Characterizing the metabolic phenotype of intestinal villus blunting in Zambian children with severe acute malnutrition and persistent diarrhea

Background: Environmental enteric dysfunction (EED) is widespread throughout the tropics and in children is associated with stunting and other adverse health outcomes. One of the hallmarks of EED is villus damage. In children with severe acute malnutrition (SAM) the severity of enteropathy is greater and short term mortality is high, but the metabolic consequences of enteropathy are unknown. Here, we characterize the urinary metabolic alterations associated with villus health, classic enteropathy biomarkers and anthropometric measurements in severely malnourished children in Zambia. Methods/Principal findings: We analysed 20 hospitalised children with acute malnutrition aged 6 to 23 months in Zambia. Small intestinal biopsies were assessed histologically (n = 15), anthropometric and gut function measurements were collected and the metabolic phenotypes were characterized by 1H nuclear magnetic resonance (NMR) spectroscopy. Endoscopy could not be performed on community controls children. Growth parameters were inversely correlated with enteropathy biomarkers (p = 0.011) and parameters of villus health were inversely correlated with translocation and permeability biomarkers (p = 0.000 and p = 0.015). Shorter villus height was associated with reduced abundance of metabolites related to gut microbial metabolism, energy and muscle metabolism (p = 0.034). Villus blunting was also related to increased sucrose excretion (p = 0.013). Conclusions/Significance: Intestinal villus blunting is associated with several metabolic perturbations in hospitalized children with severe undernutrition. Such alterations include altered muscle metabolism, reinforcing the link between EED and growth faltering, and a disruption in the biochemical exchange between the gut microbiota and host. These findings extend our understanding on the downstream consequences of villus blunting and provide novel non-invasive biomarkers of enteropathy dysfunction. The major limitations of this study are the lack of comparative control group and gut microbiota characterization

The Art of Questioning Used in CED Departmental Examination: An Analysis

Assessment plays a vital role in the development and improvement of quality education. In addition, assessment refers to anything that diagnoses the student’s learning and monitors their level of understanding. It is also considered to be the key to evaluating the effectiveness of teaching strategies (Hans, 2015). Traditionally, the most common way to measure achievement and proficiency in language learning has been the paper and pen test. However, various forms of assessment and the design of classroom tests have also undergone some changes in line with the latest development in foreign language teaching specifically the communicative language teaching method. At Rizal Technological University, the College of Education devised a departmental examination program. This program is initiated to determine the capacity of the learners to answer test-item questions patterned after the licensure examination for teachers which aims to eventually prepare them in taking the said examination. Utilizing the quantitative descriptive method, the researchers tried to analyze the levels of questions used in the Departmental Examination.  Specifically, this paper sought to identify the types of questions given in the CED departmental examination, determine the level of questions given in the CED departmental examination in terms of the Revised Blooms Taxonomy and Webb’s Depth Knowledge (DOK) model and evaluate the overall distribution of cognitive rigor present in the CED departmental examination

Optimally Sorting Evolving Data

We give optimal sorting algorithms in the evolving data framework, where an algorithm\u27s input data is changing while the algorithm is executing. In this framework, instead of producing a final output, an algorithm attempts to maintain an output close to the correct output for the current state of the data, repeatedly updating its best estimate of a correct output over time. We show that a simple repeated insertion-sort algorithm can maintain an O(n) Kendall tau distance, with high probability, between a maintained list and an underlying total order of n items in an evolving data model where each comparison is followed by a swap between a random consecutive pair of items in the underlying total order. This result is asymptotically optimal, since there is an Omega(n) lower bound for Kendall tau distance for this problem. Our result closes the gap between this lower bound and the previous best algorithm for this problem, which maintains a Kendall tau distance of O(n log log n) with high probability. It also confirms previous experimental results that suggested that insertion sort tends to perform better than quicksort in practice

BRP-187: A potent inhibitor of leukotriene biosynthesis that acts through impeding the dynamic 5-lipoxygenase/5-lipoxygenase-activating protein (FLAP) complex assembly

