Full-length transcript alterations in human bronchial epithelial cells with U2AF1 S34F mutations.

U2AF1 is one of the most recurrently mutated splicing factors in lung adenocarcinoma and has been shown to cause transcriptome-wide pre-mRNA splicing alterations; however, the full-length altered mRNA isoforms associated with the mutation are largely unknown. To better understand the impact U2AF1 has on full-length isoform fate and function, we conducted high-throughput long-read cDNA sequencing from isogenic human bronchial epithelial cells with and without a U2AF1 S34F mutation. We identified 49,366 multi-exon transcript isoforms, more than half of which did not match GENCODE or short-read-assembled isoforms. We found 198 transcript isoforms with significant expression and usage changes relative to WT, only 68% of which were assembled by short reads. Expression of isoforms from immune-related genes is largely down-regulated in mutant cells and without observed splicing changes. Finally, we reveal that isoforms likely targeted by nonsense-mediated decay are down-regulated in U2AF1 S34F cells, suggesting that isoform changes may alter the translational output of those affected genes. Altogether, our work provides a resource of full-length isoforms associated with U2AF1 S34F in lung cells.

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.

Cellular exposure to free fatty acids (FFAs) is implicated in the pathogenesis of obesity-associated diseases. However, there are no scalable approaches to comprehensively assess the diverse FFAs circulating in human plasma. Furthermore, assessing how FFA-mediated processes interact with genetic risk for disease remains elusive. Here, we report the design and implementation of fatty acid library for comprehensive ontologies (FALCON), an unbiased, scalable, and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids associated with decreased membrane fluidity. Furthermore, we prioritized genes that reflect the combined effects of harmful FFA exposure and genetic risk for type 2 diabetes (T2D). We found that c-MAF-inducing protein (CMIP) protects cells from FFA exposure by modulating Akt signaling. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism.

FALCON systematically interrogates free fatty acid biology and identifies a novel mediator of lipotoxicity.

Cellular exposure to free fatty acids (FFA) is implicated in the pathogenesis of obesity-associated diseases. However, studies to date have assumed that a few select FFAs are representative of broad structural categories, and there are no scalable approaches to comprehensively assess the biological processes induced by exposure to diverse FFAs circulating in human plasma. Furthermore, assessing how these FFA- mediated processes interact with genetic risk for disease remains elusive. Here we report the design and implementation of FALCON (Fatty Acid Library for Comprehensive ONtologies) as an unbiased, scalable and multimodal interrogation of 61 structurally diverse FFAs. We identified a subset of lipotoxic monounsaturated fatty acids (MUFAs) with a distinct lipidomic profile associated with decreased membrane fluidity. Furthermore, we developed a new approach to prioritize genes that reflect the combined effects of exposure to harmful FFAs and genetic risk for type 2 diabetes (T2D). Importantly, we found that c-MAF inducing protein (CMIP) protects cells from exposure to FFAs by modulating Akt signaling and we validated the role of CMIP in human pancreatic beta cells. In sum, FALCON empowers the study of fundamental FFA biology and offers an integrative approach to identify much needed targets for diverse diseases associated with disordered FFA metabolism. Highlights: FALCON (Fatty Acid Library for Comprehensive ONtologies) enables multimodal profiling of 61 free fatty acids (FFAs) to reveal 5 FFA clusters with distinct biological effectsFALCON is applicable to many and diverse cell typesA subset of monounsaturated FAs (MUFAs) equally or more toxic than canonical lipotoxic saturated FAs (SFAs) leads to decreased membrane fluidityNew approach prioritizes genes that represent the combined effects of environmental (FFA) exposure and genetic risk for diseaseC-Maf inducing protein (CMIP) is identified as a suppressor of FFA-induced lipotoxicity via Akt-mediated signaling.

A parathyroid hormone/salt-inducible kinase signaling axis controls renal vitamin D activation and organismal calcium homeostasis.

