Lipid nanoparticle structure and delivery route during pregnancy dictate mRNA potency, immunogenicity, and maternal and fetal outcomes.

Treating pregnancy-related disorders is exceptionally challenging because the threat of maternal and/or fetal toxicity discourages the use of existing medications and hinders new drug development. One potential solution is the use of lipid nanoparticle (LNP) RNA therapies, given their proven efficacy, tolerability, and lack of fetal accumulation. Here, we describe LNPs for efficacious mRNA delivery to maternal organs in pregnant mice via several routes of administration. In the placenta, our lead LNP transfected trophoblasts, endothelial cells, and immune cells, with efficacy being structurally dependent on the ionizable lipid polyamine headgroup. Next, we show that LNP-induced maternal inflammatory responses affect mRNA expression in the maternal compartment and hinder neonatal development. Specifically, pro-inflammatory LNP structures and routes of administration curtailed efficacy in maternal lymphoid organs in an IL-1ß-dependent manner. Further, immunogenic LNPs provoked the infiltration of adaptive immune cells into the placenta and restricted pup growth after birth. Together, our results provide mechanism-based structural guidance on the design of potent LNPs for safe use during pregnancy.

Detection of Histoplasma capsulatum DNA in peripheral blood from a patient with ocular histoplasmosis syndrome.

Ocular histoplasmosis syndrome (OHS) is a significant cause of vision loss in young and middle-aged adults. We report here a case of an immunocompetent 37-year-old man who presented fever, malaise, headache, and anterior cervical lymphadenopathy for one week, after which he started to experience a sudden loss in visual acuity of his right eye. Fluorescent angiography and an optical coherent tomography demonstrated the presence of a type II choroidal neo-vascular membrane in the right eye, suggesting a diagnosis of OHS. A peripheral blood sample was tested by nested PCR to detect Histoplasma capsulatum using a set of primers known to amplify a DNA sequence coding for a specific 100-kDa protein of this fungus (Hc100-PCR). The blood sample was Hc100-PCR-positive and sequence analysis showed an identity of 97% with the reference sequence. The patient received intravitreal bevacizumab injection and itraconazol therapy, leading to an improvement in media vision acuity. In this case, the molecular test provided evidence linking the ocular lesions with an earlier infection by H. capsulatum and demonstrated that the Hc100-nested PCR assay is a valuable tool in the diagnosis of histoplasmosis.

Venous thromboembolism in pediatric patients with acute lymphoblastic leukemia under chemotherapy treatment. Risk factors and usefulness of thromboprophylaxis. Results of LAL-SEHOP-PETHEMA-2013.

INTRODUCTION: Symptomatic venous thromboembolism (VTE) is diagnosed in 3%-14% of patients during pediatric acute lymphoblastic leukemia (ALL) therapy. There are well-known risk factors, but the role of others as inherited thrombophilia is still controversial. Prophylaxis with low molecular weight heparin (LMWH) has been described, but its use is not globally accepted. METHODS: A retrospective multicentric study in ALL patients 1-18 years old following SEHOP-PETHEMA-2013 treatment guideline was performed to evaluate VTE rate, anticoagulant treatment, outcome, risk factors, and safety and usefulness of LMWH administration as primary thromboprophylaxis in children with inherited thrombophilia. RESULTS: A total of 652 patients were included in the study. VTE incidence was 8.7%. Most of the cases occurred during induction therapy associated with central venous catheter. Univariant analysis showed that family history of thrombosis, presence of mediastinal mass, high-risk treatment group, and inherited thrombophilia were statistically significant risk factors. LMWH administration seemed to decrease VTE rate in patients with inherited thrombophilia and those with T-cell ALL phenotype. CONCLUSION: Most of the VTE cases occurred in patients without inherited thrombophilia, but when it is present, the VTE risk is higher. LMWH administration was useful to decrease VTE in these patients.

Interplay between tumor microenvironment and partial EMT as the driver of tumor progression.

