Unravelling the genome of the brackish water malaria vector Anopheles aquasalis.

Malaria is a severe public health problem in several developing tropical and subtropical countries. Anopheles aquasalis is the primary coastal malaria vector in Central and South America and the Caribbean Islands, and it has the peculiar feature of living in water with large changes in salinity. Recent research has recognised An. aquasalis as an important model for studying the interactions of murine and human Plasmodium parasites. This study presents the complete genome of An. aquasalis and offers insights into its evolution and physiology. The genome is similar in size and gene content to other Neotropical anophelines, with 162 Mb and 12,446 protein-coding genes. There are 1387 single-copy orthologs at the Diptera level (eg. An. gambiae, An. darlingi and Drosophila melanogaster). An. aquasalis diverged from An. darlingi, the primary malaria vector in inland South America, nearly 20 million years ago. Proteins related to ion transport and metabolism belong to the most abundant gene families with 660 genes. We identified gene families relevant to osmosis control (e.g., aquaporins, vacuolar-ATPases, Na+/K+-ATPases, and carbonic anhydrases). Evolutionary analysis suggests that all osmotic regulation genes are under strong purifying selection. We also observed low copy number variation in insecticide resistance and immunity-related genes for all known classical pathways. The data provided by this study offers candidate genes for further studies of parasite-vector interactions and for studies on how anophelines of brackish water deal with the high fluctuation in water salinity. We also established data and insights supporting An. aquasalis as an emerging Neotropical malaria vector model for genetic and molecular studies.

Evolution and assembly of Anopheles aquasalis's immune genes: primary malaria vector of coastal Central and South America and the Caribbean Islands.

Anophelines are vectors of malaria, the deadliest disease worldwide transmitted by mosquitoes. The availability of genomic data from various Anopheles species allowed evolutionary comparisons of the immune response genes in search of alternative vector control of the malarial parasites. Now, with the Anopheles aquasalis genome, it was possible to obtain more information about the evolution of the immune response genes. Anopheles aquasalis has 278 immune genes in 24 families or groups. Comparatively, the American anophelines possess fewer genes than Anopheles gambiae s. s., the most dangerous African vector. The most remarkable differences were found in the pathogen recognition and modulation families like FREPs, CLIP and C-type lectins. Even so, genes related to the modulation of the expression of effectors in response to pathogens and gene families that control the production of reactive oxygen species were more conserved. Overall, the results show a variable pattern of evolution in the immune response genes in the anopheline species. Environmental factors, such as exposure to different pathogens and differences in the microbiota composition, could shape the expression of this group of genes. The results presented here will contribute to a better knowledge of the Neotropical vector and open opportunities for malaria control in the endemic-affected areas of the New World.

Spatial analysis for the epidemiological study of cardiovascular diseases: A systematic literature search.

Cardiovascular diseases (CVDs) are the primary cause of death and disability in de world, and the detection of populations at risk as well as localization of vulnerable areas is essential for adequate epidemiological management. Techniques developed for spatial analysis, among them geographical information systems and spatial statistics, such as cluster detection and spatial correlation, are useful for the study of the distribution of the CVDs. These techniques, enabling recognition of events at different geographical levels of study (e.g., rural, deprived neighbourhoods, etc.), make it possible to relate CVDs to factors present in the immediate environment. The systemic literature presented here shows that this group of diseases is clustered with regard to incidence, mortality and hospitalization as well as obesity, smoking, increased glycated haemoglobin levels, hypertension physical activity and age. In addition, acquired variables such as income, residency (rural or urban) and education, contribute to CVD clustering. Both local cluster detection and spatial regression techniques give statistical weight to the findings providing valuable information that can influence response mechanisms in the health services by indicating locations in need of intervention and assignment of available resources.

Buddleja globosa (matico) prevents collagen-induced platelet activation by decreasing phospholipase C-gamma 2 and protein kinase C phosphorylation signaling.

