RESUMO
During the first weeks of postnatal heart development, cardiomyocytes undergo a major adaptive metabolic shift from glycolytic energy production to fatty acid oxidation. This metabolic change is contemporaneous to the up-regulation and activation of the p38γ and p38δ stress-activated protein kinases in the heart. We demonstrate that p38γ/δ contribute to the early postnatal cardiac metabolic switch through inhibitory phosphorylation of glycogen synthase 1 (GYS1) and glycogen metabolism inactivation. Premature induction of p38γ/δ activation in cardiomyocytes of newborn mice results in an early GYS1 phosphorylation and inhibition of cardiac glycogen production, triggering an early metabolic shift that induces a deficit in cardiomyocyte fuel supply, leading to whole-body metabolic deregulation and maladaptive cardiac pathogenesis. Notably, the adverse effects of forced premature cardiac p38γ/δ activation in neonate mice are prevented by maternal diet supplementation of fatty acids during pregnancy and lactation. These results suggest that diet interventions have a potential for treating human cardiac genetic diseases that affect heart metabolism.
Assuntos
Glicogênio Sintase/metabolismo , Proteína Quinase 12 Ativada por Mitógeno/metabolismo , Proteína Quinase 13 Ativada por Mitógeno/metabolismo , Miocárdio/enzimologia , Animais , Animais Recém-Nascidos , Cardiomegalia/enzimologia , Cardiomegalia/patologia , Cardiomegalia/fisiopatologia , Dieta Hiperlipídica , Ativação Enzimática , Comportamento Alimentar , Feminino , Deleção de Genes , Intolerância à Glucose/enzimologia , Glicogênio/metabolismo , Quinase 3 da Glicogênio Sintase/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Sistema de Sinalização das MAP Quinases , Camundongos Endogâmicos C57BL , Miócitos Cardíacos/enzimologia , Especificidade de Órgãos , FosforilaçãoRESUMO
SARS-CoV-2 is a type of coronavirus responsible for the international outbreak of respiratory illness termed COVID-19 that forced the World Health Organization to declare a pandemic infectious disease situation of international concern at the beginning of 2020. The need for a swift response against COVID-19 prompted to consider different sources to identify bioactive compounds that can be used as therapeutic agents, including available drugs and natural products. Accordingly, this work reports the results of a virtual screening process aimed at identifying antiviral natural product inhibitors of the SARS-CoV-2 Mpro viral protease. For this purpose, ca. 2000 compounds of the Selleck database of Natural Compounds were the subject of an ensemble docking process targeting the Mpro protease. Molecules that showed binding to most of the protein conformations were retained for a further step that involved the computation of the binding free energy of the ligand-Mpro complex along a molecular dynamics trajectory. The compounds that showed a smooth binding free energy behavior were selected for in vitro testing. From the resulting set of compounds, five compounds exhibited an antiviral profile, and they are disclosed in the present work.
Assuntos
Produtos Biológicos , COVID-19 , Antivirais/farmacologia , Produtos Biológicos/farmacologia , Humanos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Peptídeo Hidrolases , Inibidores de Proteases/farmacologia , SARS-CoV-2RESUMO
Our aim was to analyze the association between anal human papillomavirus (HPV) infection and abnormal anal cytology in women with high-grade cervical intraepithelial neoplasia (CIN 2+). We also analysed what other risk factors might be significant. We carried out a prevalence study from April 2015 to March 2017 at La Paz University Hospital. Genotyping of HPV, anal cytology and high-resolution anoscopy were performed. Of 171 patients recruited, 53 cases (31%) were diagnosed as histological CIN 2+: there were no statistically significant differences in the prevalence of anal HPV (OR = 0.8), nor the prevalence of abnormal anal cytology (OR = 2.15, 95% CI 0.8-5.7) compared to women with CIN 1 or no cervical dysplasia. Immunosuppression (OR = 2.51, 95% CI 1-6.3, p < .05), cervical HPV (OR = 3.9, 95% CI 1.9-8.0, p < .01) and being older than 40 years old (p < .05) were also associated with anomalous anal results.Impact StatementWhat is already known on this subject? Anal HR-HPV and abnormal anal cytology may precede anal intraepithelial neoplasia (AIN): a premalignant lesion that may progress to anal cancer. It is known that there are four populations which present a higher risk of developing anal cancer compared to the general population: human immunodeficiency virus (HIV)-positive patients, other immunocompromised populations, men who have sex with men and women with a history of disease secondary to HPV infection.What do the results of this study add? This study allowed us to compare the prevalence of anal HPV and abnormal anal cytology in women with CIN 2+: it analysed whether these women already presented alterations in anal tests at the moment of the diagnosis of the preneoplastic cervical lesion. It also provides information for the management of the populations at a higher risk of developing anal cancer; specifically, the group of women with a prior history of HPV-associated anogenital disease.What are the implications of these findings for clinical practice and/or further research? Our findings improve the existing evidence on anal HPV infection and anal cytology on the least studied population at risk. Data could be useful for further research in order to clarify the role of anal screening in this population and standardise the clinical practice.