The pro-inflammatory leukotrienes (LTs) are formed from arachidonic acid (AA) in activated leukocytes, where 5-lipoxygenase (5-LO) translocates to the nuclear envelope to assemble a functional complex with the integral nuclear membrane protein 5-LO-activating protein (FLAP). FLAP, a MAPEG family member, facilitates AA transfer to 5-LO for efficient conversion, and LT biosynthesis critically depends on FLAP. Here we show that the novel LT biosynthesis inhibitor BRP-187 prevents the 5-LO/FLAP interaction at the nuclear envelope of human leukocytes without blocking 5-LO nuclear redistribution. BRP-187 inhibited 5-LO product formation in human monocytes and polymorphonuclear leukocytes stimulated by lipopolysaccharide plus N-formyl-methionyl-leucyl-phenylalanine (IC50=7-10nM), and upon activation by ionophore A23187 (IC50=10-60nM). Excess of exogenous AA markedly impaired the potency of BRP-187. Direct 5-LO inhibition in cell-free assays was evident only at >35-fold higher concentrations, which was reversible and not improved under reducing conditions. BRP-187 prevented A23187-induced 5-LO/FLAP complex assembly in leukocytes but failed to block 5-LO nuclear translocation, features that were shared with the FLAP inhibitor MK886. Whereas AA release, cyclooxygenases and related LOs were unaffected, BRP-187 also potently inhibited microsomal prostaglandin E2 synthase-1 (IC50=0.2μM), another MAPEG member. In vivo, BRP-187 (10mg/kg) exhibited significant effectiveness in zymosan-induced murine peritonitis, suppressing LT levels in peritoneal exudates as well as vascular permeability and neutrophil infiltration. Together, BRP-187 potently inhibits LT biosynthesis in vitro and in vivo, which seemingly is caused by preventing the 5-LO/FLAP complex assembly and warrants further preclinical evaluation

Experiences of Justice-Involved People Transitioning to HIV Care in the Community After Prison Release in Lusaka, Zambia: A Qualitative Study

Introduction: In sub-Saharan Africa (SSA), incarcerated people experience a higher HIV burden than the general population. While access to HIV care and treatment for incarcerated people living with HIV (PLHIV) in SSA has improved in some cases, little is known about their transition to and post-release experience with care in the community. To address this gap, we conducted a qualitative study to describe factors that may influence post-release HIV care continuity in Zambia. Methods: In March-December 2018, we recruited study participants from a larger prospective cohort study following incarcerated and newly released PLHIV at 5 correctional facilities in 2 provinces in Zambia. We interviewed 50 participants immediately before release; 27 (54%) participated in a second interview approximately 6 months post-release. Demographic and psychosocial data were collected through a structured survey. Results: The pre-release setting was strongly influenced by the highly structured prison environment and assumptions about life post-release. Participants reported accessible HIV services, a destigmatizing environment, and strong informal social supports built through comradery among people facing the same trying detention conditions. Contrary to their pre-release expectations, during the immediate post-release period, participants struggled to negotiate the health system while dealing with unexpected stressors. Long-term engagement in HIV care was possible for participants with strong family support and a high level of self-efficacy. Conclusion: Our study highlights that recently released PLHIV in Zambia face acute challenges in meeting their basic subsistence needs, as well as social isolation, which can derail linkage to and retention in community HIV care. Releasees are unprepared to face these challenges due to a lack of community support services. To improve HIV care continuity in this population, new transitional care models are needed that develop client self-efficacy, facilitate health system navigation, and pragmatically address structural and psychosocial barriers like poverty, gender inequality, and substance use

The future is distributed: a vision of sustainable economies

“The Future is distributed: a vision of sustainable economies” is a collection of case studies on distributed economies, a concept describing sustainable alternatives to the existing business models. The authors of this publication are international Masters students of the Environmental Sciences, Policy and Management Programme at the International Institute for Industrial Environmental Economics at Lund University in Sweden. The aim of their work is to demonstrate that local, small-scale, community-based economies are not just part of the theory, but have already been implemented in various sectors and geographical settings

Strategy for tumor selective disruption of androgen receptor function in the spectrum of prostate cancer

