Discovery of Novel Bioactive Tanshinones and Carnosol Analogues against Breast Cancer.

The abietane diterpenoids ferruginol (1), tanshinone IIA (3), and carnosol (4) are well-known for their interesting pharmacological properties, including antitumor, similar to other natural and semisynthetic abietanes. In this study, a pair of semisynthetic C18-functionalized analogues of 3 and 4 were prepared from the commercially available (+)-dehydroabietylamine or readily obtained methyl dehydroabietate. Semisynthetic ferruginol (1) and some selected analogues, together with the synthesized analogues, were tested in vitro for the inhibition of proliferation in four breast cancer cell lines, SUM149, MDA-MB231, T47D, and MCF07. As a result, several tested abietane analogues decreased cell proliferation and enhanced cell death, with IC50 in the range 1.3-18.7 µM. This work demonstrates the antitumor activities of two tested compounds, making these molecules interesting for the development of new anticancer agents.

HIV/AIDS infection in critical care: epidemiological profile and risk factors for mortality in a Colombian cohort.

INTRODUCTION: Outcomes of human immunodeficiency virus (HIV) infected patients admitted to intensive care units (ICU) have improved with antiretroviral therapy (ART). However, whether the outcomes have improved in low- and middle-income countries, paralleling those of high-income countries is unknown. The objective of this study was to describe a cohort of HIV-infected patients admitted to ICU in a middle-income country and identify the risk factors associated with mortality. METHODOLOGY: A cohort study of HIV-infected patients admitted to five ICUs in Medellín, Colombia, between 2009 and 2014 was done. The association of demographic, clinical and laboratory variables with mortality was analyzed using a Poisson regression model with random effects. RESULTS: During this time period, 472 admissions of 453 HIV-infected patients were included. Indications for ICU admission were: respiratory failure (57%), sepsis/septic shock (30%) and central nervous system (CNS) compromise (27%). Opportunistic infections (OI) explained 80% of ICU admissions. Mortality rate was 49%. Factors associated with mortality included hematological malignancies, CNS compromise, respiratory failure, and APACHE II score ≥ 20. CONCLUSIONS: Despite advances in HIV care in the ART era, half of HIV-infected patients admitted to the ICU died. This elevated mortality was associated to underlying disease severity (respiratory failure and APACHE II score ≥ 20), and host conditions (hematological malignancies, admission for CNS compromise). Despite the high prevalence of OIs in this cohort, mortality was not directly associated to OIs.

Antiviral Profiling of C-18- or C-19-Functionalized Semisynthetic Abietane Diterpenoids.

Viral infections affect several million patients annually. Although hundreds of viruses are known to be pathogenic, only a few can be treated in the clinic with available antiviral drugs. Naturally based pharmacotherapy may be a proper alternative for treating viral diseases. Several natural and semisynthetic abietane-type diterpenoids have shown important antiviral activities. In this study, a biological evaluation of a number of either C-18- or C-19-functionalized known semisynthetic abietanes against Zika virus, Dengue virus, Herpes virus simplex type 1, and Chikungunya virus are reported. Semisynthetic abietane ferruginol and its analogue 18-(phthalimid-2-yl)ferruginol displayed broad-spectrum antiviral properties. The scale-up synthesis of this analogue has been optimized for further studies and development. This molecule displayed an EC50 between 5.0 and 10.0 µM against Colombian Zika virus strains and EC50 = 9.8 µM against Chikungunya virus. Knowing that this ferruginol analogue is also active against Dengue virus type 2 (EC50 = 1.4 µM, DENV-2), we can conclude that this compound is a promising broad-spectrum antiviral agent paving the way for the development of novel antivirals.

Recomendaciones para reumatólogos sobre el manejo farmacológico durante la emergencia sanitaria por COVID-19: opinión de un grupo de expertos / Recommendations for rheumatologists on pharmacological management during the COVID-19 health emergency: Expert group opinion

RESUMEN La enfermedad por Coronavirus 2019 (COVID-19) es una pandemia inesperada que ha pro vocado un estado de emergencia y que ha generado cambios drásticos en los protocolos de atención clínica. Para su tratamiento se ha descrito el papel de algunos medicamen tos usados habitualmente en artritis reumatoide, lupus eritematoso sistémico y otras enfermedades autoinmunitarias sistémicas. Debido a ello, existe un inminente riesgo de desabastecimiento, por lo cual el objetivo de esta revisión narrativa y opinión de expertos es formular recomendaciones generales clínicas y administrativas sobre el manejo de pacien tes ambulatorios con enfermedad autoinmunitaria o inflamatoria sistémica en el contexto de la pandemia por COVID-19.

