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A protective HIV-1 vaccine has been hampered by a limited understanding of how B cells acquire neutralizing activity. Our previous vaccines expressing two different HIV-1 envelopes elicited robust antigen specific serum IgG titers in 20 rhesus macaques; yet serum from only two animals neutralized the autologous virus. Here, we used high throughput immunoglobulin receptor and single cell RNA sequencing to characterize the overall expansion, recall, and maturation of antigen specific B cells longitudinally over 90 weeks. Diversification and expansion of many B cell clonotypes occurred broadly in the absence of serum neutralization. However, in one animal that developed neutralization, two neutralizing B cell clonotypes arose from the same immunoglobulin germline and were tracked longitudinally. Early antibody variants with high identity to germline neutralized the autologous virus while later variants acquired somatic hypermutation and increased neutralization potency. The early engagement of precursors capable of neutralization with little to no SHM followed by prolonged affinity maturation allowed the two neutralizing lineages to successfully persist despite many other antigen specific B cells. The findings provide new insight into B cells responding to HIV-1 envelope during heterologous prime and boost immunization in rhesus macaques and the development of selected autologous neutralizing antibody lineages.
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Vacunas contra el SIDA , Infecciones por VIH , Seropositividad para VIH , VIH-1 , Animales , Anticuerpos Neutralizantes , Macaca mulatta , Anticuerpos Anti-VIH , Inmunización , Productos del Gen env del Virus de la Inmunodeficiencia HumanaRESUMEN
An internal employee challenge competition is a way to promote staff engagement and generate innovative business solutions. This Spotlight on Leadership focuses on the approach that a large not-for-profit healthcare organization, the Visiting Nurse Service of New York, took in designing and executing an innovation challenge. The challenge leveraged internal staff expertise and promoted wide participation. This model is 1 that can be replicated by organizations as leaders work to engage employees at the point of service in organization-wide problem solving.
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Conducta Cooperativa , Liderazgo , Servicios de Enfermería/organización & administración , Personal de Enfermería/educación , Sistemas de Atención de Punto/organización & administración , Solución de Problemas , Desarrollo de Personal/métodos , Competencia Clínica , Humanos , New York , Cultura Organizacional , Innovación OrganizacionalRESUMEN
Vehicular ad hoc networks (VANETs) have been identified as a key technology to enable intelligent transport systems (ITS), which are aimed to radically improve the safety, comfort, and greenness of the vehicles in the road. However, in order to fully exploit VANETs potential, several issues must be addressed. Because of the high dynamic of VANETs and the impairments in the wireless channel, one key issue arising when working with VANETs is the multihop dissemination of broadcast packets for safety and infotainment applications. In this paper a reliable low-overhead multihop broadcast (RLMB) protocol is proposed to address the well-known broadcast storm problem. The proposed RLMB takes advantage of the hello messages exchanged between the vehicles and it processes such information to intelligently select a relay set and reduce the redundant broadcast. Additionally, to reduce the hello messages rate dependency, RLMB uses a point-to-zone link evaluation approach. RLMB performance is compared with one of the leading multihop broadcast protocols existing to date. Performance metrics show that our RLMB solution outperforms the leading protocol in terms of important metrics such as packet dissemination ratio, overhead, and delay.
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Redes de Comunicación de Computadores , Modelos Teóricos , Vehículos a Motor , Tecnología Inalámbrica/normasRESUMEN
INTRODUCTION: Head and Neck Cancer Awareness and Screening Programs (HNCASP) are popular community outreach events hosted by academic and community otolaryngology departments. However, long-term follow-up of participants is lacking. PATIENTS AND METHODS: Participants of a HNCASP held at an academic cancer center prospectively filled out demographic and risk factor surveys followed by HNC screening examination. A phone interview was conducted for participants between 2012 and 2016 with suspicious findings to assess outcomes. RESULTS: Participants were largely Caucasian, female, and had health insurance, reflecting the setting at an academic medical center. Despite this, there were 156 (16.8%) positive screenings; 47 of these completed follow up interviews. Twelve (1.1% of all participants) cancer cases were confirmed. DISCUSSION: A significant proportion of HNCASP participants benefited from this screening opportunity. Education regarding HNC is the primary benefit and motivational factor for attendance of HNCASPs, although a significant subset of patients was identified that needed follow-up, and several cancers were detected.
