ABSTRACT
Enzymatic DNA writing technologies based on the template-independent DNA polymerase terminal deoxynucleotidyl transferase (TdT) have the potential to advance DNA information storage. TdT is unique in its ability to synthesize single-stranded DNA de novo but has limitations, including catalytic inhibition by ribonucleotide presence and slower incorporation rates compared to replicative polymerases. We anticipate that protein engineering can improve, modulate, and tailor the enzyme's properties, but there is limited information on TdT sequence-structure-function relationships to facilitate rational approaches. Therefore, we developed an easily modifiable screening assay that can measure the TdT activity in high-throughput to evaluate large TdT mutant libraries. We demonstrated the assay's capabilities by engineering TdT mutants that exhibit both improved catalytic efficiency and improved activity in the presence of an inhibitor. We screened for and identified TdT variants with greater catalytic efficiency in both selectively incorporating deoxyribonucleotides and in the presence of deoxyribonucleotide/ribonucleotide mixes. Using this information from the screening assay, we rationally engineered other TdT homologues with the same properties. The emulsion-based assay we developed is, to the best of our knowledge, the first high-throughput screening assay that can measure TdT activity quantitatively and without the need for protein purification.
Subject(s)
DNA Nucleotidylexotransferase , DNA-Directed DNA Polymerase , Protein Engineering , Protein Engineering/methods , DNA-Directed DNA Polymerase/metabolism , DNA-Directed DNA Polymerase/genetics , DNA-Directed DNA Polymerase/chemistry , DNA Nucleotidylexotransferase/metabolism , DNA Nucleotidylexotransferase/chemistry , DNA Nucleotidylexotransferase/genetics , High-Throughput Screening Assays/methods , DNA, Single-Stranded/genetics , DNA, Single-Stranded/metabolism , Deoxyribonucleotides/metabolism , MutationABSTRACT
AIM: To investigate the usefulness of multistate models (MSM) for determining colorectal cancer (CRC) recurrence rate, to analyse the effect of different factors on tumour recurrence and death, and to assess the impact of recurrence for CRC prognosis. METHODS: Observational follow-up study of incident CRC cases disease-free after curative resection in 2006-2013 (n = 994). Recurrence and mortality were analyzed with MSM, as well as covariate effects on transition probabilities. RESULTS: Cumulative incidence of recurrence at 60 months was 13.7%. Five years after surgery, 70.3% of patients were alive and recurrence-free, and 8.4% were alive after recurrence. Recurrence has a negative impact on prognosis, with 5-year CRC-related mortality increasing from 3.8% for those who are recurrence-free 1-year after surgery to 33.6% for those with a recurrence. Advanced stage increases recurrence risk (HR = 1.53) and CRC-related mortality after recurrence (HR = 2.35). CRC-related death was associated with age in recurrence-free patients, and with comorbidity after recurrence. As expected, age≥75 years was a risk factor for non-CRC-related death with (HR = 7.76) or without recurrence (HR = 4.26), while its effect on recurrence risk was not demonstrated. CONCLUSIONS: MSM allows detailed analysis of recurrence and mortality in CRC. Recurrence has a negative impact on prognosis. Advanced stage was a determining factor for recurrence and CRC-death after recurrence.
ABSTRACT
The aim of this study was to analyze the psychometric properties of the Purpose in Life Test-Short Form (PIL-SF), a brief self-report measure of the presence of meaning in life (MiL). Participants were 349 nonclinical Spanish undergraduates (225 women, 64.5%, and 124 men, 35.5%), age ranged between 18 and 26 years (M = 20.85; SD = 2.16). The PIL-SF, the Seeking of Noetic Goals-8 Items (SONG-8), the Satisfaction with Life Scale (SWLS), and the Oxford Happiness Questionnaire (OHQ) were used. Descriptive analysis, estimation of the internal consistency, and Confirmatory Factor Analysis of the PIL-SF were conducted, and correlations between the PIL-SF and the SONG-8, the SWLS, and the OHQ were calculated. The PIL-SF showed good internal consistency and an excellent fit as a unidimensional scale confirming its factorial structure. Regarding construct validity, correlations between the PIL-SF and SWLS (r= 0.59) and OHQ (r = 0.56) were positive, significant (p < 0.001), while correlation between PIL-SF and SONG-8 was negative, significant (r = -0.23, p < 0.001). The Spanish adaptation of PIL-SF seems to be a valid measure of MiL with good internal consistency.