ABSTRACT Coronavirus 2019 (COVID-19) is an unexpected pandemic that has caused a state of emergency, as well as generating drastic changes in clinical care protocols. Some drugs commonly used in rheumatoid arthritis, systemic lupus erythematosus, and other systemic autoimmune diseases have been described for its treatment. Therefore, there is an imminent risk of shortages. The aim of this narrative review and expert opinion is to present general recommendations on the clinical and administrative management of outpatients with autoimmune or systemic inflammatory disease, in the context of the COVID-19 pandemic.

Rhinosporidiosis in the Americas: A Systematic Review of Native Cases.

Rhinosporidiosis is a chronic mucosal infection caused by Rhinosporidium seeberi, an aquatic protistan parasite. It presents as nasal or ocular polypoidal or vascularized masses. It is endemic in tropical and subtropical areas, especially in South Asia; R. seeberi´s endemicity in the Americas is often overlooked. The objective of this study was to describe the demographic and clinical characteristics of patients with rhinosporidiosis in the Americas, its management, and patient outcomes. This study is a systematic review of cases of human rhinosporidiosis in the Americas reported in the literature from 1896 to February 28, 2019. This review screened 1,994 reports, of which 115 were eligible for further analysis. The selected reports described 286 cases of human rhinosporidiosis between 1896 and 2019. Cases were diagnosed in Brazil (32.2%), Colombia (24.4%), Paraguay (12.6%), and the United States (11.9%). The majority of the cases (91%) occurred in geographic areas with altitudes < 1,000 m above sea level and in areas with median temperatures ≥ 25°C (67.3%). Most of the patients presented nasal (65%) and ocular involvement (35%). Surgical treatment was provided for 99.6% of patients, but 19.8% of them recurred. This review describes the under-recognized geographic distribution and clinical presentation of rhinosporidiosis in the Americas and highlights clinical differences to cases in Asia, specifically in reference to a higher prevalence of ocular disease and higher relapse rates.

Colopericardial fistula presenting with massive rectal bleeding.

Colopericardial fistulae constitute a condition with a very low prevalence and a high morbidity and mortality rate. In this case report, we discuss an 80-year-old male patient who presented to emergency services for massive rectal bleeding and signs of hypovolemic shock. Abdominal arteriography and upper gastrointestinal endoscopy were negative for bleeding. Findings indicative of fistula between the left ventricle and the transverse colon were described in computed tomography angiogram and the diagnosis was confirmed endoscopically. The patient was stabilized and the bleeding was self-limited. Direct communication between the gastrointestinal tract and the pericardium, or even with the heart itself, is a rare disease and constitutes a diagnostic challenge.

Estado nutricional del hierro en gestantesadolescentes, MedellÝn, Colombia / Nutritional status of iron in pregnant adolescents, MedellÝn, Colombia

Objetivo: analizar el estado nutricional del hierro en gestantesadolescentes de tercer trimestre. MetodologÝa: estudioanalÝtico de corte transversal con 276 adolescentes entre 10 y19 a±os, en tercer trimestre de gestaci¾n de la Empresa Socialdel Estado (ese) Metrosalud (MedellÝn, 2011-2012), con datosde hemoglobina, volumen corpuscular medio, concentraci¾nde hemoglobina corpuscular media e ingesta de suplementode hierro. La ferritina sÚrica se analiz¾ en 178 gestantes,controlada por proteÝna C-reactiva. Se utilizaron medidas detendencia central, dispersi¾n, porcentajes y pruebas de Chi2,anova, Kruskal-Wallis y U de Mann-Whitney. Resultados:la prevalencia de anemia fue 17,1% en el tercer trimestrede gestaci¾n y por deficiencia de hierro, 51%. La medianade ferritina sÚrica fue 13,3 Ág/L (RQ: 7,7 Ág/L-17,9 Ág/L);s¾lo el 5,6% (n = 9) present¾ valores adecuados de ferritina.Las madres que tomaron suplemento de hierro diariamentepresentaron mejores concentraciones de hemoglobina yferritina, frente a aquellas que no lo hicieron, Hb 12,1g/dL vs.11,7 g/dL (p = 0,019) y ferritina sÚrica 14,6 Ág/L vs. 7,0 Ág/L(p = 0,000). Discusi¾n: hubo altas prevalencias de anemia yferropenia en las gestantes, asociadas con la no adherencia alsuplemento de hierro...

