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This is the case of a 38-year-old man with a history of two female relatives with Systemic Lupus Erythematosus and personal factors of high cardiovascular risk (gender, stress, smoking, chronic consumption of electronic cigarette). The patient presented tamponade due to pericardial effusion secondary to Lupus-like syndrome that preceded and accompanied at all times an angiosarcoma of the roof and anterior wall of the right atrium. His clinical evolution is described, as well as the surgical and pharmacological treatment in the Cardiovascular Care Unit of a third-level hospital and the possible causes of the poor response to management that led to his death.

Malaria, the disease caused byPlasmodiumparasites, causes significant mortality and morbidity. Whole parasite vaccination with pre-erythrocytic parasite stages, attenuated through sporozoite irradiation or chemo-attenuation, confers sterilizing immunity against subsequent parasite infection. This provides a rationale for the creation of whole parasite vaccines that are attenuated using gene editing. Here, we report on the creation of a novel genetically attenuated parasite (GAP) by the deletion ofPlasmodium LINUP,encoding aliver stagenuclearprotein.Epitope-tagging of LINUP in the rodent malaria parasitePlasmodium yoeliishowed LINUP expression exclusively in liver stage nuclei after the onset of exo-erythrocytic schizogony.P. yoeliiparasites with a gene deletion ofLINUP(linup—) suffered an exclusive liver stage phenotype with developmental arrested late in exo-erythrocytic schizogony. Liver stages showed incomplete segregation of nuclei and, mitochondria and apicoplast. These cellular perturbations caused a defect in exo-erythrocytic merozoite formation and a concomitant severe attenuation of liver stage-to-blood stage transition.LINUPgene deletion inPlasmodium falciparumalso caused a severe defect in late liver stage differentiation. Importantly,P. falciparum linup—liver stages showed a severe defect in parasite transitioning from liver stage to viable blood stage infection. These results suggest thatP. falciparum LINUPis a useful target for late liver stage attenuation and an additional gene deletion that can be incorporated into a late liver stage-arresting replication competent whole parasite vaccine.

We present the case of a woman of advanced age for pregnancy, multiparous, with assisted fertilization and dichorionic diamniotic twin pregnancy of 33.5 weeks with cardiovascular risk factors (sedentary lifestyle, smoking, high degree of work stress, chronic hypertension, hypertriglyceridemia) who developed gestational diabetes and peripartum hypertensive disease (severe preeclampsia). A cesarean section was performed due to an obstetric complication, during surgery, after birth, she presented hypertensive crisis and acute pulmonary edema that required coronary critical care. Biochemical markers and electrocardiographic, radiological, and angiographic studies were conclusive of Takotsubo syndrome. Her cardiovascular condition was complicated by a cerebral thrombosis resolved with an interventional catheterization. Recovery was satisfactory after a torpid evolution, cardiac function improved remarkably, blood pressure stabilized with drugs, and metabolic morbidities remained unaltered. Mild dysarthria was the only neurological sequelae. Obstetric aspects and the most important cardiovascular data of the case are discussed. Keywords: Takotsubo syndrome; Acute coronary syndrome; Acute myocardial infarction; Maternal heart disease; Hypertensive crisis; High risk pregnancy.

Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e., sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs may augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.

Vaccine-induced sterilizing protection from infection by Plasmodium parasites, the pathogens that cause malaria, will be essential in the fight against malaria as it would prevent both malaria-related disease and transmission. Stopping the relatively small number of parasites injected by the mosquito before they can migrate from the skin to the liver is an attractive means to this goal. Antibody-eliciting vaccines have been used to pursue this objective by targeting the major parasite surface protein present during this stage, the circumsporozoite protein (CSP). While CSP-based vaccines have recently had encouraging success in disease reduction, this was only achieved with extremely high antibody titers and appeared less effective for a complete block of infection (i.e. sterile protection). While such disease reduction is important, these and other results indicate that strategies focusing on CSP alone may not achieve the high levels of sterile protection needed for malaria eradication. Here, we show that monoclonal antibodies (mAbs) recognizing another sporozoite protein, TRAP/SSP2, exhibit a range of inhibitory activity and that these mAbs can augment CSP-based protection despite conferring no sterile protection on their own. Therefore, pursuing a multivalent subunit vaccine immunization is a promising strategy for improving infection-blocking malaria vaccines.

Following their inoculation by the bite of an infected Anopheles mosquito, the malaria parasite sporozoite forms travel from the bite site in the skin into the bloodstream, which transports them to the liver. The thrombospondin-related anonymous protein (TRAP) is a type 1 transmembrane protein that is released from secretory organelles and relocalized on the sporozoite plasma membrane. TRAP is required for sporozoite motility and host infection, and its extracellular portion contains adhesive domains that are predicted to engage host receptors. Here, we identified the human platelet-derived growth factor receptor β (hPDGFRβ) as one such protein receptor. Deletion constructs showed that the von Willebrand factor type A and thrombospondin repeat domains of TRAP are both required for optimal binding to hPDGFRβ-expressing cells. We also demonstrate that this interaction is conserved in the human-infective parasite Plasmodium vivax, but not the rodent-infective parasite Plasmodium yoelii. We observed expression of hPDGFRβ mainly in cells associated with the vasculature suggesting that TRAP:hPDGFRβ interaction may play a role in the recognition of blood vessels by invading sporozoites.

