Reingeniería en los procesos de secado, molienda y tamizado de plantas aromáticas para mejorar la calidad de los derivados, caso: Empresa JAMBI KIWA

La empresa de productores de plantas medicinales JAMBI KIWA es una sociedad sin fines de lucro, cuyo objeto es la producción de té de hierbas aromáticas. Aglutina a 600 familias de 62 comunidades de la provincia de Chimborazo. Actualmente trabaja con 40 variedades de plantas medicinales, aromáticas y condimentos, comercializando té aromático y medicinal hacia el extranjero, debe cumplir estándares altos de calidad para competir y mantenerse en el mercado, a fin de obtener la certificación orgánica OKO BCS GARANTIE a nivel de los cultivos asociados cumpliendo características organolépticas, bromatológicas, microbiológicas que garanticen calidad e inocuidad para el consumo humano. Se rediseñó los procesos para optimizar las Buenas Prácticas de Manufactura (BPM), con un diagnóstico inicial (secadores, áreas de proceso de secado, molino y el tamiz de vaivén) para determinar la cantidad de producto, el tiempo de trabajo de los equipos y las características organolépticas del producto final; comprobando en las pruebas de simulación de los procesos de pre secado (variables: temperatura, tiempo y humedad) los requerimientos de las plantas aromáticas para mejorar la calidad, redefiniendo un sistema de extracción de polvo-aire, para disminuir la contaminación de partículas de bajo peso, para cumplir las Normas Técnicas de Seguridad e Higiene del Instituto Nacional de Normalización del Ecuador

Parallel sequencing of extrachromosomal circular DNAs and transcriptomes in single cancer cells

Extrachromosomal DNAs (ecDNAs) are common in cancer, but many questions about their origin, structural dynamics and impact on intratumor heterogeneity are still unresolved. Here we describe single-cell extrachromosomal circular DNA and transcriptome sequencing (scEC&T-seq), a method for parallel sequencing of circular DNAs and full-length mRNA from single cells. By applying scEC&T-seq to cancer cells, we describe intercellular differences in ecDNA content while investigating their structural heterogeneity and transcriptional impact. Oncogene-containing ecDNAs were clonally present in cancer cells and drove intercellular oncogene expression differences. In contrast, other small circular DNAs were exclusive to individual cells, indicating differences in their selection and propagation. Intercellular differences in ecDNA structure pointed to circular recombination as a mechanism of ecDNA evolution. These results demonstrate scEC&T-seq as an approach to systematically characterize both small and large circular DNA in cancer cells, which will facilitate the analysis of these DNA elements in cancer and beyond

Treatment variability and its relationships to outcomes among patients with Wernicke's encephalopathy: A multicenter retrospective study

Background: Despite guidelines and recommendations, Wernicke's encephalopathy (WE) treatment lacks evidence, leading to clinical practice variability.Aims: Given the overall lack of information on thiamine use for WE treatment, we analyzed data from a large, well-characterized multicenter sample of patients with WE, examining thiamine dosages; factors associated with the use of different doses, frequencies, and routes; and the influence of differences in thiamine treatment on the outcome.Methods: This retrospective study was conducted with data from 443 patients from 21 centers obtained from a nationwide registry of the Spanish Society of Internal Medicine (from 2000 to 2012). Discharge codes and Caine criteria were applied for WE diagnosis, and treatment-related (thiamine dosage, frequency, and route of administration) demographic, clinical, and outcome variables were analyzed.Results: We found marked variability in WE treatment and a low rate of high-dose intravenous thiamine administration. Seventy-eight patients out of 373 (20.9%) received > 300 mg/day of thiamine as initial dose. Patients fulfilling the Caine criteria or presenting with the classic WE triad more frequently received parenteral treatment. Delayed diagnosis (after 24 h hospitalization), the fulfillment of more than two Caine criteria at diagnosis, mental status alterations, and folic acid deficiency were associated significantly with the lack of complete recovery. Malnutrition, reduced consciousness, folic acid deficiency, and the lack of timely thiamine treatment were risk factors for mortality.Conclusions: Our results clearly show extreme variability in thiamine dosages and routes used in the management of WE. Measures should be implemented to ensure adherence to current guidelines and to correct potential nutritional deficits in patients with alcohol use disorders or other risk factors for WE

Clonal chromosomal mosaicism and loss of chromosome Y in elderly men increase vulnerability for SARS-CoV-2

The pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2, COVID-19) had an estimated overall case fatality ratio of 1.38% (pre-vaccination), being 53% higher in males and increasing exponentially with age. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, we found 133 cases (1.42%) with detectable clonal mosaicism for chromosome alterations (mCA) and 226 males (5.08%) with acquired loss of chromosome Y (LOY). Individuals with clonal mosaic events (mCA and/or LOY) showed a 54% increase in the risk of COVID-19 lethality. LOY is associated with transcriptomic biomarkers of immune dysfunction, pro-coagulation activity and cardiovascular risk. Interferon-induced genes involved in the initial immune response to SARS-CoV-2 are also down-regulated in LOY. Thus, mCA and LOY underlie at least part of the sex-biased severity and mortality of COVID-19 in aging patients. Given its potential therapeutic and prognostic relevance, evaluation of clonal mosaicism should be implemented as biomarker of COVID-19 severity in elderly people. Among 9578 individuals diagnosed with COVID-19 in the SCOURGE study, individuals with clonal mosaic events (clonal mosaicism for chromosome alterations and/or loss of chromosome Y) showed an increased risk of COVID-19 lethality

Extrachromosomal DNA amplifications in cancer

Extrachromosomal DNA (ecDNA) amplification is an important driver alteration in cancer. It has been observed in most cancer types and is associated with worse patient outcome. The functional impact of ecDNA has been linked to its unique properties, such as its circular structure that is associated with altered chromatinization and epigenetic regulatory landscape, as well as its ability to randomly segregate during cell division, which fuels intercellular copy number heterogeneity. Recent investigations suggest that ecDNA is structurally more complex than previously anticipated and that it localizes to specialized nuclear bodies (hubs) and can act in trans as an enhancer for genes on other ecDNAs or chromosomes. In this Review, we synthesize what is currently known about how ecDNA is generated and how its genetic and epigenetic architecture affects proto-oncogene deregulation in cancer. We discuss how recently identified ecDNA functions may impact oncogenesis but also serve as new therapeutic vulnerabilities in cancer

Formación de precios y salarios en Colombia

En este documento se desarrolla una exploración empírica sobre la información contenida en las expectativas de inflación obtenidas tanto directa (a través de encuestas) como indirectamente (implícitas en el mercado de deuda pública), se evalúa su capacidad predictiva sobre el comportamiento futuro de la inflación

Inflación y expectativas de inflación en Colombia

En este documento se desarrolla una exploración empírica sobre la información contenida en las expectativas de inflación obtenidas tanto directa (a través de encuestas) como indirectamente (implícitas en el mercado de deuda pública). Para esto, se realizan pruebas de insesgamiento y eficiencia, se exploran cuales son algunos de los determinantes de las expectativas y se evalúa su capacidad predictiva sobre el comportamiento futuro de la inflación. De acuerdo a los resultados, se puede concluir que las tres medidas de expectativas de inflación empleadas contienen información relevante para pronosticar la inflación, pero dichas medidas por si solas no son un buen pronóstico de la inflación futura

Assessing inflationary pressures in Colombia

The assessment of inflationary pressures in Colombia has faced two important challenges in the present decade. The first one occurred in 2006 and consisted of detecting an overheating economy in the midst of fast growing investment and increasing measure

Airway foreign body in children

Introduction and objective: The aspiration of a foreign body in children is a frequent emergency in pediatrics, being potentially lethal. Method: Narrative review. Results: This pathology mainly affects children under 5 years of age with a peak of incidence between the first and third years of life. The clinic will depend on the type of foreign body (size, shape, possibility of breaking, organic or not), the age of the child and the location of the object. In our environment, the most frequent is the aspiration of nuts (peanuts and sunflower seeds). After the initial picture, an asymptomatic period tends to occur, which favors delayed diagnosis and leads to possible errors in the diagnosis. Discussion: An adequate clinical history and a high diagnostic suspicion are fundamental to favor an early treatment. The presence of a normal chest X-ray does not exclude the presence of a foreign body in the airway, so a bronchoscopy is indicated if the diagnostic suspicion is high. The treatment of choice is extraction by rigid bronchoscopy, being controversial the use of flexible fibrobronchoscope. Conclusions: Conclusions: The aspiration of a foreign body is a pediatric emergency that requires a diagnosis and early treatment. The highest incidence occurs in children under 3 years and more frequently in men. The most commonly aspirated material in our environment are nuts, mainly located in the bronchial tree. The initial episode may go unnoticed, delaying the diagnosis and may lead to progressive respiratory distress in the child. A detailed clinical history and suspicion of this pathology are essential in children at risk age who present with cough and dyspnea of sudden onset. The existence of a normal chest radiograph should not postpone bronchoscopy when there is high clinical suspicion. The treatment of choice for the extraction of foreign bodies in airways in children is rigid bronchoscopy, being controversial the use of the flexible fibrobronchoscope. However, the joint use of both can be useful for locating and retrieving the object. The prevention of these accidents is essential to decrease their frequency and associated complications.Introducción y objetivo: La aspiración de un cuerpo extraño en niños supone una urgencia frecuente en pediatría, siendo potencialmente letal. Método: Revisión narrativa. Resultados: Esta patología afecta principalmente a niños menores de 5 años con un pico de incidencia entre el primer y tercer años de vida. La clínica dependerá del tipo de cuerpo extraño (tamaño, forma, posibilidad de romperse, orgánico o no), de la edad del niño y de la localización del objeto. En nuestro medio lo más frecuente es la aspiración de frutos secos (cacahuetes y pipas de girasol). Tras el cuadro inicial suele presentarse un periodo asintomático que favorece el retraso del diagnóstico y conlleva posibles errores en el mismo. Discusión: Una adecuada historia clínica y una alta sospecha diagnóstica son fundamentales para favorecer un tratamiento precoz. La presencia de una radiografía de tórax normal no excluye la presencia de un cuerpo extraño en vía aérea, por lo que está indicada la realización de una broncoscopia si la sospecha diagnóstica es alta. El tratamiento de elección es la extracción mediante broncoscopia rígida, siendo controvertida la utilización del fibrobroncoscopio flexible. Conclusiones: La aspiración de un cuerpo extraño es una urgencia pediátrica que precisa de un diagnóstico y tratamiento precoz. La máxima incidencia se presenta en menores de 3 años y más frecuentemente en varones. El material aspirado más habitual en nuestro medio son los frutos secos, localizándose principalmente en árbol bronquial. El episodio inicial puede pasar inadvertido, lo que retrasa el diagnóstico y puede dar lugar a una dificultad respiratoria progresiva en el niño. Es fundamental una historia clínica detallada y sospechar esta patología en niños en edad de riesgo que presenten tos y disnea de instauración brusca. La existencia de una radiografía de tórax normal no debe posponer la realización de una broncoscopia cuando existe alta sospecha clínica. El tratamiento de elección para la extracción de cuerpos extraño en vía aérea en niños es la broncoscopia rígida, siendo controvertido el uso del fibrobroncoscopio flexible. Sin embargo, el uso de forma conjunta de ambos puede ser útil para la localización y extracción del objeto. La prevención de estos accidentes es fundamental para disminuir su frecuencia y las complicaciones asociadas