Epithelial-to-mesenchymal transition (EMT), an evolutionary conserved phenomenon, has been extensively studied to address the unresolved variable treatment response across therapeutic regimes in cancer subtypes. EMT has long been envisaged to regulate tumor invasion, migration, and therapeutic resistance during tumorigenesis. However, recently it has been highlighted that EMT involves an intermediate partial EMT (pEMT) phenotype, defined by incomplete loss of epithelial markers and incomplete gain of mesenchymal markers. It has been further emphasized that pEMT transition involves a spectrum of intermediate hybrid states on either side of pEMT spectrum. Emerging evidence underlines bi-directional crosstalk between tumor cells and surrounding microenvironment in acquisition of pEMT phenotype. Although much work is still ongoing to gain mechanistic insights into regulation of pEMT phenotype, it is evident that pEMT plays a critical role in tumor aggressiveness, invasion, migration, and metastasis along with therapeutic resistance. In this review, we focus on important role of tumor-intrinsic factors and tumor microenvironment in driving pEMT and emphasize that engineered controlled microenvironments are instrumental to provide mechanistic insights into pEMT biology. We also discuss the significance of pEMT in regulating hallmarks of tumor progression i.e. cell cycle regulation, collective migration, and therapeutic resistance. Although constantly evolving, current progress and momentum in the pEMT field holds promise to unravel new therapeutic targets to halt tumor progression at early stages as well as tackle the complex therapeutic resistance observed across many cancer types.

Diversity patterns of vascular and non-vascular epiphytes along tropical dry forest / Patrones de diversidad de epífitas vasculares y no vasculares a lo largo del bosque seco tropical

Abstract Introduction: Epiphytes (vascular and non-vascular) are one of the most diverse groups in the Neotropics, but despite their importance in the functioning of many ecosystems, much of their taxonomy and ecology is still unknown in the dry forest of Colombia. Objective: To compare the diversity patterns and species composition of vascular and non-vascular epiphytes along tropical dry forest remnants of Cauca Valley, Colombia. Methods: Ten permanent plots (50 x 20 m2) were established in tropical dry forest remnants. The epiphytes were sampled in 40-50 trees per plot. Alpha and gamma diversity were calculated using the richness (q0) and Shannon index (q1) (alpha was estimated as the average for phorophytes). Beta diversity was measured using the Whitaker index. To evaluate the relationship between diversities and environmental variables, GLM analysis was used. Results: We found 50 morphospecies of vascular epiphytes, 77 of bryophytes and 290 of lichens. The 𝛼 and 𝛾 diversity of bryophytes from each remnant was significantly explained by temperature. The abundance of lichens per tree was significantly related with the DBH and tree height of each remnant. The 𝛼 diversity of vascular epiphytes shown can be explained by temperature and precipitation. The 𝛾 diversity was strongly influenced by the beta diversity in bryophytes and lichens. This pattern is because the sites with high disturbance present a lower diversity, as a consequence of a homogenizing effect, that is, a low turnover of species between sampling units. Conclusions: Precipitation and temperature affected the diversity of bryophytes and vascular epiphytes, while it did not show a relationship with the lichen's diversity, for which there is not a high congruence between the diversity and composition of these epiphytes.

