Influence of chitosan protonation degree in nanofibrillated cellulose/chitosan composite films and their morphological, mechanical, and surface properties.

Composite films of nanofibrillated cellulose (NFC) and chitosan (CS) were prepared by spray deposition method, and the influence of polymers ratio and protonation degree (α) of chitosan was evaluated. Films were characterized using morphological, mechanical, and surface techniques. Higher NFC content increased Young's modulus of film composites and reduced air permeability, while higher CS content increased water contact angle. Variations in the degree of protonation of chitosan from non-protonated (α = 0) to fully protonated (α = 1) in the NFC/CS composite film with a fixed composition allowed to modulate surface, mechanical, and structural properties, such as water contact angle (31.3-109.2°), Young's modulus (1.7-5.3 GPa), elongation at break (3.1-1.2 %), oxygen transmission rate (9.0-5.5 cm3/m2day) and air permeability (2074-426 s). Highly protonated chitosan composite films showed similar contact angles to pure chitosan films, while low protonated chitosan composite films presented contact angles similar to pure NFC films, suggesting a possible coating effect of NFC by CS through electrostatic interactions, evidenced by microscopy and spectroscopy analysis. By mixing both polymers and adjusting composition and protonation degree it was possible to enhance their properties, making pH adjustment a useful tool for NFC/CS composite films formation.

Structural mechanisms of autoinhibition and substrate recognition by the ubiquitin ligase HACE1.

Ubiquitin ligases (E3s) are pivotal specificity determinants in the ubiquitin system by selecting substrates and decorating them with distinct ubiquitin signals. However, structure determination of the underlying, specific E3-substrate complexes has proven challenging owing to their transient nature. In particular, it is incompletely understood how members of the catalytic cysteine-driven class of HECT-type ligases (HECTs) position substrate proteins for modification. Here, we report a cryogenic electron microscopy (cryo-EM) structure of the full-length human HECT HACE1, along with solution-based conformational analyses by small-angle X-ray scattering and hydrogen-deuterium exchange mass spectrometry. Structure-based functional analyses in vitro and in cells reveal that the activity of HACE1 is stringently regulated by dimerization-induced autoinhibition. The inhibition occurs at the first step of the catalytic cycle and is thus substrate-independent. We use mechanism-based chemical crosslinking to reconstitute a complex of activated, monomeric HACE1 with its major substrate, RAC1, determine its structure by cryo-EM and validate the binding mode by solution-based analyses. Our findings explain how HACE1 achieves selectivity in ubiquitinating the active, GTP-loaded state of RAC1 and establish a framework for interpreting mutational alterations of the HACE1-RAC1 interplay in disease. More broadly, this work illuminates central unexplored aspects in the architecture, conformational dynamics, regulation and specificity of full-length HECTs.

Non-alcoholic fatty liver disease and diabetes mellitus as growing aetiologies of hepatocellular carcinoma.

Obesity-related complications such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D) are well-established risk factors for the development of hepatocellular carcinoma (HCC). This review provides insights into the molecular mechanisms that underlie the role of steatosis, hyperinsulinemia and hepatic inflammation in HCC development and progression. We focus on recent findings linking intracellular pathways and transcription factors that can trigger the reprogramming of hepatic cells. In addition, we highlight the role of enzymes in dysregulated metabolic activity and consequent dysfunctional signalling. Finally, we discuss the potential uses and challenges of novel therapeutic strategies to prevent and treat NAFLD/T2D-associated HCC.

Physics-based tissue simulator to model multicellular systems: A study of liver regeneration and hepatocellular carcinoma recurrence.

We present a multiagent-based model that captures the interactions between different types of cells with their microenvironment, and enables the analysis of the emergent global behavior during tissue regeneration and tumor development. Using this model, we are able to reproduce the temporal dynamics of regular healthy cells and cancer cells, as well as the evolution of their three-dimensional spatial distributions. By tuning the system with the characteristics of the individual patients, our model reproduces a variety of spatial patterns of tissue regeneration and tumor growth, resembling those found in clinical imaging or biopsies. In order to calibrate and validate our model we study the process of liver regeneration after surgical hepatectomy in different degrees. In the clinical context, our model is able to predict the recurrence of a hepatocellular carcinoma after a 70% partial hepatectomy. The outcomes of our simulations are in agreement with experimental and clinical observations. By fitting the model parameters to specific patient factors, it might well become a useful platform for hypotheses testing in treatments protocols.

New challenges in cholangiocarcinoma candidates for elective surgery: harnessing the microbiome dysbiosis.

