X-ray radiation dose and associated factors in neonates from the newborn unit of Hospital Universitario San Ignacio, Bogotá, Colombia / Dosis de radiación por radiografías y factores asociados en neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia.

Introduction: Radiographs are still widely used, underestimating the risks. This situation is frequent in neonatal care units, generating radiation doses than in adults. Objective: To quantify the received radiation doses when performing radiographs on neonates and the possible factors associated with higher doses. Materials and methods: We performed an observational study of 160 neonates from the newborn unit of the Hospital Universitario San Ignacio, Bogotá, Colombia. We considered the input dose of each radiograph as the dependent variable. Patients were characterized and a multivariate analysis with multiple linear regression was performed to identify associated factors. Results: We analyzed 160 newborns and 492 radiographs. The most frequent findings were male patients (n=87, 54.4%), cesarean delivery (n=122, 76.3%), and radiograph indication for respiratory distress (n=123, 24.9%). One-point eight percent of the patients (n=9) did not have radiograph indication. The most frequently taken radiograph was chest (322, 65.4%). Most radiographs were taken with a computerized equipment (n=352, 71.5%), compared to a digital one (n=140, 28.4%). The median input dose with computerized equipment was 0.112 mGy (0.022, 0.134 mGy), and with the digital equipment was 0.020 mGy (0.019, 0.022 mGy). Conclusions: The general and specific absorbed radiation doses were measured in neonates with a computerized and a digital equipment. We identified higher doses with the computerized equipment. In addition, it was recognized the correlation between computerized radiography equipment with lower corrected gestational ages as the main factor for dose increase.

Introducción: Las radiografías continúan usándose ampliamente, subestimando los riesgos. Esto sucede, especialmente, en las unidades de cuidado neonatal, lo que implica que los neonatos reciben una dosis de radiación ionizante mayor que los adultos. Objetivo: Cuantificar las dosis de radiación recibidas al tomar radiografías y evaluar los posibles factores asociados con el aumento de la dosis. Materiales y métodos: Se llevó a cabo un estudio observacional de 160 neonatos de la Unidad de Recién Nacidos del Hospital Universitario San Ignacio, Bogotá, Colombia. Se consideró como variable dependiente la dosis de entrada en piel por cada radiografía. Se hizo la caracterización de los pacientes, seguida de un análisis multivariado con regresión lineal múltiple para identificar factores asociados. Resultados: Se analizaron 160 pacientes y 492 radiografías en total. Entre los hallazgos más frecuentes, se encuentran: pacientes de sexo masculino (n=87; 54,4 %), nacimiento por cesárea (n=122; 76,3 %) e indicación de toma de radiografías por dificultad respiratoria (n=123; 24,9 %). El 1,8 % (n=9) de los pacientes no tenían una indicación para la toma de la radiografía. La radiografía más frecuente fue la de tórax (n=322; 65,4 %). La mayoría de las radiografías se tomaron con el equipo computarizado (n=352; 71,5 %) y no con el digital (n=140, 28,4 %). La mediana de la dosis de entrada en piel con el equipo computarizado fue de 0,112 mGy (0,022; 0,134 mGy) y, con el equipo digital, de 0,020 mGy (0,019, 0,022 mGy). Conclusiones: Se cuantificaron las dosis de radiación absorbida en neonatos, general y específica, con el equipo computarizado y el digital. Se identificaron mayores dosis con el equipo computarizado. Se reconoció la interacción entre el equipo computarizado con menores edades gestacionales corregidas como principal factor para el aumento de la dosis. Además, se reconoció la relación entre el equipo computarizado y una menor edad gestacional corregida, como principal factor para una mayor dosis.

Epigenetic memory of coronavirus infection in innate immune cells and their progenitors.

Inflammation can trigger lasting phenotypes in immune and non-immune cells. Whether and how human infections and associated inflammation can form innate immune memory in hematopoietic stem and progenitor cells (HSPC) has remained unclear. We found that circulating HSPC, enriched from peripheral blood, captured the diversity of bone marrow HSPC, enabling investigation of their epigenomic reprogramming following coronavirus disease 2019 (COVID-19). Alterations in innate immune phenotypes and epigenetic programs of HSPC persisted for months to 1 year following severe COVID-19 and were associated with distinct transcription factor (TF) activities, altered regulation of inflammatory programs, and durable increases in myelopoiesis. HSPC epigenomic alterations were conveyed, through differentiation, to progeny innate immune cells. Early activity of IL-6 contributed to these persistent phenotypes in human COVID-19 and a mouse coronavirus infection model. Epigenetic reprogramming of HSPC may underlie altered immune function following infection and be broadly relevant, especially for millions of COVID-19 survivors.

Poly(ß-amino ester)s-Based Delivery Systems for Targeted Transdermal Vaccination.