Assuntos
Doenças do Ânus/epidemiologia , Papillomaviridae , Infecções por Papillomavirus/epidemiologia , Displasia do Colo do Útero/virologia , Neoplasias do Colo do Útero/virologia , Adulto , Idoso , Canal Anal/virologia , Doenças do Ânus/complicações , Doenças do Ânus/virologia , Colo do Útero/virologia , Técnicas Citológicas , Feminino , Humanos , Pessoa de Meia-Idade , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/virologia , Prevalência , Adulto JovemRESUMO
INTRODUCTION: The presence of positive para-aortic lymph nodes in advanced cervical cancer remains the most important prognostic factor for survival and also defines the treatment. Our aim was to define the influence of staging para-aortic lymphadenectomy in patients' survival. MATERIAL AND METHODS: The medical records of 74 patients with advanced cervical cancer (FIGO IIB-IVA) were reviewed. In 31 patients (41.9%), the assessment of lymph nodes was performed with imaging test (group 1) and in 43 (58.1%) within a surgical staging para-aortic lymphadenectomy (group 2). We compared both groups according to stage of disease, treatment, progression-free survival (PFS), and overall survival (OS). RESULTS: The extended-field radiotherapy was performed in 44.2 and 19.4% of patients in surgical and imaging staging group, respectively (p = 0.045). The disease-free survival rate was 17.4 ± 17.4 months in group 1 and 14.4 ± 12.6 months in group 2 (p = 0.456). No differences in OS were found between these 2 groups (p = 0.676). CONCLUSIONS: Despite the higher diagnostic accuracy of surgical staging and the higher number of patient who received extended field radiotherapy, we did not find differences between the overall and PFS rates in both the studied groups. Further prospective study on a higher number of patients would be necessary.
Assuntos
Excisão de Linfonodo/mortalidade , Estadiamento de Neoplasias/mortalidade , Neoplasias do Colo do Útero/mortalidade , Adulto , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Excisão de Linfonodo/métodos , Linfonodos/patologia , Metástase Linfática/patologia , Pessoa de Meia-Idade , Estadiamento de Neoplasias/métodos , Glomos Para-Aórticos/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/cirurgiaRESUMO
STUDY OBJECTIVE: To evaluate the surgical outcome of extraperitoneal paraaortic lymph node dissection compared with the traditional transperitoneal approach. DESIGN: Retrospective review (Canadian Task Force classification III). SETTING: University hospital. PATIENTS: Women with gynecologic malignancies admitted to our hospital between 2007 and 2011 who underwent laparoscopic paraaortic lymphadenectomy. INTERVENTIONS: Indication, diagnosis, and outcome according to type of surgery were evaluated. MEASUREMENTS AND MAIN RESULTS: Of 47 patients who underwent laparoscopic paraaortic lymphadenectomy because of gynecologic indications, 28 patients underwent extraperitoneal paraaortic lymph node dissection and 19 underwent the same procedure via the classic transperitoneal technique. The most frequent indication for extraperitoneal lymph node dissection was cervical cancer (71.4%), and for the transperitoneal technique was endometrial cancer (47.4%). The mean (SD) duration of surgery was 211 (38) minutes in the transperitoneal approach group, and 173 (51) minutes in the extraperitoneal lymphadenectomy group (p = .009). No significant differences between groups were found in the number of lymph nodes removed (15 [5.9] nodes in the extraperitoneal group vs 17.4 [8.6] in the transperitoneal group; p = .25). However, a higher rate of positive nodes was observed in the extraperitoneal group than in the transperitoneal group (42.8% vs 36.2%, respectively [p = .001]), and a significantly shorter stay in the intensive care unit in the extraperitoneal group (0.59 [0.5] vs 1.1 [0.5] days, respectively; p = .02). No significant differences in complication rate were found between groups. CONCLUSIONS: Extraperitoneal paraaortic lymph node dissection is a minimally invasive procedure that is an excellent and safe approach to the paraaortic area, with a low complication rate, sufficient number of lymph nodes, and short hospital stay. It seems to be a good alternative to the classic transperitoneal approach.