Enhancer hijacking determines extrachromosomal circular MYCN amplicon architecture in neuroblastoma

MYCN amplification drives one in six cases of neuroblastoma. The supernumerary gene copies are commonly found on highly rearranged, extrachromosomal circular DNA (ecDNA). The exact amplicon structure has not been described thus far and the functional relevance of its rearrangements is unknown. Here, we analyze the MYCN amplicon structure using short-read and Nanopore sequencing and its chromatin landscape using ChIP-seq, ATAC-seq and Hi-C. This reveals two distinct classes of amplicons which explain the regulatory requirements for MYCN overexpression. The first class always co-amplifies a proximal enhancer driven by the noradrenergic core regulatory circuit (CRC). The second class of MYCN amplicons is characterized by high structural complexity, lacks key local enhancers, and instead contains distal chromosomal fragments harboring CRC-driven enhancers. Thus, ectopic enhancer hijacking can compensate for the loss of local gene regulatory elements and explains a large component of the structural diversity observed in MYCN amplification.We thank the patients and their parents for granting access to the tumor specimen and clinical information that were analyzed in this study. We are grateful to Yingqian Zhan, Natalia Munoz Perez, Jennifer von Stebut, and Victor Bardinet for critical discussions. We thank Elisabeth Baumann and Anna Szymborska-Mell for help with imaging. We are grateful to Peter Van Loo for providing data during peer review and to B. Hero, H. Düren, and N. Hemstedt of the neuroblastoma biobank and neuroblastoma trial registry of the German Society of Pediatric Oncology and Hematology (GPOH) for providing samples and clinical data. Computation has been performed on the HPC for Research cluster of the Berlin Institute for Health. This research was funded in part through the NIH/NCI Cancer Center Support Grant P30 CA008748. R.P.K. is supported by the Berlin Institute of Health visiting professorship program. A.G.H. is supported by the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation)–398299703 and the Wilhelm Sander Stiftung. A.G.H. and P.E. are participants in the BIH-Charité Clinical Scientist Program funded by the Charité—Universitätsmedizin Berlin and the Berlin Institute of Health. A.G.H. and K. Helmsauer are supported by Berliner Krebsgesellschaft e.V. K. Helmsauer is supported by Boehringer Ingelheim Fonds. This work was also supported by the TransTumVar project—PN013600.Peer Reviewed"Article signat per 29 autors/es:Konstantin Helmsauer, Maria E. Valieva, Salaheddine Ali, Rocío Chamorro González, Robert Schöpflin, Claudia Röefzaad, Yi Bei, Heathcliff Dorado Garcia, Elias Rodriguez-Fos, Montserrat Puiggròs, Katharina Kasack, Kerstin Haase, Csilla Keskeny, Celine Y. Chen, Luis P. Kuschel, Philipp Euskirchen, Verena Heinrich, Michael I. Robson, Carolina Rosswog, Joern Toedling, Annabell Szymansky, Falk Hertwig, Matthias Fischer, David Torrents, Angelika Eggert, Johannes H. Schulte, Stefan Mundlos, Anton G. Henssen & Richard P. Koche"Postprint (published version