Purpose: Testosterone suppression in prostate cancer (PC) is limited by serious side effects and resistance via restoration of androgen receptor (AR) functionality. ELK1 is required for ARdependent growth in various hormone-dependent and castration resistant PC models. The amino terminal domain of AR docks at two sites on ELK1 to co-activate essential growth genes. This study explores the ability of small molecules to disrupt the ELK1-AR interaction in the spectrum of PC, inhibiting AR activity in a manner that would predict functional tumor selectivity. Experimental design: Small molecule drug discovery and extensive biological characterization of a lead compound. Results: We have discovered a lead molecule (KCI807) that selectively disrupts ELK1-dependent promoter activation by wild-type and variant ARs without interfering with ELK1 activation by ERK. KCI807 has an obligatory flavone scaffold and functional hydroxyl groups on C5 and C3'. KCI807 binds to AR, blocking ELK1 binding, and selectively blocks recruitment of AR to chromatin by ELK1. KCI807 primarily affects a subset of AR target growth genes selectively suppressing AR-dependent growth of PC cell lines with a better inhibitory profile than enzalutamide. KCI807 also inhibits in vivo growth of castration/enzalutamide-resistant cell line-derived and patient-derived tumor xenografts. In the rodent model, KCI807 has a plasma half-life of 6h and maintenance of its antitumor effect is limited by self-induced metabolism at its 3'-hydroxyl. Conclusions: The results offer a mechanism-based therapeutic paradigm for disrupting the AR growth-promoting axis in the spectrum of prostate tumors while reducing global suppression of testosterone actions. KCI807 offers a good lead molecule for drug development

Inflammation and epithelial repair predict mortality, hospital readmission, and growth recovery in complicated severe acute malnutrition.

Severe acute malnutrition (SAM) is the most high-risk form of undernutrition, particularly when children require hospitalization for complications. Complicated SAM is a multisystem disease with high inpatient and postdischarge mortality, especially in children with comorbidities such as HIV; however, the underlying pathogenesis of complicated SAM is poorly understood. Targeted multiplex biomarker analysis in children hospitalized with SAM (n = 264) was conducted on plasma samples, and inflammatory markers were assessed on stool samples taken at recruitment, discharge, and 12 to 24 and 48 weeks after discharge from three hospitals in Zimbabwe and Zambia. Compared with adequately nourished controls (n = 173), we found that at baseline, complicated SAM was characterized by systemic, endothelial, and intestinal inflammation, which was exacerbated by HIV infection. This persisted over 48 weeks despite nutritional recovery and was associated with children's outcomes. Baseline plasma concentrations of vascular endothelial growth factor, glucagon-like peptide-2, and intestinal fatty acid-binding protein were independently associated with lower mortality or hospital readmission over the following 48 weeks. Following principal components analysis of baseline biomarkers, higher scores of a component representing growth factors was associated with greater weight-for-height z score recovery and lower mortality or hospital readmission over the 48 weeks. Conversely, components representing higher gut and systemic inflammation were associated with higher mortality or hospital readmission. These findings highlight the interplay between inflammation, which damages tissues, and growth factors, which mediate endothelial and epithelial regeneration, and support further studies investigating interventions to reduce inflammation and promote epithelial repair as an approach to reducing mortality and improving nutritional recovery

Evaluation activities performance of the specific instrumental transversal competence in subjects of the mechanical engineering area