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Detección Precoz del Cáncer/psicología , Neoplasias de Cabeza y Cuello/diagnóstico , Entrevistas como Asunto , Tamizaje Masivo/psicología , Motivación , Adulto , Anciano , Femenino , Estudios de Seguimiento , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de RiesgoRESUMEN
Introducción. La enfermedad renal crónica es responsable de aproximadamente 2,4 millones de defunciones a nivel mundial. La supervivencia a los cinco años después de iniciar diálisis se encuentra entre un 39 a 60 % dependiendo del país. Objetivo. Describir la situación epidemiológica de los pacientes con diálisis y analizar los factores que influyen en la supervivencia de pacientes a cinco años de iniciar tratamiento sustitutivo renal en El Salvador. Metodología. Estudio de cohorte retrospectivo de los pacientes incluidos en el Registro Nacional de Diálisis y Trasplante Renal desde enero de 2016 hasta febrero de 2023. El seguimiento se comenzó al inicio de la diálisis, el evento de interés fue la muerte del paciente. Se utilizó el método de Kaplan-Meier para determinar la supervivencia al año y a los cinco años y la regresión de Cox con el modelo de Royston-Parmar para analizar los factores que influyen sobre la supervivencia a los cinco años. Resultados. El estudio incluyó 7088 pacientes, la supervivencia a uno y cinco años fue del 79,5 % (IC 95 %: 78,6-80,5) y 50,6 % (IC 95 %: 49,1-52,1) respectivamente. La regresión de Cox para la edad de inicio de tratamiento resultó en un hazard ratio de 1,02 (IC 95 %: 1,01-1,02), mientras que para el oficio de ser agricultor el hazard ratio fue 1,1 (IC 95 %: 1,01-1,18) y para la etiología hipertensiva el hazard ratio fue de 0,7 (IC 95 %: 0,64-0,78). Conclusión. La edad de inicio de tratamiento y el ser agricultor están asociados con una menor supervivencia a cinco años en pacientes con diálisis
Introduction. The chronic kidney disease is responsible for approximately 2.4 million deaths worldwide, in El Salvador during 2019 death rate was 72.9 for 100 000 habitants, five year survival in patients after starting dialysis was between 39 and 60 % depending on the country. Objective. Analyze the factors that influence the five years survival in patients after starting renal replacement therapy in El Salvador. Methodology. It is a retrospective cohort study from patients included in dialysis and renal replacement therapy national registry from January 2016 to February 2023, the start point for the following was the initiation of dialysis, the event of interest was patient Ìs death, the Kaplan-Meier method was used to determine one year and five year survival; and Cox regression with Royston-Parmar model was used to analyze the factors that influence survival. Results. The study included 7088 patients, one and five-years survival was 79.5 % (CI 95 %: 78.6-80.5) and 50.6 % (CI 95 %: 49.1-52.1) respectively. The Cox regression for age of treatment initiation resulted in a hazard ratio of 1.02 (CI 95 %: 1.01-1.02), while for farmers, the hazard ratio was 1.09 (CI 95 %: 1.00-1.18), for hypertensive etiology the hazard ratio was 0.7 (CI 95 %: 0.64-0.78). Conclusion. Data suggest that age of treatment initiation, and jobs related to agriculture were associated with less five year survival in dialysis patients.
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Insuficiencia Renal , El SalvadorRESUMEN
RESUMEN Introducción: La enfermedad renal crónica afecta alrededor de la décima parte de la población mundial y los métodos analíticos que más se utilizan para su diagnóstico tienen una baja sensibilidad y precisión. Objetivo: Determinar las concentraciones de cistatina C para la evaluación del filtrado glomerular en fases predialíticas de la enfermedad renal crónica. Métodos: Se realizó un estudio descriptivo, transversal. El universo de estudio estuvo conformado por 102 pacientes con enfermedad renal crónica en estadios del uno al cuatroque se atendieron en consulta externa del servicio de Nefrología.La muestra fueron 81 pacientes que no presentaron factores modificadores del filtrado glomerular, creatinina y cistatina C relacionados con la enfermedad renal crónica. Resultados: Predominaron los pacientes mayores de 61 años. La cistatina C se elevó en más pacientes que la creatinina. La cistatina C se elevó por igual en ambos sexos y la creatinina más en hombres. La media de los resultados se alejó más de la media del valor de referencia en la cistatina C y la creatinina no presentó valores normales en pacientes con insuficiencia renal crónica. Las ecuaciones que utilizan la cistatina C fueron mejor predictoras de daño renal. Conclusiones: La cistatina C fue mejor predictora de daño renal.