BACKGROUND: The gut microbiota, composed by several species of microorganisms, works to preserve the liver-gut homeostasis and plays an important role during digestion and absorption of nutrients, and in the immune response of the host. In this review, we analyzed the influence of microbiota in patients with cholangiocarcinoma (CCA) who were candidates for elective surgery. METHODS: A literature review was conducted to identify papers that provided empiric evidence to support that the altered microbiota composition (dysbiosis) is related also to CCA development. RESULTS: Bacteria such as Helicobacter pylori, Helicobacter hepaticus, and Opisthorchis viverrini increase the risk of CCA. The most abundant genera were Enterococcus, Streptococcus, Bacteroides, Klebsiella, and Pyramidobacter in CCA's biliary microbiota. Additionally, levels of Bacteroides, Geobacillus, Meiothermus, and Anoxybacillus genera were significantly higher. An enrichment of Bifidobacteriaceae, Enterobacteriaceae, and Enterococcaceae families has also been observed in CCA tumor tissue. Microbiota is related to postoperative outcomes in abdominal surgery. The combination of caloric restriction diets in liver cancer or CCA increases the effect of the chemotherapy treatment. CONCLUSION: The correct use of nutrition for microbiota modulation according to each patient's needs could be a therapeutic tool in combination with elective surgery and chemotherapy to diminish side effects and improve prognosis. Further investigations are needed to fully understand the mechanisms by which they are related.

Evaluation of sampling frequency impact on the accuracy of water quality status as determined considering different water quality monitoring objectives.

Water quality sampling is a key element in tracking water quality monitoring objectives. However, frequencies adapted by different agencies might not be sufficient to provide an accurate indication of water quality status. In this study, data from low- and high-resolution water quality datasets were analyzed to determine the extent to which monitoring objectives could be achieved with different sampling frequencies, with a view to providing recommendations and best practices for water quality monitoring frequency in places with limited resources with which to implement a high-frequency monitoring plan. Water quality data from two watersheds (Maumee River and Raisin River) located in the Western Lake Erie Basin (WLEB) were used since these watersheds have consistent records over substantial periods of time, and the water quality data available have a high resolution (at least daily). The water quality constituents analyzed included suspended solids (SS), total phosphorus (TP), soluble reactive phosphorus (SRP), and nitrate + nitrite (NO2+3). Sources of pollutants for watersheds located in the WLEB include contributions from point sources like discharges from sewage treatment plants and non-point sources such as agricultural and urban storm runoff. Weekly, bi-weekly, monthly, and seasonal datasets were created from the original datasets, following different sampling rules based on the day of the week, week of the month, and month of the year. The resulting datasets were then compared to the original dataset to determine how the sampling frequency would affect the results obtained in a water quality assessment when different monitoring objectives are considered. Results indicated that constituents easily transported by water (such as sediments and nutrients) require more than 50 samples/year to provide a small error (< 10%) with a confidence interval of 95%. Monthly and seasonal sampling were found appropriate to report a stream's prevailing water quality status and statistical properties. However, these resolutions might not be sufficient to capture long-term trends, in which case bi-weekly samples would be preferable. Limitations of low-resolution sampling frequency could be overcome by including rainfall events and random sampling during specific time windows as part of the monitoring plan.

Unilateral and Bilateral Post-Activation Performance Enhancement on Jump Performance and Agility.

This study aimed to compare the effects of the post-activation performance enhancement (PAPE) of two different types of warm-ups, unilateral and bilateral, on the performance in vertical jumping and agility of healthy subjects with strength training experience. In the study, 17 subjects (12 men and 5 women) performed two different PAPE protocols: unilateral squat (UT) and bilateral squat (BT). The height of the subjects' countermovement jump (CMJ) and the subjects' time to perform the T-agility test (TAT) were measured before and after executing the PAPE warm-up. The squats were performed at a velocity of 0.59 m·s-1 with three sets of three repetitions, with a 3-min rest between sets and a 5-min rest after both uni- and bilateral PAPE warm-ups before taking the tests again. For statistical analysis, we applied ANOVA and calculated the effect size. The results showed that the PAPE for each case decreased the CMJ height but generated significant improvements in the total time taken for the T-agility test (p < 0.01); however, in both cases, the effect sizes were trivial. In conclusion, it is possible to observe that the PAPE, performed both unilaterally and bilaterally, negatively affects the performance in the vertical jump, showing moderate effect sizes. However, both PAPE protocols show performance benefits in agility tests, with a large effect size for the unilateral protocol and moderate for the bilateral protocol.

Performance evaluation of ceramic pot filters combined with adsorption processes for the removal of heavy metals and phenolic compounds.