The renal actions of parathyroid hormone (PTH) promote 1,25-vitamin D generation; however, the signaling mechanisms that control PTH-dependent vitamin D activation remain unknown. Here, we demonstrated that salt-inducible kinases (SIKs) orchestrated renal 1,25-vitamin D production downstream of PTH signaling. PTH inhibited SIK cellular activity by cAMP-dependent PKA phosphorylation. Whole-tissue and single-cell transcriptomics demonstrated that both PTH and pharmacologic SIK inhibitors regulated a vitamin D gene module in the proximal tubule. SIK inhibitors increased 1,25-vitamin D production and renal Cyp27b1 mRNA expression in mice and in human embryonic stem cell-derived kidney organoids. Global- and kidney-specific Sik2/Sik3 mutant mice showed Cyp27b1 upregulation, elevated serum 1,25-vitamin D, and PTH-independent hypercalcemia. The SIK substrate CRTC2 showed PTH and SIK inhibitor-inducible binding to key Cyp27b1 regulatory enhancers in the kidney, which were also required for SIK inhibitors to increase Cyp27b1 in vivo. Finally, in a podocyte injury model of chronic kidney disease-mineral bone disorder (CKD-MBD), SIK inhibitor treatment stimulated renal Cyp27b1 expression and 1,25-vitamin D production. Together, these results demonstrated a PTH/SIK/CRTC signaling axis in the kidney that controls Cyp27b1 expression and 1,25-vitamin D synthesis. These findings indicate that SIK inhibitors might be helpful for stimulation of 1,25-vitamin D production in CKD-MBD.

Assessing the Crop-Water Status in Almond (Prunus dulcis Mill.) Trees via Thermal Imaging Camera Connected to Smartphone.

Different tools are being implemented in order to improve the water management in agricultural irrigated areas of semiarid environments. Thermography has been progressively introduced as a promising technique for irrigation scheduling and the assessing of crop-water status, especially when deficit irrigation is being implemented. However, an important limitation is related to the cost of the actual cameras, this being a severe limitation to its practical usage by farmers and technicians. This work evaluates the potential and the robustness of a thermal imaging camera that is connected to smartphone (Flir One) recently developed by Flir Systems Inc. as a first step to assess the crop water status. The trial was developed in mature almond (Prunus dulcis Mill.) trees that are subjected to different irrigation treatments. Thermal information obtained by the Flir One camera was deal with the thermal information obtained with a conventional Thermal Camera (Flir SC660) with a high resolution, and subsequently, confronted with other related plant physiological parameters (leaf water potential, Ψleaf, and stomatal conductance, gs). Thermal imaging camera connected to smartphone provided useful information in estimating the crop-water status in almond trees, being a potential promising tool to accelerate the monitoring process and thereby enhance water-stress management of almond orchards.

Solid bioprocess of tarbush (Flourensia cernua) leaves for ß-glucosidase production by Aspergillus niger: initial approach to fiber-glycoside interaction for enzyme induction.

Commercial cellulase production has increased in recent years and consistent research has been carried out to improve levels of ß-glucosidase. Bioprocesses have been successfully adapted to produce this enzyme, with solid-state fermentations as the best-suited technique involving fungi. The aim of this study was to use leaves of tarbush (Flourensia cernua), an abundant shrub of the Chihuahuan Desert, as a carbon source for ß-glucosidase production by Aspergillus niger. During the solid bioprocess, this enzyme reached its peak production at 36 h of culture with 3876.6 U/L. There is a particular interest in the substrate composition because of the possibility of phenolic glycosides having an important role in ß-glucosidase production. HPLC-MS analyses showed that glycosides were present with the highest accumulation at 36 h of fungal culture. Luteolin and apigenin glycosides [1.8 and 2.4 absorbance units, respectively] were also detected and showed their highest point of detection alongside the highest ß-glucosidase activity. No apparent changes in cellulose were observed, while hemicellulose content decreased, which could be related to production and activity of ß-glucosidase. This study shows that leaves of F. cernua are an important raw material for ß-glucosidase production and give a source of compounds of added value which also may have an important role for ß-glucosidase production.

Utilización de la PAAF guiada por ecografía en el Hospital Carlos Andrade Marín / Echography-guided use of Puncture Breast Echography in the Carlos Andrade Marin Hospital

Introducción: El objetivo del presente estudio es describir la frecuencia con la que realizamos este examen y el tipo de tejidos obtenidos con el procedimiento. Materiales y Métodos: La muestra obtenida fue de 300 pacientes a quienes se les realizó una PAAF desde septiembre 2014 a diciembre del mismo año. Los resultados se presentan en tablas de frecuencia clasificadas por órgano puncionado y resultado citológico. Resultados: En los cuatro meses, el órgano más puncionado fue la glándula tiroides (73%); el segundo lugar, la mama (19.3%); siguen, los ganglios cervicales (5%); ganglios axilares (1.3%); y, finalmente, las glándulas salivales (1.3%). Discusión: La PAFF guiada por ultrasonografía es uno de los procedimientos diagnósticos más utilizados en todo el mundo, cuando se trata de lesiones accesibles e identificables por ecografía. De allí la alta frecuencia de su uso en nuestro medio y particularmente en el HCAM, cuyos resultados son similares a los reportes de estándares internacionales.