Plasmodium sporozoites exhibit a complex infection biology in the mosquito and mammalian hosts. The sporozoite apical secretory organelles, the micronemes and rhoptries, store protein mediators of parasite/host/vector interactions and must secrete them in a temporally and spatially well orchestrated manner. Micronemal proteins are critical for sporozoite motility throughout its journey from the mosquito midgut oocyst to the mammalian liver, and also for cell traversal (CT) and hepatocyte invasion. Rhoptry proteins, until recently thought to be only important for hepatocyte invasion, appear to also play an unexpected role in motility and in the interaction with mosquito tissue. Therefore, navigating the different microenvironments with secretion likely requires the sporozoite to have a more complex system of secretory organelles than previously appreciated.

El plan de desarrollo de 2012-2015 denominado “Medellín un hogar para la vida” hace énfasis en la Alianza Antioquia-Medellín y establece unos principios fundamentales entre los que se destacan la equidad regional y la sostenibilidad como fundamentos del actuar de la Alianza. Sin embargo, la revisión del plan desde sus diferentes enfoques, líneas y componentes genera algunos interrogan-tes frente al territorio rural de Medellín, el cual es desconocido desde el momento mismo de la planeación y no se evidencia una política clara para lo rural como territorio, sino como una asociación del término a la oferta eco-sistémica para lo urbano, lo cual hace que los territorios rurales pierdan por completo su identidad e incluso su vocación económica. Se hace un análisis de los elementos del plan desarrollo “Medellín un hogar para la vida”, a través de la ejecución de los programas que lo componen y que apuntan a la sostenibilidad del territorio en el corregimiento de San Cristóbal, una zona considerada rural, de tradición agrícola y que ha soportado un conflicto social importante en los últimos años. Se identificaron e interpretaron algunos elementos del plan de desarrollo Medellín 2012-2015, que contribuyen a la sostenibilidad del corregimiento seleccionado como territorio rural. The development plan of 2012-2015 called “Medellin a home for life” emphasizes the Alliance Antioquia Medellin and establishes some fundamental principles which include the regional equity and sustainability as the basis of the act of the Alliance. However, the revision of the plan from their different approaches, lines and components generates some questions facing the rural territory of Medellin, which is unknown since the very moment of the planning and there is no evidence of a clear policy for the rural as territory but as an association of the term to the offer eco-systemic for the urban, which makes the rural territories lost completely their identity and even their vocation economic. An analysis is made of the elements of the plan development “Medellin a home for life”, through the implementation of programs that compose it and pointing to the sustainability of the te-rritory in the Corregimiento of San Cristobal, an area considered rural, agricultural tradition and that has endured a major social upheaval in recent years. Identified and interpreted some elements of the development plan Medellin 2012-2015, which contribute to the sustainability of the Corregimiento selected as rural territory.

Within the liver, Plasmodium sporozoites traverse cells searching for a "suitable" hepatocyte, invading these cells through a process that results in the formation of a parasitophorous vacuole (PV), within which the parasite undergoes intracellular replication as a liver stage. It was previously established that two members of the Plasmodium s48/45 protein family, P36 and P52, are essential for productive invasion of host hepatocytes by sporozoites as their simultaneous deletion results in growth-arrested parasites that lack a PV. Recent studies point toward a pathway of entry possibly involving the interaction of P36 with hepatocyte receptors EphA2, CD81, and SR-B1. However, the relationship between P36 and P52 during sporozoite invasion remains unknown. Here we show that parasites with a single P52 or P36 gene deletion each lack a PV after hepatocyte invasion, thereby pheno-copying the lack of a PV observed for the P52/P36 dual gene deletion parasite line. This indicates that both proteins are equally important in the establishment of a PV and act in the same pathway. We created a Plasmodium yoelii P36mCherry tagged parasite line that allowed us to visualize the subcellular localization of P36 and found that it partially co-localizes with P52 in the sporozoite secretory microneme organelles. Furthermore, through co-immunoprecipitation studies in vivo, we determined that P36 and P52 form a protein complex in sporozoites, indicating a concerted function for both proteins within the PV formation pathway. However, upon sporozoite stimulation, only P36 was released as a secreted protein while P52 was not. Our results support a model in which the putatively glycosylphosphatidylinositol (GPI)-anchored P52 may serve as a scaffold to facilitate the interaction of secreted P36 with the host cell during sporozoite invasion of hepatocytes.