Subject(s)
Psychometrics , Adolescent , Adult , Female , Humans , Male , Young Adult , Factor Analysis, Statistical , Psychometrics/methods , Reproducibility of Results , Self Report , Surveys and Questionnaires , Middle Aged , Aged , Aged, 80 and over , SpainABSTRACT
La Bioética es la disciplina que estudia los problemas éticos que surgen en relación con la salud. Es el educador quien desempeña el papel principal al analizar los aspectos metodológicos en el proceso de articulación docente-asistencial para lograr una enseñanza con valores éticos en los futuros profesionales, apoya al estudiante con un enfoque personalizado, afectivo, comunicativo y reflexivo, enmarcado en el cumplimiento de la misión social y humana que implica ser un profesional de la Medicina. El objetivo de los autores es socializar elementos del pensamiento bioético relacionados con la formación de valores en los estudiantes, destacando el humanismo y la solidaridad, con una coherente sistematización del conocimiento sobre las diferentes corrientes bioéticas en el proceso formativo en el campo de la salud.
Bioethics is the discipline which studies ethical problems that arise in relation to health. Teachers are the ones who play the main role when analyzing methodological aspects in the teaching-care process to achieve teaching with ethical values in future professionals and support students with a personalized, affective, communicative and reflective approach, framed in the fulfillment of the social and human mission that being a medical professional implies. The objective of the authors is to socialize elements of bioethical thought related to the formation of values in students, highlighting humanism and solidarity, with a coherent systematization of knowledge about the different bioethical currents in the health training process.
Subject(s)
Teaching , Education, Medical , Ethics, Medical , Faculty , Social NormsABSTRACT
The development of new tuberculosis vaccines remains a global priority, and recombinant vaccines are a frequently investigated option. These vaccines follow a molecular strategy that may enhance protective efficacy. However, their functional differences, particularly with respect to glycosylation, remain unknown. Recent studies have shown that glycosylation plays a key role in the host-pathogen interactions during immune recognition. The aim of this study was to determine the differences in the glycosylation profiles of two recombinant strains of Mycobacterium microti, overexpressing Ag85B (Rv1886c) and PstS-1 (Rv0934) antigens of M. tuberculosis. For each strain, the glycosylation profile was determined by Western blotting with lectins. The results showed the presence of mannosylated proteins and evidence of linked sialic acid proteins. Interestingly, different proteome and glycoproteome profiles were observed between the two recombinant strains and the wild-type strain. We have shown here that the construction of the recombinant strains of M. microti has altered the proteome and glycosylation profiles of these strains, leading us to ask what impact these changes might have on the immune response.