Introduction: The objective of this study was describing the frequency this procedure is performed and detailing the kind of tissue samples obtained. Methods: Descritptive study that included 300 patients who underwent Fine Needle Aspiration (FNA) guided by ultrasound to obtain samples from different organs for cytology at Carlos Andrade Marin hospital. Results: During a four-month period 192(73%) subjects underwent FNA of the thyroid gland; 57(19.3%) of the breast; 14(5%) from cervical lymph nodes; 4(1.3%) from axillary lymph nodes AND 2 (1.3%) samples were taken from salivary glands. Discusion: FNA guided by ultrasound is a frequent procedure worldwide performed when accessible lesions are identified by ultrasound. That explains the frequency of its use anda particularly at Carlos Andrade Marin Hospital. Our reports are simResumen

Punción de la arteria radial guiada por ultrasonido para obtención de gases arteriales / Puncture of the radial artery guided by ultrasound for the obtaining of arterial blood gases

Introducción: La punción de la arteria radial es utilizada para tomar muestras de sangre arterial y realizar exàmentes gasométricos. Es un procedimiento que se realiza de manera frecuente en el área de emergencias, sin embargo, no está exento de complicaciones, por lo que es necesario evaluar técnicas accesorias que permitan reducir los riesgos para el paciente. El objetivo del estudio fue comparar la técnica de punción arterial convencional guiada por palpación con la punción arterial guiada por ultrasonido. Materiales y métodos: Estudio prospectivo en pacientes que ingresaron al Servicio de Emergencia del Hospital Carlos Andrade Marín a quienes se les solicitó gasometría arterial. Para obtener la muestra de sangre arterial se asignó en forma aleatoria a cada paciente a uno de los dos grupos de estudio, el primero en el que se utilizó el método convencional, guiados por palpación y el segundo, guiados por ultrasonido. Los participantes fueron pacientes adultos a quienes se les solicitó gasometría arterial, excluyendo aquellos que tenían alguna contraindicación para el procedimiento. El enrolamiento tuvo lugar en un período de 2 meses. El desenlace primario fue la punción arterial exitosa en el primer intento. Se consideró fracaso, cuando los pacientes requirieron 2 o más punciones para obtener la muestra. Resultados: Noventa y ocho pacientes, fueron enrolados. Cincuenta asignados al grupo guiado por ultrasonido y 48 al grupo control. La punción arterial fue exitosa al primer intento en el 92% del grupo guiado por ultrasonido y 9.6% en el grupo control. El tiempo requerido para obtener la muestra fue similar en los dos grupos (p=0.91). Discusión: La punción arterial guiada por ultrasonido no fue más efectiva que la técnica convencional.

Introduction: Arterial blood gas (ABG) sampling by direct vascular puncture guided by pulse palpation is a common procedure performed in the emergency setting. Reducing the number of attempts to draw arterial blood samples was one of our main goals. The other goal was comparing the standard technique with the ultrasound-guided arterial puncture. Methods: Prospective study in patients admitted to the Emergency Department at Carlos Andrade Marín Hospital, who needed arterial blood gas exams. Patients allocation to draw arterial blood by palpation or guided by ultrasound was chosen at random. Participants were adult patients who needed ABG analysis and excluded patients with any contraindication. The enrollment period lasted two months. The primary endpoint was the successful arterial blood gas sample obtained at first attempt. Failure was taken when patients required more than two punctures to obtain the blood sample. Surrogate endpoint was the amount of time employed in the procedure. Statistical analysis, including Fisher's exact test for categorical variables and independent t-test for quantitative variables, was performed. Results: Ninety-eight patients were enrolled. Fifty were assigned to the ultrasound-guided group and 48 to the control group. The proportion of successful first attempts was 92% in the ultrasound group, and 91.6% in the control group . The amount of time required to draw the blood sample was similar in both groups (p= 0.91). Discusion: Arterial puncture guided by ultrasound was not more effective than the conventional technique to draw arterial blood sample by pulse palpation.