Nucleic acid vaccines have become a transformative technology to fight emerging infectious diseases and cancer. Delivery of such via the transdermal route could boost their efficacy given the complex immune cell reservoir present in the skin that is capable of engendering robust immune responses. We have generated a novel library of vectors derived from poly(ß-amino ester)s (PBAEs) including oligopeptide-termini and a natural ligand, mannose, for targeted transfection of antigen presenting cells (APCs) such as Langerhans cells and macrophages in the dermal milieu. Our results reaffirmed terminal decoration of PBAEs with oligopeptide chains as a powerful tool to induce cell-specific transfection, identifying an outstanding candidate with a ten-fold increased transfection efficiency over commercial controls in vitro. The inclusion of mannose in the PBAE backbone rendered an additive effect and increased transfection levels, achieving superior gene expression in human monocyte-derived dendritic cells and other accessory antigen presenting cells. Moreover, top performing candidates were capable of mediating surface gene transfer when deposited as polyelectrolyte films onto transdermal devices such as microneedles, offering alternatives to conventional hypodermic administration. We predict that the use of highly efficient delivery vectors derived from PBAEs could advance clinical translation of nucleic acid vaccination over protein- and peptide-based strategies.

Distinct gene expression by expanded clones of quiescent memory CD4+ T cells harboring intact latent HIV-1 proviruses.

Antiretroviral therapy controls, but does not cure, HIV-1 infection due to a reservoir of rare CD4+ T cells harboring latent proviruses. Little is known about the transcriptional program of latent cells. Here, we report a strategy to enrich clones of latent cells carrying intact, replication-competent HIV-1 proviruses from blood based on their expression of unique T cell receptors. Latent cell enrichment enabled single-cell transcriptomic analysis of 1,050 CD4+ T cells belonging to expanded clones harboring intact HIV-1 proviruses from 6 different individuals. The analysis reveals that most of these cells are T effector memory cells that are enriched for expression of HLA-DR, HLA-DP, CD74, CCL5, granzymes A and K, cystatin F, LYAR, and DUSP2. We conclude that expanded clones of latent cells carrying intact HIV-1 proviruses persist preferentially in a distinct CD4+ T cell population, opening possibilities for eradication.

Plasma and memory antibody responses to Gamma SARS-CoV-2 provide limited cross-protection to other variants.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) continues to be a global problem in part because of the emergence of variants of concern that evade neutralization by antibodies elicited by prior infection or vaccination. Here we report on human neutralizing antibody and memory responses to the Gamma variant in a cohort of hospitalized individuals. Plasma from infected individuals potently neutralized viruses pseudotyped with Gamma SARS-CoV-2 spike protein, but neutralizing activity against Wuhan-Hu-1-1, Beta, Delta, or Omicron was significantly lower. Monoclonal antibodies from memory B cells also neutralized Gamma and Beta pseudoviruses more effectively than Wuhan-Hu-1. 69% and 34% of Gamma-neutralizing antibodies failed to neutralize Delta or Wuhan-Hu-1. Although Class 1 and 2 antibodies dominate the response to Wuhan-Hu-1 or Beta, 54% of antibodies elicited by Gamma infection recognized Class 3 epitopes. The results have implications for variant-specific vaccines and infections, suggesting that exposure to variants generally provides more limited protection to other variants.

Root canal microbiota as an augmented reservoir of antimicrobial resistance genes in type 2 diabetes mellitus patients

Abstract Antimicrobial resistance is a global public health problem. Root canal microbiota associated with apical periodontitis represents a well-known reservoir of antimicrobial resistance genes (ARGs). However, the effect of type 2 diabetes mellitus (T2DM) in this reservoir is unknown. This study aimed to establish if root canal microbiota associated with apical periodontitis in T2DM patients is an augmented reservoir by identifying the prevalence of nine common ARGs and comparing it with the prevalence in nondiabetic patients. Methodology This cross-sectional study included two groups: A T2DM group conformed of 20 patients with at least ten years of living with T2DM and a control group of 30 nondiabetic participants. Premolar or molar teeth with pulp necrosis and apical periodontitis were included. A sample was collected from each root canal before endodontic treatment. DNA was extracted, and ARGs were identified by polymerase chain reaction. Results tetW and tetM genes were the most frequent (93.3 and 91.6%, respectively), while ermA was the least frequent (8.3%) in the total population. The distribution of the ARGs was similar in both groups, but a significant difference (p<0.005) was present in ermB, ermC, cfxA, and tetQ genes, being more frequent in the T2DM group. A total of eighty percent of the T2DM patients presented a minimum of four ARGs, while 76.6% of the control group presented a maximum of three. Conclusions Root canal microbiota associated with apical periodontitis in T2DM patients carries more ARGs. Therefore, this pathological niche could be considered an augmented reservoir.