Assuntos
Neoplasias dos Genitais Femininos/cirurgia , Excisão de Linfonodo/métodos , Adulto , Idoso , Canadá , Feminino , Neoplasias dos Genitais Femininos/patologia , Humanos , Pessoa de Meia-Idade , Estudos Retrospectivos , Resultado do TratamentoRESUMO
Uterine fibroids are the most frequent solid benign tumors of the female pelvis. The most frequent location is the uterine corpus; however, it has been also reported in cervical placement and broad ligament. Rarely it has been reported a case of intestinal fibroid after previous history of myomectomy. We report the case of a patient, with no surgical history of interest, who underwent a diagnostic laparoscopy due to suspicion of malignant abdominal mass. Ajejunal fibroid was found, which was removed via laparoscopy without complications. Laparoscopy may be considered in case of intestinal fibriod despite its rarity, due to the better postoperative recovery and cosmetic outcomes compared to laparotomy.
Assuntos
Neoplasias do Jejuno/cirurgia , Laparoscopia , Leiomioma/cirurgia , Idoso de 80 Anos ou mais , Feminino , HumanosRESUMO
Hepatitis C virus (HCV) infection remains a global health problem, detected only in the early stages by molecular tests. Molecular tests detect HCV RNA, which is very prone to degradation by ribonucleases, reason why blood samples must be transported and stored at - 20 °C, or even - 70 °C for long-term storage. Flinders Technology Associates (FTA) cards are a useful sampling collecting device for dry blood spot (DBS) storage, especially for low and middle-income countries (LMIC). In this study, we analyzed viral HCV RNA integrity for long-term storage at room temperature compared to - 20 °C using two different types of cards for DBS: FTA Classic and 903 Protein Saver cards. For this purpose, DBS were prepared on these cards using blood or plasma samples from HCV infected patients, and samples were analysed by conventional RT-PCR. Our results showed that 903 Protein Saver cards are the best and cheapest alternative for DBS storage at room temperature. In these conditions, we found that HCV RNA integrity lasted for up to 9 months.
Assuntos
Hepatite C , RNA Viral , Teste em Amostras de Sangue Seco/métodos , Hepacivirus/genética , Humanos , RNA Viral/análise , Sensibilidade e Especificidade , Manejo de Espécimes/métodos , TemperaturaRESUMO
No disponible
Assuntos
Humanos , Masculino , Feminino , Idoso , Idoso de 80 Anos ou mais , Diagnóstico de Enfermagem/métodos , Cateteres de Demora/efeitos adversos , Diálise Renal/enfermagem , Insuficiência Renal Crônica/enfermagemRESUMO
Resumen OBJETIVO: Investigar las posibles causas de los conos blancos, establecer estrategias para disminuir su incidencia y desarrollar protocolos de seguimiento. MATERIALES Y MÉTODOS: Estudio observacional, retrospectivo, de casos y controles. Se incluyeron las pacientes a quienes se efectuó una conización en el Hospital Universitario La Paz. Las variables analizadas más importantes fueron: anatomía patológica de la pieza y su relación con la biopsia y citologías previas, longitud del cono, presencia o no de artefacto y de cervicitis. Para el análisis estadístico se utilizaron: χ2, prueba exacta de Fisher, t de Student, U de Mann-Whitney, Kruskal-Wallis y Kolmogorov-Smirnov. RESULTADOS: Se integraron dos grupos: 371 conos positivos (85.9%) y 61 negativos (14.1%), con diferencias estadísticamente significativas en la citología, colposcopia y biopsia. Hubo mayor porcentaje de lesiones de menor grado en las pacientes con conización blanca. La longitud del cono fue menor en el grupo de análisis y en éste también se observó mayor porcentaje de cervicitis y artefactos. CONCLUSIONES: Las causas de lesión residual luego de una conización son variadas y difíciles de demostrar. Las pacientes con citología anómala e inflamación o atrofia deben recibir tratamiento para evitar falsos positivos y mejorar la técnica quirúrgica para impedir artefactos.
