRNA, PIWI-interacting RNA (piRNA), small nucleolar RNA (snoRNA), and small nuclear RNA (snRNA) in patients with TB (n = 8), latent TB infection (LTBI; n = 21), and treated LTBI (LTBItt; n = 6) and in uninfected exposed controls (ExC; n = 14). As expected, sncRNA reprogramming was greater in TB than in LTBI, with the greatest changes seen in miRNA populations. However, substantial dynamics were also evident in piRNA and snoRNA populations. One miRNA and 2 piRNAs were identified as moderately accurate (area under the curve [AUC] = 0.70 to 0.74) biomarkers for LTBI, as were 1 miRNA, 1 piRNA, and 2 snoRNAs (AUC = 0.79 to 0.91) for accomplished LTBI treatment. Logistic regression identified the combination of 4 sncRNA (let-7a-5p, miR-589-5p, miR-196b-5p, and SNORD104) as a highly sensitive (100%) classifier to discriminate TB from all non-TB groups. Notably, it reclassified 8 presumed LTBI cases as TB cases, 5 of which turned out to have features of Mycobacterium tuberculosis infection on chest radiographs. SNORD104 expression decreased during M. tuberculosis infection of primary human peripheral blood mononuclear cells (PBMC) and M2-like (P = 0.03) but not M1-like (P = 0.31) macrophages, suggesting that its downregulation in peripheral blood in TB is biologically relevant. Taken together, the results demonstrate that snoRNA and piRNA should be considered in addition to miRNA as biomarkers and pathogenesis factors in the various stages of TB.

Cyclic di-nucleotides (CDN) are potent stimulators of innate and adaptive immune responses. Cyclic di-AMP (CDA) is a promising adjuvant that generates humoral and cellular immunity. The strong STING-dependent stimulation of type I IFN represents a key feature of CDA. However, recent studies suggested that this is dispensable for adjuvanticity. Here we demonstrate that stimulation of IFN-γ-secreting CD8+ cytotoxic T lymphocytes (CTL) is significantly decreased after vaccination in the absence of type I IFN signaling. The biological significance of this CTL response was confirmed by the stimulation of MHC class I-restricted protection against influenza virus challenge. We show here that type I IFN (and not TNF-α) is essential for CDA-mediated cross-presentation by a cathepsin independent, TAP and proteosome dependent cytosolic antigen processing pathway, which promotes effective cross-priming and further CTL induction. Our data clearly demonstrate that type I IFN signaling is critical for CDN-mediated cross-presentation., Highlights • Cyclic di-AMP is a potent adjuvant with a proven capacity to promote cellular and humoral immunity. • It was postulated that type I IFN is irrelevant for CDA-generated immunity. • We show that CDA-mediated IFN-α/β signaling is essential for cytosolic cross-presentation, generating CTL by cross-priming. Antigen cross-presentation generates cross-priming of CD8 cytotoxic T cells (CTL), which kill intracellular pathogens and cancer cells. The generation of CTL is the main feature of cyclic di- nucleotide adjuvants (CDN). The production of type I IFN has been shown to be essential for the generation of CTL by other adjuvants, but not for cyclic di-AMP, a paramount CDN. Surprisingly, it was recently claimed that type I IFN is dispensable for the immunogenicity of CDN. We show here that type I IFN (and not TNF) is necessary for the cytosolic cross-presentation pathway activated by CDN, which results in CTL generation. This finding and the knowledge of the mechanism are of crucial importance for the safe development of CDN-adjuvanted vaccines.

Infection of healthy individuals with human cytomegalovirus (HCMV) is usually unnoticed and results in life-long latency, whereas HCMV reactivation as well as infection of newborns or immunocompromised patients can cause life-threatening disease. To better understand HCMV pathogenesis we studied mechanisms that restrict HCMV spread. We discovered that HCMV-infected cells can directly trigger plasmacytoid dendritic cells (pDC) to mount antiviral type I interferon (IFN-I) responses, even in the absence of cell-free virus. In contrast, monocyte-derived cells only expressed IFN-I when stimulated by cell-free HCMV, or upon encounter of HCMV-infected cells that already produced cell-free virus. Nevertheless, also in the absence of cell-free virus, i.e., upon co-culture of infected epithelial/endothelial cells and monocyte-derived macrophages (moMΦ) or dendritic cells (moDC), antiviral responses were induced that limited HCMV spread. The induction of this antiviral effect was dependent on cell-cell contact, whereas cell-free supernatants from co-culture experiments also inhibited virus spread, implying that soluble factors were critically needed. Interestingly, the antiviral effect was independent of IFN-γ, TNF-α, and IFN-I as indicated by cytokine inhibition experiments using neutralizing antibodies or the vaccinia virus-derived soluble IFN-I binding protein B18R, which traps human IFN-α and IFN-β. In conclusion, our results indicate that human macrophages and dendritic cells can limit HCMV spread by IFN-I dependent as well as independent mechanisms, whereas the latter ones might be particularly relevant for the restriction of HCMV transmission via cell-to-cell spread., German Research Foundation (DFG) [SFB900 (TP B2)]; and the Helmholtz Virtual Institute “Viral Strategies of Immune Evasion (VISTRIE)” [VH-VI-424]

