Model of fibrolamellar hepatocellular carcinomas reveals striking enrichment in cancer stem cells

The aetiology of human fibrolamellar hepatocellular carcinomas (hFL-HCCs), cancers occurring increasingly in children to young adults, is poorly understood. We present a transplantable tumour line, maintained in immune-compromised mice, and validate it as a bona fide model of hFL-HCCs by multiple methods. RNA-seq analysis confirms the presence of a fusion transcript (DNAJB1-PRKACA) characteristic of hFL-HCC tumours. The hFL-HCC tumour line is highly enriched for cancer stem cells as indicated by limited dilution tumourigenicity assays, spheroid formation and flow cytometry. Immunohistochemistry on the hFL-HCC model, with parallel studies on 27 primary hFL-HCC tumours, provides robust evidence for expression of endodermal stem cell traits. Transcriptomic analyses of the tumour line and of multiple, normal hepatic lineage stages reveal a gene signature for hFL-HCCs closely resembling that of biliary tree stem cells-newly discovered precursors for liver and pancreas. This model offers unprecedented opportunities to investigate mechanisms underlying hFL-HCCs pathogenesis and potential therapies

Visión panorámica actual del Ingeniero de Planta en el proceso de fabricación del cennento

The energy crisis and subsequent retraction of sales on the market have demanded a greater exigency in the productive aspect of cement, requiring lower production costs and making the quality of the product more appropriate to the nature of its use in construction. This article focuses on the perspectives which should be considered by the Plant Engineer in order to achieve these objectives. The importance and necessity of projecting the process to the characteristics of the end product are stressed, as well as the usefulness of an adequate knowledge of the raw materials. Other factors which could also be considered as work tools of the Plant Engineer are mentioned, always taking into consideration, however, the fact that their best use will basically depend on the criterion with which they are put to use, since each factory constitutes a different world of its own.La crisis energética y la subsecuente retracción de ventas en el mercado han demandado una mayor exigencia en el aspecto productivo del cemento, requiriéndose menores costos de producción y una mejor adecuación de la calidad del producto a las características de su empleo en obra. En este artículo se enfoca las perspectivas que debe considerar el Ingeniero de Planta para el logro de estos objetivos. Se destaca la importancia y necesidad de la proyección del proceso a las características del producto final, así como la utilidad de un conocimiento adecuado de las materias primas. Se mencionan otros factores que podrían considerarse igualmente como herramientas de trabajo para el Ingeniero de Planta, pero siempre bajo la consideración de que su mejor utilización dependerá fundamentalmente del criterio con que sean empleadas, por constituir cada fábrica un mundo diferente y particular

Buried waveguides in Nd:YLF crystals obtained by femtosecond laser writing under double line approach

In this paper, we present buried waveguides fabricated by fs laser writing in Nd3+ doped YLF crystal under double line approach (Miura et al. in Appl. Phys. Lett. 71:3329–3331, 1997). The waveguides were made by focusing two consecutive optical breakdown tracks (OBT) separated by about 20 μm. To make the optimal OBT, we focused the fs-laser pulses 200 μm below surface at intensities above the OB threshold for the material and controlled the writing speed. The guiding structures were fabricated by using a Chirped Pulse Amplification (CPA) femtosecond (fs) laser system. We chose the optimal writing parameters in order to obtain suitable waveguides, using around 3 μJ energy and writing speed from 15 to 50 μm/s. After optically exploring the waveguides by end-fire coupling, the guiding structures showed good optical performance. Guiding index profiles were retrieved from modal analysis by using BeamProp (RSoft) commercial software. This spatial distribution of the index increment, taking into account a lower refractive barrier on the OBT region plus the compressed region between the tracks, was obtained correctly fitting profiles modes. Finally, optical spectroscopy measurements were also performed in the waveguides. The results showed that the luminescence properties of Nd3+ ions are preserved in the waveguides compared with the values obtained for bulk.This work was partially supported by Agencia Nacional de Promoción Científica y Tecnólogica. (Argentina) under project PICT-2575 and CONICET (Argentina) under project PIP 0394 and by “Ministerio de Educación y Ciencia,” Spain (Grant no FIS2009-09522 and Consolider Program SAUUL CSD2007-00013). D.B. wishes to thank Comisión de Investigaciones Científicas (Bs. As., Argentina) for his student fellowship