Abstract OBJECTIVES: to investigate the possible causes of the negative cones, to establish strategies to reduce their incidence and to develop monitoring protocols. MATERIALS AND METHODS: This is a retrospective observational cases and controls study of 432 conizations made in the Hospital Universitario La Paz (HULP) between 2013 and 2015. The most important analysed variables were the pathological anatomy of the piece and its relationship with the biopsy and previous cytology, the cone length, as well as the presence and artefact and cervicitis. The analysis it was used Chi - Square and Fisher´s test, T-Student, Mann Whitney U, Kruskal-Wallis and Kolmogorov- Smirnov. RESULTS: There are two groups: 371 positive (85,9%) and 61 negative cones (14,1%). We find statistically significant differences in the cytology, colposcopy and biopsy pre-conization, finding a major percentage of injuries of lesser degree in the patients with negative cone. The length of the cone was lower in the analysis group and in this we also observed a greater percentage of cervicitis and artefacts. CONCLUSIONS: The causes that make the remaining injury not appear after a diagnosed and/or therapeutic conization are a wide variety and difficult to prove. We should try to treat the patients with inflammation or atrophy to avoid false positives in the cytology and biopsy, improve the surgical technique to avoid artefacts and perform conservative management of low-risk injuries.
Assuntos
Adenocarcinoma/complicações , Complicações Neoplásicas na Gravidez/terapia , Resultado da Gravidez , Neoplasias do Colo do Útero/complicações , Adenocarcinoma/patologia , Adenocarcinoma/terapia , Adulto , Feminino , Humanos , Gravidez , Complicações Neoplásicas na Gravidez/diagnóstico , Complicações Neoplásicas na Gravidez/patologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/terapiaRESUMO
Las complicaciones cardiovasculares son la principal causa de enfermedad renal crónica, y a su vez uno de los principales factores de riesgo cardiovascular. Por otro lado, la enfermedad cardiovascular está íntimamente relacionada con la obesidad central o androide. Nuestro objetivo es determinar los factores de riesgo cardiovascular presentes en nuestros pacientes en tratamiento sustitutivo de hemodiálisis para elaborar una hoja de seguimiento que nos sirva de apoyo para valorarla progresión o regresión de los factores de riesgo. Se diseñó un estudio descriptivo transversal prospectivo y abierto, la población de referencia se determinó por una muestra de los pacientes en tratamiento hemodialítico en nuestros centros. Analizados los 14 factores de riesgo cardiovascular presentes en el estudio, encontramos una media de factores presentes de 5,11 ± 2,15. La población estudiada presentaba: valores altos en cuanto a sobrepeso, uno de cada cuatro pacientes del estudio presentaba Síndrome Metabólico, niveles mayores detroponina basal en pacientes con más tiempo en hemodiálisis, encontramos una variedad entre 0 y9 factores de riesgo presentes de los 14 analizados en el estudio, no encontramos correlación entre el tiempo en hemodiálisis y aumento de los factores de riesgo o entre la presencia de síndrome metabólico y el tiempo en hemodiálisis (AU)
Cardiovascular complications are the main cause of the Chronic Kidney Disease and also one of the main cardiovascular risk factors. On the other hand, a cardiovascular disease is directly related to android or central obesity. Our goal is to define cardiovascular risk factors on our patients receiving haemodialysis therapy, in order to provide a follow-up form as a support to estimate the progression or regression of risk factors. A transversal descriptive study, prospective and opened, has been elaborated. Reference population has been determined by a simple of our patients in haemodialysis therapy of our centres. Having analyzed the 14cardiovascular risk factors we present in the study, the average factors founded are 5.11 ± 2,157. Population to study showed: high level of overweight, Metabolic Syndrome (1 in 4 patients), Metabolic Syndrome, higher level of basal troponin inhaemodialysis patients treated for a long period of time. It has been found an oscillation from 0 to 9 risk factors out of the 14 studied ones. Neither a correlation between duration of haemodialysis treatment and increase of cardiovascular risk factors either between the appearing of Metabolic Syndrome and the duration of haemodialysis has been found (AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Diálise Renal/métodos , Doenças Cardiovasculares/complicações , Doenças Cardiovasculares/diagnóstico , Fatores de Risco , Índice de Massa Corporal , Diálise Renal/efeitos adversos , Estudos Transversais , Estudos Prospectivos , Inquéritos e QuestionáriosRESUMO