Cuidados crónicos en pacientes con síndrome pos-COVID-19 tras el egreso de la unidad de cuidados intensivos / Chronic care for patients with post-COVID-19 syndrome after discharge from an intensive care unit / Cuidados prolongados de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva

RESUMEN Objetivo. Describir las características clínicas de pacientes con síndrome pos-COVID-19 recién egresados de unidades cuidado intensivo (UCI) incluidos en un programa de cuidados crónicos en Colombia. Métodos. Estudio descriptivo de serie de casos procedentes de una cohorte de pacientes con síndrome pos-COVID-19 que ingresaron al programa de cuidados crónicos Remeo® entre julio de 2020 y mayo de 2021. Se describen las características clínicas, las complicaciones y el tratamiento de estos pacientes. Resultados. Se identificaron 122 casos de síndrome pos-COVID-19 dados de alta de la UCI para continuar en el Programa. La media de la edad fue de 66,9 años (IC 64-68); 62,29% fueron hombres, 88,9% (109) tenían traqueostomía, 72,8% (90) gastrostomía, y 99% requerían oxígeno suplementario. Se llevaron a cabo 9 518 intervenciones en los primeros 4 meses, inclusive terapia física (x̄:20,7), terapia ocupacional (x̄:10,9), terapia respiratoria (x̄:41,4) y psicología (x̄:4,8). Conclusiones. El Programa de cuidados crónicos representó una alternativa para pacientes con síndrome pos-COVID-19 recién egresados de las UCI, dirigido a minimizar la ocupación de estas y facilitar el paso del paciente desde la UCI al domicilio.

ABSTRACT Objective. To describe the clinical features of patients with post-COVID-19 syndrome who have recently been discharged from intensive care units (ICUs) included in a chronic care program in Colombia. Methods. Descriptive case series study of a cohort of patients with post-COVID-19 syndrome who entered the Remeo® chronic care program between July 2020 and May 2021. Clinical features, complications, and treatments are described. Results. Among patients in the program discharged from an ICU, 122 cases of post-COVID-19 syndrome were identified. These patients continued in the program. The mean age was 66.9 years (CI 64-68); 62.29% were men, 88.9% (109) had a tracheostomy, 72.8% (90) had a gastrostomy, and 99% required supplemental oxygen. In the first four months, 9,518 interventions were carried out, including physical therapy (x̄:20.7), occupational therapy (x̄:10.9), respiratory therapy (x̄:41.4), and psychology (x̄:4.8). Conclusions. The chronic care program was an option for patients with post-COVID-19 syndrome recently discharged from an ICU, with a view to minimizing ICU occupation rates and facilitating patients' return to their homes.

RESUMO Objetivo. Descrever as características clínicas de pacientes com síndrome pós-COVID-19 após internação em unidade de terapia intensiva (UTI), acompanhados em um programa de cuidados prolongados na Colômbia. Métodos. Estudo descritivo de série de casos oriundos de uma coorte de pacientes com síndrome pós-COVID-19 admitidos no programa de cuidados prolongados Remeo® entre julho de 2020 e maio de 2021. Foram descritas as características clínicas desses pacientes, assim como complicações e tratamentos. Resultados. Foram identificados 122 casos de pacientes com síndrome pós-COVID-19 que foram acompanhados no programa após alta da UTI. A média de idade foi 66,9 anos (IC 64-68), 62,29% pertenciam ao sexo masculino, 88,9% (109) haviam sido submetidos a traqueostomia, 72,8% (90) a gastrostomia e 99% precisavam usar oxigênio suplementar. Ao todo, 9.518 intervenções foram realizadas nos 4 meses iniciais de acompanhamento no programa, incluindo fisioterapia (x̄ 20,7), terapia ocupacional (x̄ 10,9), terapia respiratória (x̄ 41,4) e atendimento psicológico (x̄ 4,8). Conclusões. O programa de cuidados prolongados ofereceu uma alternativa aos pacientes com síndrome pós-COVID-19 após internação em UTI e teve o objetivo de reduzir a ocupação das UTIs e facilitar a transição do paciente da UTI para casa.

Diagnosing hospital bacteraemia in the framework of predictive, preventive and personalised medicine using electronic health records and machine learning classifiers.

Background: The bacteraemia prediction is relevant because sepsis is one of the most important causes of morbidity and mortality. Bacteraemia prognosis primarily depends on a rapid diagnosis. The bacteraemia prediction would shorten up to 6 days the diagnosis, and, in conjunction with individual patient variables, should be considered to start the early administration of personalised antibiotic treatment and medical services, the election of specific diagnostic techniques and the determination of additional treatments, such as surgery, that would prevent subsequent complications. Machine learning techniques could help physicians make these informed decisions by predicting bacteraemia using the data already available in electronic hospital records. Objective: This study presents the application of machine learning techniques to these records to predict the blood culture's outcome, which would reduce the lag in starting a personalised antibiotic treatment and the medical costs associated with erroneous treatments due to conservative assumptions about blood culture outcomes. Methods: Six supervised classifiers were created using three machine learning techniques, Support Vector Machine, Random Forest and K-Nearest Neighbours, on the electronic health records of hospital patients. The best approach to handle missing data was chosen and, for each machine learning technique, two classification models were created: the first uses the features known at the time of blood extraction, whereas the second uses four extra features revealed during the blood culture. Results: The six classifiers were trained and tested using a dataset of 4357 patients with 117 features per patient. The models obtain predictions that, for the best case, are up to a state-of-the-art accuracy of 85.9%, a sensitivity of 87.4% and an AUC of 0.93. Conclusions: Our results provide cutting-edge metrics of interest in predictive medical models with values that exceed the medical practice threshold and previous results in the literature using classical modelling techniques in specific types of bacteraemia. Additionally, the consistency of results is reasserted because the three classifiers' importance ranking shows similar features that coincide with those that physicians use in their manual heuristics. Therefore, the efficacy of these machine learning techniques confirms their viability to assist in the aims of predictive and personalised medicine once the disease presents bacteraemia-compatible symptoms and to assist in improving the healthcare economy.