Objective: to analyze the nutritional status of iron in pregnantadolescents in their third trimester. Methodology: a crosssectionalanalytical study with 276 adolescents between theages of 10 and 19 in the third trimester of pregnancy fromthe ESE Metrosalud State Social Enterprise (MedellÝn 2011-2012). Data was collected for hemoglobin, mean corpuscularvolume, mean corpuscular concentration and the ingestionof iron supplements. Serum ferritin levels were analyzed in178 pregnant adolescents and were controlled by C-reactiveprotein. Central tendency measures, dispersion, percentagesand Chi 2, anova, Kruskal-Wallis and Mann-Witney U testswere employed. Results: anemia prevalence was 17.1% inthe third trimester, 51% because of iron deficiency. Medianserum ferritin was 13.3 Ág/L (RQ: 7.7 Ág/L-17.9 Ág/L); only5.6% (n=9) showed adequate ferritin levels. Mothers who tookdaily iron supplements exhibited greater concentrations ofhemoglobin and ferritin when compared with those who did nottake any supplement, Hb: 12.1g/dL vs 11.7 g/dL ( p = 0.019) andserum ferritin 14.6 Ág/L vs7.0 Ág/L (p = 0.000). Discussion:there was high prevalence of anemia and iron deficiency inthe expectant mothers, which was associated with a lack ofadherence to the iron supplement...

MicroRNA signatures of iPSCs and endoderm-derived tissues.

MicroRNAs (miRNAs), small non-coding RNAs that fine-tune gene expression, play multiple roles in the cell, including cell fate specification. We have analyzed the differential expression of miRNAs during fibroblast reprogramming into induced pluripotent stem cells (iPSCs) and endoderm induction from iPSCs upon treatment with high concentrations of Activin-A. The reprogrammed iPSCs assumed an embryonic stem cell (ESC)-like miRNA signature, marked by the induction of pluripotency clusters miR-290-295 and miR-302/367 and conversely the downregulation of the let-7 family. On the other hand, endoderm induction in iPSCs resulted in the upregulation of 13 miRNAs. Given that the liver and the pancreas are common derivatives of the endoderm, analysis of the expression of these 13 upregulated miRNAs in hepatocytes and pancreatic islets revealed a tendency for these miRNAs to be expressed more in pancreatic islets than in hepatocytes. These observations provide insights into how differentiation may be guided more efficiently towards the endoderm and further into the liver or pancreas. Moreover, we also report novel miRNAs enriched for each of the cell types analyzed.

Referentes de significado de la alimentación durante el periodo gestacional / References of the nutrition importance during the gestation period

Fundamentos: El desconocimiento de los factores socioculturales que inciden en la alimentación en el periodo gestacional impide a los profesionales del área de la salud articular el saber científico, con el saber popular. Con esta investigación se indagó acerca de los referentes de significados de la alimentación durante la gestación para contribuir a fortalecer la atención en salud. Métodos: Se realizó un estudio cualitativo bajo la perspectiva de etnografía focalizada, la población de estudio fueron las gestantes participantes del programa MANA para la vida. Resultados: La alimentación de las gestantes se ve influenciada por la situación económica que condiciona la disponibilidad de alimentos en el hogar. El proceso educativo del cual participaron las gestantes del estudio contribuyó a Que éstas tuvieran una mejor selección de los alimentos en comparación con embarazos pasados. La mayor parte de las maternas coincidieron en afirmar Que el sabor es la primera razón Que las conduce a preferir los alimentos, la causa principal de las aversiones es la remembranza de algún recuerdo y la característica común de los antojos es no pertenecer al inventario cotidiano. Conclusión: Se concluye que la situación económica fue el principal condicionante para determinar la cantidad y calidad de los alimentos que consumen las gestantes (AU)

Background: The lack of knowledge of the social and cultural factors affecting the feeding during the gestation period impedes to the health professional, to articulate scientific knowledge, with common knowledge. By this study, it was investigated the references of the nutrition importance during the gestation period to contribute to reinforce the attention in health. Methods: A qualitative study was realized under the perspective of ethnography focalized, the study population were pregnant women who were participating of the program "MANA for the life". Results: The pregnant women feeding are influenced by the economic situation that determines the food availability in the hearth. The educational process that the pregnant women received, contributed to they to have a better selection of the food compared to past pregnancies. Most of the mothers coincided in affirming that the taste is the first reason that drives them to prefer the food, the principal a los cause of the distastes is the remembrance of some memories and the common characteristic of the whims is not belong to the daily inventory. Conclusion: Is a conclusion that the economic situation was the principal determinant to influence the quantity and quality of the food that the pregnant consume (AU)