Subject(s)
Mycobacterium tuberculosis , Tuberculosis Vaccines , Tuberculosis , Humans , Mycobacterium tuberculosis/genetics , Proteome/genetics , Bacterial Proteins , Tuberculosis/microbiologyABSTRACT
Objetivo: Conocer el estado de salud de la población sin hogar. Diseño: Estudio descriptivo transversal. Emplazamiento: Centro de Salud de Atención Primaria de Raval Sud (Barcelona). Participantes: Personas mayores de edad en situación de sinhogarismo que han pernoctado en la calle en algún momento. Mediciones principales: Datos sociodemográficos y tiempo en situación de sinhogarismo. Patologías crónicas, enfermedades infecciosas transmisibles, enfermedades mentales y trastornos por uso de sustancias adictivas. Cuestionario HAD sobre ansiedad y depresión. Cuestionario CVRS EQ-5D-3L. Estadística descriptiva. Resultados: Se analizó la información de 146 pacientes con una media de edad de 51,6 años (DE=12,8), 87% de sexo masculino y una media de 12 años (DE=11,9) en situación de sinhogarismo. Se comparó la carga de enfermedad entre el perfil CAS Drogodependencias (Baluard) y el perfil sociosanitario (Arrels Fundació). Los usuarios del CAS presentaron mayores porcentajes de trastornos por uso de sustancias, enfermedades mentales y enfermedades infecciosas transmisibles. Las personas de perfil sociosanitario presentaron en mayor porcentaje enfermedades crónicas (respiratorias, cardiovasculares y oncológicas) y más de la mitad presentaron un trastorno por uso de alcohol y un mayor porcentaje de enfermedad asociada a su consumo. Conclusiones: La población sin hogar presenta una elevada carga de enfermedad especialmente para enfermedad mental, adicciones y enfermedades infecciosas transmisibles. Creemos que son necesarios estudios para evaluar el exceso de enfermedad respecto a la población general con sus costes derivados y el diseño de nuevas estrategias para atender dicha carga de enfermedad y su especificidad.(AU)
Objective: To assess the health status of the homeless population. Design: Cross-sectional descriptive study. Setting: Raval Sud Primary Care Health Center (Barcelona). Participants: Homeless legal age people who have slept rough at some point in their lives. Main measurements: Sociodemographic data and time in a situation of homelessness. Chronic pathologies, transmissible infectious diseases, mental illnesses and substance use disorders. HAD questionnaire on anxiety and depression. CVRS EQ-5D-3L questionnaire. Descriptive statistics. Results: The information of 146 patients with a mean age of 51.6 years (SD=12.8), 87% male and a mean of 12 years (SD=11.9) in a situation of homelessness was analyzed. The burden of disease was compared between the CAS profile (Drug addiction center Baluard) and the socio-sanitary profile (Arrels Foundation). CAS users presented higher percentages of substance use disorders, mental illnesses and transmissible infectious diseases. People with a socio-health profile presented a higher percentage of chronic diseases (respiratory, cardiovascular and oncological) and more than half presented an alcohol use disorder and a higher percentage of disease associated with its consumption. Conclusions: The homeless population presents a high burden of disease, especially for mental illness, addictions and transmissible infectious diseases. We believe that studies are necessary to evaluate the disease excess compared to the general population with its derived costs and to design new strategies to address this burden of disease and its specificity.(AU)
Subject(s)
Humans , Male , Female , Aged , Ill-Housed Persons , Health Status , 29161 , Epidemiology , Vulnerable Populations , Spain , Primary Health Care , Epidemiology, Descriptive , Cross-Sectional StudiesABSTRACT
OBJECTIVE: To assess the health status of the homeless population. DESIGN: Cross-sectional descriptive study. SETTING: Raval Sud Primary Care Health Center (Barcelona). PARTICIPANTS: Homeless legal age people who have slept rough at some point in their lives. MAIN MEASUREMENTS: Sociodemographic data and time in a situation of homelessness. Chronic pathologies, transmissible infectious diseases, mental illnesses and substance use disorders. HAD questionnaire on anxiety and depression. CVRS EQ-5D-3L questionnaire. Descriptive statistics. RESULTS: The information of 146 patients with a mean age of 51.6 years (SD=12.8), 87% male and a mean of 12 years (SD=11.9) in a situation of homelessness was analyzed. The burden of disease was compared between the CAS profile (Drug addiction center - Baluard) and the socio-sanitary profile (Arrels Foundation). CAS users presented higher percentages of substance use disorders, mental illnesses and transmissible infectious diseases. People with a socio-health profile presented a higher percentage of chronic diseases (respiratory, cardiovascular and oncological) and more than half presented an alcohol use disorder and a higher percentage of disease associated with its consumption. CONCLUSIONS: The homeless population presents a high burden of disease, especially for mental illness, addictions and transmissible infectious diseases. We believe that studies are necessary to evaluate the disease excess compared to the general population with its derived costs and to design new strategies to address this burden of disease and its specificity.