Platelets play a key role in thrombosis and cardiovascular diseases. Medicinal plants could be one of the most important factors that influence risks for platelet activation. Buddleja globosa (known as "matico") is a medicinal plant with many biological activities. The high content of polyphenols suggest that matico could have antiplatelet activity. The present study was aimed at evaluating mechanisms of antiplatelet action of an extract of matico. We demonstrated that matico extract at low concentrations and in a concentration dependent manner (0.05-1 mg/mL) was a potent inhibitor of platelet aggregation in response to collagen, convulsion and ADP (IC50 values was 61 µg/mL, 72 µg/mL and 290 µg/mL, respectively). In this sense matico extract exerted the greatest antiaggregant activity induced by collagen. Similarly, matico showed a decrease in % of positive platelet for P-selectina (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 32 ± 2%, 29 ± 2 (p < 0.05), 19 ± 1 (p < 0.01), 15 ± 2 (p < 0.01), 10 ± 1% (p < 0.01) and 7 ± 2% (p < 0.01), respectively) and PAC-1 binding (vehicle, 0.01, 0.05, 0.1, 0.5 and 1 mg/mL were 59 ± 1, 58 ± 3 (n.s), 55 ± 2 (p < 0.05), 50 ± 2 (p < 0.01), 38 ± 1 (p < 0.01), 36 ± 2 (p < 0.01). The cellular mechanism for the antiplatelet activity of matico might be mediated by the inhibition of phospholipase C-gamma 2 and protein kinase C phosphorylation. This beneficial property of matico may be of importance in thrombosis, in which platelet activation and aggregation are important determinants of thrombus initiation and development, and may contribute to the beneficial effects of matico intake in the prevention of cardiovascular diseases.

Impact of walkability with regard to physical activity in the prevention of diabetes.

Walkability, a component of urban design intended to facilitate pedestrian traffic, depends on parameters associated with the connectivity of routes, population density and availability of destinations in the neighbourhood. The aim is to achieve levels of physical activity related to the prevention of risk factors associated with diseases, such as diabetes and the improvement of glycaemia control. It is important to consider that the effects of walkability depend on its relation with other variables present in the neighbourhood, e.g., environmental and socioeconomic factors. Considering this, improving walkability levels could be an effective strategy to reduce disease, the prevalence of diabetes in particular, in the population and thus reduce public spending. To investigate these relationships, PUBMED and ScienceDirect databases were searched using the following key words: Diabetes, Walkability and Physical activity.

Study of the interactions between Edaglitazone and Ciglitazone with PPARγ and their antiplatelet profile.

Peroxisome proliferator-activated receptor γ (PPARγ) is a ligand-activated transcription factor with an important role in lipid metabolism, inflammation and cardiovascular diseases. PPARγ ligands have inhibitory effects on platelet aggregation via the cAMP pathway, which may confer them a protective cardioprotective role. Edaglitazone and Ciglitazone are two chemically-similar thiazolidinedione (TZD) drugs that have been described as potent PPARγ agonists; however, Edaglitazone is over 100 times more potent than Ciglitazone. Here, we report a computational study to describe the ligand binding and the experimental antiplatelet profiles of Edaglitazone and Ciglitazone. Both ligands presented similar orientations within the PPARγ binding site. Their polar heads exhibit complex hydrogen bond networks with the residues at arm I pocket, while their hydrophobic tails are oriented inside arm II or the entrance pocket. The bulkier and longer tail of Edaglitazone exhibited additional hydrophobic interactions, explaining its stronger binding to PPARγ supported by binding affinity calculations. On the other hand, both Edaglitazone and Ciglitazone displayed an antiplatelet activity, but only Edaglitazone retained such effect at low concentrations. Furthermore, we evidenced that Edaglitazone increases intraplatelet cAMP levels and prevents PPARγ secretion, explaining its greater antiplatelet activity. Altogether, the more potent PPARγ agonist Edaglitazone seems to be a potent antiplatelet agent.

Mechanisms of endothelial dysfunction during aging: Predisposition to thrombosis.

One of the risk factors for developing cardiovascular disease (CVD) is aging. In the elderly endothelial dysfunction occurs as altered endothelial ability to regulate hemostasis, vascular tone and cell permeability. In addition, there are changes in the expression and plasma levels of important endothelial components related to endothelial-mediated modulation in hemostasis. These include alterations in the metabolism of nitric oxide and prostanoides, endothelin-1, thrombomodulin and Von Willebrand factor. These alterations potentiate the pro-coagulant status developed with aging, highlighting the endothelial role in the development of thrombosis in aging.

Antiplatelet activity of drugs used in hypertension, dyslipidemia and diabetes: Additional benefit in cardiovascular diseases prevention.

Beyond its function in hemostasis, platelets activation has an important role in cardiovascular diseases (CVD) development. There are different clinical conditions that can mediate abnormal platelet activation and favors pathological thrombosis and CVD. These include Hypertension, diabetes and dyslipidemia, all risks factors from CVD development. Different drugs employed in the handled of these conditions have showed decreases platelet activation and related markers. This effect is in part by improved the base condition; however someone of these drugs can modulate platelet targets. We discuss about underlying mechanisms and the possible implications in the treatment of CVD.