Complications in blepharoplasty: how to avoid and manage them.

UNLABELLED: Complications in blepharoplasty are uncommon and, when they occur, they are usually mild and transient, such as hematomas and chemosis. However, sometimes they can be severe, such as blindness, or they might require surgical correction, such as ectropion. OBJECTIVE: To evaluate the results and complications of transcutaneous blepharoplasty performed in the same procedure, discussing how to treat and how to avoid them. METHODS: A retrospective study of 200 medical records of consecutive patients that underwent transcutaneous blepharoplasty from January 2007 to January 2009. The variables analyzed were age, gender, complications, clinical outcome, patient satisfaction, and photographic documentation. RESULTS: The incidence of complications was 9.5% (19 patients). The complications were 1 hematoma, 12 cases of chemosis and 13 patients who underwent canthoplasty, 6 patients with malposition of the lower eyelid (5 retractions and 1 ectropion). Medical treatment was performed in 12 patients and revision surgery in 7 cases of all the patients who had complications. CONCLUSIONS: We demonstrated that blepharoplasty is a procedure with a high satisfaction and a low complication rate, and it is an excellent surgical procedure, when properly indicated.

Complications in blepharoplasty: how to avoid and manage them / Complicações em blefaroplastia: como evitá-las e corrigi-las

Complications in blepharoplasty are uncommon and, when they occur, they are usually mild and transient, such as hematomas and chemosis. However, sometimes they can be severe, such as blindness, or they might require surgical correction, such as ectropion. OBJECTIVE: To evaluate the results and complications of transcutaneous blepharoplasty performed in the same procedure, discussing how to treat and how to avoid them. METHODS: A retrospective study of 200 medical records of consecutive patients that underwent transcutaneous blepharoplasty from January 2007 to January 2009. The variables analyzed were age, gender, complications, clinical outcome, patient satisfaction, and photographic documentation. RESULTS: The incidence of complications was 9.5 percent (19 patients). The complications were 1 hematoma, 12 cases of chemosis and 13 patients who underwent canthoplasty, 6 patients with malposition of the lower eyelid (5 retractions and 1 ectropion). Medical treatment was performed in 12 patients and revision surgery in 7 cases of all the patients who had complications. CONCLUSIONS: We demonstrated that blepharoplasty is a procedure with a high satisfaction and a low complication rate, and it is an excellent surgical procedure, when properly indicated.

As complicações em blefaroplastia não são comuns e quando ocorrem são geralmente discretas e transitórias, como hematoma e quemose. Entretanto, algumas vezes podem ser definitivas, como cegueira, ou necessitarem de novas abordagens cirúrgicas para correção, como ectrópio. OBJETIVO: Avaliar resultados e complicações das blefaroplastias transcutâneas realizadas em um mesmo serviço, demonstrando como tratá-las e evitá-las. CASUÍSTICA E MÉTODO: Estudo retrospectivo de 200 prontuários de pacientes consecutivos submetidos à blefaroplastia transcutânea entre o período de janeiro de 2007 a janeiro de 2009 em um mesmo serviço. As variáveis analisadas foram: idade, sexo, complicações, evolução clínica, grau de satisfação e documentação fotográfica. RESULTADOS: A incidência de complicações foi de 9,5 por cento (19 pacientes). As complicações encontradas foram: 1 hematoma, 12 casos de quemose, sendo que esta ocorreu em 61,5 por cento dos 13 pacientes que realizaram cantoplastia, 6 pacientes com mau posicionamento de pálpebra inferior, sendo que, destes, 5 correspondem à retração e 1 ao ectrópio. Foi realizado tratamento clínico com acompanhamento ambulatorial em 12 pacientes e cirurgia revisional em 7 casos do total de pacientes com complicações. CONCLUSÕES: Demonstrou-se que a blefaroplastia é uma cirurgia com alta taxa de satisfação e baixo número de complicações, sendo um excelente procedimento cirúrgico, quando corretamente indicada.

A prospective, randomized, controlled trial of noninvasive ventilation in pediatric acute respiratory failure.