Subject(s)
Ill-Housed Persons , Mental Disorders , Population Health , Substance-Related Disorders , Cross-Sectional Studies , Female , Health Status , Humans , Male , Mental Disorders/epidemiology , Middle Aged , Substance-Related Disorders/epidemiologyABSTRACT
RESUMEN Introducción: los programas de Atención Temprana son favorecedores del neurodesarrollo y resultan altamente eficaces en su conjunto para los niños con trastornos en el desarrollo. Objetivo: determinar factores epidemiológicos y clínico-terapéuticos en niños con retardo del desarrollo psicomotor tratados en consulta de Atención Temprana del policlínico Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Métodos: se realizó un estudio epidemiológico observacional descriptivo, longitudinal, que incluyó a 88 niños diagnosticados con retardo del desarrollo psicomotor y tratados en la consulta de Atención Temprana del policlínico Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Variables estudiadas: edad en el momento del diagnóstico en la consulta de Atención Temprana, sexo, procedencia, factores de riesgo perinatal y evolución a los 12 meses del diagnóstico e inicio del tratamiento rehabilitador. Se empleó la estadística descriptiva para el procesamiento de los datos. Resultados: predominaron los niños diagnosticados entre los 6 meses y 11 meses y 29 días (52.3%), del sexo femenino (65,9%) y procedencia urbana (69,3%). El 82.9 % presentó factores de riesgo perinatal, con predominio del bajo peso al nacer y las infecciones perinatales. El 90.9% evolucionó favorablemente, destacando los diagnosticados entre 6 y 11 meses y 29 días, y los que no tuvieron o tuvieron uno o dos factores de riesgo perinatal. Conclusiones: la mayoría de los niños estudiados fueron diagnosticados en consulta de Atención Temprana entre los seis y doce meses de edad, presentaron uno o dos factores de riesgo perinatal (siendo el más frecuente el bajo peso al nacer), y evolucionaron favorablemente.
ABSTRACT Introduction: Early Care programs are pro-developmental and highly effective as a whole for children with developmental disorders. Objective: to determine epidemiological and clinical-therapeutic factors in children with psychomotor development delay treated in the Early Care consultation of the Jimmy Hirzel Polyclinic, Bayamo, Granma, during 2018-2019. Methods: a descriptive, longitudinal observational epidemiological study was conducted, which included 88 children diagnosed with psychomotor developmental delay and treated in the Early Care consultation of the Jimmy Hirzel Polyclinic, Bayamo, Granma, during 2018-2019. Variables studied: age at the time of diagnosis in the Early Care consultation, sex, origin, perinatal risk factors and evolution at 12 months of diagnosis and initiation of rehabilitative treatment. Descriptive statistics were used for data processing. Results: children diagnosed between 6 months and 11 months and 29 days (52.3%), female (65.9%) and urban origin (69.3%) predominated. 82.9% presented perinatal risk factors, with a predominance of low birth weight and perinatal infections. 90.9% evolved favorably, highlighting those diagnosed between 6 and 11 months and 29 days, and those who did not have or had one or two perinatal risk factors. Conclusions: most of the children studied were diagnosed in the Early Care consultation between six and twelve months of age, presented one or two perinatal risk factors (the most frequent being low birth weight), and evolved favorably.