Role of adenosine A2b receptor overexpression in tumor progression.

The adenosine A2b receptor is a G-protein coupled receptor. Its activation occurs with high extracellular adenosine concentration, for example in inflammation or hypoxia. These conditions are generated in the tumor environment. Studies show that A2b receptor is overexpressed in various tumor lines and biopsies from patients with different cancers. This suggests that A2b receptor can be used by tumor cells to promote progression. Thus A2b participates in different events, such as angiogenesis and metastasis, besides exerting immunomodulatory effects that protect tumor cells. Therefore, adenosine A2b receptor appears as an interesting therapeutic target for cancer treatment.

Endometriosis diafragmática: a propósito de un caso / Diaphragmatic endometriosis: about a case

ANTECEDENTES: La endometriosis afecta entre 5 al 15% de las mujeres en edad reproductiva. La presentación torácica es una entidad de baja frecuencia (menos del 1% de todos los casos de endometriosis), y puede localizarse en vía aérea, parénquima, pleuras o diafragma. Sus manifestaciones clínicas habitualmente se presentan dentro de las primeras 72 horas del inicio de la menstruación y consisten en dolor torácico, neumotórax o hemoptisis. El mejor manejo consiste en supresión hormonal y manejo quirúrgico en casos refractarios. OBJETIVOS: Describir un caso de endometriosis diafragmática tratada satisfactoriamente por videotoracoscopia. CASO CLÍNICO: Mujer de 27 años, con antecedentes de endometriosis ovárica operada con electrofulguración dos años previo. Consulta por omalgia derecha y dado antecedentes de endometriosis pélvica, se solicita TAC torácico, que informa formación sólida, ovoídea, de 30 mm x 13 mm, que capta contraste en forma parcial ubicado en la región subdifragmática derecha. Se interpreta imagen como posible foco de endometriosis, se complementa con RNM que es concordante con el diagnóstico. Se realiza videotoracoscopia derecha con resección diafragmática y reparación primaria. Anatomía patológica informa focos de endometriosis con márgenes negativos. Se retira la pleurostomía a las 48 horas, siendo dada de alta a los tres días. A un año de seguimiento, está asintomatica y sin evidencia de recidiva. CONCLUSIÓN: A pesar de su baja frecuencia, la endometriosis torácica representa un importante compromiso de la calidad de vida. Casos con complicaciones torácicas, con regular o deficiente respuesta a terapia hormonal, se benefician de resolución quirúrgica por vía mínimamente invasiva.

BACKGROUND: Endometriosis affects between 5 to 15% of women of reproductive age. Thoracic presentation entity is infrequent (less than 1% of all cases of endometriosis) and may be located in airway parenchyma, pleura or diaphragm. Its clinical manifestations usually occur within the first 72 hours of onset of menstruation and include chest pain, pneumothorax or hemoptysis. Better management consists of hormonal suppression and surgical management in refractory cases. OBJECTIVE: To describe a case of diaphragmatic endometriosis, successfully treated by video-assisted thoracoscopic surgery (VATS). CASE REPORT: Woman of 27 years old, with a history of ovarian endometriosis operated by electrofulguration two years before. She present right omalgia and a history of pelvic endometriosis. Chest CT report a solid, ovoid formation, 30 mm x 13 mm, which captures contrast partially, located in the right sub diaphragmatic region. Image is interpreted as a possible focus of endometriosis, it is complemented by RNM that is consistent with the diagnosis. It is performed VATS right with diaphragmatic resection and primary repair. Pathology reports endometriosis with negative margins. The pleurostomy is removed after 48 hours, she was discharged after three days. A one year follow up, it is asymptomatic and without evidence of recurrence. CONCLUSION: Despite its low frequency, the thoracic endometriosis represents an important commitment to the quality of life. Cases with chest complications, and with fair or poor response to hormone therapy, benefit with minimally invasive surgical resolution.

Primary and secondary haemostasis changes related to aging.

Life expectancy has increased in many countries as a result the world's population is aging. The projections indicate that the proportion of the elderly in a few decades will increase significantly. Aging carries with it a series of physiological changes; one of them is an imbalance in the hemostatic system. Thus the levels or activity of various proteins involved, such as most coagulation factors, natural anticoagulants and the fibrinolytic system are altered so that the hemostatic balance leans toward thrombosis. Also, platelet activity suggests a state of abnormal activation (P-selectin, beta thromboglobulin and platelet factor). In this review we will systematically examine the alterations in the hemostatic components that occur during aging. Therefore, understanding these hemostatic changes could contribute to developing strategies for the proper management of health in old age.