Synthesis and Antimicrobial Properties of Highly Cross-Linked pH-Sensitive Hydrogels through Gamma Radiation.

The design of new polymeric systems for antimicrobial drug release focused on medical/surgical procedures is of great interest in the biomedical area due to the high prevalence of bacterial infections in patients with wounds or burns. For this reason, in this work, we present a new design of pH-sensitive hydrogels copolymerized by a graft polymerization method (gamma rays), intended for localized prophylactic release of ciprofloxacin and silver nanoparticles (AgNPs) for potential topical bacterial infections. The synthesized hydrogels were copolymerized from acrylic acid (AAc) and agar. Cross-linked hydrogel film formation depended on monomer concentrations and the degree of radiation used (Cobalt-60). The obtained hydrogel films were characterized by attenuated total reflectance Fourier-transform infrared spectroscopy (ATR-FTIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC), and mechanical testing. The swelling of the hydrogels was evidenced by the influence of their pH-sensitiveness. The hydrogel was loaded with antimicrobial agents (AgNPs or ciprofloxacin), and their related activity was evaluated. Finally, the antimicrobial activity of biocidal-loaded hydrogel was tested against Escherichia coli (E. coli) and methicillin-resistant Staphylococcus aureus (MRSA) on in vitro conditions.

Polymer stealthing and mucin-1 retargeting for enhanced pharmacokinetics of an oncolytic vaccinia virus.

Vaccinia virus (VV) is a powerful tool for cancer treatment with the potential for tumor tropism, efficient cell-to-cell spread, rapid replication in cancer cells, and stimulation of anti-tumor immunity. It has a well-defined safety profile and is being assessed in late-stage clinical trials. However, VV clinical utility is limited by rapid bloodstream neutralization and poor penetration into tumors. These factors have often restricted its route of delivery to intratumoral or intrahepatic artery injection and may impede repeat dosing. Chemical stealthing improves the pharmacokinetics of non-enveloped viruses, but it has not yet been applied to enveloped viruses such as VV. In the present study, amphiphilic polymer was used to coat VV, leading to reduced binding of a neutralizing anti-VV antibody (81.8% of polymer-coated VV [PCVV] staining positive versus 97.1% of VV [p = 0.0038]). Attachment of anti-mucin-1 (aMUC1) targeting antibody, to give aMUC1-PCVV, enabled binding of the construct to MUC1. In high MUC1 expressing CAPAN-2 cells, infection with PCVV was reduced compared to VV, while infection was restored with aMUC1-PCVV. Pharmacokinetics of aMUC1-PCVV, PCVV, and VV were evaluated. After intravenous (i.v.) injection of 1 × 108 viral genomes (VG) or 5 × 108 VG, circulation time for PCVV and aMUC1-PCVV was increased, with ~5-fold higher circulating dose at 5 min versus VV.

Evolution of antibody immunity to SARS-CoV-2.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected 78 million individuals and is responsible for over 1.7 million deaths to date. Infection is associated with the development of variable levels of antibodies with neutralizing activity, which can protect against infection in animal models1,2. Antibody levels decrease with time, but, to our knowledge, the nature and quality of the memory B cells that would be required to produce antibodies upon reinfection has not been examined. Here we report on the humoral memory response in a cohort of 87 individuals assessed at 1.3 and 6.2 months after infection with SARS-CoV-2. We find that titres of IgM and IgG antibodies against the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 decrease significantly over this time period, with IgA being less affected. Concurrently, neutralizing activity in plasma decreases by fivefold in pseudotype virus assays. By contrast, the number of RBD-specific memory B cells remains unchanged at 6.2 months after infection. Memory B cells display clonal turnover after 6.2 months, and the antibodies that they express have greater somatic hypermutation, resistance to RBD mutations and increased potency, indicative of continued evolution of the humoral response. Immunofluorescence and PCR analyses of intestinal biopsies obtained from asymptomatic individuals at 4 months after the onset of coronavirus disease 2019 (COVID-19) revealed the persistence of SARS-CoV-2 nucleic acids and immunoreactivity in the small bowel of 7 out of 14 individuals. We conclude that the memory B cell response to SARS-CoV-2 evolves between 1.3 and 6.2 months after infection in a manner that is consistent with antigen persistence.