Varicella zoster virus (VZV) is a highly prevalent human pathogen that establishes latency in neurons of the peripheral nervous system. Primary infection causes varicella whereas reactivation results in zoster, which is often followed by chronic pain in adults. Following infection of epithelial cells in the respiratory tract, VZV spreads within the host by hijacking leukocytes, including T cells, in the tonsils and other regional lymph nodes, and modifying their activity. In spite of its importance in pathogenesis, the mechanism of dissemination remains poorly understood. Here we addressed the influence of VZV on leukocyte migration and found that the purified recombinant soluble ectodomain of VZV glycoprotein C (rSgC) binds chemokines with high affinity. Functional experiments show that VZV rSgC potentiates chemokine activity, enhancing the migration of monocyte and T cell lines and, most importantly, human tonsillar leukocytes at low chemokine concentrations. Binding and potentiation of chemokine activity occurs through the C-terminal part of gC ectodomain, containing predicted immunoglobulin-like domains. The mechanism of action of VZV rSgC requires interaction with the chemokine and signalling through the chemokine receptor. Finally, we show that VZV viral particles enhance chemokine-dependent T cell migration and that gC is partially required for this activity. We propose that VZV gC activity facilitates the recruitment and subsequent infection of leukocytes and thereby enhances VZV systemic dissemination in humans., Author summary Varicella zoster virus (VZV) causes two main pathologies in humans, chickenpox during primary infection, and shingles following reactivation. The latter is a painful condition that is often followed by chronic pain in a large numbers of shingles patients. Despite the existence of a vaccine, shingles-related complications cause expenses of more than $1 billion per year in the USA alone. Following primary infection, the virus infects leukocytes including T cells, spreading to the skin causing chickenpox. Direct infection of neurons from leukocytes has also been postulated. Given the relevance of leukocytes in VZV biology and the importance of chemokines in directing their migration, we investigated whether VZV modulates the function of chemokines. Our results show that VZV glycoprotein C potentiates the activity of chemokines, inducing higher migration of human leukocytes at low chemokine concentration. This may attract additional susceptible leukocytes to the site of infection enhancing virus spread and pathogenesis.

Biodegradable polymeric nanoparticles (NP) made from poly (lactid-co-glycolide) acid (PLGA) and chitosan (CS) hold promise as innovative formulations for targeted delivery. Since interactions of such NP with primary human immune cells have not been characterized, yet, here we assessed the effect of PLGA or CS-PLGA NP treatment on human peripheral blood mononuclear cells (PBMC), as well as on monocyte-derived DC (moDC). Amongst PBMC, antigen presenting cells (APC) showed higher uptake of both NP preparations than lymphocytes. Furthermore, moDC internalized CS-PLGA NP more efficiently than PLGA NP, presumably because of receptor-mediated endocytosis. Consequently, CS-PLGA NP were delivered mostly to endosomal compartments, whereas PLGA NP primarily ended up in lysosomes. Thus, CS-PLGA NP confer enhanced delivery to endosomal compartments of APC, offering new therapeutic options to either induce or modulate APC function and to inhibit pathogens that preferentially infect APC.

Targeted drug delivery systems hold promise for selective provision of active compounds to distinct tissues or cell subsets. Thus, locally enhanced drug concentrations are obtained that would confer improved efficacy. As a consequence adverse effects should be diminished, as innocent bystander cells are less affected. Currently, several controlled drug delivery systems based on diverse materials are being developed. Some systems exhibit material-associated toxic effects and/or show low drug loading capacity. In contrast, liposomal nanocarriers are particularly favorable because they are well tolerated, poorly immunogenic, can be produced in defined sizes, and offer a reasonable payload capacity. Compared with other immune cells, professional antigen-presenting cells (APCs) demonstrate enhanced liposome uptake mediated by macropinocytosis, phagocytosis and presumably also by clathrin- and caveolae-mediated endocytosis. In order to further enhance the targeting efficacy toward APCs, receptor-mediated uptake appears advisable. Since APC subsets generally do not express single linage-specific receptors, members of the C-type lectin receptor (CLR) family are compelling targets. Examples of CLR expressed by APCs include DEC-205 (CD205) expressed by myeloid dendritic cells (DC) and monocytes, the mannose receptor C type 1 (MR, CD206) expressed by DC, monocytes and macrophages, DC-SIGN (CD209) expressed by DC, and several others. These receptors bind glycans, which are typically displayed by pathogens and thus support pathogen uptake and endocytosis. Further research will elucidate whether glycan-decorated liposomes will not only enhance APCs targeting but also enable preferential delivery of their payload to discrete subcellular compartments.

The care of elderly patients requires an evaluation that deserves a host of special considerations, such as biological aspects of aging, those related to activities of daily living and functionality, neuro-psychological conceptions, family dynamics and economic conditions. The growth of the aging population in our country is accompanied by an increase in chronic diseases and more individuals have greater vulnerability, requiring a more consumption of resources because of the high demand for services. This requires the incorporation of specialized care in the institutional system, which has caused serious consequences in the current health system, benefiting specialization and technology, but with a loss of an integrated and horizontal view of the patient. Therefore it is necessary to develop a practical tool that allows the family physician to identify and differentiate the geriatric population that requires specialized care from who does not, identifying problems that may improve and allow the design of strategies to improve health status and maintain functional autonomy of the elderly. Comprehensive Geriatric Assessment (CGA) is a fundamental tool for clinical practice of any medical care to the elderly.

In this paper we present a model that studies firm mergers in a spatial setting. A new model is formulated that addresses the issue of finding the number of branches that have to be eliminated by a firm after merging with another one, in order to maximize profits. The model is then applied to an example of bank mergers in the city of Barcelona. Finally, a variant of the formulation that introduces competition is presented together with some conclusions.