ABSTRACT Introduction: The renal chronic disease affects around a tenth part of the worldwide population and the most used analytical methods for its diagnosis have a low sensibility and precision. Objective: To determine cystatin C's concentrations for evaluation of glomerular masking in pre-dialytic phases of the renal chronic disease. Methods: A descriptive, cross-sectional study was carried out.The study universe was made up of 102 patients with chronic kidney disease in stages from one to four who were treated in an outpatient department of the Nephrology service. The samplewas 81 patients who did not present the modifier factors of glomerular masking, creatinine and cystatin C related with the renal chronic disease. Results: The patients older than 61 years predominated. The cystatin C augmented in more patients than the creatinine. The cystatin C augmented equally in both sexes and the creatinine more in men. The average of the results moved away over the average of the value of reference in the cystatin C and the creatinine did not present normal values in patients with renal chronic insufficiency. The equations that they use cystatin C were better forecaster of damage renal. Conclusions: The cystatin C was the best predictor of renal damage.
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The Trypanosoma cruzi hexokinase gene has been cloned, sequenced, and expressed as an active enzyme in Escherichia coli. Sequence analysis revealed 67% identity with its counterpart in Trypanosoma brucei but low similarity with all other available hexokinase sequences including those of human. It contains an N-terminal peroxisome-targeting signal (PTS-2) and has a calculated basic isoelectric point (pI = 9.67), a feature often associated with glycosomal proteins. The polypeptide has a predicted mass of approximately 50 kDa similar to that of many non-vertebrate hexokinases and the vertebrate hexokinase isoenzyme IV. The natural enzyme was purified to homogeneity from T. cruzi epimastigotes and appeared to exist in several aggregation states, an apparent tetramer being the predominant form. Its kinetic properties were compared with those of the purified recombinant protein. Higher K(m) values for glucose and ATP were found for the (His)(6)-tag-containing recombinant hexokinase. However, removal of the tag produced an enzyme displaying similar values as the natural enzyme (K(m) for glucose = 43 and 60 microM for the natural and the recombinant protein, respectively). None of these enzymes presented activity with fructose. As reported previously for hexokinases from several trypanosomatids, no inhibition was exerted by glucose 6-phosphate (G6-P). In contrast, a mixed-type inhibition was observed with inorganic pyrophosphate (PPi, K(i) = 0.5mM).
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Hexoquinasa/genética , Hexoquinasa/metabolismo , Trypanosoma cruzi/enzimología , Secuencia de Aminoácidos , Animales , Secuencia de Bases , Clonación Molecular , Cartilla de ADN , Escherichia coli/enzimología , Escherichia coli/genética , Hexoquinasa/química , Humanos , Isoenzimas/química , Isoenzimas/genética , Cinética , Datos de Secuencia Molecular , Proteínas Recombinantes/química , Proteínas Recombinantes/metabolismo , Saccharomyces cerevisiae/enzimología , Saccharomyces cerevisiae/genética , Alineación de Secuencia , Homología de Secuencia de Aminoácido , Trypanosoma cruzi/genéticaRESUMEN
Se realizó un estudio descriptivo y retrospectivo con el objetivo de describir las características clínicas y epidemiológicas de los pacientes con infección relacionada con los cuidados sanitarios en la unidad de cuidados intensivos del Hospital Provincial General Docente Carlos Manuel de Céspedes, de Bayamo, Granma, Cuba en el período comprendido desde el 1ero de enero de 2011 hasta el 31 de diciembre de 2011. De 556 pacientes ingresados, 47 (8.6 por ciento) cumplieron los criterios de infección asociada a cuidados sanitarios. Se seleccionaron variables como: edad, sexo, tipo de paciente, evolución final, localización de la infección, gérmenes aislados, cultivos indicados, factores de riesgos relacionados y tiempo de aparición de la enfermedad. Para el análisis estadístico se utilizaron como medidas de resumen el porcentaje, la razón, la proporción; la media aritmética y la desviación estándar. La infección se desarrolló con mayor frecuencia en enfermos entre los 66 y 75 años (23.4 por ciento). Hubo ligero predominio del sexo femenino (51.1 por ciento). El paciente quirúrgico fue el más afectado (66,0 por ciento). La neumonía asociada a ventilación (46.8 por ciento) fue la localización más frecuente. Existió predominio de los gérmenes gramnegativos, entre ellos el Enterobácter sp. (28 por ciento). Se indicaron 67 cultivos, 54 de ellos fueron positivos. La sonda vesical (80.9 por ciento) constituyó el factor de riesgo fundamental. El mayor número de infecciones apareció entre el primer y el quinto día de ingreso (42.6 por ciento). Fallecieron seis pacientes (12,8 por ciento)(AU)