Delivery of Anti-microRNA-712 to Inflamed Endothelial Cells Using Poly(ß-amino ester) Nanoparticles Conjugated with VCAM-1 Targeting Peptide.

Endothelial cells (ECs) are an important target for therapy in a wide range of diseases, most notably atherosclerosis. Developing efficient nanoparticle (NP) systems that deliver RNA interference (RNAi) drugs specifically to dysfunctional ECs in vivo to modulate their gene expression remains a challenge. To date, several lipid-based NPs are developed and shown to deliver RNAi to ECs, but few of them are optimized to specifically target dysfunctional endothelium. Here, a novel, targeted poly(ß-amino ester) (pBAE) NP is demonstrated. This pBAE NP is conjugated with VHPK peptides that target vascular cell adhesion molecule 1 protein, overexpressed on inflamed EC membranes. To test this approach, the novel NPs are used to deliver anti-microRNA-712 (anti-miR-712) specifically to inflamed ECs both in vitro and in vivo, reducing the high expression of pro-atherogenic miR-712. A single administration of anti-miR-712 using the VHPK-conjugated-pBAE NPs in mice significantly reduce miR-712 expression, while preventing the loss of its target gene, tissue inhibitor of metalloproteinase 3 (TIMP3) in inflamed endothelium. miR-712 and TIMP3 expression are unchanged in non-inflamed endothelium. This novel, targeted-delivery platform may be used to deliver RNA therapeutics specifically to dysfunctional endothelium for the treatment of vascular disease.

Enhanced SARS-CoV-2 neutralization by dimeric IgA.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19), primarily infects cells at mucosal surfaces. Serum neutralizing antibody responses are variable and generally low in individuals that suffer mild forms of COVID-19. Although potent immunoglobulin G (IgG) antibodies can neutralize the virus, less is known about secretory antibodies such as IgA that might affect the initial viral spread and transmissibility from the mucosa. Here, we characterize the IgA response to SARS-CoV-2 in a cohort of 149 convalescent individuals after diagnosis with COVID-19. IgA responses in plasma generally correlated with IgG responses. Furthermore, clones of IgM-, IgG-, and IgA-producing B cells were derived from common progenitor cells. Plasma IgA monomers specific to SARS-CoV-2 proteins were demonstrated to be twofold less potent than IgG equivalents. However, IgA dimers, the primary form of antibody in the nasopharynx, were, on average, 15 times more potent than IgA monomers against the same target. Thus, dimeric IgA responses may be particularly valuable for protection against SARS-CoV-2 and for vaccine efficacy.

Ejercicios especiales para mejorar la ejecución de técnicas de piernas en judocas escolares / Exercícios especiais para melhorar a execução de técnicas de pernas em judocas escolares / Special exercises to improve the execution of leg techniques in school judo

Resumen Insuficiencias detectadas en la realización de técnicas de piernas de los judocas escolares de Pinar del Río motivaron la realización de esta investigación que tiene como objetivo: elaborar un conjunto de ejercicios especiales que contribuyan al desarrollo del trabajo de los entrenadores con este grupo de técnicas para mejorar la ejecución de los 14 atletas de esta categoría. Al inicio de este estudio, se realizaron observaciones a sesiones de entrenamiento, topes de control y competencias preparatorias para obtener información directa sobre el modo en que se manifiestan estas acciones. También se utilizó una entrevista a los entrenadores para conocer sus conocimientos, criterios y desempeño en el trabajo con estas técnicas y la encuesta para valorar el conocimiento de los atletas acerca de la importancia de la preparación técnica en estas acciones. Además, se practicó una medición mediante una prueba técnica para conocer el comportamiento de la ejecución de estas en los atletas motivo de investigación, en la cual las variables analizadas fueron: puntuación obtenida, total de acciones y forma de realización (directa, combinación o como contraataque). Este estudio permitió el conocimiento de las deficiencias presentadas por estos atletas en la ejecución de las técnicas de piernas, las cuales influyen de forma negativa en los resultados competitivos ya que estas se realizan con gran frecuencia durante el combate por su vinculación con otras técnicas en la realización de combinaciones y contraataques. Este trabajo es una herramienta valiosa para la labor de los entrenadores, dirigida a la preparación técnica del judoca.