RESUMO Introdução: Os programas de Atenção Precocesão pró-desenvolvimento e altamente eficazes como um todo para crianças com transtornos do desenvolvimento. Objetivo: determinar fatores epidemiológicos e clínico-terapêuticos em crianças com atraso no desenvolvimento psicomotor tratado na consulta de Atenção Precoce da Policlínica Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Métodos: foi realizado um estudo epidemiológico observacional descritivo e longitudinal, que incluiu 88 crianças diagnosticadas com atraso no desenvolvimento psicomotor e tratadas na consulta de Cuidados Precoces da Policlínica Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Variáveis estudadas: idade no momento do diagnóstico na consulta de Atenção Precoce, sexo, origem, fatores de risco perinatais e evolução aos 12 meses de diagnóstico e início do tratamento reabilitatório. Foram utilizadas estatísticas descritivas para o processamento de dados. Resultados: predominaram as crianças diagnosticadas entre 6 meses e 11 meses e 29 dias (52,3%), do sexo feminino (65,9%) e da origem urbana (69,3%). 82,9% apresentaram fatores de risco perinatais, com predominância de baixo peso ao nascer e infecções perinatais. 90,9% evoluíram favoravelmente, destacando aqueles diagnosticados entre 6 e 11 meses e 29 dias, e aqueles que não tinham ou tinham um ou dois fatores de risco perinatais. Conclusões: a maioria das crianças estudadas foi diagnosticada na consulta de Atenção Precoce entre seis e doze meses de idade, apresentou um ou dois fatores de risco perinatais (sendo o mais frequente o baixo peso ao nascer) e evoluiu favoravelmente.
ABSTRACT
RESUMEN Fundamento: el consumo de tabaco es un factor de riesgo que predispone a diversas enfermedades. La adolescencia es la etapa donde fundamentalmente se inician los fumadores, por tanto es necesario el trabajo preventivo desde etapas tempranas de la vida. Objetivo: determinar las características del tabaquismo activo en adolescentes. Métodos: estudio descriptivo de corte transversal, con estudiantes de noveno de la Secundaria Básica Frank País García, de Cienfuegos. Se analizaron las variables edad, sexo, características clínicas (dadas por intensidad, frecuencia y señales de dependencia), conocimientos acerca del tabaquismo y actitudes hacia este. Resultados: la muestra quedó conformada por 180 estudiantes; 56,6 % femeninos y 43,3 % masculinos. Predominaron los estudiantes de 14 años y no fumadores. El nivel de conocimiento sobre el tabaquismo fue inadecuado para ambos grupos. No hubo relación significativa entre el sexo, el conocimiento y el hábito de fumar; la mayoría mostró una actitud de rechazo al cigarro. Más de la mitad de los fumadores consumía casi todos los días del mes. La frecuencia fue de 6 a 10 cigarros al día, un grupo menor de estudiantes (30,8 %) presentó dependencia nicotínica. Conclusiones: se corroboró que el consumo de tabaco estuvo presente en algunos de los estudiantes de la muestra y también la dependencia nicotínica lo cual es de gran relevancia debido a la etapa de la vida en que se encuentran.
ABSTRACT Background: tobacco use is a risk factor that predisposes to various diseases. Adolescence is the stage where smokers mainly start, therefore preventive work is necessary from the early stages of life. Objective: to determine the characteristics of active smoking in adolescents. Methods: descriptive cross-sectional study with ninth-grade students from Frank País García Elementary School in Cienfuegos. The variables age, sex, clinical characteristics (given by intensity, frequency and signs of dependence), knowledge about smoking and attitudes towards it were analyzed. Results: the sample was made up of 180 students; 56.6% female and 43.3% male. 14-year-old non-smoking students predominated. The level of knowledge about smoking was inadequate for both groups. There was no significant relationship between sex, knowledge, and smoking; the majority showed an attitude of rejection of cigarettes. More than half of the smokers consumed almost every day of the month. The frequency was 6 to 10 cigarettes a day, a smaller group of students presented nicotinic dependence (30.8%). Conclusions: it was confirmed that tobacco consumption was present in some of the students in the sample and also nicotinic dependence, which is of great relevance due to the stage of life in which they are.