It has been demonstrated that the ceramic pot filters (CPFs) with impregnated colloidal silver are efficient for the removal of turbidity and pathogens for household water treatment. This investigation evaluated the efficiency of two filter models for the removal of chemical contaminants (Hg, Pb, As and phenolic compounds) during 175 days. The first model is a traditional CPF impregnated with colloidal silver and the second consists of the ceramic silver-impregnated pot plus a post-filtration column with granular activated carbon and zeolite (CPF + GAC-Z). The results of the CPF showed average efficiencies of 91.5% (Hg), 92% (Pb), 50.2% (As) and 78.7% (phenols). The CPF + GAC-Z showed similar efficiencies for the removal of heavy metals (92.5% Hg, 98.1% Pb and 52.3% As) and a considerably higher efficiency for the removal of phenols (96.4%). The As concentration of the filtered water in both systems was higher than the regulatory limit. The ceramic pot was responsible for the highest removal of chemical compounds. It can be concluded that the traditional CPF is a viable option for water supply treatment at the household level for the removal of chemical contaminants. The efficiency of this filter can be improved with the post-filtration column mainly for the removal of organic constituents.

A Computational Investigation of In Vivo Cytosolic Protein Delivery for Cancer Therapy.

The ability to specifically block or degrade cytosolic targets using therapeutic proteins would bring tremendous therapeutic opportunities in cancer therapy. Over the last few years, significant progress has been made with respect to tissue targeting, cytosolic delivery, and catalytic inactivation of targets, placing this aim within reach. Here, we developed a mathematical model specifically built for the evaluation of approaches towards cytosolic protein delivery, involving all steps from systemic administration to translocation into the cytosol and target engagement. Focusing on solid cancer tissues, we utilized the model to investigate the effects of microvascular permeability, receptor affinity, the cellular density of targeted receptors, as well as the mode of activity (blocking/degradation) on therapeutic potential. Our analyses provide guidance for the rational optimization of protein design for enhanced activity and highlight the importance of tuning the receptor affinity as a function of receptor density as well as the receptor internalization rate. Furthermore, we provide quantitative insights into how enzymatic cargoes can enhance the distribution, extent, and duration of therapeutic activity, already at very low catalytic rates. Our results illustrate that with current protein engineering approaches, the goal of delivery of cytosolic delivery of proteins for therapeutic effects is well within reach.

Determinación de actividades profesionales confiables en una escuela de medicina en Chile / Determination of entrustable professional activities at a school of medicine in Chile

Introducción: La concepción actual de competencia considera que son habilidades complejas que los estudiantes desarrollarán durante su formación, lo que no necesariamente se traduce en una acción laboral concreta y genera incertidumbre en la enseñanza, el aprendizaje y la evaluación. Las actividades profesionales confiables (APROC) se definen como una unidad de práctica profesional que se puede confiar plenamente a un aprendiz, tan pronto como él o ella haya demostrado la competencia necesaria para ejecutar esta actividad con niveles crecientes de autonomía. Objetivo:Determinar las APROC que los médicos generales formados en la Universidad Diego Portales deben ejecutar al finalizar su formación. Sujetos y métodos:Se usó un enfoque cualitativo. La población considerada fueron internos de medicina, tutores clínicos y titulados. Se efectuaron 10 entrevistas semiestructuradas a docentes y titulados, y un grupo focal con internos de medicina. Se realizó un análisis comparativo constante hasta determinar las categorías axiales. Resultados:Las APROC resultantes fueron las siguientes: realizar atención clínica, manejar pacientes con urgencias médicas, efectuar acciones clínicas de prevención y promoción, ejecutar procedimientos médicos diagnósticos y terapéuticos necesarios en la atención clínica, y articular los recursos involucrados en la atención del paciente. Conclusiones:Las APROC identificadas muestran diferencias con las descritas internacionalmente para la educación médica de pregrado. El marco de las APROC permitirá dar un sustento mayor a las actividades de evaluación del aprendizaje en la carrera de medicina de la universidad, y disminuir la incertidumbre en la enseñanza y el aprendizaje.(AU)