Resumo As insuficiências detectadas no desempenho das técnicas de perna das judocas escolares de Pinar del Río motivaram a realização desta investigação que tem como objetivo: elaborar um conjunto de exercícios especiais que contribuam para o desenvolvimento do trabalho dos treinadores com este grupo de técnicas para melhorar o desempenho dos 14 atletas desta categoria. No início deste estudo, foram feitas observações a sessões de formação, paragens de controlo e concursos preparatórios para obter informações diretas sobre a forma como estas ações se manifestam. Uma entrevista com os treinadores foi também utilizada para descobrir os seus conhecimentos, critérios e desempenho no trabalho com estas técnicas e o inquérito foi utilizado para avaliar os conhecimentos dos atletas sobre a importância da preparação técnica nestas ações. Além disso, foi feita uma medição através de um teste técnico para conhecer o comportamento da execução destes nos atletas sob investigação, no qual as variáveis analisadas foram: pontuação obtida, total de ações e forma de execução (direta, combinada ou como contra-ataque). Este estudo permitiu o conhecimento das deficiências apresentadas por estes atletas na execução das técnicas de pernas, que influenciam de forma negativa nos resultados competitivos, uma vez que estes são feitos com grande frequência durante o combate pela sua implicação com outras técnicas na realização de combinações e contra-ataques. Este trabalho é um instrumento valioso para o trabalho dos treinadores, destinado à preparação técnica do judoca.

Abstract Insufficiencies detected in the performance of leg techniques of the school judokas of Pinar del Río motivated the realization of this research, which aims to develop a set of special exercises that contribute to the development of the work of coaches with this group of techniques to improve the performance of the 14 athletes in this category. At the beginning of this study, observations were made of training sessions, control stops and preparatory competitions to obtain direct information on how these actions are manifested. An interview with the coaches was also used to find out their knowledge, criteria, and performance at work with these techniques, and the survey was used to assess the athletes' knowledge about the importance of technical preparation in these actions. In addition, a measurement was carried out by means of a technical test, to know the behavior of the execution of these in the athletes reason for research, in which the variables analyzed were: score obtained, total of actions and form of performance (direct, combination or as a counterattack). This study found the knowledge of the deficiencies presented by these athletes, in the execution of leg techniques, which negatively influence competitive results since these are performed with great frequency during combat due to their link with other techniques in performing combinations and counterattacks. This work is a valuable tool for the work of the coaches aimed at the technical preparation of the judoka.

Antimicrobial Polymer-Peptide Conjugates Based on Maximin H5 and PEG to Prevent Biofouling of E. coli and P. aeruginosa.

Many pathogens, such as Pseudomonas aeruginosa and Escherichia coli bacteria can easily attach to surfaces and form stable biofilms. The formation of such biofilms in surfaces presents a problem in environmental, biomedical, and industrial processes, among many others. Aiming to provide a plausible solution to this issue, the anionic and hydrophobic peptide Maximin H5 C-terminally deaminated isoform (MH5C) has been modified with a cysteine in the C-terminal (MH5C-Cys) and coupled to polyethylene glycol (PEG) polymers of varying sizes (i.e., 2 kDa and 5 kDa) to serve as a surface protective coating. Briefly, the MH5C-Cys was bioconjugated to PEG and purified by size exclusion chromatography while the reaction was confirmed via SDS-PAGE and MALDI ToF. Moreover, the preventive antimicrobial activity of the MH5C-Cys-PEG conjugates was performed via the growth curves method, showing inhibition of bacterial growth after 24 h. The efficacy of these peptide-polymer conjugates was extensively characterized via scanning electron microscopy (SEM), minimum inhibition concentration (MIC), minimum biofilm inhibition concentration (MBIC), and minimum biofilm eradication concentration (MBEC) assays to evaluate their ability to eradicate and prevent the biofilms. Interestingly, this work demonstrated a critical PEG polymer weight of 5 kDa as ideal when coupled to the peptide to achieve inhibition and eradication of the biofilm formation in both bacteria strains. According to the MICs (40 µM) and MBICs (300 µM), we can conclude that this conjugate (MH5C-Cys-5 kDa) has an action that prevents/inhibits the formation of biofilms and the eradication of biofilms (MBEC 500 µM). In contrast, the MH5C-Cys peptide with PEG polymer of 2 kDa did not show inhibition or eradication of the biofilms.

Maternal 5mCpG Imprints at the PARD6G-AS1 and GCSAML Differentially Methylated Regions Are Decoupled From Parent-of-Origin Expression Effects in Multiple Human Tissues.