Resumen Introducción: Los epífitos (vasculares y no vasculares) son uno de los más diversos grupos de plantas en el Neotrópico, pero a pesar de su importancia para el funcionamiento de varios ecosistemas, existen grandes vacíos en su conocimiento taxonómico y ecológico en el bosque seco de Colombia. Objetivo: Comparar los patrones de diversidad y composición de especies de epífitas vasculares y no vasculares a lo largo de remanentes de bosque seco tropical del Valle del Cauca, Colombia. Métodos: Se establecieron diez parcelas permanentes (50 x 20 m2) en remanentes de bosque seco tropical. Las epífitas se muestrearon en 40-50 árboles por parcela. La diversidad alfa y gamma se calculó utilizando la riqueza (q0) y el índice de Shannon (q1) (alfa se estimó como el promedio para los forófitos). La diversidad beta se midió utilizando el índice de Whitaker. Para evaluar la relación entre diversidades y variables ambientales se utilizó el análisis GLM. Resultados: Se encontraron 50 morfoespecies de epífitas vasculares, 77 de briófitas y 290 de líquenes. La diversidad de 𝛼 y 𝛾 de briófitas de cada remanente fue explicada significativamente por la temperatura. La abundancia de líquenes por árbol se relacionó significativamente con el DAP y la altura del árbol de cada remanente. La diversidad 𝛼 de epífitas vasculares que se muestra puede explicarse por la temperatura y la precipitación. La diversidad 𝛾 estuvo fuertemente influenciada por la diversidad beta en briófitas y líquenes. Este patrón se debe a que los sitios con alta perturbación presentan una menor diversidad, como consecuencia de un efecto homogeneizador, es decir, un bajo recambio de especies entre unidades de muestreo. Conclusiones: La precipitación y la temperatura afectaron la diversidad de briófitas y epífitas vasculares, mientras que no mostró relación con la diversidad de líquenes, por lo que no existe una alta congruencia entre la diversidad y composición de estas epífitas.

Contenido de ácidos grasos en carne de bovinos cebados en diferentes sistemas de producción en el trópico colombiano / Fatty acids in meat from cattle fattened in different production systems in the colombian tropics

Antecedentes: La carne es un alimento altamente nutritivo y un componente principal de la canasta básica familiar. Los consumidores seleccionan alimentos no solo por su gusto y satisfacción, sino por sus efectos en la nutrición y en la salud humana. Además se conoce muy poco sobre la calidad de carne producida en los sistemas colombianos y su contenido de ácidos grasos. Objetivo: Determinar el contenido y la composición de ácidos grasos en carne de bovinos cebados en distintos sistemas de producción colombianos. Métodos: Se obtuvieron lomos (Longissimus dorsi) de bovinos Cebú provenientes de cuatro sistemas de producción del trópico colombiano: Dos arreglos silvopastoriles (Centro Experimental Cotové, Universidad Nacional de Colombia y Montenegro, Quindío), una pradera mejorada (Montenegro, Quindío) y un sistema de pastoreo tradicional (Montería, Córdoba). Se extrajo grasa de 64 muestras de carne (dos por lomo) en el laboratorio de Química Analítica de la Universidad Nacional de Colombia, en la que se realizó un análisis cuantitativo de ácidos grasos por cromatografía de gases en el laboratorio de Análisis Instrumental de la Universidad Nacional de Colombia, sede Medellín. Los resultados se evaluaron siguiendo un diseño completamente al azar y la separación de medias se realizó por Duncan. Resultados: Hubo diferencias significativas en el contenido de ácido mirístico y palmítico entre el sistema tradicional y la pastura mejorada, siendo ambos mayores en el sistema tradicional. Hubo diferencias significativas en el contenido de ácidos insaturados, siendo el sistema silvopastoril del Quindío y la pradera mejorada, los de mayor relación de ácidos grasos polisaturados: insaturados (0,19). En la relación linoleico: α-linolénico no hubo diferencias entre los sistemas. Conclusión: La composición y el contenido de ácidos grasos variaron en la carne de los sistemas evaluados. Los principales componentes de la grasa fueron el ácido palmítico y el ácido oleico (30,73 y 35, 62 g/100 g de ácidos grasos)