[Otros] Nowadays, the European higher education space is concerned, not only about the transmission of theoretical knowledge, but also about the acquisition of soft-skills, which are increasingly demanded in the professional profiles of graduates. Therefore, the Universitat Politècnica de València (UPV) has elaborated its own program aiming to develop these generic capabilities, which are embedded in 13 Transversal Competences (CT in Spanish). All of them are worked on and evaluated in all UPV degrees, whether undergraduate or graduate. Specifically, the "Specific Instrumental" transversal competence has been working for two years by a team of lecturers from the Department of Mechanical and Materials Engineering (DIMM in Spanish). Their objective is to develop an effective methodology to work on the acquisition and evaluation of this competence. The tool chosen to work with is ANSYS®, which is widely used in the field of mechanical engineering. This commercial software provides numerical solutions to complex problems using the Finite Element Method (FEM). The proposed methodology has been implemented during this year in three different subjects with a total of 335 students and is based on previous experience carried out in small groups last year. The objective is also to consolidate a procedure suitable for large groups without increasing lecturer's dedication time. After analysing the characteristics that were not entirely satisfactory, the new proposal seeks to improve them while maintaining the correct actions of the previous experience. Thus, laboratory training sessions and a different timed exercise for each student are kept. The most important changes affect the distribution of the worktime of the student and the assessable exercises. The number of evaluable exercises has been reduced to one, as well as the content and the test score. The proposed exercise consists of modelling a mechanical component and carrying out several tasks related to the mechanical study of a component. The correct completion of the different sections allows a numerical evaluation of the laboratory sessions and the suitability of the methodology. At the same time, the justification of the steps followed, and the adequacy of the strategies followed give the level reached in the ¿Specific Instrumental¿ transversal competence. The results reveal that students have achieved a greater degree of autonomy in managing the software. Furthermore, the new evaluation system discriminates the mastery with greater rigor, in the past there were no intermediate marks, the capability was achieved or not. Additionally, all the practical sessions have been adapted to the sanitary situation following an online format. This adaptation to the COVID scenario has provided the opportunity to introduce changes in the lecturing material that will be maintained in the next courses.Authors gratefully acknowledge the financial support of the Vicerrectorado de Estudios, Calidad y Acreditación, the Vicerrectorado de Recursos Digitales y Documentación of the Universitat Politècnica de València (Project PIME B/19-20/165 and Project PIME C/20-21/201) and the Instituto de Ciencias de la Educación of the Universitat Politècnica de València (EICE INTEGRAL).Pedrosa, AM.; Lozano-Mínguez, E.; Besa Gonzálvez, AJ.; Vila Tortosa, MP.; Martinez-Sanchis, S.; Sánchez Orgaz, EM. (2021). Evaluation activities performance of the specific instrumental transversal competence in subjects of the mechanical engineering area. IATED Academy. 4347-4354. https://doi.org/10.21125/edulearn.2021.0915S4347435

Propuesta metodológica para la evaluación de competencias transversales en el Máster en Ingeniería Mecánica de la Universitat Politècnica de València

[ES] En esta comunicación se presentan los trabajos desarrollados en el marco de un proyecto de innovación y mejora educativa llevado a cabo durante los dos últimos cursos en el Máster Universitario en Ingeniería Mecánica de la Universitat Politècnica de València. Uno de los principales objetivos de este proyecto es el desarrollo y puesta en marcha de nuevas metodologías para la evaluación de competencias transversales. Entre estas nuevas metodologías está una aproximación mediante el aprendizaje basado en proyectos, que permite incorporar la evaluación de algunas competencias transversales que no se hacía de forma adecuada con anterioridad. En esta línea se han coordinado varias asignaturas, se ha planteado un nuevo tipo de Trabajo Fin de Máster, con la colaboración de una empresa, y se han diseñado nuevas herramientas de evaluación.[EN] This contribution presents the work carried out within the framework of an educational innovation and improvement project developed during the last two years in the Master's Degree in Mechanical Engineering at the Technical University of Valencia. One of the main objectives of this project is the development and implementation of new methodologies for the evaluation of generic competences. Among these new methodologies, there is an approach through projectbased learning, which allows for the incorporation of the assessment of some generic competences that was not done previously in a proper way. Therefore, several subjects have been coordinated, a new type of Master’s Thesis has been proposed, with the collaboration of a company, and new assessment tools have been designedCarballeira, J.; Tur, M.; Besa, AJ.; Albelda J.; Tarancón, JE.; Martínez-Casas, J.; Denia, FD.... (2021). Propuesta metodológica para la evaluación de competencias transversales en el Máster en Ingeniería Mecánica de la Universitat Politècnica de València. En IN-RED 2020: VI Congreso de Innovación Educativa y Docencia en Red. Editorial Universitat Politècnica de València. 11332-1138. https://doi.org/10.4995/INRED2020.2020.11998OCS11332113