A hallmark of imprinted genes in mammals is the occurrence of parent-of-origin-dependent asymmetry of DNA cytosine methylation (5mC) of alleles at CpG islands (CGIs) in their promoter regions. This 5mCpG asymmetry between the parental alleles creates allele-specific imprinted differentially methylated regions (iDMRs). iDMRs are often coupled to the transcriptional repression of the methylated allele and the activation of the unmethylated allele in a tissue-specific, developmental-stage-specific and/or isoform-specific fashion. iDMRs function as regulatory platforms, built through the recruitment of chemical modifications to histones to achieve differential, parent-of-origin-dependent chromatin segmentation states. Here, we used a comparative computational data mining approach to identify 125 novel constitutive candidate iDMRs that integrate the maximal number of allele-specific methylation region records overlapping CGIs in human methylomes. Twenty-nine candidate iDMRs display gametic 5mCpG asymmetry, and another 96 are candidate secondary iDMRs. We established the maternal origin of the 5mCpG imprints of one gametic (PARD6G-AS1) and one secondary (GCSAML) iDMRs. We also found a constitutively hemimethylated, nonimprinted domain at the PWWP2AP1 promoter CGI with oocyte-derived methylation asymmetry. Given that the 5mCpG level at the iDMRs is not a sufficient criterion to predict active or silent locus states and that iDMRs can regulate genes from a distance of more than 1 Mb, we used RNA-Seq experiments from the Genotype-Tissue Expression project and public archives to assess the transcriptional expression profiles of SNPs across 4.6 Mb spans around the novel maternal iDMRs. We showed that PARD6G-AS1 and GCSAML are expressed biallelically in multiple tissues. We found evidence of tissue-specific monoallelic expression of ZNF124 and OR2L13, located 363 kb upstream and 419 kb downstream, respectively, of the GCSAML iDMR. We hypothesize that the GCSAML iDMR regulates the tissue-specific, monoallelic expression of ZNF124 but not of OR2L13. We annotated the non-coding epigenomic marks in the two maternal iDMRs using data from the Roadmap Epigenomics project and showed that the PARD6G-AS1 and GCSAML iDMRs achieve contrasting activation and repression chromatin segmentations. Lastly, we found that the maternal 5mCpG imprints are perturbed in several hematopoietic cancers. We conclude that the maternal 5mCpG imprints at PARD6G-AS1 and GCSAML iDMRs are decoupled from parent-of-origin transcriptional expression effects in multiple tissues.

Unidades de Saúde Familiar e Clínicas da Família - essência e semelhanças / Family Healthcare Units in Portugal and Family Clinics in Rio de Janeiro - their essence and similarities

Resumo O desenvolvimento, desde 2009, das Clínicas da Família (CF) no Rio de Janeiro tem paralelismos com as Unidades de Saúde Familiar (USF) implementadas em Portugal desde 2006. Neste ensaio, os autores assinalam o encontro em Portugal, em outubro de 2009, com gestores do Ministério da Saúde e da Subsecretaria de Atenção Primária, Vigilância e Promoção da Saúde do Rio de Janeiro, e destacam alguns aspetos essenciais tais como: a organização em equipes multiprofissionais com caráter estrutural permanente; as características das equipes; o seu desenvolvimento ("teambulding"); a organização e a autonomia técnica; os laços emocionais entre os elementos de cada equipe; os instrumentos formais de regulação da autonomia; a responsabilização e a prestação de contas/contratualização; os dispositivos de monitorização e de avaliação; o sistema de lideranças; fatores motivacionais dos profissionais e das equipes; as USF e as CF como organizações aprendentes. Estes aspectos podem resumir-se em "3P": propósitos, orientação para objetivos de saúde e de bem estar; pessoas, que são a razão das organizações de saúde; processos, continuamente questionados, avaliados e aperfeiçoados.

Abstract The authors address parallel developments in Family Healthcare Units (USF) in Portugal (since 2006) and in primary care Family Clinics (CF) in Rio de Janeiro (since 2009). In this essay, they highlight the meeting that took place in Portugal with Brazilian Health Ministry and Rio de Janeiro Department of Health members in October 2009. Being directly involved (since May 2016) in the development of USF in the Lisbon Region, and having visited, in November 2016, several CF in Rio de Janeiro, they analyze aspects such as: organization in permanent structural multi-professional teams; main common characteristics of the teams; teambuilding processes; organization and technical autonomy; instruments to regulate autonomy; responsibility and accountability - contracting processes; monitoring and evaluation; leadership system; motivational factors for professionals and for the team as a whole; learning organizations. All these aspects converge to a "3P" framework: "purposes" - organizing and orienting multi-professional teams towards health gains and the wellbeing of the individuals and the population; "people" - both those who are beneficiaries of health care services, as well as the health care professionals; "processes" - that must be permanently questioned, evaluated and enhanced.

Improvement of osteogenesis in dental pulp pluripotent-like stem cells by oligopeptide-modified poly(ß-amino ester)s.

Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. Recently, a new family of poly(ß-amino ester)s (pBAEs) with oligopeptide-modified termini showing high transfection efficiency of both siRNA and DNA plasmid has been developed. In this study, oligopeptide-modified pBAEs were used to simultaneously deliver anti-OCT3/4 siRNA, anti-NANOG siRNA, and RUNX2 plasmid to cells from the dental pulp with pluripotent-like characteristics (DPPSC) in order to promote their osteogenic differentiation. Results indicate that transient inhibition of the pluripotency marker OCT3/4 and the overexpression of RUNX2 at day 7 of differentiation markedly increased and accelerated the expression of osteogenic markers. Furthermore, terminally-differentiated cells exhibited higher matrix mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicate that this co-delivery system has high chromosomal stability and minimal cytotoxicity. Therefore, we conclude that such co-delivery strategy is a safe and a quick option for the improvement of DPPSC osteogenic differentiation. STATEMENT OF SIGNIFICANCE: Controlling pluripotent stem cell differentiation via genetic manipulation is a promising technique in regenerative medicine. However, the lack of safe and efficient delivery vehicles limits this application. In this study, we propose the use of a new family of oligopeptide-modified pBAEs developed in our group to control the differentiation of dental pulp pluripotential stem cells (DPPSC). In order to promote their osteogenic differentiation. The strategy proposed markedly increased and accelerated the expression of osteogenic markers, cell mineralization and alkaline phosphatase activity. Finally, cell viability and genetic stability assays indicated that this co-delivery system has high chromosomal stability and minimal cytotoxicity. These findings open a new interesting path in the usage of non-viral gene delivery systems for the control of pluripotential stem cell differentiation.