ABSTRACT
No disponible
Subject(s)
Humans , Male , Aged, 80 and over , Dementia , Bipolar Disorder , Geriatrics , Alzheimer DiseaseABSTRACT
Everolimus is an immunosuppressant agent used in organ transplantation and, more recently, in cancer therapy. It has demonstrated beneficial effects in breast cancer, renal cancer, and neuroendocrine tumours. However, the treatment is not without side effects, some of which are still little known. We report the case of a 56 year-old man with a diagnosis of neuroendocrine tumour who developed a complex regional pain syndrome (CRPS) secondary to treatment with everolimus. CRPS has been linked to treatments with everolimus in renal and breast cancer patients as well as in renal transplant patients. To our knowledge, this is the first case of CRPS in a neuroendocrine tumour patient on everolimus treatment.
Subject(s)
Complex Regional Pain Syndromes , Neuroendocrine Tumors , Reflex Sympathetic Dystrophy , Complex Regional Pain Syndromes/chemically induced , Complex Regional Pain Syndromes/drug therapy , Everolimus/adverse effects , Humans , Male , Middle Aged , Neuroendocrine Tumors/complications , Neuroendocrine Tumors/drug therapyABSTRACT
Introducción: los programas de Atención Temprana son favorecedores del neurodesarrollo y resultan altamente eficaces en su conjunto para los niños con trastornos en el desarrollo. Objetivo: determinar factores epidemiológicos y clínico-terapéuticos en niños con retardo del desarrollo psicomotor tratados en consulta de Atención Temprana del policlínico Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Métodos: se realizó un estudio epidemiológico, observacional, descriptivo, longitudinal, que incluyó a 88 niños diagnosticados con retardo del desarrollo psicomotor y tratados en la consulta de Atención Temprana del policlínico Jimmy Hirzel, Bayamo, Granma, durante 2018-2019. Variables estudiadas: edad en el momento del diagnóstico en la consulta de Atención Temprana, sexo, procedencia, factores de riesgo perinatal y evolución a los 12 meses del diagnóstico e inicio del tratamiento rehabilitador. Se empleó la estadística descriptiva para el procesamiento de los datos. Resultados: predominaron los niños diagnosticados entre los 6 meses y 11 meses y 29 días (52.3 por ciento), del sexo femenino (65,9 por ciento) y procedencia urbana (69,3 por ciento). El 82.9 por ciento presentó factores de riesgo perinatal, con predominio del bajo peso al nacer y las infecciones perinatales. El 90.9 por ciento evolucionó favorablemente, destacando los diagnosticados entre 6 y 11 meses y 29 días, y los que no tuvieron o tuvieron uno o dos factores de riesgo perinatal. Conclusiones: la mayoría de los niños estudiados fueron diagnosticados en consulta de Atención Temprana entre los seis y doce meses de edad, presentaron uno o dos factores de riesgo perinatal (siendo el más frecuente el bajo peso al nacer), y evolucionaron favorablemente(AU)
Introduction: Early Care programs are pro-developmental and highly effective as a whole for children with developmental disorders. Objective: to determine epidemiological and clinical-therapeutic factors in children with psychomotor development delay treated in the Early Care consultation of the Jimmy Hirzel Polyclinic, Bayamo, Granma, during 2018-2019. Methods: a descriptive, longitudinal observational epidemiological study was conducted, which included 88 children diagnosed with psychomotor developmental delay and treated in the Early Care consultation of the Jimmy Hirzel Polyclinic, Bayamo, Granma, during 2018-2019. Variables studied: age at the time of diagnosis in the Early Care consultation, sex, origin, perinatal risk factors and evolution at 12 months of diagnosis and initiation of rehabilitative treatment. Descriptive statistics were used for data processing. Results: children diagnosed between 6 months and 11 months and 29 days (52.3 percent), female (65.9 percent) and urban origin (69.3 percent) predominated. 82.9 percent presented perinatal risk factors, with a predominance of low birth weight and perinatal infections. 90.9 percent evolved favorably, highlighting those diagnosed between 6 and 11 months and 29 days, and those who did not have or had one or two perinatal risk factors. Conclusions: most of the children studied were diagnosed in the Early Care consultation between six and twelve months of age, presented one or two perinatal risk factors (the most frequent being low birth weight), and evolved favorably(AU)