Introducción. Gracias a la bioimpedancia es posible valorar el estado de hidratación del paciente independientemente del peso corporal. También identifica las reservas proteicas/magras y reservas grasas en el paciente. Objetivos. 1. Descripción del estado nutricional de la población estable en un centro periférico medido por: bioimpedancia, antropometría, valoración global subjetiva y datos analíticos. 2. Comparación y análisis de los diferentes métodos de valoración nutricional. Metodología. Estudio analítico, prospectivo, comparativo de diferentes formas de valorar el estado nutricional de los 52 pacientes estables de nuestro centro. Estudiamos la concordancia entre variables y comparamos parámetros significativos de cada método de valoración nutricional: Resultados. Por valoración global subjetiva encontramos alto riesgo de desnutrición en un 63,46%; de los pacientes, la bioimpedancia indica una malnutrición de un 59,61%. La albúmina sérica muestra un 56,8% de los pacientes con un estado nutricional adecuado, mientras que están en este estado un 51,21% si se considera la transferrinasérica. Existen muchos métodos para valorar el estado nutricional de nuestros pacientes. Se observa correlación entre la valoración global subjetiva y la analítica nutricional (AU)
Introduction. Thanks to bioimpedance it is possible to evaluate the state of hydration of the patient independently of body weight. It also identifies the lean protein reserves and fat reserves in the patient. Objectives. 1. Description of the nutritional state of the stable population in a peripheral centre measured by: bioimpedance, anthropometrics, subjective global assessment and analytical data. 2. Comparison and analysis of the different nutritional evaluation methods. Methodology. Analytical, prospective, comparative study of the different ways of evaluating the nutritional state of the 52 stable patients in our centre. We studied the match between variables and we compared significant parameters of each nutritional evaluation method: Results. By subjective global assessment we found a high risk of malnutrition in 63.46% of patients, bioimpedance indicated malnutrition in 59.61%. Serum albumin showed 56.8% of patients in an adequate nutritional state while 51.21% are in this state if serum transferrin is considered. There are many methods for evaluating the nutritional state of our patients. A correlation is observed between the subjective global assessment and the nutritional analysis (AU)
Assuntos
Humanos , Diálise Renal/efeitos adversos , Desnutrição/epidemiologia , Impedância Elétrica , Estado Nutricional , Fatores de Risco , Estudos Prospectivos , Risco AjustadoRESUMO
Para el buen desarrollo de nuestras funciones como enfermeros se necesita una formación complementaria y especializada por lo que nos propusimos elaborar un plan de formación que cubriera tal necesidad. Durante tres meses impartimos un curso para enfermeros que se incorporarían a las sustituciones por vacaciones en nuestra unidad. Tras la finalización del programa formativo, se realizó una evaluación del mismo por parte del alumnado y el profesorado, y se realizó un estudio comparativo de la evaluación de ambas partes. También se extrajeron datos de los cuestionarios de calidad asistencial que se realizan periódicamente a los pacientes. Como conclusiones más destacables cabe citar: 1) El programa formativo ha servido para que el alumnado adquiera conocimientos y actitudes necesarios para el desarrollo de su labor una unidad de hemodiálisis. 2) Dicho desarrollo favorece el contar con personal cualificado para sustituciones, con escasa o nula afectación de la calidad asistencial. 3) Se ha favorecido la motivación en la plantilla de Enfermería de nuestro centro, basada en el desarrollo de la faceta docente y el reciclaje en los conocimientos básicos de Enfermería Nefrológica. 4) Quince semanas parece ser un tiempo escaso para el desarrollo de todas las cualidades y actitudes, principalmente en la adquisición de conocimientos en el programa teórico. 5) Los pacientes denotan en nuestra labor y así lo reflejan en su evaluación del personal, la mejor cualificación de la plantilla (AU)
To carry out properly our work as nurses, complementary specialized training is required and we there fore proposed to draw up a training plan to cover this need. For three months we gave a course for nurses who would join our unit to cover staff on vacation. After completing the training programme, an appraisal of it was carried out by pupils and teaching staff, and a comparative study of the appraisal by both groups was carried out. Data were also extracted from the quality of care questionnaires distributed among patients on a regular basis. The most notable conclusions were: 1) The training programme has enabled pupils to acquire the necessary knowledge and attitudes to carry out their work in a haemodialysis unit. 2) This development enhances having qualified replacement staff, with little or no detriment to quality of care. 3) Motivating has been favoured in the Nursing staff of our centres based on the development of the teaching facet and refreshment of basic Kidney Nursing knowledge. 4) Fifteen weeks appear to be insufficient time to develop all the qualities and attitudes, mainly in acquiring knowledge in the theoretical programme.5) Patients observed and reflected in their evaluation that staff were better qualified (AU)