Within the liver, Plasmodium sporozoites traverse cells searching for a “suitable” hepatocyte, invading these cells through a process that results in the formation of a parasitophorous vacuole (PV), within which the parasite undergoes intracellular replication as a liver stage. It was previously established that two members of the Plasmodium s48/45 protein family, P36 and P52, are essential for productive invasion of host hepatocytes by sporozoites as their simultaneous deletion results in growth-arrested parasites that lack a PV. Recent studies point toward a pathway of entry possibly involving the interaction of P36 with hepatocyte receptors EphA2, CD81, and SR-B1. However, the relationship between P36 and P52 during sporozoite invasion remains unknown. Here we show that parasites with a single P52 or P36 gene deletion each lack a PV after hepatocyte invasion, thereby pheno-copying the lack of a PV observed for the P52/P36 dual gene deletion parasite line. This indicates that both proteins are equally important in the establishment of a PV and act in the same pathway. We created a Plasmodium yoelii P36mCherry tagged parasite line that allowed us to visualize the subcellular localization of P36 and found that it partially co-localizes with P52 in the sporozoite secretory microneme organelles. Furthermore, through co-immunoprecipitation studies in vivo, we determined that P36 and P52 form a protein complex in sporozoites, indicating a concerted function for both proteins within the PV formation pathway. However, upon sporozoite stimulation, only P36 was released as a secreted protein while P52 was not. Our results support a model in which the putatively glycosylphosphatidylinositol (GPI)-anchored P52 may serve as a scaffold to facilitate the interaction of secreted P36 with the host cell during sporozoite invasion of hepatocytes.

During their life cycle Plasmodium parasites rely upon an arsenal of proteins that establish key interactions with the host and vector, and between the parasite sexual stages, with the purpose of ensuring infection, reproduction and proliferation. Among these is a group of secreted or membrane-anchored proteins known as the six-cysteine (6-cys) family. This is a small but important family with only 14 members thus far identified, each stage-specifically expressed during the parasite life cycle. 6-cys proteins often localise at the parasite surface or interface with the host and vector, and are conserved in different Plasmodium species. The unifying feature of the family is the s48/45 domain, presumably involved in adhesion and structurally related to Ephrins, the ligands of Eph receptors. The most prominent s48/45 members are currently under functional investigation and are being pursued as vaccine candidates. In this review, we examine what is known about the 6-cys family, their structure and function, and discuss future research directions.

The s48/45 domain was first noted in Plasmodium proteins more than 15 y ago. Previously believed to be unique to Plasmodium , the s48/45 domain is present in other aconoidasidans. In Plasmodium , members of the s48/45 family of proteins are localized on the surface of the parasite in different stages, mostly by glycosylphosphatydylinositol-anchoring. Members such as P52 and P36 seem to play a role in invasion of hepatocytes, and Pfs230 and Pfs48/45 are involved in fertilization in the sexual stages and have been consistently studied as targets of transmission-blocking vaccines for years. In this report, we present the molecular structure for the s48/45 domain corresponding to the C-terminal domain of the blood-stage protein Pf12 from Plasmodium falciparum , obtained by NMR. Our results indicate that this domain is a β-sandwich formed by two sheets with a mixture of parallel and antiparallel strands. Of the six conserved cysteines, two pairs link the β-sheets by two disulfide bonds, and the third pair forms a bond outside the core. The structure of the s48/45 domain conforms well to the previously defined surface antigen 1 (SAG1)-related-sequence (SRS) fold observed in the SAG family of surface antigens found in Toxoplasma gondii . Despite extreme sequence divergence, remarkable spatial conservation of one of the disulfide bonds is observed, supporting the hypothesis that the domains have evolved from a common ancestor. Furthermore, a homologous domain is present in ephrins, raising the possibility that the precursor of the s48/45 and SRS domains emerged from an ancient transfer to Apicomplexa from metazoan hosts.

Plasmodium falciparum is the most devastating agent of human malaria. A major contributor to its virulence is a complex lifecycle with multiple parasite forms, each presenting a different repertoire of surface antigens. Importantly, members of the 6-Cys s48/45 family of proteins are found on the surface of P. falciparum in every stage, and several of these antigens have been investigated as vaccine targets. Pf12 is the archetypal member of the 6-Cys protein family, containing just two s48/45 domains, whereas other members have up to 14 of these domains. Pf12 is strongly recognized by immune sera from naturally infected patients. Here we show that Pf12 is highly conserved and under purifying selection. Immunofluorescence data reveals a punctate staining pattern with an apical organization in late schizonts. Together, these data are consistent with an important functional role for Pf12 in parasite-host cell attachment or invasion. To infer the structural and functional diversity between Pf12 and the other 11 6-Cys domain proteins, we solved the 1.90 A resolution crystal structure of the Pf12 ectodomain. Structural analysis reveals a unique organization between the membrane proximal and membrane distal domains and clear homology with the SRS-domain containing proteins of Toxoplasma gondii. Cross-linking and mass spectrometry confirm the previously identified Pf12-Pf41 heterodimeric complex, and analysis of individual cross-links supports an unexpected antiparallel organization. Collectively, the localization and structure of Pf12 and details of its interaction with Pf41 reveal important insight into the structural and functional properties of this archetypal member of the 6-Cys protein family.