Background: Meat is a highly nutritious food and a major component of the basic food basket. Consumers select foods not only for taste and satisfaction, but also for their effects on human nutrition and health. In addition there is very little knowledge about the quality of meat produced in the Colombian systems and their fatty acid content which undoubtedly affect human health. Objetive: To determine the content and composition of fatty acids in meat from steers managed in different Colombian systems. Methods: Meat (Longissimus dorsi) samples were obtained from Zebu cattle from four production systems inthe Colombian tropics: Two silvopastoral arrangements (Cotové Research Center, National University of Colombia and Montenegro, Quindío), improved pastures (Montenegro, Quindío) and a traditional grazing system (Monteria, Cordoba). Fat was extracted from 64 meat samples in the laboratory of Analytical Chemistry of the National University of Colombia, and a quantitative analysis of fatty acids was performed by gas chromatography in the laboratory of Instrumental Analysis of the National University of Colombia in Medellin. The results were evaluated following a complete randomized design and means were separated by the Duncan test. Results: There were significant differences in the content of myristic and palmitic acids between meat from the traditional and improved pasture system, with both acids being higher in the traditional system. There were also differences in the content of linoleic and linolenic acid, being lower in the Cotové silvopastoral system. There were significant differences in the content of unsaturated acids, with the meat from silvopastoral system Quindío and the improved pastures showing the highest fatty acid saturated: polyunsaturated ratio (0.19). In the linoleic: α-linolenic ratio there were no differences. Conclusions: Although the composition and the fatty acid content in beef varied between systems evaluated, the main components of such systems fat were palmitic acid and oleic acid (30.73 and 35.62 g/100 g fatty acid).

Síndrome de Allgrove: informe de casos / Allgrove syndrome: cases report

El síndrome de Allgrove fue descrito en 1978 por Allgrove et al. como una entidad familiar de origen desconocido caracterizada por deficiencia aislada de glucorticoides, acalasia esofágica y producción defectuosa de lágrimas, por lo que ha sido denominado síndrome triple AAA (adrenal insufficiency, achalasia, alacrima); por lo general aparece durante la primera década de la vida con disfagia o con crisis suprarrenal severa; son pocos los casos diagnosticados de novo en los adultos en quienes predominan síntomas autonómicos y manifestaciones neurológicas como retardo mental, hiperreflexia, voz nasal, anisocoria, ataxia, hipotensión postural y disfunción sexual. En la consulta de Endocrinología Pediátrica del Hospital Universitario San Vicente de Paúl de Medellín se han identificado 5 pacientes con las características clínicas propias del síndrome. Todos mostraron alacrimia e insuficiencia suprarrenal y sólo en uno de los pacientes la acalasia aún no se ha diagnosticado pero la sintomatología que presenta es muy sugestiva de la misma; la alteración neurológica más común en esta serie es el retraso mental. La edad media de aparición de la alacrimia es 3.8 años, de la insuficiencia suprarrena 4.7 años y de la acalasia 7.2 años. Un hallazgo interesante y poco informado es el hipotiroidismo, que es subclínico en tres pacientes, permanente en uno y transitorio en otro.

The Allgrove syndrome (also known as Triple A syndromes), was described by Allgrove et al. in 1978 as a familiar clinical entity of unknown etiology whose characteristic features are adrenal insufficiency, achalasia and alacrima. The usual presentation is during the first 10 years of life with dysphagia or severe adrenal insufficiency, few new cases have been discovered in adults, whose autonomic symptoms and neurological manifestations such as mental retardation, hyperreflexia, nasal speech, anisocoria, ataxia, postural hypotension and sexual dysfunction are predominant. At the Pediatric Endocrinology Service of Hospital Universitario San Vicente de Paúl, Medellín, Colombia, 5 patients have been identified with the clinical features of Allgrove syndrome. All patients have showed both alacrima and adrenal insufficiency. Achalasia has not been diagnosed in one patient, whose symptomatology is highly suggestive to the syndrome. Mental retardation is the most frequent neurological alteration seen. The mean age of presentation for alacrima was 3.8 years, for adrenal insufficiency was 4.7 years and for achalasia was 7.2 years. An interesting finding and occasionally reported is the presence of hypothyroidism, which is subclinic in three patients, transient hypothyroidism in one patient and clinical hypothyroidism in the other one.

Enfermedad de BehÇet: espectro clínico de ocho pacientes en la ciudad de Medellín / BehÇet's disease: clinical findings in eight patients from Medellín, Colombia

El presente estudio, primero en nuestro medio, nos ha permitido conocer más sobre los aspectos clínicos de la enfermedad de Behçet sugiriendo además que existen pocas diferencias en comparación con otras series del mundo.