Radiation Grafting for the Functionalization and Development of Smart Polymeric Materials.

Gamma radiation has been shown particularly useful for the functionalization of surfaces with stimuli-responsive polymers. This method involves the formation of active sites (free radicals) onto the polymeric backbone as a result of the high-energy radiation exposition over the polymeric material. Thus, a microenvironment suitable for the reaction among monomer and/or polymer and the active sites is formed and then leading to propagation to form side-chain grafts. The modification of polymers using high-energy irradiation can be performed by the following methods: direct or simultaneous, pre-irradiation oxidative, and pre-irradiation. The most frequently used ones correspond to the pre-irradiation oxidative method as well as the direct one. Radiation-grafting has many advantages over other conventional methods because it does not require the use of catalyst nor additives to initiate the reaction and usually no changes on the mechanical properties with respect to the pristine polymeric matrix are observed. This chapter is focused on the synthesis of smart polymers and coatings obtained by the use of gamma radiation. In addition, the diverse applications of these materials in the biomedical area are also reported, with focus in drug delivery, sutures, and biosensors.

Células de la cresta neural y su relación con cardiopatía congénita: revisión sistemática de la literatura / Neural crest cells and their relation to congenital heart disease: systematic review of the literature

Las cardiopatías congénitas corresponden al grupo de anomalías del desarrollo que se presentan con mayor frecuencia. Durante el desarrollo cardíaco participan distintos linajes celulares, donde destacan las Células de la Cresta Neural (CCN) por su amplia gama de derivados embriológicos y la susceptibilidad de afectar a múltiples sistemas si su función es alterada. El objetivo fue determinar el rol que cumplen las CCN durante el desarrollo cardíaco y las cardiopatías congénitas asociadas. Se diseñó un estudio descriptivo en base a una revisión sistemática de la literatura de las bases de datos MEDLINE y Scopus, utilizando la combinación de términos MeSH: ("Heart Diseases/congenital" OR "Heart Diseases/embriology" OR "Heart Diseases/etiology" OR "Heart Disesaes/epidemiology") AND ("Neural Crest/abnormalities"). Se restringió la búsqueda a artículos de los últimos 10 años. De un total de 35 artículos obtenidos, 22 fueron incluidos para su revisión por estar relacionados con los objetivos de este estudio, excluyéndose duplicados entre bases de datos. Posteriormente se hizo un análisis individual y en conjunto de la información obtenida de los artículos seleccionados. La evidencia indica la participación directa o indirecta de las CCN durante la formación de las estructuras derivadas del polo arterioso del corazón en desarrollo, los grandes vasos arteriales y sus ramas colaterales, así como en su inervación y sistema de conducción. La alteración del funcionamiento normal de las CCN produce fenotipos cardíacos alterados, siendo la persistencia del tronco arterioso, doble salida ventricular derecha, defectos septales interventriculares y malformación de los aparatos valvares aórtico y pulmonar, los más frecuentes.

Congenital heart defects are the group of most frequent anomalies of development. Cardiac development in different cell lines, which include the Neural crest cells (NCC) for their wide range of embryological derivatives and susceptibility to affect multiple systems if their function is altered participate. The objective was to determine the role of the NCC during heart development and associated congenital heart disease. A descriptive study was designed based on a systematic review of the literature from the MEDLINE and Scopus data, using a combination of MeSH terms ("Heart Diseases / congenital" OR "Heart Diseases / Embryology" OR "Heart Diseases/etiology "OR" Heart Diseases/epidemiology ") AND ("Neural Crest/abnormalities"). Search for articles in the last 10 years was restricted. From a total of 35 articles retrieved, 22 were included related to the objectives of this study for review, excluding duplicated between databases. Subsequently, an individual and joint analysis was realized with the information from the selected items. Evidence indicates the direct or indirect involvement of NCC during the formation of the structures derived from arterial pole of the developing heart, the large arterial vessels and their collateral branches, as well as its innervation and conduction system. The disruption of normal operation of the NCC produces altered cardiac phenotypes, with the Persistence Truncus Arteriosus, Double-Outlet Right Ventricle, ventricular Septal Defects and malformation of the most common valvular aortic and pulmonary devices.