Genetic identification of newborns in Peru: a pilot study

Objective: To determine the feasibility of genetic identification in a group of newborns from a public hospital in Lima, Peru. Material and Method: Descriptive cross-sectional study, carried out by the National Registry of Identification and Civil Status of Peru, on live newborns and their mothers, from the Carlos Lanfranco La Hoz Hospital (Puente Piedra, Lima) during January. 2015. The samples were collected in FTA (Fast Technology for Analysis of nucleic acids) cards that allowed a direct analysis by PCR (Polymerase Chain Reaction) and capillary electrophoresis of 21 STR markers (Short Tandem Repeats), including the amelogenin marker for gender determination. Results: 44 mothers and 45 newborns were included (there was a twin birth). The probability of maternity was higher than 99.9% in all cases. There were no difficulties in the sampling or in transporting the material. The obtained biological material was enough to collect DNA to identify the newborn. Conclusions: The genetic identification procedure was possible to perform in this hospital. Stages of the process that could be improved were identified for the eventual application of this procedure on a larger scale in Peru

In silico exploration of Red Sea Bacillus genomes for natural product biosynthetic gene clusters

Background: The increasing spectrum of multidrug-resistant bacteria is a major global public health concern, necessitating discovery of novel antimicrobial agents. Here, members of the genus Bacillus are investigated as a potentially attractive source of novel antibiotics due to their broad spectrum of antimicrobial activities. We specifically focus on a computational analysis of the distinctive biosynthetic potential of Bacillus paralicheniformis strains isolated from the Red Sea, an ecosystem exposed to adverse, highly saline and hot conditions. Results: We report the complete circular and annotated genomes of two Red Sea strains, B. paralicheniformis Bac48 isolated from mangrove mud and B. paralicheniformis Bac84 isolated from microbial mat collected from Rabigh Harbor Lagoon in Saudi Arabia. Comparing the genomes of B. paralicheniformis Bac48 and B. paralicheniformis Bac84 with nine publicly available complete genomes of B. licheniformis and three genomes of B. paralicheniformis, revealed that all of the B. paralicheniformis strains in this study are more enriched in nonribosomal peptides (NRPs). We further report the first computationally identified trans-acyltransferase (trans-AT) nonribosomal peptide synthetase/polyketide synthase (PKS/ NRPS) cluster in strains of this species. Conclusions:B. paralicheniformis species have more genes associated with biosynthesis of antimicrobial bioactive compounds than other previously characterized species of B. licheniformis, which suggests that these species are better potential sources for novel antibiotics. Moreover, the genome of the Red Sea strain B. paralicheniformis Bac48 is more enriched in modular PKS genes compared to B. licheniformis strains and other B. paralicheniformis strains. This may be linked to adaptations that strains surviving in the Red Sea underwent to survive in the relatively hot and saline ecosystems

Impact of Acute Kidney Injury and CKD on Adverse Outcomes in Critically Ill Septic Patients

Introduction: Chronic kidney disease (CKD) and acute kidney injury (AKI) are strongly associated with excess morbidity and mortality and frequently co-occur in critically ill septic patients, but how their interplay affects clinical outcomes is not well elucidated. Methods: We conducted a single-center, retrospective cohort study of 2632 adult patients admitted to the intensive care unit (ICU) with severe sepsis or septic shock. Subjects were classified into 6 groups according to baseline CKD (no-CKD: estimated glomerular filtration rate [eGFR] ≥60; CKD: eGFR 15−59 ml/min per 1.73 m2) and incident AKI by the Kidney Disease: Improving Global Outcomes (KDIGO) serum creatinine criteria (no-AKI, AKI stage 1, AKI stages ≥2) during ICU stay. Study outcomes were 90-day mortality (in hospital or within 90 days of discharge) and incident/progressive CKD. Results: Prevalent CKD was 46% and incident AKI was 57%. Adjusted hazard ratios (95% confidence intervals) for 90-day mortality relative to the reference group of no-CKD/no-AKI were 1.5 (1.1−2.0) in no-CKD/AKI stage 1, 2.4 (1.9−3.1) in no-CKD/AKI stages≥2, 1.1 (0.8−1.4) in CKD/no-AKI, 1.2 (0.9−1.6) in CKD/AKI stage 1, and 2.2 (1.7−2.9) in CKD/AKI stages ≥2. A similar trend was observed for incident/progressive CKD during a median follow-up of 15.3 months. Conclusion: Stage 1 AKI on CKD was not associated with an independent increased risk of adverse outcomes in critically ill septic patients. AKI stages ≥2 on CKD and any level of AKI in no-CKD patients were strongly and independently associated with adverse outcomes. Sepsis-associated stage 1 AKI on CKD may represent distinct underlying pathophysiology, with more prerenal cases and less severe de novo intrinsic damage, which needs further investigation