It was performed a descriptive and retrospective study with the aim of describing the clinical and epidemiological features of patients with infections related to health care in the Intensive Care Unit at "Carlos Manuel de Céspedes" General Teaching Province Hospital in Bayamo, Granma, during the period January 1rst, 2011 to December 31rst, 2011. From the 556 patients admitted, 47 (8.6 percent) fullfiled the criteria of infection associated with health care. There were selected variables such as: age, sex, type of patient, final evolution, location of the infection, isolated germs, indicated cultures, time of the appearance of the disease and related risk factors. For the statistical analysis there were used as summary measures the percentage, reason, proportion; the arithmetic mean and deviation standard. The infection was most frequently developed in patients between 66 and 75 years (23.4 percent). There was a slight female predominance (51.1 percent). The surgical patient was the most affected (66,0 percent). The pneumonia associated to ventilation (46.8 percent) was the most common location. There was a predominance of the gram-negative bacteria, including Enterobacter sp. (28 percent). There were indicated 67 cultures, 54 of them were positive. The urinary catheter (80.9 percent) constituted the main risk factor. The largest number of infections appeared between the first and the fifth day of hospitalizations (42.6 percent). Six patients died (12.8 percent)(EU)
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Humanos , Infección Hospitalaria/epidemiología , Unidades de Cuidados Intensivos , Infección Hospitalaria/mortalidad , Factores de Riesgo , Epidemiología Descriptiva , Estudios RetrospectivosRESUMEN
An electrophoretic and microbiological study more probable number (NMP), total (CT) and fecal coliforms (CF); aerobic-mesophils bacteria (BAM), molds and yeasts in worm's flour of Eisenia fetida was carried out. In the electrophoretic profiles using gels of standard concentration, different protein fractions with molecular weights between 39.6 and 43.5 kDa were separated. When gels with growing gradient of concentration were used, proteins with higher molecular weights (124.4 and 106.8 kDa) were separated with more detail. The protein characterization using different electrophoretic systems used in this study allows studying different protein fractions that could have a nutritional importance. The counts of BAM, CT, CF, molds and yeasts in this flour were low, indicating an innocuous product. With the use of this non-conventional resource, an interesting field of investigation begins involving food enrichment, representing an alternative at the industrial level.
Se realizó un estudio electroforético y microbio-lógico [número más probable (NMP), coliformes totales (CT) y fecales (CF); bacterias aerobias-mesófilas (BAM), mohos y levaduras] en harina de lombriz Eisenia fétida. En los perfiles electroforéticos con geles de concentración estándar se separaron diferentes fracciones proteicas con pesos moleculares comprendidos entre 39,6 y 43,5 kDa, valores similares a los reportados por otros investigadores. Cuando se usaron geles con gradiente creciente de concentración, se lograron separar en forma mas detallada proteínas con pesos moleculares más altos (124,4 y 106,8 kDa). En este estudio, la caracterización de proteínas utilizando distintos sistemas electroforéticos permitió analizar las diferentes fracciones proteicas que pudiesen tener una importancia nutricional. Los recuentos de BAM, CT, CF, mohos y levaduras en esta harina fueron bajos, lográndose un producto inocuo. Es importante destacar, que con la utilización de este recurso no convencional, se inicia un interesante campo de investigación en lo que se refiere al enriquecimiento de alimentos, representando una alternativa a nivel industrial.
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Bacterias Aerobias/aislamiento & purificación , Coliformes/análisis , Harina/microbiología , Hongos/aislamiento & purificación , Oligoquetos , Proteínas/análisis , Electroforesis en Gel de Poliacrilamida , Técnicas Microbiológicas , Peso MolecularRESUMEN
Los quistes epidermoides del testículo son raros, representando solo el 1 por ciento de todos los tumores de esta gónada. Los autores analizan 4 casos tratados, en ninguno de los cuales hubo sospecha clínica preoperatoria. Esto llevó a realizar cirugía radical en tres casos y parcial en un paciente. La naturaleza benigna de esta lesión podría permitir realizar cirugía conservadora en casos con sospecha preoperatoria, ecografía concordante y biopsia contemporánea confiable