OUTCOMES: To compare the benefits of noninvasive ventilation (NIV) plus standard therapy vs. standard therapy alone in children with acute respiratory failure; assess method effectiveness in improving gas exchange and vital signs; and assess method safety. DESIGN: Prospective, randomized, controlled study. SITE: Two pediatric intensive care units in Santiago, Chile, at Clínica Santa María and Clínica Dávila, respectively. PATIENTS AND METHODS: Fifty patients with acute respiratory failure admitted to pediatric intensive care units were recruited; 25 patients were randomly allocated to noninvasive inspiratory positive airway pressure and expiratory positive airway pressure plus standard therapy (study group); the remaining 25 were given standard therapy (control group). Both groups were comparable in demographic terms. INTERVENTIONS AND MEASUREMENTS: The study group received NIV under inspiratory positive airway pressure ranging between 12 cm and 18 cm H2O and expiratory positive airway pressure between 6 cm and 12 cm H2O. Vital signs (cardiac and respiratory frequency), Po2, Pco2, pH, and Po2/Fio2 were recorded at the start and 1, 6, 12, 24, and 48 hrs into the study. RESULTS: Heart rate and respiratory rate improved significantly with NIV. Heart rate and respiratory rate were significantly lower after 1 hr of treatment compared with admission (p = 0.0009 and p = 0.004, respectively). The trend continued over time, heart rate being significantly lower than control after the first hour and heart rate after 6 hrs. With NIV, Po2/Fio2 improved significantly from the first hour. The endotracheal intubation was significantly lower (28%) in the NIV group than in the control group (60%; p = 0.045). CONCLUSIONS: NIV improves hypoxemia and the signs and symptoms of acute respiratory failure. NIV seems to afford these patients protection from endotracheal intubation.

Laryngeal granular cell tumor.

Granular cell tumor (GCT) of the larynx is an uncommon, benign laryngeal neoplasm. Abrikossoff first described the tumor in 1926 as myoblastoma. The origin of this tumor has been debated in the literature. Most of the authors believe that the tumor is of neural origin due to the characteristic immunohistochemical-staining pattern. The authors describe two cases of laryngeal GCTs located in different sites with a review of the histological and clinical features, the differential diagnosis, and the treatment and the prognosis of the tumor.

Presencia de Aedes albopictus en Leticia, Amazonas, Colombia / Aedes albopictus presence in Leticia, Amazonas, Colombia

La especie Aedes albopictus es un eficiente vector del dengue en Asia y posiblemente, de otros arbovirus incluyendo la fiebre amarilla y la encefalitis. En la última década se ha extendido la distribución de A. albopictus a las Américas. En la ciudad de Tabatinga, Brasil, muy cerca de la frontera con Colombia, se ha informado la presencia de esta especie en 1996 y posteriormente, en octubre de 1997. En marzo de 1998, en desarrollo de un estudio sobre enfermedades tropicales realizado por el Programa de Estudio y Control de Enfermedades Tropicales, PECET, de la Universidad de Antioquia y la Secretaria de Salud del Amazonas, se capturaron 8 ejemplares adultos de A. albopictus en la ciudad de Leticia, departamento del Amazonas, siendo éste el primer hallazgo de esta especie en Colombia. La presencia en Colombia de A. albopictus vuelve más complejo el problema del dengue por la mayor adaptación de este vector a climas más fríos, la capacidad de transmisión transovariana, la buena capacidad vectorial para transmitir los cuatro serotipos del virus y la mayor dificultad para su control dado que sus criaderos están en áreas peridomésticas y rurales. La distribución de esta especie tanto en zonas selváticas como rurales y urbanas presenta un peligro potencial de urbanizar la transmisión de la fiebre amarilla. Se presenta el plan de contigencia que se debe implementar por parte de la Secretaría de Salud del Amazonas con miras a evitar la propagación de este vector a otras regiones del país

Importancia de los anticuerpos IgG como indicadores de prevalencia del helicobacter pylori en población de alto riesgo / Importance of serology IgG antibody prevalence of helicobacter pylori

Desde 1994, la Organización Mundial de la Salud categorizó al Helicobacter Pylory como carcinógeno tipo 1. Conscientes de la importancia de determinar la prevalencia de esta bacteria en nuestro medio, nos decidimos investigar esta última en un muestreo de 206 pacientes provenientes del litoral ecuatoriano con sintomatología del tracto gastrointestinal superior, sus hallazgos endoscópicos y sus resultados histopatológicos, cuyos resultados citamos a continuación