ENSEÑANZA EN INGENIERÍA EN ENTORNOS VIRTUALES CON ENFOQUE CONSTRUCTIVISTA, UNA REVISIÓN TEÓRICA

Hasta 2020, la mayoría de las asignaturas de ingeniería en la UNET se impartían de forma presencial. La llegada de la COVID-19 y las condiciones socioeconómicas del país exigieron la adaptación a modalidades semipresenciales y virtuales, lo que provocó un cambio en los procesos de enseñanza. En este contexto, se presenta un estudio cuyo objetivo fue analizar las tendencias en la enseñanza de la ingeniería en entornos virtuales con un enfoque constructivista. La metodología cualitativa se basó en un estudio documental, a través del análisis de contenido de publicaciones. Los resultados ofrecen planteamientos relacionados con: (a) el enfoque constructivista, que promueve el aprendizaje colaborativo entre estudiantes, el aprendizaje autónomo y autorregulado, así como estrategias como el aprendizaje por proyectos, basado en problemas reales y en estudios de caso; (b) una enseñanza en ingeniería que enfatiza el papel activo de la tutoría, la comunicación e interacción, y la evaluación continua; y, (c) entornos virtuales dinámicos que consideran herramientas tecnológicas y plataformas de aprendizaje, recursos TIC y la asincronía de actividades. Una enseñanza virtual centrada en el estudiante, con la ampliación del rol docente, la actualización de recursos y actividades, y la promoción del protagonismo del estudiante, son aspectos clave en la enseñanza en la era digital

Use of Individual-Level Covariates to Improve Latent Class Analysis of Trypanosoma Cruzi Diagnostic Tests

Statistical methods such as latent class analysis can estimate the sensitivity and specificity of diagnostic tests when no perfect reference test exists. Traditional latent class methods assume a constant disease prevalence in one or more tested populations. When the risk of disease varies in a known way, these models fail to take advantage of additional information that can be obtained by measuring risk factors at the level of the individual. We show that by incorporating complex field-based epidemiologic data, in which the disease prevalence varies as a continuous function of individual-level covariates, our model produces more accurate sensitivity and specificity estimates than previous methods. We apply this technique to several simulated populations and to actual Chagas disease test data from a community near Arequipa, Peru. Results from our model estimate that the first-line enzyme-linked immunosorbent assay has a sensitivity of 78% (95% CI: 62-100%) and a specificity of 100% (95% CI: 99-100%). The confirmatory immunofluorescence assay is estimated to be 73% sensitive (95% CI: 65-81%) and 99% specific (95% CI: 96-100%)

Safety, Feasibility, and Efficacy of Early Rehabilitation in Patients Requiring Continuous Renal Replacement: A Quality Improvement Study

Introduction: Early rehabilitation in critically ill patients is associated with improved outcomes. Recent research demonstrates that patients requiring continuous renal replacement therapy (CRRT) can safely engage in mobility. The purpose of this study was to assess safety and feasibility of early rehabilitation with focus on mobility in patients requiring CRRT. Methods: Study design was a mixed methods analysis of a quality improvement protocol. The setting was an intensive care unit (ICU) at a tertiary medical center. Safety was prospectively recorded by incidence of major adverse events including dislodgement of CRRT catheter, accidental extubation, bleeding, and hemodynamic emergency; and minor adverse events such as transient oxygen desaturation \u3e 10% of resting. Limited efficacy testing was performed to determine if rehabilitation parameters were associated with clinical outcomes. Results: A total of 67 patients (54.0 ± 15.6 years old, 44% women, body mass index 29.2 ± 9.3 kg/m2) received early rehabilitation under this protocol. The median days of CRRT were 6.0 (interquartile range [IQR], 2–11) and 72% of patients were on mechanical ventilation concomitantly with CRRT at the time of rehabilitation. A total of 112 rehabilitation sessions were performed of 152 attempts (74% completion rate). No major adverse events occurred. Patients achieving higher levels of mobility were more likely to be alive at discharge (P = 0.076). Conclusions: The provision of early rehabilitation in critically ill patients requiring CRRT is safe and feasible. Further, these preliminary results suggest that early rehabilitation with focus on mobility may improve patient outcomes in this susceptible population