Introduction: The current conception of competence considers them as complex skills that students will develop during their training, which does not necessarily translate into a concrete work action, generating uncertainty in teaching, learning and evaluation. Entrustable professional activities (EPAs) are defined as a unit of professional practice that can be fully entrusted to an apprentice, as soon as he or she has demonstrated the necessary competence to carry out this activity with increasing levels of autonomy. Aim:To determine the EPAs that general practitioners trained in the Diego Portales University should carry out at the end of their academic training. Subjects and methods:A qualitative approach was used, the population included were medical interns, clinical tutors and alumni. Ten semi-structured interviews with teachers and alumni, and one focus group with medical interns. Comparative-constant analysis was performed until the axial categories were determined. Results:The resulting EPAs were the following: to perform clinical care; to manage patients with medical emergencies; to carry out clinical prevention and promotion actions; to execute the necessary diagnostic and therapeutic medical procedures in clinical care; and to articulate the resources involved in patient care. Conclusion:The herein identified EPAs showed differences with those described internationally for undergraduate medical education. The framework of these EPAs will allow to give a greater support to the activities of evaluation of the learning in the medical career of the university, diminishing the uncertainty in the teaching and learning.(AU)

Re-imagining environmental governance: Gold dredge mining vs Territorial Health in the Colombian Amazon.

This article describes and analyses an encounter in the Colombian Amazon between Indigenous practices and arrangements to manage their environment and the conservation policies of the State. Indigenous peoples understand their world as populated by powerful human and nonhuman beings; for them, the moral duty of achieving happiness and abundance for all implies sustaining reciprocal and respectful relations with these beings (including the State). In contrast Colombian environmental policy distinguishes between nature and culture, seeking to safeguard landscapes from human interference so that natural processes can unfold unhindered. In practice these partially connected, yet incommensurable worldviews make for a 'perfect storm' - opening opportunities for illegal mining. Drawing on recent fieldwork among the Andoke, an ethnic group well acquainted with extractivism in its different historical modalities and presently affronting the fallout of gold dredge mining we narrate how a parallel, non-state governance system makes it difficult for them to care for their land and entertain mutual and respectful relations with human and nonhuman beings (which we translate as 'territorial health'). We conclude by arguing for the need to re-imagine environmental governance in ways that more closely engage with what we call pluriversal governance: a form of (environmental) governance that does ontological justice to those involved in the environmental conflict - including, crucially, Indigenous people.

Intelligent Telehealth System To Support Epilepsy Diagnosis.

BACKGROUND: Availability and opportunity of epilepsy diagnostic services is a significant challenge, especially in developing countries with a low number of neurologists. The most commonly used test to diagnose epilepsy is electroencephalogram (EEG). A typical EEG recording lasts for 20 to 30 minutes; however, a specialist requires much more time to read it. Furthermore, no evidence was found in the literature on open-source systems for the cost-effective management of patient information using electronic health records (EHR) that adequately integrate EEG analysis for automatic identification of abnormal signals. OBJECTIVE: To develop an integrated open-source EHR system for the management of the patients' personal, clinical, and EEG data, and for automatic identification of abnormal EEG signals. METHODS: The core of the system is an EHR and telehealth service based on the OpenMRS platform. On top of that, we developed an intelligent component to automatically detect abnormal segments of EEG tests using machine learning algorithms, as well as a service to annotate and visualize abnormal segments in EEG signals. Finally, we evaluated the intelligent component and the integrated system using precision, recall, and accuracy metrics. RESULTS: The system allowed to manage patients' information properly, store and manage the EEG tests recorded with a medical EEG device, and to detect abnormal segments of signals with a precision of 85.10%, a recall of 97.16%, and an accuracy of 99.92%. CONCLUSION: Digital health is a multidisciplinary field of research in which artificial intelligence is playing a significant role in boosting traditional health services. Notably, the developed system could significantly reduce the time a neurologist spends in the reading of an EEG for the diagnosis of epilepsy, saving approximately 65-75% of the time consumed. It can be used in a telehealth environment. In this way, the availability and provision of diagnostic services for epilepsy management could be improved, especially in developing countries where the number of neurologists is low.

Vitamin D and other environmental risk factors in Colombian patients with multiple sclerosis.

OBJECTIVE: The aim of this study was to explore the association between MS and vitamin D levels, as well as Epstein-Barr virus (EBV) seropositivity and smoking history in a Colombian population. METHODS: We conducted a cross-sectional study between 2017 and 2018. We measured vitamin D levels and EBV antibody titers and administered a questionnaire to assess dietary habits, smoking, second-hand smoking and duration of smoking, sunlight exposure, physical activity, and personal and family history in individuals with and without multiple sclerosis during adolescence. A multivariable logistic regression model was then performed to explore the association between vitamin D status and MS. RESULTS: A total of 87 individuals with MS (mean age 40.9 years; 65.52% females) and 87 without MS (mean age 55 years; 65.52% females) were included in the analysis. In the multivariable analysis, after controlling for supplementation vitamin D levels did not differ between both groups and no difference was found regarding tobacco smoke exposure. The proportion of individuals who tested positive for anti-EBV nuclear antigen was significantly higher in individuals with MS (95.4% vs 82.76%, p = 0.028) CONCLUSION: : We did not find a statistically significant association between MS and vitamin D levels while anti-EBV nuclear antigen titers behaved as previously described in the literature. This study provides new evidence of the association between MS and different risk factors in our country, reinforcing the hypothesis that the pathogenesis of MS is multifactorial. Further studies are needed to better define the association between environmental factors and the development of MS in low prevalence areas.

Entrustable Professional Activities: Una propuesta innovadora para la evaluación de competencias médicas / Entrustable professional activities: a new proposal for the evaluation of the medical competencies

Medical education migrated from a practice-based to a knowledge-based discipline after the publication of the Flexner Report. The emergence of competence-based medical education led to a greater standardization of teaching, allowing students to integrate knowledge, skills and attitudes for the execution of a given task. A challenge is the evaluation of learning. Complex evaluation systems and a consequent atomization that independently assesses different competence components. However, the evaluation carried out at the clinical practice sites allows assessing the overall level of learning. Supervisors observe students' performance and decide if the apprentice can execute a specific task independently. This decision is based upon the trust that the tutor places on the student. Consequently, Ten Cate (2005) proposed the term Entrustable Professional Activities (EPAs), as a framework for professional practice tasks or responsibilities that can be fully entrusted to students, when they demonstrate the competences that are necessary to execute such activity with an increasing level of autonomy.

Hemangioma gástrico neonatal. Reporte de un caso y revisión de la literatura / Neonatal gastric hemangioma. Literature review and a case report

Resumen Los hemangiomas son las neoplasias más comunes en la infancia; incluyen diferentes tipos según su histología, expresión proteica y curso clínico. Por lo general, aparecen en piel y tejidos blandos. Son lesiones raras a nivel intestinal, y más aún en un recién nacido; por ello, decidimos publicar un caso que ocurrió en nuestro hospital y el manejo que se le dio; revisamos la literatura.

Abstract The most common neoplastic lesions in the infancy are hemangiomas; they are classified according to their histology, proteic expression, and clinical presentation. They normally appear in the skin and soft tissue. They are very rare in the viscera, in the stomach, and in neonates they are even more unusual; this is the reason why we decided to review the literature and present this case.

[Entrustable professional activities: a new proposal for the evaluation of the medical competencies]. / Entrustable Professional Activities: Una propuesta innovadora para la evaluación de competencias médicas.

Medical education migrated from a practice-based to a knowledge-based discipline after the publication of the Flexner Report. The emergence of competence-based medical education led to a greater standardization of teaching, allowing students to integrate knowledge, skills and attitudes for the execution of a given task. A challenge is the evaluation of learning. Complex evaluation systems and a consequent atomization that independently assesses different competence components. However, the evaluation carried out at the clinical practice sites allows assessing the overall level of learning. Supervisors observe students' performance and decide if the apprentice can execute a specific task independently. This decision is based upon the trust that the tutor places on the student. Consequently, Ten Cate (2005) proposed the term Entrustable Professional Activities (EPAs), as a framework for professional practice tasks or responsibilities that can be fully entrusted to students, when they demonstrate the competences that are necessary to execute such activity with an increasing level of autonomy.

Hígado graso no alcohólico y diabetes / Non-alcoholic fatty liver disease and diabetes

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Calidad de vida en pacientes chilenas sobrevivientes de cáncer de mama / Quality of life in Chilean breast cancer survivors

Background: Quality of Life (QOL) assessment may evaluate the impact of diseases and their treatment on the overall well-being of patients. Aim: To assess QOL in Chilean breast cancer survivors. Patients and Methods: Ninety one female breast cancer patients aged 60 ± 10 years, who finished their oncologic treatment at least a year prior to the assessment, who were disease free and in medical follow-up were included in the study. They completed the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 core questionnaire and the breast cancer module QLQ-BR23. Results: Forty eight percent of respondents were long term survivors (more than five years). Global QOL scores were high (73.6 ± 18.2), emotional scale had the lowest scores in QLQ-C30 functional scales (72.1). Symptoms with the highest scores were: Insomnia (= 21.2), pain (= 20.8), and fatigue (= 19.1). Body image, sexual function, and concern about the future were the most relevant problems. Body image was superior in patients with breast-conserving surgery (p = 0.008), and cognitive function was better in patients in early disease stage (p = 0.03) and in those with more than five years of survival (p = 0.04). Conclusions: Even when global QOL scores were high, some symptoms were prevalent. Awareness about these problems and symptoms should improve their diagnosis and treatment.